The Correlation Between Serum Adiponectin Levels and Proinflammatory Cytokines" Levels, Apache-Ii Scores and Mortality In Patients With Intra-Abdominal Sepsis

Kürşat Dikmen; Tonguç Utku Yılmaz; Mustafa Kerem; Hasan Bostancı; Asiye Dikmen Uğraş; Özge Paşaoğlu; Öge Taşçılar; Tarkan Karakan

The Correlation Between Serum Adiponectin Levels and Proinflammatory Cytokines" Levels, Apache-Ii Scores and Mortality In Patients With Intra-Abdominal Sepsis

Year 2019, Issue: 2, 288 - 294, 01.06.2019

Kürşat Dikmen Tonguç Utku Yılmaz Mustafa Kerem Hasan Bostancı Asiye Dikmen Uğraş Özge Paşaoğlu Öge Taşçılar Tarkan Karakan

Abstract

Objectives: Adiponectin is an anti-inflammatory cytokine that is abundantly produced by adipocytes and have a wide range of effects in sepsis pathophysiology. This study was conducted to investigate whether there is a correlation between serum adiponectin, proinflammatory cytokines’ levels, APACHE-II scores and mortality rates of the patients with sepsis, severe sepsis and septic shock. Patients and Methods: Forty-five patients who met the criteria for sepsis n=18 , severe sepsis n=14 and septic shock n=13 were included in this prospective study. Patients who underwent elective abdominal surgery without sepsis were identified as the control group. After the diagnosis of sepsis, blood samples were taken on the following 5 days for adiponectin, IL-6, IL-1β, TNF-α and procalcitonin levels. APACHE-II scores of the patients were calculated daily. All patients were followed for 28 days and mortalities were observed. Results: Ten of the patients died within 28 days. The serum adiponectin levels of the patients in the study group were statistically higher than those in the control group. Statistically, the adiponectin levels of the patients in the septic shock group were markedly lower than those of the patients in sepsis and severe sepsis groups. Serum adiponectin levels inversely correlated with blood levels of IL-6, IL-1β, TNF-α, procalcitonin, lactate and APACHE-II scores. Serum adiponectin levels were significantly higher in survivors. Conclusion: Adiponectin levels reveal differences between sepsis, severe sepsis and septic shock groups. In patients with septic shock, serum adiponectin levels were associated with mortality among patients. Serum adiponectin levels might be a negative predictive marker in patients with sepsis, severe sepsis and septic shock.

Keywords

Adiponectin, sepsis, APACHE, survival

References

1. Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med. 2013; 41:1167–74. [CrossRef]
2. Prescott HC, Chang VW, O’Brien JM, Langa KM, Iwashyna TJ. Obesity and 1-year outcomes in older Americans with severe sepsis. Crit Care Med. 2014; 42: 1766–74. [CrossRef]
3. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis: the ACCP/SCCM Consensus Conference Committee: American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992;101:1644-55.
4. Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet 2005;365:63-78. [CrossRef]
5. Aboab J, Nardi O, Lipiner D, Sharshar T, Annane D. Emerging drugs for the treatment of sepsis. Expert Opain Emerg Drugs. 2006;11:7-22. [CrossRef]
6. Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet. 2005;365:63- 78. [CrossRef] https://doi.org/10.1016/S0140-6736(04)17667-8
7. Li S, Boa H, Han L, Liu L, Wang X. Effects of adiponectin on mortality and its mechanism in a sepsis mouse model. J Invest Surg. 2012;25:214-9. [CrossRef]
8. Hillenbrand A, Knippschild U, Weiss M, Schrezenmeier H, HenneBruns D, Huber-Lang, Wolf AM. Sepsis induced changes of adipokines and cytokines-septic patients compered to morbidly obese patients. BMC Surgery. 2010; 10: 26. [CrossRef]
9. Riedemann NC, Guo RF, Ward PA: The enigma of sepsis. J Clin Invest. 2003; 112: 460-7. [CrossRef]
10. Vincent JL, Abraham E: The last 100 years of sepsis. Am J Respir Crit Care Med. 2006; 173: 256-63. [CrossRef]
11. Knaus WA, Draper EA, Wagner DP, Zimmerman JE: APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818-29.
12. Fernandez-Riejos P, Najib S, Santos-Alvarez J, Martin-Romero C, Perez-Perez A, Gonzalez-Yanes C, et al. Role of leptin in the activation of immune cells. Mediators Inflam. 2010; 2010: 568343. [CrossRef]
13. Lappas M, Permezel M, Rice GE. Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factorkappaB, peroxisomal proliferator-activated receptor-gamma and extracellularly regulated kinase ½. Endocrinology. 2005;146:3334- 42. [CrossRef]
14. Guerre-Millo M. Adipose tissue and adipokines: for better or worse. Diabetes Metab. 2004; 30: 13-9.
15. Arner P. Insulin resistance in type 2 diabetes-role of the adipokines. Curr Mol Med. 2005;5:333-9.
16. Hillenbrand A, Knippschild U, Weiss M, Schrezenmeier H, HenneBruns D, Huber-Lang M, et al. Sepsis induced changes of adipokines and cytokines - septic patients compared to morbidly obese patients. BMC Surg. 2010; 10: 26. [CrossRef]
17. Kougias P, Chai H, Lin PH, Yao Q, Lumsden AB, Chen C. Effects of adipocyte-derived cytokines on endothelial functions: implication of vascular disease. J Surg Res. 2005; 126:121-9. [CrossRef]
18. Ouchi N, Kihara S, Arita Y, et al. Novel modulator for endothelial adhesion molecules: Adipocyte- derived plasma protein adiponectin. Circulation. 1999; 100: 2473–6.
19. Ohashi K, Parker JL, Ouchi N, et al. Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype. J Biol Chem. 2010; 285: 6153–60. [CrossRef]
20. Walkey AJ, Rice TW, Konter J, Ouchi N, Shibata R, Walsh K, deBoisblanc BP, Summer R. Plasma adiponectin and mortality in critically ill subjects with acute respiratory failure. Crit Care Med. 2010;38:2329- 34. [CrossRef]
21. Koch A, Sanson E, Voigt S, Helm A, Trautwein C, Tacke F. Serum adiponectin upon admission to the intensive care unit may predict mortality in critically ill patients. J Crit Care. 2011;26:166-74. [CrossRef]
22. Vassilliadi DA, Tzanela M, Kotanidou A, Orfanos SE, Nikitas N, Armaganidis A, Koutsilieris M, Roussos C, Tsagarakis S, Dimopoulou I. Serial changes in adiponectin and resistin in critically ill patients with sepsis: associations with sepsis phase, severity, and circulating cytokine levels. J Crit Care. 2012; 27: 400-9. [CrossRef]
23. Yousef AA, Amr YM, Suliman GA. The diagnostic value of serum leptin monitoring and its correlation with tumor necrosis factoralpha in critically ill patients: a prospective observational study. Crit Care. 2010; 14: R33. [CrossRef]
24. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/ Society of Critical Care Medicine. Chest. 1992; 101: 1644–55.
25. Vassiliadi DA, Tzanela M, Kotanidou A, Orfanos SE, Nikitas N, Armaganidis A, et al. Serial changes in adiponectin and resistin in critically ill patients with sepsis: associations with sepsis phase, severity, and circulating cytokine levels. J Crit Care. 2012; 27: 400–9. [CrossRef]
26. Tschop J, Dattilo JR, Prakash PS, Kasten KR, Tschop MH, Caldwell CC. The leptin system: a potential target for sepsis induced immune suppression. Endocr Metab Immune Disord Drug Targets. 2010;10:336–47.
27. Hillenbrand A, Xu P, Zhou S, Blatz A, Weiss M, Hafner S, Henne-Bruns D, Knippschild U. Circulating adiponekine levels and prognostic value in septic patients. Journal of Inflammation. 2016; 13: 30. [CrossRef]
28. Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993; 270: 2957–63.
29. Kappes A, Loffler G. Influences of ionomycin, dibutyryl-cycloAMP and tumour necrosis factor-alpha on intracellular amount and secretion of apM1 in differentiating primary human preadipocytes. Horm Metab Res. 2000; 32: 548–54. [CrossRef]
30. Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002;8:731–7. [CrossRef]
31. Robinson K, Prins J, Venkatesh B. Clinical review: Adiponectin biology and its role in inflammation and critical illness. Critical Care. 2011; 15: 221. [CrossRef]
32. Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000; 96: 1723-32.
33. Tsuchihashi H, Yamamoto H, Maeda K, Ugi Si, Mori T, Shimizu T, et al. Circulating concentrations of adiponectin, an endogenous lipopolysaccharide neutralizing protein, decrease in rats with polymicrobial sepsis. J Sur Res. 2006; 134: 348-53. [CrossRef]
34. Uji Y, Yamamoto H, Maeda K, Tsuchihashi H, Akabori H, Shimizu T, et al. Adiponectin deficiency promotes the production of inflammatory mediators while severely exacerbating hepatic injury in mice with polymicrobial sepsis. J Surg Res. 2010; 161: 301-11. [CrossRef]
35. Swarbrick MM, Havel PJ. Physiological, pharmacological, and nutritional regulation of circulating adiponectin concentrations in humans. Metab Syndr Relat Diord. 2008; 6: 87-102. [CrossRef]
36. Teoh H, Quan A, Bang KW, Wang G, Lovren F, Vu V, Haitsma JJ, Szmitko PE, Al-omran M, Wang CH, Gupta MM, Peterson MD. Adiponectin deficiency promotes endothelial activation and profound exacerbates sepsis-related mortality. Am J Physiol Endocrinol Metab. 2008; 295: 658-64. [CrossRef]
37. Comuzzie AG, Funahashi T, Sonnenberg G, Martin LJ, Jacopb HJ, Black AE, et al. The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic sydrome. J Clin Endocrinol Metab. 2001; 86: 4321-5. [CrossRef]
38. Ozgen M, Koca SS, Dagli N, Balin M, Ustundag B, Isik A. Serum adiponectin and vaspin levels in rheumatoid arthritis. Arch Med Res. 2010; 41: 457-63. [CrossRef]
39. Oguz A, Dogan EG, Uzunlulu M, Oguz FM. Insulin resistance and adiponectin levels in Behçet’s syndrome. Clin Exp Rheumatol. 2007;25:118-9.
40. Oberholzer A, Souza SM, Tschoeke SK, Oberholzer C, Abouhamze A, Pribble JP, Moldawer LL. Plasma cytokine measurements augment prognostic scores as indicators of outcome in patients with severe sepsis. Shock. 2005; 23: 488-93.

İNTRABDOMINAL SEPSISLI HASTALARDA SERUM ADIPONEKTIN SEVIYELERI ILE PROINFLAMATUAR SITOKIN DÜZEYLERI, APACHE-II SKORLARI VE MORTALITE ARASINDAKI ILIŞKI

Year 2019, Issue: 2, 288 - 294, 01.06.2019

Kürşat Dikmen Tonguç Utku Yılmaz Mustafa Kerem Hasan Bostancı Asiye Dikmen Uğraş Özge Paşaoğlu Öge Taşçılar Tarkan Karakan

Abstract

Amaç: Adiponektin, adipositler tarafından salgılanan anti-inflamatuar bir sitokindir ve sepsis fizyopatolojisinde geniş etkilere sahiptir. Sepsis, ciddi sepsis ve septik şoklu hastalarda serum adiponektin, proinflamatuar sitokin seviyeleri, APACHE-II skorları ve mortalite arasında ilişki olup olmadığını incelemek için bu çalışma hazırlanmıştır. Hastalar ve Yöntemler: Bu prospektif çalışmaya sepsis n=18 , ciddi sepsis n=14 ve septik şok n=13 kriterlerine uyan 45 hasta dahil edildi. Elektif karın ameliyatı geçiren ama sepsis tanısı olmayan hastalar control grubu olarak belirlendi. Sepsis tanısı konulduktan sonra takip eden 5 gün boyunca hastalardan serum adiponektin, interlökin-6 IL , IL-1β, Tümör Nekrozis Faktör-α ve prokalsitonin ölçümü için kan örneği alındı. Hastalara ait APACHE-II skorları günlük kayıt edildi. Hastalar 28 gün boyunca takip edilip mortaliteler izlendi. Bulgular: Takip edilen 28 gün boyunca 10 hasta öldü. Çalışma grubundaki hastaların serum adiponektin düzeyleri kontrol grubundaki hastalara göre istatistiksel olarak yüksekti. Septik şok grubundaki hastaların adiponektin düzeyleri sepsis ve ciddi sepsis grubundaki hastalardan istatistiksel olarak belirgin düşüktü. Serum adiponektin düzeyleri ile serum IL-6, IL-1β, TNF-α, prolaktin ve laktat düzeyleri ters orantılı bulundu. Hayatta kalan hastalarda serum adiponektin seviyesi istatistiksel olarak belirgin yüksek bulundu. Sonuç: Adiponektin seviyeleri sepsis, ciddi sepsis ve septik şok gruplarında değişiklik göstermektedir. Septik şoklu hastalarda serum adiponektin seviyeleri mortalite ile ilişkiliydi. Sepsis, ciddi sepsis ve septik şoklu hastalarda serum adiponektin düzeyi negative prediktif bir belirteç olabilir.

Keywords

Adiponektin, sepsis, APACHE-II, sağkalım

References

1. Gaieski DF, Edwards JM, Kallan MJ, Carr BG. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit Care Med. 2013; 41:1167–74. [CrossRef]
2. Prescott HC, Chang VW, O’Brien JM, Langa KM, Iwashyna TJ. Obesity and 1-year outcomes in older Americans with severe sepsis. Crit Care Med. 2014; 42: 1766–74. [CrossRef]
3. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM, Sibbald WJ: Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis: the ACCP/SCCM Consensus Conference Committee: American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992;101:1644-55.
4. Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet 2005;365:63-78. [CrossRef]
5. Aboab J, Nardi O, Lipiner D, Sharshar T, Annane D. Emerging drugs for the treatment of sepsis. Expert Opain Emerg Drugs. 2006;11:7-22. [CrossRef]
6. Annane D, Bellissant E, Cavaillon JM. Septic shock. Lancet. 2005;365:63- 78. [CrossRef] https://doi.org/10.1016/S0140-6736(04)17667-8
7. Li S, Boa H, Han L, Liu L, Wang X. Effects of adiponectin on mortality and its mechanism in a sepsis mouse model. J Invest Surg. 2012;25:214-9. [CrossRef]
8. Hillenbrand A, Knippschild U, Weiss M, Schrezenmeier H, HenneBruns D, Huber-Lang, Wolf AM. Sepsis induced changes of adipokines and cytokines-septic patients compered to morbidly obese patients. BMC Surgery. 2010; 10: 26. [CrossRef]
9. Riedemann NC, Guo RF, Ward PA: The enigma of sepsis. J Clin Invest. 2003; 112: 460-7. [CrossRef]
10. Vincent JL, Abraham E: The last 100 years of sepsis. Am J Respir Crit Care Med. 2006; 173: 256-63. [CrossRef]
11. Knaus WA, Draper EA, Wagner DP, Zimmerman JE: APACHE II: a severity of disease classification system. Crit Care Med. 1985;13:818-29.
12. Fernandez-Riejos P, Najib S, Santos-Alvarez J, Martin-Romero C, Perez-Perez A, Gonzalez-Yanes C, et al. Role of leptin in the activation of immune cells. Mediators Inflam. 2010; 2010: 568343. [CrossRef]
13. Lappas M, Permezel M, Rice GE. Leptin and adiponectin stimulate the release of proinflammatory cytokines and prostaglandins from human placenta and maternal adipose tissue via nuclear factorkappaB, peroxisomal proliferator-activated receptor-gamma and extracellularly regulated kinase ½. Endocrinology. 2005;146:3334- 42. [CrossRef]
14. Guerre-Millo M. Adipose tissue and adipokines: for better or worse. Diabetes Metab. 2004; 30: 13-9.
15. Arner P. Insulin resistance in type 2 diabetes-role of the adipokines. Curr Mol Med. 2005;5:333-9.
16. Hillenbrand A, Knippschild U, Weiss M, Schrezenmeier H, HenneBruns D, Huber-Lang M, et al. Sepsis induced changes of adipokines and cytokines - septic patients compared to morbidly obese patients. BMC Surg. 2010; 10: 26. [CrossRef]
17. Kougias P, Chai H, Lin PH, Yao Q, Lumsden AB, Chen C. Effects of adipocyte-derived cytokines on endothelial functions: implication of vascular disease. J Surg Res. 2005; 126:121-9. [CrossRef]
18. Ouchi N, Kihara S, Arita Y, et al. Novel modulator for endothelial adhesion molecules: Adipocyte- derived plasma protein adiponectin. Circulation. 1999; 100: 2473–6.
19. Ohashi K, Parker JL, Ouchi N, et al. Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype. J Biol Chem. 2010; 285: 6153–60. [CrossRef]
20. Walkey AJ, Rice TW, Konter J, Ouchi N, Shibata R, Walsh K, deBoisblanc BP, Summer R. Plasma adiponectin and mortality in critically ill subjects with acute respiratory failure. Crit Care Med. 2010;38:2329- 34. [CrossRef]
21. Koch A, Sanson E, Voigt S, Helm A, Trautwein C, Tacke F. Serum adiponectin upon admission to the intensive care unit may predict mortality in critically ill patients. J Crit Care. 2011;26:166-74. [CrossRef]
22. Vassilliadi DA, Tzanela M, Kotanidou A, Orfanos SE, Nikitas N, Armaganidis A, Koutsilieris M, Roussos C, Tsagarakis S, Dimopoulou I. Serial changes in adiponectin and resistin in critically ill patients with sepsis: associations with sepsis phase, severity, and circulating cytokine levels. J Crit Care. 2012; 27: 400-9. [CrossRef]
23. Yousef AA, Amr YM, Suliman GA. The diagnostic value of serum leptin monitoring and its correlation with tumor necrosis factoralpha in critically ill patients: a prospective observational study. Crit Care. 2010; 14: R33. [CrossRef]
24. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/ Society of Critical Care Medicine. Chest. 1992; 101: 1644–55.
25. Vassiliadi DA, Tzanela M, Kotanidou A, Orfanos SE, Nikitas N, Armaganidis A, et al. Serial changes in adiponectin and resistin in critically ill patients with sepsis: associations with sepsis phase, severity, and circulating cytokine levels. J Crit Care. 2012; 27: 400–9. [CrossRef]
26. Tschop J, Dattilo JR, Prakash PS, Kasten KR, Tschop MH, Caldwell CC. The leptin system: a potential target for sepsis induced immune suppression. Endocr Metab Immune Disord Drug Targets. 2010;10:336–47.
27. Hillenbrand A, Xu P, Zhou S, Blatz A, Weiss M, Hafner S, Henne-Bruns D, Knippschild U. Circulating adiponekine levels and prognostic value in septic patients. Journal of Inflammation. 2016; 13: 30. [CrossRef]
28. Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993; 270: 2957–63.
29. Kappes A, Loffler G. Influences of ionomycin, dibutyryl-cycloAMP and tumour necrosis factor-alpha on intracellular amount and secretion of apM1 in differentiating primary human preadipocytes. Horm Metab Res. 2000; 32: 548–54. [CrossRef]
30. Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002;8:731–7. [CrossRef]
31. Robinson K, Prins J, Venkatesh B. Clinical review: Adiponectin biology and its role in inflammation and critical illness. Critical Care. 2011; 15: 221. [CrossRef]
32. Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000; 96: 1723-32.
33. Tsuchihashi H, Yamamoto H, Maeda K, Ugi Si, Mori T, Shimizu T, et al. Circulating concentrations of adiponectin, an endogenous lipopolysaccharide neutralizing protein, decrease in rats with polymicrobial sepsis. J Sur Res. 2006; 134: 348-53. [CrossRef]
34. Uji Y, Yamamoto H, Maeda K, Tsuchihashi H, Akabori H, Shimizu T, et al. Adiponectin deficiency promotes the production of inflammatory mediators while severely exacerbating hepatic injury in mice with polymicrobial sepsis. J Surg Res. 2010; 161: 301-11. [CrossRef]
35. Swarbrick MM, Havel PJ. Physiological, pharmacological, and nutritional regulation of circulating adiponectin concentrations in humans. Metab Syndr Relat Diord. 2008; 6: 87-102. [CrossRef]
36. Teoh H, Quan A, Bang KW, Wang G, Lovren F, Vu V, Haitsma JJ, Szmitko PE, Al-omran M, Wang CH, Gupta MM, Peterson MD. Adiponectin deficiency promotes endothelial activation and profound exacerbates sepsis-related mortality. Am J Physiol Endocrinol Metab. 2008; 295: 658-64. [CrossRef]
37. Comuzzie AG, Funahashi T, Sonnenberg G, Martin LJ, Jacopb HJ, Black AE, et al. The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic sydrome. J Clin Endocrinol Metab. 2001; 86: 4321-5. [CrossRef]
38. Ozgen M, Koca SS, Dagli N, Balin M, Ustundag B, Isik A. Serum adiponectin and vaspin levels in rheumatoid arthritis. Arch Med Res. 2010; 41: 457-63. [CrossRef]
39. Oguz A, Dogan EG, Uzunlulu M, Oguz FM. Insulin resistance and adiponectin levels in Behçet’s syndrome. Clin Exp Rheumatol. 2007;25:118-9.
40. Oberholzer A, Souza SM, Tschoeke SK, Oberholzer C, Abouhamze A, Pribble JP, Moldawer LL. Plasma cytokine measurements augment prognostic scores as indicators of outcome in patients with severe sepsis. Shock. 2005; 23: 488-93.

There are 40 citations in total.

Details

Primary Language	English
Journal Section	Research Article
Authors	Kürşat Dikmen Tonguç Utku Yılmaz Mustafa Kerem Hasan Bostancı Asiye Dikmen Uğraş Özge Paşaoğlu Öge Taşçılar Tarkan Karakan
Publication Date	June 1, 2019
Published in Issue	Year 2019Issue: 2

Cite

EndNote	Dikmen K, Yılmaz TU, Kerem M, Bostancı H, Uğraş AD, Paşaoğlu Ö, Taşçılar Ö, Karakan T (June 1, 2019) The Correlation Between Serum Adiponectin Levels and Proinflammatory Cytokines" Levels, Apache-Ii Scores and Mortality In Patients With Intra-Abdominal Sepsis. Acıbadem Üniversitesi Sağlık Bilimleri Dergisi 2 288–294.

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