Monthly Archives: December 2019

Blood Transfusion Guided by Physiological Markers

DOI: 10.31038/IMROJ.2019425

Abstract

Introduction: For decades, intraoperative anemia has been treated with red blood cell transfusions since it was believed that oxygen supply would increase by increasing hemoglobin levels. There is evidence that blood transfusion is associated with adverse events and should be avoid as much as possible. For this purpose, it is essential to know the compensatory physiological mechanisms during anemia. Venous oxygen saturation is a clinical tool that integrates the relationship between oxygen intake and consumption, which is easy to obtain once a central venous catheter, is available.

Material and methods: A longitudinal, prospective, observational study was conducted which included patients schedule for elective or emergency procedures that, due to their clinical conditions, had a central venous catheter. A sample of venous blood was taken from the central venous catheter and sent to the laboratory for gasometry. The results were correlated with the clinical status and vital signs of the patient. The following variables were evaluated: vital signs, hemoglobin, and hematocrit and oxygen saturation before and after transfusion.

Results: 34 patients were evaluated with an average age of 52 years. 58.8% was transfused. Despite the transfusion and variations of hemoglobin, the SaO2 in the pulse oximeter remained without changes pre and post transfusion. In gasometry, a difference between hemoglobin and initial hematocrit and pre-transfusion was observed, this due to bleeding that occurred. No differences in SaO2 values were observed for pre-transfusion vs post-transfusion pulse oximetry.

Conclusions: We found no evidence to support the linear correlation of ScvO2 with the hemoglobin levels, there is great variability of ScvO2 at different hemoglobin level, we suggest the use of venous central saturation as a physiological marker for transfusions, avoiding with this practice making decisions only with the hemoglobin levels.

Keywords

Transfusion, Oxygenation, Saturation, Blood, Hemoglobin, Catheter

Introduction

For decades, intraoperative anemia has been treated with red blood cell transfusions based on the concept that the oxygen supply to the tissues is increased by increasing hemoglobin levels. Likewise, arbitrary transfusion rules such as the “10/30 rule” have been used indicating that the transfusion of erythrocyte concentrates is required when the hemoglobin concentration is less than 10g / dl or the hematocrit decreases by 30% [1]. There is evidence that blood transfusion is associated with adverse events, so it should be avoided as much as possible [1–3]. For this purpose, it is essential to know the compensatory physiological mechanisms during anemia. The main function of red blood cells is the transport of oxygen from the pulmonary capillaries to the peripherals. The oxygen delivery (DO2) is defined as the product of cardiac output (CO) and arterial oxygen concentration (CaO2). DO2 = CO × CaO2 where DO2 is expressed in mL/min, CO in dL/min, and CaO2 in mL/dL.

The arterial oxygen concentration can be defined with the following formula: CaO2 = (SaO2 × 1.34 × Hb) + (0.0031 × PaO2)

Where SaO2 is the arterial saturation (in %), 1.34 is the amount of oxygen carried on the hemoglobin (in mL/g), Hb represents the hemoglobin level (in g/dL), 0.0031 is the solubility coefficient of oxygen in human plasma at 37°C (in mL/dL*mmHg) and PaO2 the arterial tension measure in mmHg. From this equation, we can infer that to maintain the tissue oxygen supply the organism must adjust some variables such as: Hb, CO, oxygen consumption (VO2) and SaO2. The ratio of oxygen consumption (VO2) to oxygen delivery (DO2) is defined as “Oxygen extraction ratio” (O2ER) in normal circumstances the normal range is from 20–30% because the DO2 (800- 1200 mL/min) exceeds VO2 (200–300 mL/min) three to five times. In this way the hemoglobin concentration and the oxygen delivery (DO2) can decrease significantly without affecting the oxygen consumption, which makes it independent of DO2 [4,5].

However, below a critical threshold of hemoglobin concentration (HbCRIT) and critical oxygen delivery (DO2 CRIT), a level of VO2 / DO2 dependence is reached. This means that below this threshold any decrease in DO2 or Hb also results in a decrease in VO2 and therefore in tissue hypoxia. Venous oxygen saturation is a clinical tool that integrates the relationship between the intake and oxygen consumption in the body, in absence of a mixed venous saturation sample (SvO2) obtained through a pulmonary arterial catheter, central venous oxygen saturation (SvcO2) is being used as an accurate substitute. Central venous catheters are simpler to insert, safer and cheaper than pulmonary artery catheters [6].

By means of a central venous catheter, it is possible to take blood samples for the measurement of ScvO2, whose value ranges around 73% – 82% [6, 7]. Since, as stated, the Hb level does not guarantee an adequate tissue perfusion. Accordingly, the physiological transfusion markers should replace the arbitrary markers currently used based only on hemoglobin levels [8, 9]. In this way, we could avoid the unnecessary use of transfusions with the consequent savings in blood banks, reserving it only to those patients who really require it, avoid adverse transfusion reactions such as acute lung injury, infection transmission, among others. Transfusion guidelines should consider the individual ability of each patient to tolerate and compensate the acute decrement of hemoglobin concentration in the account that there is not a universal threshold to indicate a transfusion [10]. The markers should instead consider signs of tissue dysoxia, which may occur at different hemoglobin concentrations depending on the comorbidities of each patient. These signs may be based on signs and symptoms of inadequate oxygenation, however, before a decision is made regarding transfusion, it must be ensured that there is an adequate supply of volume with crystalloids and / or colloids and that the anesthetic management at the time is optimal. The objective of the present study was to demonstrate that physiological markers, specifically central venous saturation, are parameters that are useful to determine the use of blood transfusion

Materials and Methods

Study design and ethical aspects

A longitudinal, prospective, observational study was conducted which included patients from 18 to 60 years, of indistinct gender, who entered the operating room for any surgical procedure of any specialty in in a third level hospital. The procedures included needed to carry a risk of bleeding greater than 15–20% of the circulating blood volume and the patients that, due to its clinical conditions, required a central venous catheter. Exclusion criteria included patients who refuse to participate in the study, with active bleeding from the gastrointestinal tract, with anemia or blood dysrcrasias and hemodynamically unstable. The elimination criteria included patients in whom the history of blood dyscrasias is unknown or confirmed, patients who have some other pathological condition that alters the results and interpretation of the study, patients with active bleeding and who require an urgent blood transfusion. This protocol was submitted for evaluation to the ethics committee. Because the study was carried out only in patients who already have a central venous catheter in place, patient authorization was not required by informed consent. In the same way the patient was not intervened, since this is an observational study, only the data was collected and analyzed.

Study variables

For each patient who met the criteria a sample of venous blood was taken from the central venous catheter. The sample was then taken to the hospital’s gasometry laboratory where the study was conducted. Once the result of the sample was obtained, it was captured in a database including as variables the results of arterial gasometries, vital signs and laboratory tests that the patient will have, such as blood count and blood chemistry.

Statistical analysis

Epidemiological data such as age and sex will be obtained. The data will be analyzed with measures of central tendency such as mean, median and dispersion measures such as the standard deviation. In the bivariate analysis, it is planned to use the Shapiro-Wilk test to observe the dispersion of the data and classify it as parametric or non-parametric. Based on the results obtained, non-parametric statistical tests such as square chi for two groups and Wilcoxon were performed, given that related groups are compared. If the results obtained are parametric, tests such as Student’s T will be performed for related groups. The SPSS version 24 program was used to perform the statistical tests described above.

Results

34 patients were evaluated with an age average of 76 years (± 16 years). The average weight of the patients was 80 kg and the average size was 164 cm. 64.7% of the patients were male and 35.3% female (Table 1). 58.8% of the patients evaluated had the need to be transfused. An average of 777 cm3 of blood was transfused; the most common amount of transfused packets was two globular packages. Vital signs were evaluated with a range of 83–84 beats per minute, respiratory frequency varied from 21 breaths per minute prior the surgical procedure and an average pulse oximeter saturation of 98%. Systolic blood pressure fluctuated from 127–109 mmHg at the end of the procedure and the initial diastolic pressure was 74-mmHg compare to the 66 mmHg at the end of the procedure. (Figure 1–4). An initial mean Hb was obtained in venous gases of 8.9, pre-transfusion of 7.8 and post transfusion of 10. A statistically significant difference was observed in pre and post transfusion hemoglobin, as well as in pre and post transfusion hematocrit unlike SaO2, where there was no difference between pre-transfusion and post transfusion. In arterial gases, a statistically significant difference was found in the initial hematocrit levels and the hemoglobin levels pre transfusion, no differences were observed in SaO2 values or in any of the pre-transfusion vs. post-transfusion data (Table 2). Finally, a comparative analysis between the markets as cut- off points in the literature reviewed was made. A chi-square cross-tabulation table analysis was performed for qualitative variables, where no statistically significant differences were found in patients with indication of transfusion at the beginning of the procedure; pre-intervention and post-intervention (Table 3).

Table 1. Demographic characteristics of the patients.

Demographic data

Patients

34

Age (years)

52

Size (cm)

164 ± 11

Weight (kg)

80 ±20

Gender

Female 11 (%)

22 (64.7)

Male 11 (%)

12(35.3)

Table 2. Venous and arterial gases, pre transfusion and post transfusion.

Initial

Pre­ transfusion

P

Pre­ transfusion

Post transfusion

P

Venous Gases

Hb

8.980

7.800

0.074

7.800

10.028

0.008

Hcto

29.500

24.631

0.031

24.631

32.011

0.008

SaO2

118.35

72.94

0.198

72.94

114.50

0.683

Arterial Gases

Hb

9.970

8.893

0.035

8.93

9.817

0.239

Hcto

31.65

28.53

0.035

28.53

31.67

0.195

SaO2

99.00

98.73

0.627

98.73

98.83

0.219

Table 3. Patients with indication of transfusion at the beginning of the procedure, pre intervention and post intervention.

Venous Hb

Venous
SaO2

P

Arterial Hb

Arterial
SaO2

P

Initials

Requires transfusion

17

6

0.05

19

0

*

No transfusion required

15

32

14

32

*

Pre intervention

Requires transfusion

17

6

0.554

15

19

*

No transfusion required

2

13

4

15

Post intervention

Requires transfusion

12

9

0.056

13

21

0.05

No transfusion required

10

12

8

13

* The variables evaluated are constant, so there is no statistically significant difference.

IMROJ 19 - 141_Rodriguez Dominguez_f1

Figure 1. Average Hear Rate.

IMROJ 19 - 141_Rodríguez Domínguez_f2

Figure 2. Average Breathing Rate.

IMROJ 19 - 141_Rodríguez Domínguez_f3

Figure 3. Average Systolic Pressure.

IMROJ 19 - 141_Rodríguez Domínguez_f4

Figure 4. Average Diastolic Pressure.

IMROJ 19 - 141_Rodríguez Domínguez_f5

Figure 5. Average Arterial Oxygen Saturation.

Discussion

Based on the considerations above, the present investigation was carried out, with the aim of demonstrating, within our institution and in the operating room environment, the need to take other considerations in addition to a laboratory value when indicating a transfusion. The transfusion of erythrocyte concentrates is a very common practice within the operating room, it is very important for those who are responsible for carrying out this work to have deep knowledge about the physiology and biochemistry involved in the oxygenation process. This in order to achieve the main objective of hemotransfusion, without neglecting the other two variables that the blood influences, which are the rheological and volume effect [11, 12].

Unfortunately, routinely monitored variables such as blood pressure, heart rate, urine output, arterial gases and filling pressures do not necessarily reflect tissue perfusion. The mixed venous saturation (SvO2) and central venous oxygen saturation (SvcO2) are better indicators of oxygen delivery (DO2) and perfusion [13, 14]. The hemoglobin value has been considered as the determinant to indicate blood transfusion for many years. Although there are guides from different associations and different countries that provide us with great support when deciding if it is necessary to administer blood components to our patients, we propose that we also seek the support of physiological variables and markers when making this important decision. Taking into consideration that nowadays, at an international level, the transfusion of blood components cannot yet be performed without a residual risk [15,16].

The appropriate use of blood components should be promoted, avoiding abuse, by developing medical guidelines for therapeutic use by specialties based on scientific evidence. Awareness should be made of the high cost of production, the permanent existence of residual risks of infectious diseases and the possibility of causing immediate or late post-transfusion reactions in the patient [17]. Understanding the costs associated with blood products requires extensive knowledge about transfusion medicine and this is attracting not only clinicians but also administrative personnel from the health care sector worldwide. To improve both the clinical and the economic situation, the use of blood bank resources should be optimized [17–19]. Estimate the costs of storage, procurement, transfer among others is complex, however they should be minimized and used only when strictly necessary based on clinical judgment and on the use of technology and tools that allow estimating the state of patient oxygenation. With a rapid and accessible examination in many of the hospitals where surgical procedures are performed, we can obtain data about tissue oxygenation and thus be able to decide more effectively the use of blood bank resources.

Conclusion

This study does not find enough evidence to support the correlation of ScVO2 with hemoglobin, that is, there is great variability in venous saturation at different hemoglobin levels, and however, there is a tendency to increase ScvO2 after transfusion of globular packages. In the absent of a mixed venous saturation sample (SvO2) which is obtain via a Swan Ganz catheter, the central venous oxygen saturation (SvcO2) is a precise substitute and a reliable tool that integrates the relationship between the supply and consumption of oxygen in the body. By means of a central venous catheter, it is possible to take blood samples for the measurement of ScvO. We recommend that in patients who have this catheter use it to obtain a sample for gasometry and guide better decision-making regarding blood administration. There is an increase in interest in the use of mixed venous saturation and central venous saturation to guide therapeutic interventions during the intraoperative period. However, an understanding of the physiological principles and venous oximetry are essential for safe use in clinical practice. The venous oxygen saturation reflects the balance between the overall oxygen supply and its consumption, which can be affected by a large number of factors during the intraoperative period.

References

  1. Madjdpour C, Spahn DR, Weiskopf RB (2006) Anemia and perioperative red blood cell transfusion: a matter of tolerance. Crit Care Med 34: S102–108. [crossref]
  2. Vazquez Flores JA (2006) La seguridad de las reservas sanguíneas en la república mexicana. Revista de Investigación Clínica 58: 101–108.
  3. Añón JM, García de Lorenzo A, Quintana M, González E, Bruscas MJ (2010) [Transfusion-related acute lung injury]. Med Intensiva 34: 139–149. [crossref]
  4. Walley KR (2011) Use of central venous oxygen saturation to guide therapy. Am J Resp Crit Care 184(5): 514–520.
  5. Cain SM (1965) Appearance of excess lactate in anesthetized dogs during anemic and hypoxic hypoxia. Am J Physiol 209: 604–610. [crossref]
  6. Vallet B, Emmanuel Robin, Lebuffe G (2010) Venous oxygen saturation as a physiologic transfusion trigger. Critical Care 14: 213.
  7. Reinhart K, Kuhn HJ, Hartog C, Bredle DL (2004) Continuous central venous and pulmonary artery oxygen saturation monitoring in the critically ill. Intens Care Med 30: 1572–1578.
  8. Adamczyk S, Robin E, Barreau O, Fleyfel M, Tavernier B, et al. (2009) Contribution of central venous oxygen saturation in postoperative blood transfusion decision. Ann Fr Anesth 28: 522–530.
  9. Vincent JL (2012) Transfusion triggers: getting it right! Crit Care Med 40: 3308–3309. [crossref]
  10. Vallet B, Adamczyk S, Lebuffe G (2007) Physiologic transfusion triggers. Best Pract Res Clin Anaesthesiol. 21: 173–181.
  11. Colomina M, Guilabert P (2016) Transfusion according to haemoglobin levels or therapeutic objectives. Rev Esp Anestesiol Reanim 63: 65–68.
  12. Shander A, Gross I, Hill S, Javidroozi M, Sledge S (2013) A new perspective on best transfusion practices. Blood Transfus 11: 193–202.
  13. Carrillo R, Núñez J (2007) Saturación venosa central. Conceptos actuales. Rev Mex Anestesiol 30: 165–171.
  14. Cabrales P, Intaglietta M, Tsai AG (2007) Transfusion restores blood viscosity and reinstates microvascular conditions from hemorrhagic shock independent of oxygen carrying capacity. Resuscitation 75: 124–134. [crossref]
  15. Shander A, Hofmann A, Gombotz H, Theusinger OM, Spahn DR (2007) Estimating the cost of blood: past, present, and future directions. Best Pract Res Clin Anaesthesiol 21: 271–289. [crossref]
  16. Rojo J (2014) Enfermedades infecciosas transmitidas por transfusión. Panorama internacional y en México. Gac Med Mex 150: 78–83
  17. Goodnough LT (2005) Risks of blood transfusion. Anesthesiol Clin North Am 23: 241–252, [crossref].
  18. Shepherd SJ1, Pearse RM (2009) Role of central and mixed venous oxygen saturation measurement in perioperative care. Anesthesiology 111: 649–656. [crossref]
  19. Park D, Chun B, Kwon S (2012) Red blood cell transfusions are associated with lower mortality in patients with severe sepsis and septic shock: A propensity-matched analysis. Crit Care Med 40: 3140–3145.

Role of Corticosteroids in Rhabdomyolysis

DOI: 10.31038/IJNUS.2019111

Background

Rhabdomyolysis is a medical condition that involves rapid breakdown of injured skeletal muscle, resulting in the leakage of muscle contents into the circulation. The most common causes of rhabdomyolysis include trauma, muscle overexertion, alcohol abuse, and the use of certain medications and illicit drugs. The goal of the treatment is usually to maintain adequate volume repletion to prevent renal failure and metabolic abnormalities. Hemodialysis is an alternative therapy to prevent renal failure when there is no response to aggressive intravenous hydration. We present a case of severe rhabdomyolysis that was refractory to the current standard of care and showed dramatic improvement with corticosteroids.

Case Report

We present a case of a 52-year-old African American male who presented to the emergency department from an outside hospital for acute hypoxemic respiratory failure requiring intubation and septic shock. On presentation, his vital signs were as follows: temperature, 39.2°C; heart rate, 114 beats/min; respiratory rate, 48 breaths/min; blood pressure, 122/74 mm Hg on two vasopressors; oxygen saturation, 98% on pressure-regulated volume control with FiO2 of 80%; BMI, 51.9. Of note, his creatine kinase (CK) upon admission was 231,000 U/L. Before the transfer; the patient received about 2 liters of intravenous hydration. Physical examination revealed a morbidly obese adult male with an erythematous and swollen right lower extremity with palpable posterior tibial and dorsalis pedispulses without any evidence of crepitus, pustular drainage, or a central punctum. The right lower extremity was warm to the touch in comparison to the left lower extremity. Findings on physical examination were otherwise unremarkable. We were unable to obtain any of his medical or medication history or any of his prior records. He was admitted to the medical intensive care unit and laboratory results were obtained, as shown in Table 1. ICU Day 5 and Day 11 are provided to show changes over the time of his admission. In the setting of rhabdomyolysis, the working diagnosis was septic shock secondary to right lower extremity cellulitis. Empiric intravenous vancomycin, cefepime, and metronidazole were initiated after blood cultures were obtained. Imaging studies ruled out any evidence of deep vein thrombosis in the lower extremities.

Table 1. Laboratory Data.

Admission

ICU Day 5

ICU Day 11

White blood count

22.7 thousand/mm3

37.6 thousand/mm3

64.9 thousand/mm3

Red blood count

5.61 million/mm3

4.24 million/mm3

3.12  million/mm3

Hemoglobin

14.6 g/dL

11.1 g/dL

8.1 g/dL

Hematocrit

45.9%

34.6%

27.1%

Platelet

246 thousand/mm3

224 thousand/mm3

157 thousand/mm3

Sodium

133 mEq/L

132mEq/L

136mEq/L

Potassium

5.3 mEq/L

4.5mEq/L

5.9mEq/L

Chloride

93 mEq/L

99mEq/L

110mEq/L

Bicarbonate

31 mEq/L

21mEq/L

8 mEq/L

Blood Urea Nitrogen

41 mg/dL

49 mg/dL

20 mg/dL

Creatinine

6.42 mg/dL

3.44 mg/dL

1.65 mg/dL

Glucose

217 mg/dL

265 mg/dL

235 mg/dL

Calcium

7.0 mg/dL

7.0 mg/dL

7.0 mg/dL

Total Protein

7.4 g/dL

8.0 g/dL

6.0 g/dL

Albumin

3.3 g/dL

2.7 g/dL

2.1 g/dL

Aspartate Aminotransferase (AST)

1889 U/L

1371 U/L

140 U/L

Alanine Aminotransferase (ALT)

135 U/L

786 U/L

135 U/L

Alkaline Phosphatase

75 U/L

104 U/L

71 U/L

Total Bilirubin

0.7 mg/dL

1.3 mg/dL

0.8 mg/dL

Phosphorus

13 mg/dL

5.6 mg/dL

7.7 mg/dL

Blood Natriuretic Peptide

21 pg/mL

Creatine Kinase

231000 U/L

181412 U/L

4638 U/L

Lactic Acid

7.9 mmol/L

2.8mmol/L

5.7mmol/L

Magnesium

2.6 mg/dL

2.2 mg/dL

2.3 mg/dL

Ammonia

66 umol/L (High)

On Day 1 of admission into the ICU, Nephrology was consulted for an uric renal failure and metabolic abnormalities despite aggressive intravenous hydration and vasopressors support. Since a urine analysis and urine toxicology could not be performed, the acute kidney injury (AKI) waspresumed to be secondary to rhabdomyolysis and septic shock. He was originally started on hemodialysis on Day 1, but given the worsening electrolyte and acid derangements, renal replacement therapy (RRT) with intermittent hemodialysis followed by continuous veno-venous hemodiafiltration (CVVHDF) was initiated on Day 2. Despite aggressive therapy, the CK levels increased to 1,006,167 U/L on Day 3, prompting a surgical consult and necrotizing fasciitis was ruled out. Given the severity of rhabdomyolysis, rheumatology was consulted and the workup including double stranded-deoxyribonucleic acid (ds-DNA), antibodies against La/SSB and Ro/SSA, Jo 1 and cyclic-citrullinated peptide (CCP) were negative. With CK levels over one million, we recommended intravenous corticosteroids, but the treatment was initiated onDay 4 when the CK levels dropped to 652,798 U/L. A 3-day pulse dose therapy of 1000 mg of intravenous Methylprednisolone was then initiated on Day 4.After corticosteroid treatment, the patient’s labs continued to show a significant decline in CK levels, as seen in Figure 1. A proximal muscle biopsy was performed on Day 6, which was also the day the patient received his final dose of IV Methyl prednisolone. The final pathology report stated that there was extensive acute rhabdomyolysis with minimal macrophage infiltration suggesting minimal inflammatory, reactive or regenerative activity that may have been due to the effect of the corticosteroids.CK levels trended down to 10,005 U/L over the course of six days. Despite the improvement of the rhabdomyolysis and ongoing CRRT throughout the course of his ICU stay, the patient clinically worsened secondary to methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and Candida albicans bacteremia. The patient ultimately died secondary to multisystem organ failure.

IJNUS-19-101_Sandeep AP_F1

Figure 1. Graph showing the response of CK levels after administration of IV Methyl prednisolone 1000mg.

Discussion

Rhabdomyolysis is characterized by skeletal muscle necrosis and dissolution of intracellular muscle components leading to the release of myoglobin, electrolytes, and proteins into the circulation [1].It can be multifactorial in etiology including trauma, drugs, muscle hypoxia, exercise, genetic and metabolic disorders, electrolyte abnormalities, infections and idiopathic[1–3]. Also, any defects in muscle metabolism may present with recurrent episodes of rhabdomyolysis [4–6]. In the United States, the incidence of AKI as a complication of rhabdomyolysis accounts for 7 to 10% of all the AKI cases [6, 7]. The pathogenesis of rhabdomyolysis involvesthe depletion of adenosine triphosphate (ATP) within the myocyte, causingan unregulated increase in intracellular calcium [8, 9]. Under normal conditions, the sarcoplasmic calcium is strictly regulated, and it maintains low levels of calcium when the muscle is at rest and allows the increase that is necessary for actin–myosin binding and muscle contraction. ATP depletion impairs the function of these pumps, resulting in a persistent increase in sarcoplasmic calcium leading to persistent contraction which further depletes ATP. This leads to the eventual destruction of myofibrillar, cytoskeletal, and membrane proteins causing large amounts of myoglobin and CK release[1].Myoglobin is a heme-containing protein measuring about 17.8-kDa that is freely filtered by the glomerulus and metabolized by tubular epithelial cells. It can be seen in the urine only when the renal threshold of 0.5 to 1.5 mg/dL of myoglobin is exceeded and can present with reddish-brown colored urine when the serum myoglobin levels reach 100 mg/dL [10].Myoglobinuria can be picked up on the urinary dipstick as positive for blood in the absence of red blood cells. Though the serum myoglobin levels peaks before the serum creatinine kinase, the serum myoglobin has a rapid and unpredictable metabolism via the kidney and the liver or spleen [11].

Depending upon the extent of the muscle damage, the clinical presentation can vary. Greater than 50% of patients do not present with the classic triad of myalgias, weakness and tea-colored urine [10]. Limb weakness, swelling, myalgias, and gross pigmenturia without hematuria are commonly seen in cases with severe muscle necrosis. The complications of rhabdomyolysis include intravascular volume depletion, renal failure, arrhythmias due to electrolyte abnormalities, compartment syndrome, acidosis, and disseminated intravascular coagulation. Patients admitted to the intensive care unit have a concomitant mortality rate of 22%, and if there is an associated kidney insult, then the mortality rate can be as high as 59% [6]. Under normal conditions at resting stage, intracellularly there are low concentrations of sodium and calcium and higher potassium concentrations which are tightly controlled with the sodium-potassium and sodium-calcium exchangers. Whenever there is a muscle injury or ATP depletion, the functioning of this channel is compromised leading to excessive calcium and sodium within the cells and extravasation of potassium into the bloodstream. High intracellular sodium leads to water influx, cell swelling, and intravascular volume depletion [12]. Fluid sequestration within damaged muscle causes intravascular volume depletion resulting in activation of the renin–angiotensin-aldosterone system and sympathetic nervous system, thus precipitating the pre-existing renal injury [12]. First-line treatment for rhabdomyolysis is aggressive fluid resuscitation to maintain an adequate urine output of at least 200 to 300mL per hour to prevent the accumulation of intracellular toxins in circulation which can subsequently lead to AKI. Diuretics are recommended only when there are signs of fluid overload. Dialysis becomes necessary when the patient has unremitting metabolic abnormalities inspite of conservative management. However, dialysis is not a valid treatment option for rhabdomyolysis because myoglobin cannot be removed effectively due to the size of the protein. Dialysis is usually recommended by renal indications, such as acid/base disorders, electrolyte disturbances, volume overload, and uremia [13]. In the case of our patient, dialysis was initiated because he was an uric and had metabolic disturbances. Treatment becomes significantly challenging if patients fail to show improvement to dialysis and the cause of the insult remains unknown.

Literature review shows that there are only four cases in which intravenous corticosteroid use is administered in the treatment of rhabdomyolysis [13–16].The rationale for steroids in these cases is that the muscle necrosis in rhabdomyolysis has a significant inflammatory element, which is supported by the successful reduction of CK levels after the administration of IV Methylprednisolone. However, none of the above-mentioned case reports had such high levels of CK. In our case, the laboratory values showed continued improvement after beginning the three-day pulse dose therapy, with levels declining from 652,798 U/L to 58,947 U/L. We cannot exclude the possibility that this patient’s recovery status was predominantly secondary to the natural history of the disease as improvement was seen prior to commencing steroids. Nonetheless, the significant improvement in CK levels and a biopsy revealing minimal inflammation suggest the pharmacologic effect of the corticosteroids exhibited a noteworthy component. Rhabdomyolysis muscle biopsies show inflammation and neutrophilic infiltration with muscle necrosis due to a pathologic interaction between actin and myosin. Histochemical analysis is done if a genetic myopathy is suspected. Generally, muscle biopsies can help differentiate acquired from inherited causes by the use of histochemistry, but the pathological findings are similar in all cases that are acquired [17, 18]. When comparing our patient’s muscle biopsy to one depicting an acute inflammatory state, our patient showed significantly less inflammation.

Conclusion

Rhabdomyolysis is a medical condition that involves the breakdown of injured muscle leading to electrolyte abnormalities including hyperkalemia, hypocalcemia, hyperphosphatemia, hyperuricemia, acute renal failure, compartment syndrome, disseminated intravascular coagulation and or death.Despite multiple causes of rhabdomyolysis, there are limited treatment options for patients who do not show clinical improvementwith aggressive intravenous fluid hydration and dialysis. Short-term administration of high-dose corticosteroids may decrease the inflammatory reaction of rhabdomyolysis and lead to improvement in the patients CK levels. Further studies are needed to identify the most appropriate duration and the time to administer the steroids for the greatest success rate.

References

  1. Xavier B, Esteban P, Josep G (2009) Rhabdomyolysis and Acute Kidney Injury. N Engl J Med 361: 62–72.
  2. Chavez LO, Leon M, Einav S, Varon J (2016) Beyond muscle destruction: a systematic review of rhabdomyolysis for clinical practice. Crit Care 20: 135. [crossref]
  3. Nance JR, Mammen AL (2015) Diagnostic evaluation of rhabdomyolysis. Muscle Nerve 51: 793–810. [crossref]
  4. Tein I, DiMauro S, Rowland LP (1992) Myoglobinuria. In: Rowland LP, DiMauro S, (eds.). Myopathies. Handbook of clinical neurology. Vol. 62. Amsterdam: Elsevier Science Publishers Pg No: 553–593.
  5. Allison RC, Bedsole DL (2003) The other medical causes of rhabdomyolysis. Am J Med Sci 326: 79–88. [crossref]
  6. Bagley WH, Yang H, Shah KH (2007) Rhabdomyolysis. Intern Emerg Med 2: 210–218.
  7. Holt SG, Moore KP (2001) Pathogenesis and treatment of renal dysfunction in rhabdomyolysis. Intensive Care Med 27: 803–811. [crossref]
  8. Giannoglou GD, Chatzizisis YS, Misirli G (2007) The syndrome of rhabdomyolysis: pathophysiology and diagnosis. Eur J Intern Med 18: 90–100. [crossref]
  9. Wrogemann K, Pena SD (1976) Mitochondrial calcium overload: a general mechanism for cell-necrosis in muscle diseases. Lancet 1: 672–674. [crossref]
  10. Knochel JP (1982) Rhabdomyolysis and myoglobinuria. Annu Rev Med 33: 435–443. [crossref]
  11. Mikkelsen TS, Toft P (2005) Prognostic value, kinetics and effect of CVVHDF on serum of the myoglobin and creatine kinase in critically ill patients with rhabdomyolysis. ActaAnaesthesiol Scand 49: 859–864. [crossref]
  12. Zager RA (1989) Studies of mechanisms and protective maneuvers in myoglobinuric acute renal injury. Lab Invest 60: 619–629. [crossref]
  13. Brown J, Mitchell S (1992) A complicated case of exertional heat stroke in a military setting with persistent elevation of creatine phosphokinase. Mil Med 157: 101–103. [crossref]
  14. Sato K1, Yoneda M, Hayashi K, Nakagawa H, Higuchi I et al. (2006) A steroid-responsive case of severe rhabdomyolysis associated with cytomegalovirus infection. Rinsho Shinkeigaku 46: 312–316. [crossref]
  15. Zarlasht F, Salehi M, Sattar A, Abu-Hishmeh M, Khan M (2017) Short-Term High-Dose Steroid Therapy in a Case of Rhabdomyolysis Refractory to Intravenous Fluids. Am J Case Rep18: 1110–1113. [crossref]
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Seismicity of Antarctica: Features

DOI: 10.31038/GEMS.2019112

Abstract

In this paper, the spectral characteristics of seismic data obtained at various seismic stations in Antarctica are studied using the spectral histogram method developed by the authors and the study of regional structures. This takes into account the fundamental features of the geological, geophysical and astrophysical picture of the entire continent; significant component of fragile crustal structures. The possibility of the existence in the polar region of the ancient structures of the plume during its formation experienced the impact of centrifugal forces from the rotation of the Earth and the inhibition of the top of the plume in the low-temperature near-surface layer. One of the most significant attractions of the region is the existence of a large-sized ozone “hole”. All the above features have found their reflection in the seismic fields of Antarctica.

Keywords

Antarctica, seismic fields, plume tectonics, ozone holes, modulated solar wind, solar oscillations

Introduction

Probable plume tectonics It is likely that the Antarctic bears the signs of a super plume (Fig. 1). A similar example of a modern “hot spot” is about. Iceland. The thickness of the ocean-type crust under this island reaches 40 km. (usually the thickness is 7 km). Paleo – Iceland’s counterparts – a giant Antarctic uplift, etc. Until now, volcanic activity has been observed in Antarctica (Figure 1).

GEMS-19-101_Khavroshkin OB_F1

Figure 1. There is an example of the plume development. At the final stage, the tip of the Antarctic plume, due to the anomalously cooled surface rocks of the crust, will assume a more subtle and probably not continuous form.

The modern map of Antarctica quite well shows similarities with the elements of the super – plume  (Fig. 2.) (Figure. 2a,b).

GEMS-19-101_Khavroshkin OB_F2

GEMS-19-101_Khavroshkin OB_F2b

Figure 2. A, B. This is modern map of Antarctica. With the exception of the peninsula, the coasts are rounded, forming a super plume.

Given the thickness of the ice cover (up to 9 km), and the structure of the crustal rocks, as well as thermal and coastal processes, we should expect the existence of various seismic fields. In addition, there are many caves in the coastal zone, possibly remnants from the periphery of the plume. During the Second World War, a submarine base of Germany existed in the caves off the coast. There is the existence of the ozone hole over the continent. Large-scale, ozone-free atmospheric space above the continent (Figure 3) makes radical additions to the description of Antarctic seismicity. There are such effects that are impossible for terrestrial seismicity. The absence of ozone protection makes available the effect on the surface of many solar processes: radiation (from ultraviolet radiation to x-rays and gamma radiation), solar cosmic rays and flares, muons, modulated solar wind and interplanetary shock waves (MUV). A similar picture is observed for lunar seismicity. Many of the effects are almost constantly modulated, for example, by solar oscillations which make it possible to observe waves at solar frequencies in the spectrum of the seismic field (Table 1).

GEMS-19-101_Khavroshkin OB_F3

Figure 3. Map of the ozone hole over Antarctica.

Table 1. Periods of oscillations of the standard model of the Sun with the relative content of heavy elements Z = 0.02 according to calculations by Iben n Makhefi

Mode

Period (min)

Mode

Period (min)

l=0

l=1

l=2

l=3

l=4

l=1

l=2

l=3

l=4

p1

62,29

57,25

42,50

39,53

37,58

f

45,90

40,97

38.82

p2

40,94

36,98

32,19

29,42

27,62

g1

61,58

55,05

47.94

44,15

P3

30,93

27,88

25,09

23,21

21,92

g2

84,4

63.03

54.88

49,59

p4

24,49

22,30

20,52

19,26

18,31

g 3

105,3

72,58

61.88

57,73

p5

20,19

18,08

17,39

16,44

15,72

g 4

127,3

83,49

67,78

61,11

p6

17,17

16,04

15,10

14,38

13,81

g 5

148.2

95.38

74,9

64,89

p7

14,93

14,08

13,35

12,77

12,32

g 6

171,1

107,7

88,1

70,30

p8

13,21

12.55

11,97

11,51

11,14

g 7

120,2

91,8

76.83

p9

11,85

11,34

10,87

10,49

10,18

g 8

132.9

100,7

83.62

p10

10,78

10.35

9,97

9,85

9,39

g 9

145.9

109,7

90,56

p11

9,90

9,54

9.21

8.94

8,71

g 10

158,9

118,9

97,62

p12

9.15

8,84

8,56

8,32

8,11

g 11

172.1

128,1

104,5

p23

8,50

8,25

7,99

7.78

7.60

g 12

137,8

111,7

p14

7.94

7,71

7,49

7,31

7,15

g 23

147,0

118,9

p15

7.45

7,25

7,06

6,89

6,75

g 14

156.5

126,5

p16

7.02

6,84

6,67

6,52

6,39

g 15

166,7

133,3

p17

6.64

6,47

6,32

6,18

6,06

g 16

175,9

141,5

p18

6.39

6.14

6,00

5,87

5,77

g 17

148,6

p19

5.98

5,84

5,71

5,60

5,50

g 18

156,4

p20

5.69

5,58

5,45

5.34

5.25

g 19

164,0

g 20

171,1

In Table 1: p, g, f-modes of the natural oscillations of the Sun; L-form of natural oscillations.

Moreover, the excitation of these waves is not due to the indirect interaction of terrestrial radioactive geological structures with solar neutrinos, but directly. This means that instrumental and methodological development of seismic expeditions to the Moon, Mars and other space bodies devoid of ozone protection should be carried out on Antarctica, as the closest to the external conditions of the landfill (Figure 3).

The ozone hole over the Antarctic and its adjacent territories is quite dynamic: it grew for the first time in recent years, covering an area of 28 million square kilometers (press service of the NASA Goddard Space Flight Center). Previously, the ozone layer was considered to be a natural shield that protects the surface of the Earth from hard ultraviolet radiation, which is dangerous to living organisms. Now it is a parameter of the atmosphere, which allows studying the Sun, solar-terrestrial relations and some astrophysical problems. A sharp drop in the concentration of stratospheric ozone during the winter season was first detected over the Antarctica in the 1980s. Every winter, the ozone hole over Antarctica grows, reaching a maximum area in September, and shrinking in summer. Large sizes fully correspond to how ozone behaves in relatively cold weather in the upper atmosphere of the Earth (Paul Newman, Paul Newman, USA). Due to the slow reduction, the thickness of the ozone layer in some deep regions of the Antarctic has fallen to absolute zero for the first time in many years. This means that the Suns freely “bombard” the polar ice that is under similar areas, for example, the Amundsen – Scott station at the South Pole. The level of ozone began to fall sharply in September, with the result that its concentration decreased by 95% by the first of October. This year, the fall continued for two “extra weeks”, which led to a 100% decrease in the level of ozone by October 15”says another climatologist, Brian Johnson, USA. However, the smaller ozone hole in 2017 is the result of natural variability and is not necessarily a signal of rapid “healing”. Scientists use the word “hole” as a metaphor for an area in which the ozone concentration falls below the historical threshold of 220 Dobson units. A sharp drop in the concentration of stratospheric ozone during the winter season was first discovered over Antarctica in the 1980s. The reason for this was the release of a large number of Freon’s into the atmosphere of the Earth, whose molecules destroy ozone in the upper layers of the atmosphere at low air temperatures. Every winter, the ozone hole over Antarctica grows, reaching a maximum area in September, and shrinking in summer. January 29, 2016, 14:31 – January 27, a huge ozone hole covered northern Eurasia from the Atlantic to the Pacific Ocean. Most of it fell on the territory of Russia. The anomaly center is located in the north of Western Siberia, however, the effect of ozone holes is not yet known to seismologists.  Observations in 2017 showed that the hole in the ozone layer of the Earth, which forms over Antarctica at the end of the southern winter, has become the smallest since 1988. According to NASA satellites, the ozone hole reached its one-year maximum of September 11, spreading to 7.6 million square miles (19.6 sq. km), which is 2.5 times the area of the United States. Ground-based measurements and measurements from balloons, carried out by the National Oceanic and Atmospheric Administration, confirmed satellite data. Since 1991, the average maximum area of ozone holes has been approximately 26 million square kilometers (Fig. 4.)  (Figure  4).

In view of the above, a start was made to study the seismic fields of Antarctica (Figure 5).

As follows from Figure 5, considerable seismic material has been collected and processed, primarily relating to the coastal zone and partly of the shelf The IRIS Data Management Center (IRISDMC): http://service.iris.edu/fdsnws/dataselect/1/. The study of data was started with spectral analysis (see Fig. 6) (Figure 6).

GEMS-19-101_Khavroshkin OB_F4

Figure 4. Concentration of ozone over Antarctica. October, 2017. © NASA

GEMS-19-101_Khavroshkin OB_F5

Figure 5. Seismic recording of LHZ-component 60 channel Streckeisen STS-2.5 sensor IU network of QSPA station (89.9289°S, 144.4382°E). The record contains 2265013 seconds. For convenience, the graphical representation is averaged over 120 points in 1 minute increments.

GEMS-19-101_Khavroshkin OB_F6

Figure 6. There is amplitude spectrum of seismic data in the range from 2 to 102 sec. in increments of 0.01 seconds. with averaging values of 1 sec.

According to fig.6 the spectrum of seismicity has two peaks dominant in amplitude, for 18 and 20 sec., which, probably, given the proximity of the ocean, should be referred to as “storm” and note also the existence of resonant structures at the Antarctic ice sheet (Figure 7).

GEMS-19-101_Khavroshkin OB_F7

Figure 7. There is the energy spectrum of data Figure 6.

The energy spectrum revealed a more subtle structure of the peaks, at 4 and 18 sec. These peaks are not uncommon when considering seismic fields of complexly constructed and non-linear structures. For greater clarity, the same seismic material was processed by a more complex, but informative method (Fig.8 A, B)  (Figure 8 a,b).

GEMS-19-101_Khavroshkin OB_F8

GEMS-19-101_Khavroshkin OB_F8b

Figure 8. A, B. These are dependence of the maximum amplitude of seismic vibrations A) and its logarithm B), from the observation time and the corresponding period. The interval of the period change is from 2 to 102 sec with a step of 0.1 sec. The time step is 2 minutes (120 seconds). The window is 628 seconds.

According to Fig. 8 (A) for several days, resonant peaks of good quality on micro seismic periods of 14–20 sec can be observed in the wave field; their double period manifests itself in the form of ill-galling small amplitude manifestations. According to Fig. 8 (B) in Antarctica in the general seismic wave field it is possible to distinguish three groups of waves with ranges of periods: relatively high-frequency (periods 3–25 seconds), the longest and with maximum amplitude (periods 49–60 seconds) and short duration of existence as a single peak on period ~ 100 sec. Probably, the longest are associated with existing in the coastal zone and on the shelf of the network of caves and channels (Figure 9).

GEMS-19-101_Khavroshkin OB_F9

Figure 9. There is the dependence of the logarithm of the maximum amplitude of oscillations on the observation time.

According to Fig. 9, there are two independent types of noise – one high-frequency, constantly existing with an unstable modulation frequency (~ 4–5 days) and the second in the form of very short irregular high-amplitude emissions (Figure 10,11).

GEMS-19-101_Khavroshkin OB_F10

Figure 10. The dependence of the period corresponding to the logarithm of the maximum amplitude of oscillations from the time of observation.

The dependence of the logarithm of the maximum amplitude on the period (Fig. 11) most clearly highlights the zone 3.0 – 7–8.0 s, that is, a known section of storm microseisms. Since such habitual microseisms are usually recorded, for example, in the Baltic and in Europe, and the geological and structural environment of this region and the Antarctic are fundamentally different, a source of probable general influence should be found. Since high-frequency solar oscillations have a constant activity, especially at periods of 5–6 min, and the lack of ozone protection from the Sun allows for higher frequency effects, these microseisms are inherently strongly associated with solar activity. Another, even more active area lies within 20–25 seconds, which is also recorded in other regions of the Earth (Figure-12).

GEMS-19-101_Khavroshkin OB_F11

Figure 11. The dependence of the logarithm of the maximum amplitude of oscillations on the period.

GEMS-19-101_Khavroshkin OB_F12

Figure 12. The density distribution of the maximum amplitude of the period.

The distribution of the maximum amplitude over periods divides the seismic vibrations into two groups – powerful ~ 3–6 sec and weak, but connected as resonant harmonics ~ 18–20 sec., which was observed earlier in other regions of the Earth (Figure 13–20).

GEMS-19-101_Khavroshkin OB_F13

Figure 13. There is amplitude spectrum from 2 to 302 min with a step of 0.03 min.

GEMS-19-101_Khavroshkin OB_F14

Figure 14. The dependence of the period corresponding to the maximum amplitude of oscillations from the time of observation.

GEMS-19-101_Khavroshkin OB_F15

Figure 15. Dependence of the logarithm of the maximum amplitude of oscillations on the period

GEMS-19-101_Khavroshkin OB_F16

Figure 16. The density distribution of the maximum amplitude of the period.

GEMS-19-101_Khavroshkin OB_F17

Figure 17. The dependence of the period corresponding to the maximum amplitude of oscillations from the time of observation.

GEMS-19-101_Khavroshkin OB_F18

Figure 18. The density distribution of the maximum amplitude of the period.

GEMS-19-101_Khavroshkin OB_F19

Figure 19. The dependence of the logarithm of the maximum amplitude of oscillations on the time of observation and the corresponding period. The interval of the period is change from 2 to 302 minutes. in 0.3 min steps Time step 2 min. Window – 314 minutes.

GEMS-19-101_Khavroshkin OB_F20

Figure 20. There is energy spectrum data Figure 19.

This energy spectrum characterizes the constant component. Therefore, it is still early to draw final conclusions about their reliability and significance. We must try to modify the program a bit, or use the resonance method (Table-2).

Table 2. Distribution of time intervals for which the periods correspond (N≥10)

Period (min)

N

Period (min)

N

Period (min)

N

Period (min)

N

Period (min)

N

Period (min)

N

5.4002

153

124.5683

11

149.7827

12

161.0891

26

167.6929

30

173.1961

18

5.5003

153

124.6683

10

150.5831

12

161.1892

20

167.7930

39

173.2961

16

5.6003

117

124.7684

15

150.6832

10

161.2893

25

167.8930

46

173.3962

13

5.7004

25

124.8685

14

150.7833

22

161.3893

22

167.9931

50

173.5963

15

5.9005

476

124.9685

23

150.8833

15

161.4894

26

168.0931

38

173.6963

15

6.0006

266

125.0686

28

150.9834

25

161.5894

18

168.1932

58

173.7964

10

6.1006

24

125.1686

28

151.0834

64

161.6895

21

168.2933

84

173.8965

16

6.2007

690

125.2687

27

151.1835

73

161.7895

23

168.3933

94

173.9965

21

6.7010

53

125.3687

43

151.2835

93

161.8896

18

168.4934

100

174.0966

12

6.9011

47

125.4688

36

151.3836

79

161.9897

16

168.5934

123

174.1966

11

7.0011

25

125.5689

41

151.4837

86

162.0897

16

168.6935

131

174.4968

16

7.1012

22

125.6689

26

151.5837

104

162.1898

14

168.7935

187

174.5969

11

7.4014

10

125.7690

38

151.6838

113

162.2898

16

168.8936

180

174.9971

11

8.0017

493

125.8690

16

151.7838

139

162.3899

16

168.9937

214

175.0971

14

8.2018

36

125.9691

13

151.8839

139

162.4899

15

169.0937

229

175.3973

14

8.3019

25

126.0691

12

151.9839

131

162.5900

12

169.1938

211

175.5974

10

8.4019

176

126.1692

10

152.0840

119

162.6901

13

169.2938

201

175.6975

12

8.7021

25

126.2693

13

152.1841

196

162.7901

12

169.3939

199

175.7975

10

9.0023

129

135.8747

10

152.2841

155

162.8902

10

169.4939

177

175.8976

10

9.1023

12

135.9748

10

152.3842

105

163.0903

10

169.5940

196

175.9977

11

11.1035

55

136.0749

10

152.4842

88

163.1903

12

169.6941

203

176.0977

18

11.4037

50

136.1749

14

152.5843

64

163.2904

10

169.7941

215

176.3979

17

11.9039

119

136.2750

10

152.6843

52

163.3905

11

169.8942

161

176.5980

14

13.9051

14

136.3750

12

152.7844

36

163.6906

10

169.9942

190

176.6981

12

15.2058

124

136.4751

10

152.8845

39

163.9908

13

170.0943

192

176.7981

14

17.2070

22

136.5751

15

152.9845

25

164.1909

14

170.1943

178

176.9982

10

18.9079

12

136.6752

17

153.0846

28

164.4911

16

170.2944

140

177.0983

14

22.8102

53

136.7753

17

153.1846

24

164.5911

13

170.3945

122

177.1983

16

22.9102

17

136.8753

17

153.2847

18

164.6912

12

170.4945

96

177.2984

11

23.0103

22

136.9754

24

153.3847

14

164.7913

13

170.5946

86

177.3985

19

23.1103

10

137.0754

37

153.4848

22

164.8913

11

170.6946

61

177.4985

11

23.2104

9

137.1755

45

153.5849

15

164.9914

13

170.7947

69

177.5986

17

23.3105

35

137.2755

54

153.7850

14

165.0914

15

170.8947

54

177.6986

16

23.4105

15

137.3756

73

158.6878

10

165.1915

10

170.9948

44

177.7987

17

26.6123

46

137.4757

53

158.8879

10

165.2915

12

171.0949

41

177.8987

17

26.7124

48

137.5757

47

158.9879

17

165.3916

15

171.1949

27

177.9988

13

26.8125

28

137.6758

47

159.1881

13

165.4917

12

171.2950

28

178.0989

17

27.5129

16

137.7758

46

159.2881

15

165.6918

18

171.3950

32

178.1989

19

27.6129

30

137.8759

32

159.3882

13

165.7918

10

171.4951

25

178.2990

10

103.2561

20

137.9759

49

159.4882

19

165.9919

13

171.5951

37

178.3990

16

114.5626

15

138.0760

30

159.5883

23

166.0920

14

171.6952

22

178.4991

26

114.7627

11

138.1761

20

159.6883

27

166.1921

14

171.7953

23

178.5991

22

114.8627

22

138.2761

26

159.7884

31

166.2921

10

171.8953

25

178.6992

25

115.0629

15

138.3762

16

159.8885

19

166.3922

11

171.9954

18

178.7993

23

115.1629

37

138.4762

13

159.9885

28

166.4922

12

172.0954

24

178.8993

21

115.2630

45

138.5763

11

160.0886

19

166.5923

10

172.1955

24

178.9994

24

115.3630

57

144.1795

11

160.1886

38

166.6923

12

172.2955

17

179.0994

28

115.4631

39

144.2795

16

160.2887

26

166.8925

18

172.3956

20

179.1995

31

115.5631

23

144.4797

10

160.3887

37

166.9925

16

172.4957

24

179.2995

35

115.6632

47

144.9799

11

160.4888

32

167.0926

18

172.5957

16

179.3996

31

115.7633

25

145.0800

12

160.5889

39

167.1926

21

172.6958

22

179.4997

44

115.8633

18

145.1801

14

160.6889

40

167.2927

13

172.7958

15

179.5997

37

116.0634

13

145.2801

17

160.7890

34

167.3927

29

172.8959

14

179.6998

36

119.4654

11

145.3802

11

160.8890

34

167.4928

21

172.9959

18

179.7998

33

120.4659

12

149.2824

10

160.9891

27

167.5929

28

173.0960

9

179.8999

44

This table could also be rebuilt according to a different number of intervals by period. It is noteworthy that in the range of 28÷103 min the number of intervals is very small (Table 3) (Figure 21) (Table 4).

GEMS-19-101_Khavroshkin OB_F21

Figure 21. There is amplitude spectrum of the daily range.

Table 3. The distribution of time intervals for which the periods correspond to Amax

Period (min)

N

Period (min)

N

Period (min)

N

2.6000

946

146.3120

4

221.1620

2686

5.5940

325

149.3060

4

224.1560

762

8.5880

122

152.3000

1

227.1500

332

11.5820

1

155.2940

9

230.1440

196

14.5760

30

158.2880

13

233.1380

140

17.5700

15

161.2820

18

236.1320

71

20.5640

1

164.2760

17

239.1260

54

23.5580

9

167.2700

25

242.1200

36

26.5520

20

170.2640

36

245.1140

36

32.5400

2

173.2580

42

248.1080

24

68.4680

17

176.2520

44

251.1020

31

71.4620

6

179.2460

26

254.0960

13

74.4560

2

182.2400

20

257.0900

15

77.4500

2

185.2340

18

260.0840

10

80.4440

7

188.2280

33

263.0780

10

116.3720

3

191.2220

22

266.0720

9

119.3660

6

194.2160

35

269.0660

7

122.3600

15

197.2100

47

272.0600

11

125.3540

48

200.2040

71

275.0540

11

128.3480

128

203.1980

86

278.0480

17

131.3420

19

206.1920

135

281.0420

10

134.3360

14

209.1860

359

284.0360

5

137.3300

5

212.1800

868

287.0300

7

140.3240

4

215.1740

2932

290.0240

3

143.3180

6

218.1680

5189

293.0180

6

296.0120

6

Table 4. The summary of daily periods.

Period
(day)

Amplitude
fluctuations

(rel. units)

Period
(day)

 Amplitude
fluctuations
(rel. units)

Period
(day)

Amplitude
fluctuations
(rel. units)

  0.00417

  2.19146

  0.38750

  2.34914

  0.79306

  7.95374

  0.00972

  1.39646

  0.39861

  3.12503

  0.82917

  4.96194

  0.11806

  1.05268

  0.40694

  4.69761

  0.88750

  9.37318

  0.13194

  1.14954

  0.41806

  2.71686

  0.93750

  7.53833

  0.13750

  1.06967

  0.42917

  2.80484

  0.97639

  7.36167

  0.16806

  1.43672

  0.43750

  3.39350

  1.04583

  8.34664

  0.18750

  1.28783

  0.44583

  3.64884

  1.09583

 12.86868

  0.20139

  1.51607

  0.46250

  1.25450

  1.15139

  9.73151

  0.20972

  1.87710

  0.47083

  3.53236

  1.20972

  6.42397

  0.22083

  1.91259

  0.48750

  3.70950

  1.31806

 12.39736

  0.22917

  2.03499

  0.50417

  2.77930

  1.40139

 18.42374

  0.24028

  2.07343

  0.51528

  3.61388

  1.49028

 14.78352

  0.25139

  1.51939

  0.52917

  6.31336

  1.59306

 14.11028

  0.26528

  1.78014

  0.54028

  7.88273

  1.79306

 17.42602

  0.28194

  1.69116

  0.55417

  3.96956

  1.95972

 18.00527

  0.29306

  1.73287

  0.56528

  1.75607

  2.07917

 18.77936

  0.29861

  2.50799

  0.57639

  1.94631

  2.32639

 25.01781

  0.30972

  2.22962

  0.59028

  4.55191

  2.99028

 45.80661

  0.31528

  2.12205

  0.60694

  6.98497

  3.49583

 36.81036

  0.32917

  2.22865

  0.62361

  4.12886

  4.17083

 57.67608

  0.33472

  3.07918

  0.64861

  3.80290

  5.22083

 52.97682

  0.35139

  2.24693

  0.66806

  3.72560

  7.37917

 53.38868

  0.35694

  4.71118

  0.68750

  6.98646

 11.85972

 70.47160

  0.37361

  2.58232

  0.71528

  4.98707

  0.38194

  3.51410

  0.76250

  7.11657

Conclusion

As expected, (see Tables 2–4), the structure of the seismic fields of Antarctica is saturated with wave fields determined by cosmic processes, primarily by the Sun’s own oscillations (see Table 1). Seismic Antarctica turns it into a unique and indispensable landfill for testing and testing of seismic and geophysical equipment intended for the study of the Moon and planets.

Attachments

GEMS-19-101_Khavroshkin OB_F22

References

  1. Khavroshkin OB, Tsyplakov VV (2001) Meteoroid stream impacts on the Moon: information of duration of seismograms // Proc. Conf. Meteoroids 2001 (ESA SP-495). Noordwijk, The Netherlands: ESA Publ Division Pg No: 13–21.
  2. Khavroshkin OB, Tsyplakov VV (2001) Temporal structure of meteoroid stream and lunar seismicity according to Nakamura’s catalogue // Proc. Conf. Meteoroids 2001 (ESA SP-495). Noordwijk, The Netherlands: ESA Publ. Division Pg No: 95–105.
  3. Khavroshkin OB, Tsyplakov VV, Sobko AA (2011) Solar activity and seismicity of the Moon. Engineering Physics 3: 40–45.
  4. Christensen Dalsgaard J, Gough DO, Morgan JG (1979) Dirty Solar Models. Astron. Astrophys 73: 121–128 .
  5. Patrick S. McIntosh, Murray Dryer (1972) Solar activity: observations and predictions. The Massachusetts Institute of Technology, Virginia, USA.
  6. Syun-Ichi Akasofu, Sydney Chapman (1972) Solar-Terrestrial Physics. The Clarendon Press, California, USA.
  7. Khavroshkin O, Tsyplakov V (2013) Nonlinear Seismology: The Cosmic Component. Saarbrücken: Palmarium Academic Publishing.
  8. Oleg Khavroshkin, Vladislav Tsyplakov (2013) Sun, Earth, radioactive ore: common periodicity. The Natural Science (NS) 5: 1001–1005.
  9. Khavroshkin OB, Tsyplakov VV (2013) Radioactivity, solar neutrinos, interactions. Engineering Physics 8: 53–61.
  10. Khavroshkin OB, Tsyplakov VV (2013) Ore sample radioactivity: monitoring. Engineering Physics 8: 53–62.
  11. Khavroshkin OB, Tsyplakov VV (2013) Natural radioactivity as an open system. Engineering Physics 12: 40–54.
  12. Starodubov AV, Khavroshkin OB, Tsyplakov VV (2014) From periodicities of radioactivity to cosmic and metaphysical oscillations. Metaphysics. Moscow. Peoples’ Friendship University of Russia 1: 137–149.
  13. Rukhadze AA, Khavroshkin OB, Tsyplakov VV (2015) The frequency of natural radioactivity. Engineering Physics 5.
  14. Khavroshkin OB, Tsyplakov VV (2014) Hydrogen maser: solar periodicity. Engineering Physics 3: 25–31.

Capillary Hemangioma of the Hard Palate: A Rare Childhood Tumor

DOI: 10.31038/JDMR.2019245

Abstract

Hemangioma are benign tumor of childhood occurs due to proliferation of endothelial cells of blood vessels. Although hemangioma of the head and neck region are common, these tumors are rarely seen in the oral cavity especially hard palate. Normally, such rare cases of hemangiomas can be misdiagnosed as any other pathologies. So the proper diagnosis and management is very important to reduce the intraoperative and postoperative complications.This case report presents a case of a 7 years old male who was reported in the department of Oral and Maxillofacial Surgery with the chief complaints of swelling in the left maxilla since 4 months. After excisional biopsy and histopathological study, the lesion was finally diagnosed as capillary hemangioma of the palate.No recurrence was noted at 6 months follow-up.

Keywords

Hemangioma, intraoperative complication, excision

Introduction

Hemangiomas are benign tumor of vascular endothelial origin which are painless, slow progressive in growth and can involve superficial and deep blood vessels .They are mostly seen during early childhood occurring in about 5–10% of children <1 year of age, which involutes over time [1]. Hemangiomas are common in the head and neck region but rare in the oral cavity2. The lesions in the oral cavity generally appear on the lips, buccal mucosa and tongue, but rarely on hard and soft palate [2,3]. Incidence of hemangiomas are more in female than males. These proliferative tumors can be seen as a single lesion in 80% of the time but 20% it can be seen as multiple lesions. The proliferation of endothelial cells does not usually undergo malignant transformation. They appear as pale macules which can be lobulated sessile or pedunculated with variable size. They may have smooth or irregular boarders. As the lesion can be confused with other common lesions in oral cavity like pyogenic granuloma, histopathological examination is very important for the final diagnosis. The variants of hemangiomas are capillary, cavernous or central depending on the vasculization system. Following case report represent an unusual location of capillary hemangioma on the hard palate of a 7 years old male patient who reported to the department of oral and maxillofacial surgery. Following the surgical excision, lesion was sent for histopathological diagnosis and confirmed as capillary hemangioma. Regular follow up of the patient was done.

Case History

A male patient aged 7 years reported to the department of oral and maxillofacial surgery with a progressively enlarging painless swelling in upper left posterior teeth region for the past 4 months. The swelling was insidious in onset, gradually progressive and there was no history of any pain, discharge or bleeding. Extra orally no abnormalities detected (Figure 1). Intraoral examination revealed a solitary broad based pinkish growth of size 1.5×1.5 cm, present on the left posterolateral part of the hard palate just 0.5 cm lateral to the midline on the left side in relation to the deciduous left maxillary first and second molars. Swelling has a well-defined border, which was not interfering the occlusion (Figure 2). On palpation swelling was non-tender and firm in consistency. Panoramic radiograph did not reveal any pathological changes in relation to 64 and 65 (Figure 3). A provisional diagnosis of hemangioma was made based on clinical and radiographic findings. The lesion was excised under general anesthesia and tooth no. 64 and 65 were extracted (Figure 4). Wound was sutured. . Following that, the tissue specimen was sent for histopathological study, which shows lobulated cellular growth which containing proliferating endothelial cells, combination of numerous well and poorly canalized blood vessels which are lined by endothelial cells. The epithelium is parakeratotic stratified squamous type. The intervening connective tissue stroma is fibrillar composed of loose bundles of collagen fibers. It is sparsely infiltrated with chronic inflammatory cells predominantly lymphocytes and plasma cells. On the basis of clinical and histopathological findings lesion was finally diagnosed as capillary hemangioma of the hard palate. Satisfactory uneventful wound healing occurred after 1 month .Nance palatal arch space maintainer was delivered to the patient .No recurrence of the lesion was noted after 6 months of follow-up.

JDMR-19-125- Rilna P_India_f1

Figure 1.

JDMR-19-125- Rilna P_India_f2

Figure 2.

JDMR-19-125- Rilna P_India_f3

Figure 3.

JDMR-19-125- Rilna P_India_f4

Figure 4.

Discussion

Vascular lesions can be generally divided into hemangiomas and vascular malformations. In 1982, Mullikan and Glowacki described the classification based on clinical and microscopic features [4]. Hemangiomas are considered as true neoplasm of the vascular endothelial cells, but some controversy still occurs whether to classify hemangiomas as malformation or hamartomas [5]. Lesions commonly occurs as small or large superficial growth and can be unicentric or multicentric. Normally capillary hemangiomas are seen as superficial small pedunculated lesions which differ from other variants like central and cavernous which occurs as large superficial or deep lesions [1]. Also capillary hemangiomas can be seen as sessile or pedunculated lesions which are painless unless traumatized. In the present case, lesion was superficial and pedunculated which suggestive of capillary variant. Since there are no particular criteria for the diagnosis of capillary hemangiomas, proper clinical history and histopathological study can help to diagnose the lesion. In the present case, history of occurrence of lesion within few months with slow progressive in growth and clinical examination helps to suggest the lesion as capillary hemangioma. Ocurrence of hemangiomas is very rare especially in the hard palate and very few cases were reported in literature of occurrence in the oral cavity. Usually hemangiomas do not affect the adjacent bone which supports the present study which does not shows any involvement of adjacent bone. Pyogenic Granuloma (PG), peripheral giant cell granuloma, epulis granulomatosa, and squamous cell carcinoma should be included in the differential diagnosis of hemangiomas [6,7]. Management is based on age of the patient, size extend and variant of hemangiomas in the oral cavity [8]. Normally no intervention is required in early stages since there is a chance of involution of the lesion on aging. But in the present case, since the lesion was small without any bony involvement and to finalize the diagnosis, excisional biopsy was planned. Small lesions can successfully excised without any complications and with the support of proper bleeding control [9,10].

In the present case, since the hemangioma was small and superficial, excision of the lesion was done as the management. Most common complication which can occurs can be intraoperative bleeding, which has to be controlled with proper measures to minimize the blood loss. In the present case bleeding was controlled using local pressure application and cauterization. And the wound healing was uneventful. Recently reported treatment modalities for hemangiomas in the literature includes steroid therapy, electrosurgery, Nd:YAG laser, CO2 laser, cryosurgery, and sclerotherapy [11,12]. Nowadays, sclerotherapy is used largely because of its ability and efficiency to preserve the surrounding tissue [13].

In our patient, since the tumor was causing difficulty in swallowing and was impairing speech, surgical excision was carried out. Some studies have reported the recurrence of hemangioma after surgical management [14,15]. The case described here demonstrates that there has been no subsequent hemorrhage or other evidence of recurrence.

Conclusion

Dental practitioners and oral surgeons need to be aware with such unusual presentations of hemangioma in the oral cavity, so that they are treated appropriately without any serious intraoperative and postoperative bleeding risks.

References

  1. Neville BW, Damm DD, Allen CM et al. (2009) Oral and maxillofacial pathology. (3rdedn), St Louis: Saunders 2008.
  2. Dilsiz A, Aydin T, Gursan N (2009) Capillary hemangioma as a rare benign tumor of the oral cavity: a case report. Cases J 2: 8622.
  3. Yoon RK, Chussid S, Sinnarajah N (2007) Characteristics of a pediatric patient with a capillary hemangioma of the palatal mucosa: a case report. Pediatr Dent 29: 239–42.
  4. Mulliken JB, Glowaki J (1982) Hemangioma and vascular malformation in infants and children: classification based on endothelial characterstics. Plast Reconstruct Surg 69: 412–20.
  5. Barnes L (1985) Tumours and tumour-like lesions of the soft tissues. In: Barnes L (ed.), Surgical pathology of the head and neck. New York, NY: Marcel Dekker Pg No: 725–880
  6. Singh P, Parihar AS, Siddique SN, et al. (2016) Capillary hemangioma on the palate: a diagnostic conundrum. BMJ Case Rep 2016.
  7. Mufeed A, Hafiz A, George A, et al. (2015) Pedunculated hemangioma of the palate. BMJ Case Rep 2015
  8. Kumari VR, Vallabhan CG, Geetha S, Nair MS, Jacob TV (2015) Atypical presentation of capillary hemangioma in oral cavity- A case report. J Clin Diagn Res 9: 26–8.
  9. Rachappa M, Trivedi MN (2010) Capillary haemangioma or pyogenic granuloma: a diagnostic dilemma. Contem Clin Dent 1: 119–22.
  10. Van Doorne L, De Maeseneer M, Stricker C, Vanrensbergen R, Stricker M (2002) Diagnosis and treatment of vascular lesions of the lip. Br J Oral Maxillofac Surg. 40: 497–503.
  11. Varma S, Gangavati R, Sundaresh KJ, et al. (2013) Lobulated capillary haemangioma: a common lesion in an uncommon site. BMJ Case Rep 2013.
  12. Acikgo¨z A, Sakallioglu U, Ozdamar S, et al. (2010) Rare benign tumours of oral cavity—capillary haemangioma of palatal mucosa: a case report. Int J Paediatr Dent 10: 161–165
  13. Kamala KA, Ashok L, Sujatha GP (2014) Cavernous hemangioma of the tongue: A rare case report. Contemp Clin Dent 5: 95–8.
  14. Kocer U, Ozdemir R, Tiftikcioglu YO, Karaaslan O (2004) Soft tissue hemangioma formation within a previously excised intraosseous hemangioma site. J Craniofac Surg 15: 82–3.
  15. Sznajder N, Dominguez FV, Carraro JJ, Lis G (1973) Hemorrhagic hemangioma of gingiva: report of a case. J Periodontol 44: 579–82.

Body Composition Changes in Patients with Head and Neck Cancer Underactive Treatment: A Scoping Review

DOI: 10.31038/NDN.2019112

Abstract

Background: Head and neck cancer (HNC) patients experience significant weight loss before diagnosis, during and after treatment, and even during the first year of follow-up. However, the prognostic value of weight loss depends on body mass index, and this may be associated with low skeletal muscle mass, masking its loss. Thus, body composition changes occurring during HNC management warrant further investigation.

Objective: The aim of this scoping review was to evaluate body composition changes and the methods to assess it in HNC patients under oncological treatment with curative intent.

Inclusion Criteria: All published studies in English, Spanish and Portuguese during 2000-2019 focusing on body composition changes in HNC patients aged 18 years or older in the context of treatment with curative intent were considered. Surgical treatment approach was excluded to avoid excess heterogeneity. A three-step search strategy was undertaken.

Presentation of results: HNC patients suffer from serious loss of lean body mass, skeletal muscle or free fat mass after treatment compared with baseline. This can be demonstrated either by triceps skin fold thickness, bioelectrical impedance analysis, dual-energy x-ray absorptiometry or computed tomography. Nutritional deterioration occurs up to 8-12 months after treatment and has a remarkable impact on survival, quality of life, and risk for complications.

Conclusion: HNC patients experience a significant depletion of lean body mass, fat-free mass and skeletal muscle, accompanied by body fat mass, while undergoing (chemo) radiotherapy. Bioelectrical impedance analysis seems to be a feasible body composition assessment tool as it is inexpensive and non-invasive and usually readily available.

Keywords

Head and Neck Cancer, Body Composition, Skeletal Muscle, Lean Body Mass, Adipose Tissue, Fat Free Mass

Background

Head and neck cancer (HNC) is a term that refers to a heterogenous group of cancers that occur in the upper aerodigestive tract i.e. oral cavity, pharynx, larynx, paranasal sinuses, nasal cavity or salivary glands [1, 2]. Certain subtypes of these cancers demonstrate a strong increasing incidence and in general they are related to a low survival outcome. The most frequently found risk factors for HNC are the use of alcohol, tobacco, human papillomavirus (HPV)/Epstein-Barr virus (EBV) infection and poor oral hygiene3. Given their complexity and location, interference with the anatomical and physiological characteristics, the tumors and their treatment are able to promote aesthetic alterations and disturbance of functions such as phonation, swallowing, hearing and breathing [2, 4]. Dysphagia (difficulty in swallowing) is a prevalent risk factor for morbidity prior, during and following oncological treatment for HNCs, affecting most patients at some stage over the course of treatment, and is often rated as the most significant factor affecting quality of life amongst HNC survivors [1, 5]. Prior to treatment, HNC patients may experience swallowing dysfunction due to pain, obstruction or an uncoordinated swallowing mechanism[5], contributing to insufficient dietary intake, which may occur if the estimated energy intake is <60% of the individual requirement for more than 1 and 2 weeks [6]. However, not only the location of the tumor may result in problems in eating and drinking, but the cancer treatments (surgery and (chemo)radiotherapy either alone or in combination) also cause, in addition to dysphagia, alterations in swallowing function, which may persist for several months or even years, as xerostomia, thick saliva, difficulty in chewing, anorexia and nausea/vomiting [1-8]. These symptoms, either related to the acute toxicity or the anatomic changes caused by these treatments, may exacerbate nutrition deterioration by compromising dietary intake [2]. Even partial reduction in dietary intake (i.e. daily deficit >25%, >50%, or >75% of energy requirements) results in large caloric deficits over time, and the expected duration, as well as the degree of depletion of body reserves, should be considered. Both conditions result in weight loss and, consequently, in body mass index (BMI) reduction, which may be severe [6]. Apparently, age, race, gender, smoking and alcohol consumption, and radiation dose, do not independently predict severe weight loss [7]. The negative energy balance and skeletal muscle mass (SMM) loss observed in cancer patients is driven by a combination of reduced food intake and metabolic derangements (e.g. elevated resting metabolic rate, insulin resistance, lipolysis, and proteolysis which aggravate weight loss and are caused by systemic inflammation and catabolic factors), which may be host- or tumor-derived [6].

When compared with other cancer-patient populations, patients with HNC have the second highest prevalence of malnutrition, after upper gastrointestinal tract cancer patients [9]: 20-67% are malnourished or at high risk of becoming malnourished at diagnosis [7] and this will worsen throughout the treatment [2]. Significant weight loss (i.e., the involuntary weight loss of 5% body weight in 1 month or 10% in 6 months)[10]  is a common phenomenon before HNC diagnosis, during and after treatment, and occurs for up to a year following treatment [7]. A meta-analysis conducted by Couch et al. (2015) showed a relation between the extent and prevalence of weight loss and the location and stage of the tumor. Patients with advanced-stage HNC (stage III/IV) experience weight loss significantly more often when compared with those with early-stage (stage I/II) disease [10]. Weight loss alone is often the most common clinical measurement of cachexia [10] and forms one of the independent negative prognostic factors [2] for HNC patients, having a negative impact on quality of life (QOL) and morbidity as well [10]. Cancer cachexia is a term that refers to a multifactorial syndrome defined by an ongoing loss of SMM (with or without loss of fat mass) unable to be fully reversed by conventional nutritional support and leading to progressive functional impairment [11]. An early detection of malnutrition aims to improve oncological outcomes, and minimize acute toxicities, treatment interruptions and enhance survival [2]. Body composition (BC) has gained increasing interest in oncology and refers to the amount and distribution of lean tissue and adipose tissue in the human body [12]. The published studies have shown the importance of the changes in BC in various cancer patients [2] and more specifically loss of SMM, with or without loss of fat has proven to be a significant parameter [8]. Further, muscle loss determines the limiting dose of some antineoplastic drugs due to high distribution volume in adipose tissue, resulting in a slower drug elimination [2], and in a higher chemotherapy toxicity, and increase in mortality [8]. Different parameters can be used to assess BC, but the best-known parameter is BMI [12]. However, the role of this anthropometric tool is still unclear in HNC patients [8]. In recent years, several studies have shown a clear dissociation between total body weight loss and SMM loss, reflecting the increased prevalence of obesity in the population. The prognostic value of weight loss depends on the BMI, and this may be associated with low SMM, masking its loss. Thus, weight loss itself poorly predicts outcome in HNC patients when compared with depleted SMM, illustrating the inadequacy of BMI as an accurate method to reflect nutritional status [8]. An assessment method would be needed for rapid clinical implementation, to adequately evaluate BC in HNC patients in order to reveal significant malnutrition, appropriate chemotherapy dose, and to identify high risk patients [8]. Besides questionnaires like Patient-Generated Subjective Global Assessment (PG-SGA) that allow the assessment of the nutritional status, the existing techniques to evaluate nutritional status and/or BC include anthropometric measurements for weight and BMI, measurement of skinfold thickness, biochemical parameters, bioelectrical impedance analysis (BIA), computed tomography (CT), magnetic resonance (MRI) or dual-energy x-ray absorptiometry (DEXA) [13].

Many studies have shown the impact of CT image of L3 as the reference method to measure BC2. Chamchod et al. (2016) showed that lean body mass (LBM) estimation for HNC patients, especially post-therapy, should be performed using CT image-based assessment, otherwise, measurement error of >10 kg should be presupposed. However, because all HNC patients do not routinely have this image available, bioelectrical impedance analysis (BIA) has been reported as a method with a good consistency along the treatment [2]. This method is widely used, non-invasive, portable, inexpensive, and feasible to assess BC in humans [14]. It is based on impedance of a low-voltage current passing through the body [14], which can then be used to calculate an estimate of total body water (TBW). Further, TBW can be used to estimate fat-free mass (FFM) by comparing with body weight and body fat [8]. Dual-energy X-ray absorptiometry (DEXA) has gained popularity in quantifying LBM for being non-invasive, carrying low cost and radiation dose, and being able to measure LBM, fat mass, and bone mineral density. However, DEXA values depend on the precision error of the DEXA machine, which may be affected by the diffuse inflammatory changes caused by chemotherapy. It remains an important area for research, because there are no recommendations on this issue, and it is important to understand how chemotherapy may affect precision error, in order to accurately interpret changes in BC [15]. This scoping review was guided by the methodologically rigorous manual by The Joanna Briggs Institute (JBI), for scoping reviews [16], and aimed to synthesise and map the BC changes in HNC patients, which occur during treatment. The main objective was to provide a descriptive overview of what these changes are and how they can be measured. The purpose of a scoping review is to map and examine the existing evidence in literature in a given field, providing an overview, as a preliminary exercise prior to the conduct of a systematic review, regardless of quality of the contributing studies, unless otherwise specified. Therefore, a scoping review does not intend to recommend clinical practices or to provide guidelines [16]. An initial search of the JBI Database of Systematic Reviews and Implementation Reports, MEDLINE and CINAHL demonstrated that there were no systematic reviews, meta-analyses or scoping reviews (published or in progress) on this topic. The objective, inclusion criteria and methods for this scoping review were specified in advance and documented in a protocol [16].

Review question/objective

The purpose of this scoping review was to examine and map the BC changes in HNC patients, under active treatment, and to determine which methods are useful to assess BC in these patients. The current review was guided by the following research questions, built on the ‘PCC’ mnemonic (Population, Concept and Context):

  1. What is known from the existing literature about the changes in BC in head and neck cancer patients under active oncological treatment?

    Two other questions were identified to guide the subsequent steps of the scoping review, and broader complement the research question above.

  2. Which methods are useful for assessing BC changes in HNC patients under active treatment?
  3. What are their reported strengths and weaknesses?

Inclusion Criteria

As well as the title and the research question, the eligibility criteriawere built on the ‘PCC’ mnemonic (Population, Concept and Context):

Types of participants

The current review considered HNC patients, aged 18 years or older, who had not been submitted to any training or dietary program.

Concept

This scoping review considered all studies that focused on the BC changes.

Context

This scoping review considered the studies that evaluated the BC changes in the context of treatment, with curative intent. These included antineoplastic agents, chemotherapy, adjuvant chemotherapy, radiotherapy, adjuvant radiotherapy, and adjuvant chemoradiotherapy. Surgical treatment approach was not included. Adjuvant treatment was included, but not when this was surgery alone.

Types of sources

This scoping review considered only published studies, both quantitative and qualitative data, with an abstract available. Due to time constraints, only published studies were considered for the review, retrieved from databases, excluding unpublished studies.

Search strategy

The search strategy aimed to find only published studies, within the last 19 years from 2000 to 2019. A three-step search strategy was conducted on this review.An initial limited search of MEDLINE (via PubMed) and CINAHL Plus with Full Text (via EBSCO) was undertaken through an analysis of the index terms used to describe the articles. A second search using all index terms identified was undertaken across both databases included. Thirdly, the reference lists of all identified reports and articles will be searched for additional studies. Studies published between January 2000 and July 10, 2019 in English, Spanish and Portuguese were considered for inclusion in this review.  Initial keywords/search terms were used: head and neck cancer; body composition OR body weight OR body weight change OR body mass index OR fat-free mass OR skeletal muscle; antineoplastic agents OR radiotherapy OR radiotherapy, adjuvant OR chemotherapy, adjuvant OR chemoradiotherapy OR chemoradiotherapy, adjuvant.  The search in PubMed provided most articles, and the search are shown in Appendix I. The search strategy conducted in Cinahl Plus with Full Text followed the same strategy mentioned in Appendix I. Search results run in the different databases were consolidated, and duplicated studies were excluded. After the duplicates were removed, two independent reviewers screened the articles to exclude those that do not meet the eligibility criteria identified in the second stage of the protocol, based on the titles and abstracts. For those fulfilling the eligibility criteria, the full-text article was obtained. Disagreements on study eligibility of the sampled articles were discussed between the two independent reviewers. Studies identified from reference lists were assessed for relevance based on their title and abstract.

Extraction of results

Relevant data were extracted from the included studies to address the review question using the template developed in the protocol (Appendix II), as indicated by the methodology for scoping reviews developed by the Joanna Briggs Institute [16]. In accordance with the purpose of scoping reviews, the quality of data extracted was not appraised before inclusion. Two reviewers extracted data independently. Disagreements on study eligibility of the sampled articles were discussed between the two independent reviewers, or with a third reviewer. The data extracted included author(s)/year of publication, aims and purpose of the study, sample size, study design, type of treatment, measurement points and component(s) of BC evaluated, BC assessment methods, main results/findings.

Results

The database searches provided a total of 1180 citations after duplicates were removed. One additional citation was found in the reference list review. A total of 17 papers met the inclusion criteria, based on the titles and abstracts. The full-text, of these 17 citations, were obtained and read, and 5 of them were excluded for the following reasons: only assessing skeletal muscle before treatment (n=1), only assessing phase-angle variations during radiotherapy (n=1), only assessing nutrition status, phase-angle and body weight (n=1), patients received exercise training, during and after treatment (n=2), which may serve as a possible confounding for changes body weight or lean body mass. A total of 12 studies were included in this review. A flowchart showing the study selection process is detailed in Figure 1.

NDN-19-101- Paula Ravasco_F1

Figure 1. PRISMA flow chart for the scoping review process.

From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and MetaAnalyses: The PRISMA Statement. PLoS Med 2009; 6 (7): e1000097

Characteristics of Study Design and Data Collection

The review reports found from 12 studies published from 2004 to 2018, had been conducted almost worldwide: China (2) [17, 18] Netherlands (2) [14, 19], United States of America (3) [8, 20, 21] Turkey (1) [22], Brazil (1) [23], Spain (1) [2], Canada (1) [24] and Sweden (1) [25]. A summary of the characteristics of studies included are described in Appendix III. The population size for the included studies ranged from 202to 215 participants [8] comprising a total of 891 HNC patients (75, 3% male; 24, 7% female), over 18 years old. Ten studies had used a prospective cohort design [2, 14, 17, 18-21, 22-25] and two studies had used a retrospective cohort design [8, 20].

Body Composition Changes (Concept)

BC analysis included variables such as: LBM, measured by five studies [8, 17, 19-21] FFM measured by five studies [2, 14, 18, 23, 25] two of which estimated fat-free mass index (FFM (kg) divided by body height2 (m2)) [18, 25]. Fat mass/adipose tissue were measured by seven studies [8, 17, 18, 19, 22-24] one of which estimated fat mass index (FM (kg) divided by body height2 (m2)) [18], and another estimated subcutaneous fat [22].. Skeletal muscle was measured by two studies, normalized for height in meters squared, reported by skeletal muscle index (SMI) [18, 24]. Reviewing the articles and synthesizing findings from baseline to the end of treatment, all studies reported BC changes, especially loss of LBM or FFM. Appendix IV shows the BC changes reported from the baseline to the end of treatment. The BC analysis data collected at baseline were set as the reference to analyses whether significant changes were observed at different measurement points. One study [2] reported a positive change in FFM during induction chemotherapy (iCT), which increased until the begin of concomitance treatment, and then declined significantly, while another study [21] reported also a positive change during iCT, but this was related to weight gain and not specifically to FFM. The greatest change in body mass occurred in LBM at 1-month post-concurrent chemoradiotherapy (CRT). The loss in LBM occurred despite dietary consumption, and reduced significantly for all body compartments: arms, legs, and trunk [21]. One study [25] reported a decrease of FFM of 6, 5 kg in >10% weight loss group, and 2, 7 kg in ≤ 10% weight loss group. One study [24] including 28 HNC patients found that approximately half of lost body weight was attributed specifically to muscle loss (3.4 kg) and the other half could be explained by 3.6 kg fat loss, both visceral and subcutaneous adipose tissue. The same results were reported in another the study [19], where LBM significantly declined during treatment, corresponding a sixty-two percent of weight loss. However, there were no significant changes between first and second post treatment assessment, which is in agreement with the results found by the same authors, but in a more recent study14 showing a significant decline in FFM (p<.05) during the treatment period but remaining stable 4 months after the end of treatment. One study [17] reported a significant decline in body fat mass and LBM at the different time points after radiotherapy (RT) compared with pre-RT. During the recovery time from the end of treatment to 6 months post-RT, lean body mass remained largely static, whereas body fat mass continued to decrease. Two studies [7, 20] reported different results by sex. In men, a significantly dropped of LBM post-treatment compared with pre-treatment was found, decreased from @ 58kg to @ 51kg after RT, whereas mean estimated LBM in women remained fairly stable, decreasing from @ 38.0 kg to @ 36 kg RT. Additionally, another study [8] reported that the mean fat mass dropped in both men and women after treatment. Two studies [22, 23] showed that TST measurements significantly deteriorated in the end of RT, what means a significant loss of subcutaneous fat, corroborated by BIA analysis, which demonstrated a significant reduction in body fat and FFM, which continued to decline one month after the end of treatment [23]. One study [18] reported statistically and clinically significant changes also in fat mass, FFM, and SMM, during concurrent CRT.  Synthesizing these findings shows how HNC patients suffer from serious LBM, skeletal muscle, body fat or FFM loss, during and after treatment compared with baseline.

Body composition assessment methods

In five studies [2, 14, 18, 23] BC was assessed by BIA, two of which also used DEXA [14] or TSF [23], respectively. In three studies [8, 20, 24] the assessment method was CT, at the level of the third lumbar (L3) vertebra. DEXA, as a single measurement, was applied in other three studies [17, 19, 21] and in one study [22] BC was assessed by TSF. One study [2] considered BIA as a method with good application consistency in patients with locally advanced HNC providing useful information, especially for evaluating FFM, since these patients do not have image of L3 at the CT available in a regular daily basis. However, also referred that the validity and interpretation of maintenance in FFM through the treatment in his study, need to be taken cautiously as the BC values were estimated from changes in voltage across the body. In another study [17] on nasopharyngeal cancer patients managed in Hong Kong, the authors did not find a systematic difference between BIA and DEXA measures, although the BIA had slightly underestimated FFM by <1 kg, both pre- and post-treatment, and accordingly to these results, one study [18] in locally advanced nasopharyngeal carcinoma patients showed that BC assessed by BIA could reflect the change of nutritional status when compared with other methods such as DEXA. One study [8] including HNC patients (various tumor subsites) recommended routine use of quantitative imaging (CT and DEXA) in HNC patients, especially in those prone to changes in nutritional status, as opposed to general population-based height-weight formulae, because the last are not sufficient for body mass quantification. One study [22] used triceps skinfold thickness (TSF) to estimate subscutaneous fat in a series of 54 HNC patients. This is a inexpensive and non-invasive method, and it is widely available [13]. On the other hand, eight studies [17, 19-25] did not report any advantage or disadvantage of using BIA, L3 image at CT, TSF or DEXA. In summary, these findings show that BIA has the great advantage for being available on a regular basis for assessing BC in HNC patients, is inexpensive, noninvasive, and it is a good method to be applied when no imaging techniquesare available. Further, it can be performed by a clinical dietitian [18] if the protocol is followed.

Discussion

This scoping review report’s findings from 12 articles identified through a systematic literature search, published over a 14-year period, that investigated or described the BC changes in HNC patients under active oncological treatment, with curative intent. The patient group with surgical treatment approach was not included in this review for uniformity reasons, as this would have increased the heterogenous nature of the patient population. In general, the studies displayed different oncological treatment modalities, the sample sizes in the retrospective studies suffer from dropout, and the prospective studies from small samples. The studies included in this scoping review also comprised different ‘’measurement points’’, evaluated different components of BC, as well as the methods to assess it in HNC patients, which makes it challenge to synthesizing findings. Studies of human BC using CT scans have provided proof-of-concept that variability in drug disposition and toxicity profiles may be partially explained by different features in BC [26]. The depletion of skeletal muscle before and after RT is strongly associated with decreased survival in patients with solid tumors [20], a higher risk for complications and reduced response to cancer treatment [19]. BC analysis results indicated that the BC components, such as LBM, FFM, body fat and skeletal muscle, change at different measurement points, and that these changes in HNC patients, receiving RT, cannot be effectively monitored by measuring their weight, and BMI [27].. Two studies [19, 24] reported a loss of LBM corresponding to more than half the weight lost, showing that weight loss itself poorly predicts outcome in HNC patients [8]. Low dietary intake due to treatment related nutrition impact symptoms seems to be one of the main contributing factors for muscle loss in HNC patients, because they not meet the recommended calorie and protein intake. In additional to low dietary intake, inflammation could exacerbate muscle loss during cancer treatment [24], as well as impairments in physical performance, contributing to aberrant changes in BC [20]. However, there was a positive change in FFM during iCT [2], reported by Arribas et al. (2017), which may be related to the improvement of the symptoms that initially limited the oral intake and could contribute to minimize further deterioration, proving the role of the nutritional intervention from the beginning of the treatment [2]. Besides these two studies, and this specific measurement point, all the studies included in this review reported loss of LBM, FFM, fat mass and skeletal muscle during the treatment. Post-treatment nutritional deterioration is evident among HNC patients in all included studies, occurring up to 8-12 months during follow-up, although there appears to be a slight recovery. Different findings were observed between Jager-Wittenaar et al (2010) and Kenway et al. (2004) related to body-weight increase after treatment. Jager-Wittenaar et al. (2010) reported a weight gain, characterized by increase of fat mass instead of FFM, while Kenway et al. (2004) found a continously decline of body fat after treatment. Changes in BC after cancer treatment warrant further investigation as this phenomenon might affect recovery from therapy-related side effects and more importantly, even prevent complications. A systematic review by Correia et al.(2019) addressing the methods for BC assessment in clinical settings found that the reference methods for BC assessment in cancer patients are DEXA and L3 in CT imaging, but these examinations are not routinely performed in the management of HNC. This finding is consistent with this review where some authors chose BIA as the preferred method as an alternative to more invasive and expensive methods like DEXA and CT, and because it is available on in routine HNC management. BIA is recommended to be increasingly implemented in nutritional assessment [18]. Citak et al. (2017) used TSF to estimate subscutaneous fat, and only highlight advantages for its use, because all anthropometric measurements were performed by the same person [22]. However, poorer accuracy and precision in obese/oedematous individuals [28], and its sensitive to technician skills, type of calliper and prediction equations used it [13], need to be taken into account. All the BC changes that occur during management of HNC patients, as well as choosing the most feasible, accurate and practical method to assess these changes, represents a challenge for further investigation, in order to assess and improve nutritional status, and disease-associated processes.

Limitations of the review

Although the quality of data extracted was not appraised before inclusion, since it is not relevant for a scoping review, some limitations should be reported so as to provide valuable information to future investigation:

The present scoping review is a pragmatic mean of dealing with the lack of evidence available on BC changes in HNC patients under active treatment;

  • The present scoping review aims to use 2 electronic databases and the search has been refined to increase the likelihood of retrieving as many relevant published articles as possible;
  • Only published studies, in English, Portuguese and Spanish in scientific journals were considered eligible for inclusion;
  • A quality assessment of the articles included in the scoping review was not performed;
  • Due to time constraints, the search strategy didn’t include the MeSH term “neoplasms”, what may had excluded some relevant references;
  • The difference in results may be the result of including a heterogeneous group of patients receiving different types of treatment, and of the variability of BC assessment tools;
  • The interval of BC assessment between pre- and post- RT varied, and some patients may have recovered muscle mass during this period whereas other may have continued to lose muscle mass after the end of treatment;
  • The variability in quality of imaging, which may affect skeletal muscle mass, contouring and adipose tissue segmentation.

Conclusion

HNC patients experience a significant depletion of LBM, FFM and skeletal muscle, accompanied by body fat mass, while undergoing (chemo) radiotherapy, demonstrated either by the TSF, BIA, DEXA or CT. This loss has a significant impact on their survival, quality of life, on the risk for complications and may result in a reduced response to cancer treatment. Thus, BC assessment should become an integral component of the care of HNC patients, beyond weight and BMI, and should be carried out at different times throughout treatment. Based on this review, further investigations are recommended applying measurements at same time points and assessing BC changes with comparable methods in order to obtain evidence for the impact of body composition changes in this patient population.

Appendix I – Search Strategy

PubMed – search conducted on 10/07/2019

Search Strategy

Results

(((“Head and Neck Neoplasms”[Mesh] OR (head[Title/Abstract] AND Neck neoplasms[Title/Abstract])) OR (Head[Title/Abstract] AND neck cancer[Title/Abstract])) AND (((((((((“Muscle, Skeletal”[Mesh] OR (“muscle, skeletal”[MeSH Terms] OR (“muscle”[All Fields] AND “skeletal”[All Fields]) OR “skeletal muscle”[All Fields] OR (“muscle”[All Fields] AND “skeletal”[All Fields]) OR “muscle, skeletal”[All Fields])) OR (“Adipose Tissue”[Mesh] OR Adipose Tissue[Title/Abstract])) OR (“Adiposity”[Mesh] OR Adiposity[Title/Abstract])) OR (“Body Composition”[Mesh] OR body composition[Title/Abstract])) OR (“Body Mass Index”[Mesh] OR Body Mass Index[Title/Abstract])) OR (“Weight Loss”[Mesh] OR weight Loss[Title/Abstract])) OR (“Weight Gain”[Mesh] OR Weight Gain[Title/Abstract])) OR (Body Weight Changes[Title/Abstract] OR “Body Weight Changes”[Mesh])) OR (“Body Weight”[Mesh] OR Body Weight[Title/Abstract]))) AND ((((((“Chemoradiotherapy, Adjuvant”[Mesh] OR Adjuvant Chemoradiotherapy[Title/Abstract]) OR (“Chemoradiotherapy”[Mesh] OR Chemoradiotherapy[Title/Abstract])) OR (“Radiotherapy, Adjuvant”[Mesh] OR Adjuvant Radiotherapy[Title/Abstract])) OR (“Chemotherapy, Adjuvant”[Mesh] OR Adjuvant Chemotherapy[Title/Abstract])) OR (“Radiotherapy”[Mesh] OR Radiotherapy[Title/Abstract])) OR (“Antineoplastic Agents”[Mesh] OR Chemotherapy[Title/Abstract])) AND (hasabstract[text] AND (“2000/01/01”[PDAT] : “3000/12/31”[PDAT]) AND “humans”[MeSH Terms] AND (English[lang] OR Portuguese[lang] OR Spanish[lang]))

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Appendix II: Data extraction instrument

Scoping Review Title: Body composition changes in head and neck cancer patients under active treatment: a scoping review

Review Objective/s: Examine and map the body composition changes in head and neck cancer patients, under active treatment, and determine which methods are used to assess body composition in these patients.

Review Question/s:

  1. What do we known from the existing literature about the changes in BC in head and neck cancer patients under active treatment?
  2. Which methods are useful for assessing BC changes in head and neck cancer patients under active treatment?
  3. What are their strengths and weaknesses, reported by the authors?

Inclusion/Exclusion Criteria

Population: Head and neck cancer patients, aged 18 years or older, who have not been submitted to any training or dietary program.

Concept: Body composition changes.

Context: Treatment: This include antineoplastic agents, chemotherapy, adjuvant chemotherapy, radiotherapy, adjuvant radiotherapy, chemoradiotherapy and adjuvant chemoradiotherapy.

Types of Study: Only published studies, both quantitative and qualitative data, and systematic reviews, with abstract available.

Study Details and Characteristics

Author/Year_____________________________________________________________

Aims/Purpose of the study__________________________________________________

Sample Size_____________________________________________________________

Study design_____________________________________________________________

Type of treatment_________________________________________________________

Measurement points_______________________________________________________

Component(s) of body composition evaluated___________________________________

Body composition assessment method_________________________________________

Main results/findings_______________________________________________________

Appendix III: C haracteristics of Study Design and Data Collection

Author(s)/ Year of publication

Aims/ Purpose of the study

Sample Size/Stage

Study Design

Type of treatment

Measurement Points

Component(s) of body composition evaluated

Body composition assessment method

Main results/findings

Arribas et al2 2017

To evaluate changes in BC and nutritional status that occur throughout the oncological treatment in HNC patients

N = 20 HNSCC (Men = 19; women = 1)

Prospective cohort study

iCT flollowed by CRT or RT plus Cetuximab

Baseline Post iCT; After RT;

1 month post RT; 3 months post RT

Fat Free Mass

BIA

FFM decrease significantly over the course of treatment, but after the iCT there was an increase in FFM

Silander et al25 2012

To identify predictors of malnutrition at time of diagnosis in order to identify patients at risk and enable early nutritional support and prevent malnutrition

N = 119 Pharyngeal cancer, oral cancer, or unkwon primary with malignant neck nodes in stage III ou IV

(Men = 81; women = 38)

Prospective cohort study

Chemotherapy and RT, or surgery followed by RT

Baseline; After 5 months follow up

Fat Free Mass

BIA

The decrease of FFM was more than twofold for the malnourished patients, applying a definition of >10% weight loss compared to the non-malnourished during the 6-month time period, 6.5 kg versus 2.7 kg

Nejatinamini et al24 2018

To assess changes in vitamin status during HNC treatment in relation to BC, inflammation and mucositis

N = 28 HNSCC of the oral cavity, pharynx and larynx (Men = 23; women = 5)

Prospective cohort study

RT, with or without chemotherapy

Baseline; Post treatment (=6 months)

Skeletal muscle and body fat

Computed tomography at the level of the third lumbar (L3) vertebra

Approximately half of lost body weight was attributed specifically to muscle loss (3.4 kg) and the other half could be explained by 3.6 kg fat loss. Patients experienced a significant decrease in both visceral and subcutaneous adipose tissue

Kenway et al17 2004

To investigate the nutritional status of NPC patients before and after RT and the factors affecting nutritional by examining the relation among changes in body weight, BC, and basal metabolic rate; calorie intake; and total energy expenditure and adjusting for tumor stage, patient age, and gender

N = 38 Nasopharynx cancer (Men = 30; women = 8)

Prospective cohort study

Radiotherapy

Baseline;

post-RT;

2 months post RT; 6 months post RT

Body Fat and lean body mass

DEXA

Body fat mass and lean body mass at the different time points post-RT were all significantly lower than that at pre-RT. During the recovery time from end-RT to 6 months post-RT, lean body mass remained largely static, whereas body fat mass continued to decrease

Jager-Wittenaar eta I19 2010

To test whether nutritional status (including body weight, lean mass, and fat mass) of patients with head and neck cancer changes during and after treatment

N = 29 HNSCC of the oral cavity, pharynx and larynx (Men = 23; women = 6)

Prospective cohort study

Radiotherapy, either alone or combined with chemotherapy or surgery

1 week before treatment;

1 month posttreatment;

4 months posttreatment

Lean body mass and fat mass

DEXA

Body weight, BMI, and lean mass significantly declined during treatment. Sixty-two percent of weight loss was loss of lean mass. Lean mass declined significantly in all body regions

Grossberg et al20 2016

To determine whether lean body mass before and after RT for HNSCC predicts survival and locoregional control

N = 190 HNSCC (Men = 160; women = 30)

Retrospective cohort study

Primary surgery, single-modality RT or concurrent CRT

Before and after RT (= 8-12 months)

Lean body mass

Computed tomography at the level of the third lumbar (L3) vertebra

In Men, mean estimated LBM decreased from 58.4kg to 51.6kg after RT, whereas mean estimated LBM in women remained fairly stable, decreasing from 38.0 kg to 35.7 kg after RT

Citak et al22 2017

To assess the nutritional status and to define its determinants in patients with HNC undergoing RT

N = 54 HNC (Men = 49; women = 5)

Prospective cohort study

RT, with or without chemotherapy, after surgery, or not.

Baseline After RT;

1 month post RT; 3 months post RT

Subcutaneous fat

Triceps Skinfold Thickness (TST)

TST measurements were significantly deteriorated in the end of RT

Silver et al21 2006

To determine changes in body mass and BC in relation to energy balance, inflammatory state, and physical function before and after concurrent CRT

N = 70 HNSCC of the oral cavity, hipopharynx and larynx (Men = 15; women = 55)

Prospective cohort study

Concurrent CRT

Baseline;

1 month post CRT

Lean body mass

DEXA

The greatest change in body mass occurred in LBM at 1- month postconcurrent CRT. The loss in LBM occurred despite dietary consumption, and reduced significantly for all body compartMents: arms, legs, and trunk.

Carvalho et al23 2013

To examine the involveMent of antitumor treatment, including surgical resection and/or CRT, in the nutritional and metabolic status of patients with SCCHN

N= 32 HNSCC (Men = 31; women = 30)

Prospective cohort study

CRT, with or without previously surgery

10 to 20 days before the beginning of CRT; 30 to 40 days after finishing CRT

Body fat and FFM

BIA

There was significant reduction in body fat and FFM. The weight loss was accompanied by a significant reduction in body fat percentage calculated from TST and BIA

Ding et al18 2018

To investigate BC changes in patients with nasopharyngeal carcinoma undergoing concurrent CRT and a comparison of the Patient-Generated Subjective Global assessment (PG_SGA) and the ESPEN (European Society for Clinical Nutrition and Metabolism) diagnostic criteria as evaluation methods.

N = 48 Nasopharyngeal Carcinoma (Men = 36; women = 12)

Prospective cohort study

Concurrente CRT, with or without iCT

Baseline; weekly until the end of treatment

Fat mass, FFM and skeletal muscle

BIA

During concurrent CRT, there were statistically and clinically significant changes in most BC parameters, including body cell mass, fat mass, FFM, and SMM, as well as body weight, BMI, and PG-SGA scores

Chamchod et al8 2016

To determine if one or more height-weight formula(e) can be clinically used as a surrogate for direct CT- based imaging assessment of BC before and after RT for HNC patients, who are at risk for cancer and therapy- associated cachexia/sarcopenia.

N = 215 HNC (Men = 184; women = 31)

Retrospective cohort study

Concurrent chemotherapy or RT, with or without surgery

Pre- and posttreatment

Lean body mass

Computed tomography at the level of the third lumbar (L3) vertebra

Mean LBM dropped significantly posttreatment compared to pre-treatment for Men but didn’t reach statistical significance in women. Additionally, mean fat mass dropped in both Men and women after treatment

Jager-Wittenaar et al14 2014

To validate BIA using the Geneva equation for FFM in HNC patients

N = 24 HNC (Men = 20; women = 4)

Prospective cohort study

RT, with or without chemotherapy, or after surgery

The week before the treatment;

1 month after treatment;

4 months treatment

Fat Free Mass

DEXA and BIA

Body weight, BMI, FFM, volume of body fluids, phase angle, and impedance ratio significantly declined during the treatment period . There was no systematic difference between the BIA and DXA measurements.

Appendix IV: BC changes reported from the baseline to the end of treatment

Author(s)

Body composition assessment method

Component(s) of body composition evaluated

Baseline

Post iCT

Post RT

1-2 months post treatment

3-4 months post treatment

5-6 months post treatment

8-12 months post treatment

Arribas et al2

BIA

Fat free mass (kg)*

53,69 (8,16)

55,96 (9,06)

51,54 (5,89)

52,08 (6,70)

50,05 (7,66)

Silander et al25

BIA

Fat free mass index*

(2,6)
(WL S 10% group)
(2,7)
(WL > 10% group)

– 2,7 kg FFM (WL < 10% group) -6,5 kg FFM (WL > 10% group)

Nejatinamini et al24

Computed

Skeletal muscle index (cm2/m2)*

52,6 (11,1)

45,5 (9,1)

tomography

Body fat (kg)*

28,3 (8,1)

24,7 (6,9)

Kenway et al17

DEXA

Lean body mass (kg)*

46,2 (8,3)

42,1 (7,8)

42,8 (7,6)

43,3 (7,5)

Body fat (kg)*

15,1 (4,9)

12,4 (4,7)

10,9 (3,8)

10,4 (3,5)

Jager-Wittenaar

DEXA

Lean body mass (kg)*

54,6 (11,4)

52,1 (10,7)

52,3 (10,3)

et al 19

Body fat (kg)*

20,0 (9,8)

18,9 (8,1)

19,0 (7,0)

Grossberg et al20

Computed

tomography

Lean body mass (kg)*

58,4 (9,6) (men) 38,0 (7,3) (women)

51,6 (7,8) (men) 35,7 (6,6) (women)

Citak et al22

Triceps Skinfold Thickness (TST)

Subcutaneous fat (mm)*

21,79 (4,47)

21,31 (3,98)

21,5 (3,93)

21,81 (4,00)

Silver et al21

DEXA

Lean body mass (kg)*

52,25 (11,33)

46,64 (96,52)

Carvalho et al23

Triceps Skinfold Thickness (TST)

Subcutaneous fat (mm)*

10,84 (5,78)

8,41 (4,56)

BIA

Body fat (%)*

27,27 (7,44)

23,36 (7,70)

Fat free mass (kg)*

48,30 (9,84)

45,90 (8,75)

Fat mass index (kg2/m2)*

7,66 (1,99)

6,61(1,87)

Ding etal18

BIA

Fat free mass index (kg2/m2)*

15,79 (1,82)

14,79 (2,02)

Skeletal muscle (kg)*

24,47 (6,01)

22,93 (5,86)

Chamchod et al8

Computed

Lean body mass (kg)*

58,0 (9,69) (men) 37,56 (7,0) (women)

51,52 (8,31) (men) 36,2 (7,13) (women)

tomography

Body fat (kg)*

18,48 (1,36) (men) 17,56 (1,16) (women)

15,61 (0,98) (men) 15,42 (1,00) (women)

Jager-Wittenaar

DEXA

Fat Free Mass (kg)*

56,4 (10,9)

54,2 (10,0)

54,4 (9,9)

et al14

BIA

55,7 (10,0)

53,9 (9,4)

54,4 (9,4)

* Mean, standard deviation WL-Weigh Loss

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  24. Nejatinamini S, Debenham BJ, Clugston RD, Mawani A, Parliament M et al. (2018) Poor vitamin status is associated with skeletal muscle loss and mucositis in head and neck cancer patients. Nutrients 10. [crossref]
  25. Silander E, Nyman J, Hammerlid E (2013) An exploration of factors predicting malnutrition in patients with advanced head and neck cancer. Laryngoscope 123: 2428–2434. [crossref]
  26. Prado CMM (2013) Body composition in chemotherapy: The promising role of CT scans. CurrOpinClinNutrMetab Care 16: 525–533. [crossref]
  27. Tang PL, Wang HH, Lin HS, Liu WS, Chen LM et al. (2018) Body Composition Early Identifies Cancer Patients with Radiotherapy at Risk for Malnutrition. Journal of Pain and Symptom Management 55: 864–871. [crossref]
  28. Wells JCK, Fewtrell MS (2006) Measuring body composition. Arch Dis Child 91: 612–617.

Food industry wastewaters and Nutrition, Dietetics & Nutraceuticals

DOI: 10.31038/NDN.2019111

Editorial

I am pleased to present the inaugural issue of the journal of Nutrition, Dietetics & Nutraceuticals (NDN) from the open access international publishing house Research Open World. NDN provides a platform covering in an interdisciplinary manner all areas of Nutrition, Dietetics & Nutraceuticals. The goal of NDN is to publish actual, original and high-quality research articles, reviews, and short communications, which can be divided into three categories: The science of nutrition, Community Nutrition and Therapeutic nutrition and dietetics.

Specific studies and developments of interest for the journal comprise Nutrition and Food Sciences and Food Biotechnology. Food industry uses extensively a high quantity of water in the industrial processes, namely, heating and cooling systems and washing of equipment and facilities. Consequently, it produces a large quantity of problematic wastewaters. Food industry wastewaters constitute a complex subject for the environment and public health due to the presence of high concentrations of organic matter monitored by chemical oxygen demand (COD), biochemical oxygen demand (BOD) and total organic carbon (TOC), salinity (high conductivity values), total and suspended solids and nutrients (calcium, magnesium, phosphorus, potassium, sodium and chloride). Food industry wastewater can be responsible for soil contamination, accumulation of toxic compounds in ecosystems, eutrophication phenomena, rapid oxygen depletion, and surface and groundwater contamination. Within this type of wastewater, it can be highlighted the dairy, winery, slaughterhouse and olive oil mill wastewater. However, appropriate and innovative treatment processes are required. Conventional treatment processes of food industry wastewaters are based on biological principles, for instance, aerobic [1, 2] and anaerobic [3] digestion and wetlands [4]. However, these biological processes have some limitations. Several physicochemical processes have been applied in order to reduce organic and inorganic contamination, for example, coagulation−flocculation with FeSO4, Al2(SO4)3, and FeCl3 for cheese whey wastewater [2] and winery wastewater [5], coagulation with chitosan, starch, alum and ferric chloride for olive oil wastewater [6], acid precipitation with H2SO4, HNO3 and HCl for cheese whey and slaughterhouse wastewater [7, 8], basic precipitation with NaOH and Ca(OH)2 for cheese whey wastewater [9, 8], oxidation with Ca(ClO)₂, H2O2 and CaO₂ for slaughterhouse wastewater [7], Fenton-like oxidation system for pretreated cheese whey wastewater [10], ozone-based advanced oxidation processes (O3, O3/UV and O3/UV/H2O2) for winery wastewater [11], photocatalytic/photolytic reactor system for winery wastewater [12], solar photochemical for winery wastewater [13], electrochemical advanced oxidation [14]  and solar driven advanced oxidation [15] for the pretreated winery wastewater, use of clay–polymer nano composites for olive oil mill and winery wastewater [16], reverse osmosis for winery wastewater [17], electrolysis system for olive oil mill wastewater [18], electro-coagulation for olive oil mill wastewater [19] and slaughterhouse wastewater [20], Fenton’s Reagent for olive oil mill wastewater [21], conductive-diamond electrooxidation (CDEO), ozonation and Fenton oxidation for olive oil mill wastewater [22] and alkaline and enzymatic hydrolysis for slaughterhouse wastewater [23]. The application of these effluents on the soil can also be an alternative [24, 25]. However, some precautions should be taken when these effluents are applied at long-term. Thus, NDN can receive important works in the area of biological and physicochemical treatment, recovery and reuse of the food industry wastewaters.

Thank you for your contribution to the Journal of Nutrition, Dietetics & Nutraceuticals

Sincerely,
Ana R. Prazeres

Acknowledgments

The author thanks to the Alentejo Regional Operational Program (ALENTEJO 2020, Portugal 2020) for the financing of the HYDROREUSE project – Treatment and reuse of agro-industrial wastewater using an innovative hydroponic system with tomato plants (ALT20-03-0145-FEDER-000021), through the Regional Development European Fund (FEDER).

References

  1. Petruccioli M, Duarte JC, Eusebio A, Federici F (2002) Aerobic treatment of winery wastewater using a jet-loop activated sludge reactor. Process Biochemistry 37: 821–829.
  2. Rivas J, Prazeres AR, Carvalho F, Beltrán F (2010) Treatment of Cheese Whey Wastewater: Combined Coagulation−Flocculation and Aerobic Biodegradation. Journal of Agricultural and Food Chemistry 58: 7871–7877. [crossref]
  3. Yu H, Zhu Z, Hu W, Zhang H (2002) Hydrogen production from rice winery wastewater in an upflow anaerobic reactor by using mixed anaerobic cultures. International Journal of Hydrogen Energy 27: 1359–1365.
  4. Serrano L, de la Varga D, Ruiz I, Soto M (2011) Winery wastewater treatment in a hybrid constructed wetland. Ecological Engineering 37: 744–753.
  5. Braz R, Pirra A, Lucas MS, Peres JA (2010) Combination of long term aerated storage and chemical coagulation/flocculation to winery wastewater treatment. Desalination 263: 226–232.
  6. Meyssami B, Kasaeian AB (2005) Use of coagulants in treatment of olive oil wastewater model solutions by induced air flotation. Bioresource Technology 96: 303–307. [crossref]
  7. Prazeres AR, Fernandes F, Madeira L, Luz S, Albuquerque A et al. (2019) Treatment of slaughterhouse wastewater by acid precipitation (H2SO4, HCl and HNO3) and oxidation (Ca(ClO)2, H2O2 and CaO2). Journal of Environmental Management 250. [crossref]
  8. Prazeres AR, Luz S, Fernandes F, Jerónimo E (2019) Cheese wastewater treatment by acid and basic precipitation: application of H2SO4, HNO3, HCl, Ca(OH)2 and NaOH. Journal of Environmental Chemical Engineering. In press.
  9. Rivas J, Prazeres AR, Carvalho F (2011) Aerobic Biodegradation of Precoagulated Cheese Whey Wastewater. Journal of Agricultural and Food Chemistry 59: 2511–2517. [crossref]
  10. Prazeres AR, Carvalho F, Rivas J (2013) Fenton-like application to pretreated cheese whey wastewater. Journal of Environmental Management 129: 199–205. [crossref]
  11. Lucas MS, Peres JA, Puma GL (2010) Treatment of winery wastewater by ozone-based advanced oxidation processes (O3, O3/UV and O3/UV/H2O2) in a pilot-scale bubble column reactor and process economics. Separation and Purification Technology 72: 235–241.
  12. Agustina TE, Ang HM, Pareek VK (2008) Treatment of winery wastewater using a photocatalytic/photolytic reactor. Chemical Engineering Journal 135: 151–156.
  13. Lucas MS, Mosteo R, Maldonado MI, Malato S, Peres JA (2009) Solar Photochemical Treatment of Winery Wastewater in a CPC Reactor. Journal of Agricultural and Food Chemistry 57: 11242–11248.
  14. Moreira FC, Boaventura RA, Brillas E, Vilar VJ (2015) Remediation of a winery wastewater combining aerobic biological oxidation and electrochemical advanced oxidation processes. Water Research 75: 95–108. [crossref]
  15. Souza S, Moreira FC, Dezotti MWC, Vilar VJP, Boaventura RAR (2013) Application of biological oxidation and solar driven advanced oxidation processes to remediation of winery wastewater. Catalysis Today 209: 201–208.
  16. Rytwo G, Lavi R, Rytwo Y, Monchase H, Dultz S et al. (2013) Clarification of olive mill and winery wastewater by means of clay–polymer nanocomposites. Science of The Total Environment 442: 134–142. [crossref]
  17. Ioannou LA, Michael C, Vakondios N, Drosou K, Xekoukoulotakis NP et al. (2013) Winery wastewater purification by reverse osmosis and oxidation of the concentrate by solar photo-Fenton. Separation and Purification Technology 118: 659–669.
  18. Israilides CJ, Vlyssides AG, Mourafeti VN, Karvouni G (1997) Olive oil wastewater treatment with the use of an electrolysis system. Bioresource Technology 61: 163–170.
  19. Inan H, Anatoly Dimoglo, Şimşek H, Karpuzcu M (2004) Olive oil mill wastewater treatment by means of electro-coagulation. Separation and Purification Technology 36: 23–31.
  20. Asselin M, Drogui P, Benmoussa H, Blais JF (2008) Effectiveness of electrocoagulation process in removing organic compounds from slaughterhouse wastewater using monopolar and bipolar electrolytic cells. Chemosphere 72: 1727–1733.
  21. Rivas FJ, Beltrán FJ, Gimeno O, Frades J (2001) Treatment of Olive Oil Mill Wastewater by Fenton’s Reagent. Journal of Agricultural and Food Chemistry 49: 1873–1880. [crossref]
  22. Cañizares P, Lobato J, Paz R, Rodrigo MA, Sáez C (2007) Advanced oxidation processes for the treatment of olive-oil mills wastewater. Chemosphere 67: 832–838.
  23. Masse L, Kennedy KJ, Chou S (2001) Testing of alkaline and enzymatic hydrolysis pretreatments for fat particles in slaughterhouse wastewater. Bioresource Technology 77: 145–155. [crossref]
  24. Prazeres AR, Carvalho F, Rivas J, Patanita M, Jóse Dôres (2013) Growth and development of tomato plants Lycopersicon Esculentum Mill. under different saline conditions by fertirrigation with pretreated cheese whey wastewater. Water Science and Technology 67: 2033–2041. [crossref]
  25. Sierra J, Martı́ E, Montserrat G, Cruañas R, Garau MA (2001) Characterisation and evolution of a soil affected by olive oil mill wastewater disposal. Science of The Total Environment 279: 207–214.

A Rare Case of Sequelae of Iatrogenic Volkmann Syndrome Successfully Treated by Shortening of the Two Bones of the Forearm

DOI: 10.31038/IJOT.2019255

Abstract

Introduction: Volkmann’s syndrome, usually due to fracture of the forearm bones, is a condition that requires emergency fasciotomy. But the case that we report today is unusual: an ischemic retraction installed following immobilization of the forearm by a traditional splint without any evidence of fracture. To date, at the height of our knowledge, no similar case has been reported. The aim of this work was to show that the shortening of both bones realized is an attractive alternative to treat severe sequelae of this syndrome in our context.

Case Report: He is a 9-year-old boy who fell from games and had a closed trauma to his left forearm. At 3 months post-traumatic when we saw him, we note serious sequelae already installed consisting of wrist flexum and invincible claws fingers. The radiography realized a posteriori was normal. The preoperative electromyogram concludes that the 3 nerves of the forearm have been affected. We performed a shortening of the 2 bones of the forearm with contention by 2 intramedullary pins completed by a plaster splint to maintain the reduction obtained intraoperatively. The radio-clinical and electromyographic control post-operative showed a clear improvement anatomical and functional.

Discussion and Conclusion: The incidence of Volkmann syndrome in upper limb fractures is estimated at 1%. The absence of fractures would promote the diagnostic delay. In this case, two contributing factors were added, a fracture-free contusion treated with a traditional constrictive splint aggravating ischemia. This case of Volkmann syndrome, due in part to ignorance but treated favorably, challenges us in a cultural context where the traditional healer paradoxically enjoys great confidence. Beyond stigma, it is important for us to project the bases of a collaboration in the interest of the patients.

Keywords

Africa, Sequelae, Treatment, Volkmann Syndrome

Introduction

The ischemic retraction syndrome of the hand flexors described by Volkmann in 1881 results from a conflict between the inextensible muscular chambers and the extensible forearm muscles. It is a surgical emergency that requires rapid release of superficial but sometimes deep muscle compartments. It is most often a diaphyseal fracture of the 2 bones of the forearm or a distal fracture of the radius. This syndrome occurs even more often in supra-condylar fractures of the child’s elbow associated with vascular injury. But the case we report today is unusual: it is an ischemic retraction that has occurred following immobilization of the forearm by a traditional healer without any radiological evidence of a fracture. To date, at the best of our knowledge, no similar case has been reported.

Case Report

The 9-year-old boy, who fell to the games, had a closed trauma to his left forearm and was driven, as is often the case in the hinterland,  to a traditional healer. He was then immobilized by a splint of braided bamboo or millet stems as is often the case in our practice conditions (Figure 1). No X-ray was performed to confirm the existence of broken bones in the injured forearm. Faced with the appearance of edema, cutaneous lesions like phlyctens, cutaneous wounds, retraction and paralysis of the fingers, the splint would have been removed but it was too late because the compartments syndrome was already constituted with irreversible sequelae already installed. Unfortunately, this type of complications is not isolated in our environment. We also performed a necrotic finger amputation treated under the same conditions (Figure 2). We received it after about 3 months post-traumatic period. He then had severe sequelae consisting of wrist flexum, severe invincible fingers claw with Metacarpophalangeal (MP) hyper-extension, hyperflexion of Proximal Interphalangeal (PIP) and irreducible Distal Interphalangeal (DIP) joints (Figure 3). The radiography performed on site before the consultation shows that there was no bone lesion that required external restraint (Figure 4).

The compared Electromyogram (EMG) requested preoperatively concludes to an attack of the 3 nerves of the forearm (medial > cubital > radial) with signs of Wallerian degeneration. The involvement is more severe on the left median and the functional prognosis on the physiological basis of this nerve is considered pour. On the left ulnar and the radial nerves, the lesion is less severe with a more favorable recovery prognosis according to the neurologist who performed this examination. We intervened to try a lengthening of the flexors including the short and long palmar which a priori had no effect on the correction of retractions. We resolved to shorten proximal metaphysis of the 2 bones of the forearm and to achieve the internal fixation by 1 respective intramedullary pin at the level of the radius and the ulna. The intraoperative examination shows a good reduction of the retractions, we obtain a passive extension of the wrist, a passive flexion of the MP, an extension, at the limit of the position of function of the PIP and DIP joints of 20 ° and 30 ° respectively. We set up a plaster cast brace to sustain this reduction obtained to keep for 6 weeks. The radiographic assessment of postoperative control is satisfactory (Figure 5). We had the plaster removed and prescribed re-education of the wrist and fingers of the hand. At the last consultation, the function recovered from the wrist and the hand was satisfactory (Figure 6).

IJOT 19 - 131_Giordano S_F1

Figure 1. An example of a traditional splint used to immobilize a fracture of the 2 bones of the leg: we can see the formation of an edema of the foot upstream (white arrow).

IJOT 19 - 131_Giordano S_F2

Figure 2. Ischemic necrosis on contusion without fracture of the 3rd finger treated by traditional splint (white arrows): the finger was amputated.

IJOT 19 - 131_Giordano S_F3

Figure 3. Preoperative appearance of sequelae: scars of skin lesions, wrist flexion, and extension of metacarpophalangeal joints and hyper-flexion of proximal interphalangeal joints.

IJOT 19 - 131_Giordano S_F4

Figure 4. The radiograph performed “a posteriori” shows no fracture lesion that would have required immobilization.

IJOT 19 - 131_Giordano S_F5

Figure 5. The postoperative X-Ray (D 117) showing the shortening of the proximal metaphysis of the 2 bones and contention with intramedullary pins with onset of consolidation.

IJOT 19 - 131_Giordano S_F6

Figure 6. The anatomical (A) and functional (B) result is quite satisfactory especially for large (large objects) and fine (finer objects) pollici-digital grip.

Discussion

The Volkmann syndrome, ischemic retraction of flexors, first described in 1881 by the same one who bears his name, is a relatively rare surgical emergency [1]. This syndrome is most often associated with trauma including fractures, penetrating wounds, contusion of soft tissues, animal or insect bites, infections, reperfusion ischemia or external compression by dressing or plaster, burns or crushing injuries. The incidence of occurrence in upper limb fractures is estimated at 1% [2]. In this case we can think that there are two contributing factors, a fracture-free bruise treated by traditional constrictive splint worsening ischemia: “a chicotte on an abscess” according to a well-known Fulani saying. At this stage, an alcoholic dressing renewed 2 or 3 times a day and nonsteroidal anti-inflammatory drugs and especially a regular follow-up for a few days would have been enough. It should be noted that the absence of a fracture has been considered by some authors as a factor delaying the diagnosis and worsening the prognosis [3,4]. The fractures of the child likely to lead to the syndrome of the lodges of the forearm are essentially the diaphyseal fractures of the 2 bones of the forearm and supra-condylar fractures of the elbow with or without a fracture of the forearm, distal end of the radius in a floating elbow chart [2, 5–7]. Matsen [8] explained that the lodge syndrome has several vascular mechanisms that all contribute to cell necrosis. The clinical diagnosis is characterized by acute pain, poorly localized, not very sensitive to the usual analgesics and culminating 2 to 6 hours after the trauma. The other signs are a hard swelling, renitence, neuro-vascular disorders like pallor of the extremities, abolition of peripheral pulses, paresthesia and paralysis. Treatment of acute ischemic syndrome requires emergency fasciotomy. In this case it is a severe Volkmann syndrome according to the classification of Tsuge [9], at the stage of serious sequelae attributable to a lack of knowledge by the traditional healer of the anatomophysiological mechanisms at the origin of this syndrome. There is a therapeutic arsenal of interest to the soft tissues and the bone. For the soft tissues extensive excision of infarcted tendons with secondary reconstruction [10–12], Z lengthening of contractured tendons [13], tendon transfer [13] has been proposed. We started by lengthening the flexors but we realized that it had little effect on contracture correction. Surgical techniques concerning the bone, proximal carpectomy [13,14], wrist arthrodesis [13,15]. We preferred the shortening of the 2 forearm bones recommended by Rolands et al [16], Domanasiewicz [17], Pavanini and Volpe [18]. All these methods have their disadvantages, in particular the shortening is criticized for having a non-selective effect on both the extensors and the flexors, the worsening of the shortening already favored by ischemia and a high rate of non-union and refracture of the shortening osteotomy site of the 2 forearm bones. It is too early to say about the bone consolidation that we hope will be favorable in children in this case. However, the first current anatomical and functional results are satisfactory and encouraging.

Conclusion

This case of Volkmann syndrome and other similar pathologies that we encounter in our conditions of practice but unimaginable elsewhere in the West, due mainly to ignorance challenge us in a cultural context where however this same traditional healer enjoys great confidence. Beyond stigma, it is important for us to lay the foundations of a bridge to approach us in the interest of patients.

List of abbreviations:

Metacarpophalangeal (MP)

Proximal interphalangeal (PIP)

Distal interphalangeal (DIP)

Acknowledgement

We sincerely thank:

  1. Dr SAÏD HAMDJA for his confidence in referring us this little patient;
  2. All the Managers and Staff of the Maria Rosa Nsisim Foundation of Ahala I in Yaoundé for creating the conditions for the good conduct of this work.

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