Development Of Organ Failure Research Articles

COVID-19, septic shock and syndrome of disseminated intravascular coagulation syndrome. Part 1

The pandemic of a new coronavirus infection (Coronavirus Disease 2019, COVID-19) caused by SARS-CoV-2 became a real challenge to humanity and the medical community in 2020 and raised a number of medical, social and even philosophical questions. An almost avalanche-like increase in the number of infected people in a short time, due to the high contagiousness of viral infection, allowed us to identify groups of patients with mild, moderate and severe forms of the disease. Doctors around the world are faced with an acute problem of treating a large number of patients in critical conditions caused by COVID-19.
 From the currently available information on clinical cases of COVID-19, it follows that COVID-19 patients in critical condition have a clinical picture of disseminated intravascular coagulation (DIC), septic shock with the development of multiple organ failure.
 The first part of the article discusses the pathogenesis of non-specific universal biological responses of the body in critical condition - from the Sanarelli-Schwartzman phenomenon to the DIC, septic shock, systemic inflammatory response syndrome and the so-called neutrophil extracellular traps (NETs). The questions of cytokine storm in severe forms of systemic inflammatory response syndrome (SIRS), the role of inflammation in the activation of coagulation, and the relationship between inflammation and thrombosis are discussed. Modern ideas about the mechanisms of so-called NETosis, their role in the occurrence of immunothrombosis and inflammation-induced thrombosis in autoimmune diseases - vasculitis, antiphospholipid syndrome, and systemic lupus erythematosus is highlighted. The article discusses the possibility of participation of ADAMTS-13 metalloproteinase in the pathogenesis of multiple organ failure in severe endotheliopathy in patients with viral septic shock.

Immunoglobulin light chain amyloidosis: 2020 update on diagnosis, prognosis, and treatment

Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or MGUS." Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for diagnosis. Invasive organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy. N-terminal pro-brain natriuretic peptide (NT-proBNP), serum troponin T, and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 94.1, 40.3, 14.0, and 5.8 months. All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Stem cell transplant (SCT) is preferred, but only 20% of patients are eligible. Requirements for safe SCT include systolic blood pressure >90mmHg, troponin T <0.06 ng/mL and serum creatinine ≤1.7 mg/dL. Nontransplant candidates can be offered cyclophosphamide-bortezomib-dexamethasone or daratumumab containing regimens as it appears to be highly active in AL amyloidosis. Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. This article is protected by copyright. All rights reserved.

Acute respiratory distress syndrome in acute pancreatitis.

Development of organ failure is one of the major determinants of mortality in patients with acute pancreatitis (AP). Acute respiratory distress syndrome (ARDS) is an important cause of respiratory failure in AP and isassociated with high mortality. Pathogenesis of ARDS in AP is incompletely understood. Release of various cytokines plays an important role in development of ARDS in AP. Increased gut permeability due to various toxins, inflammatory mediators, and pancreatic enzymes potentiates lung injury by gut-lymph-lung axis leading on to increased translocation of bacterial endotoxins. Various scoring systems, serum levels of various cytokines and lung ultrasound have been evaluated for prediction of development of ARDS in AP with varying results. Various drugs have shown encouraging results in prevention of ARDS in animal models but these encouraging results in animal models are yet to be confirmed in clinical studies. There is no specific effective treatment for ARDS. Treatment of sepsis and local complications of AP should be done according to the standard management strategies. Lung protective ventilatory strategies are of paramount importance to improve outcome of patients of AP with ARDS and therefore effective coordination between gastroenterologists and intensivists is needed for effective management of these patients.

Augmentation of Hyperglycemia‐Induced Damage in a Diabetic Rat Endothelium is Potentially Regulated by the Nfκβ Signaling Pathway

Endothelial dysfunction is a key factor for the development of organ failure in type 2 diabetes mellitus (T2DM). While hyperglycemia is a well‐established factor in the development of microvascular complications in T2DM, specific mechanisms of endothelial damage remains equivocal. In a previous study, we observed that hyperglycemic states resulted in distinct alterations in proteins involved in metabolic and angiogenic processes in endothelial cells isolated from diabetic when compared to non‐diabetic rats. In the present study, we identified and validated diverse NFκβ‐regulated cellular functions that are involved in augmenting hyperglycemia‐induced damage in the diabetic endothelium. Bioinformatics and functional studies were carried out in the primary cardiac microvascular endothelial cells (RCMVECs) derived from the spontaneously T2DM Goto‐Kakizaki (GK) rat model in comparison to the control Wistar Kyoto (WKY) rat model under normal and hyperglycemic conditions. GK and WKY RCMVECs were cultured under both normal (NG; 4.5 mM) and high glucose (HG; 25 mM) conditions for two weeks, followed by tandem mass spectrometry (MS/MS), qPCR, western blotting, microplate‐based cell proliferation, metabolic and REDOX assays. Evidence of hyperglycemia‐induced cytotoxicity in GK RCMVECs was determined by employing various microplate‐based assays, wherein a 20% reduction in cell proliferation (p&lt;0.05) and a 33% increase in PMA‐induced ROS production (p&lt;0.05) was observed. Enrichment and pathway analyses of the proteomic tandem MS/MS and qPCR datasets, revealed induction of inflammatory, metabolic and apoptotic pathways, which are tightly regulated by NFκβ, in GK RCMVECs (HG vs NG). Platelet‐activating factor receptor (LogFC = 3.5, p &lt;0.01) and beta‐catenin (LogFC= 1.3, p &lt;0.01), both key inductors of NFκβ signaling, were significantly upregulated in GK RCMVECs (HG vs NG). Western blotting analysis revealed significant upregulation of NFκβ in GK RCMVECs (HG vs NG) (FC=1.6, p&lt;0.05) and in GK NG vs WKY NG RCMVECs (FC=2.5, p&lt;0.05), suggesting a potential increase in NFκβ activity in the diabetic endothelium. Additionally, the activity of hexokinase‐2, which is reported to be a transcriptional target of NFκβ, was observed to be reduced in GK NG vs WKY NG RCMVECs (20% reduction, p&lt;0.05). Furthermore, qPCR analysis identified an upregulation of several inflammatory transcripts that are that are regulated by NFκβ such as CXCR4 (FC=7.5, p&lt;0.01) and NLRP3 (FC=5.8, p&lt;0.01) expression in GK RCMVECs (HG vs NG). By the integration of high‐throughput tandem MS/MS analysis, bioinformatics analyses and in vitro functional assays, we identified a potential induction of NFκβ signaling in GK (HG vs NG) RCMVECs, resulting in metabolic reprogramming and a heightened inflammatory and apoptotic response.Support or Funding InformationSupport for this project has been provided by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (K01‐DK105043 to BRH) and the Department of Biomedical Engineering at the Medical College of Wisconsin and Marquette University, Milwaukee, WI, USA.

Necrotic Enterocolitis: Clinical and Anamnestic Parallels in Premature Infants.

Necrotic enterocolitis (NEC) in neonatal practice remains one of the major causes of morbidity and mortality in premature infants due to the combined effect of various pathogenic factors: infectious, metabolic, circulatory on the relatively immature bowel. Most often the onset of the disease occurs at the gestational age of the baby 29-32 weeks at the age of 2-3 weeks of life.Objective of study: evaluation of anamnestic, clinical and paraclinical data and course of NEC in premature infants who were hospitalized in the neonatal unit of Regional Children's Clinical Hospital (RCCH) of Chernivtsi.Materials and methods. A retrospective analysis of the diseases of 28 premature infants who were hospitalized in the neonatal intensive care unit (NICU) of RCCH was performed. While in the hospital, all children underwent general clinical, biochemical, instrumental methods of investigation and determination of immunological parameters of the infectious-inflammatory process in the blood serum, namely the level of C-reactive protein and pressepsin was made.Results. Among the examined, the proportion of deeply premature infants (up to 32 weeks of gestation) was 50%, including extremely low weight 17.8%. About 80% of children were born with signs of asphyxia of varying severity. It was shown that the development of NEC in premature children is associated with a burdened infectious history in mothers amid anemia (r = + 0.79), a short gestation period (r = + 0.44), and a low Apgar score in the fifth minute (r = + 0.45), the severity of the condition at admission to the hospital (r = + 0.74), the need for long-term mechanical ventilation (r = + 0.67), hemodynamic support with the vasoactive drugs (r = + 0.39), apnea development (r = + 0.83), feeding intolerance (r = + 0.45) and thrombocytopenia (r = +0.68). It was established that the determination of serum presepsin content makes it possible to verify the genesis of the development of NEC.Conclusion. The formation of NEC in premature infants is associated with the development of multiple organ failure in the anamnesis due to asphyxia, and its chances are increased due to the presence of a generalized infectious inflammatory process.

Concurrent RVAD Improves Survival for Patients with RV Failure at the Time of LVAD Implantation

Right ventricular (RV) failure is associated with poor outcomes after left ventricular assist device (LVAD) placement. This can be treated with a temporary right ventricular assist device (RVAD), which ideally should be placed before the development of multisystem organ failure. The purpose of this study was to determine if there is any outcome difference in patients who underwent early or concurrent RVAD as compared to delayed RVAD implantation. Via retrospective chart review, 32 patients who received temporary RVAD (30 CentriMag and 2 Protek Duo) were identified between 1/2013 and 7/2018. Subjects were divided into two groups as concurrent RVAD placement (defined as RVAD at the time of LVAD implantation) versus delayed RVAD placement (defined as an RVAD placed at any time after leaving the operating room for the LVAD implant). Survival, ICU and total length of stay (LOS), and total number of days on RVAD were compared utilizing Chi-square and two tailed t-test. Patients in the concurrent RVAD group had higher preoperative central venous pressure (p = 0.037). Survival rate at three months (χ² = 6.647, p 0.010) and one year (χ² = 3.983, p 0.046) was statistically significantly better among patients who received concurrent LVAD. ICU LOS, total hospital LOS, and number of days on RVAD were not statistically significant between the two groups. Concurrent placement of a temporary RVAD for patients with RV failure at the time of LVAD implantation improves short- and long-term survival post LVAD implantation as compared to a delayed RVAD approach.

A56 THE USE OF HIGH VOLUME PLASMAPHARESIS IN ACUTE LIVER FAILURE

Abstract Background Acute liver failure (ALF) can result in irreversible shock, cerebral herniation or development of multiple organ failure (MOF). One randomized study and a separate case series have demonstrated the safety and potential improvement in transplant-free survival with the use of high volume plasmapheresis (HVP). HVP is defined as an exchange of 8-12L or 15% of ideal body weight with fresh frozen plasma. In ALF, cytokines are responsible for the progression of MOF and HVP removes these cytokines from the systemic circulation. We report a case of implementing HVP in an adult with ALF in the intensive care unit (ICU) at a tertiary care center. Aims This case and the associated literature review highlight the value of HVP in ALF. Methods Case report and literature review. Results We report a case of a 34-year-old male who presented in ALF secondary to unknown ingestion. He was admitted to the ICU for worsening transaminitis, coagulopathy, hepatic encephalopathy, renal failure and hemodynamic instability which required vasopressor and ventilatory support. A discussion was made with hepatologists at a regional transplant center for potential consideration of either transplant or Molecular Adsorbent Recirculating System (MARS) therapy. However, the patient was too hemodynamically unstable for transport and also began to develop signs of cerebral edema. As a result, they recommended a trial of high volume plasmapheresis. Shortly after initiation, the patient’s hemodynamic, respiratory, and biochemical parameters began to improve, resulting in less vasopressor and ventilator support (Table 1). Despite improvements in these parameters, the patient’s cerebral edema continued to worsen and an electroencephalogram showed signs of a very low likelihood of functional neurological recovery. Given the overall picture, the patient’s spouse decided to withdraw care. Conclusions Presently, liver transplantation remains the only definitive management strategy for ALF patients, but many do not survive to liver transplant or are not candidates for medical or psychosocial reasons such as with this case. As a result, this case demonstrates the potential benefits of conducting HVP in centers without access to MARS or transplantation. However, although HVP did improve certain parameters for this patient, it did not improve overall prognosis. This suggests that prognosis may not improve once a certain threshold of MOF develops. Therefore, in this case and the associated literature review the optimal timing of initiating HVP remains unclear. Funding Agencies None

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Characteristics and Outcomes Among Patients With Autoimmune Rheumatic Diseases Requiring a Higher Level of Care.

Patients with autoimmune rheumatic diseases (ARDs) have a higher risk of developing organ failure, and they may require admission to the intensive care unit (ICU). The aim of our study is to determine the reasons for admission to the ICU, identify potential risk factors associated with mortality, and assess the outcomes of patients with ARD diseases admitted to the ICU. We conducted a medical records review study of patients with ARD admitted to the ICU from 2012 to 2018. Patient data included demographic and clinical characteristics, ICU admission diagnoses, length of stay, complications, and immunosuppressive regimen. Short-term and long-term outcomes were assessed. A total of 80 ARD patients were identified with the mean age of 48.8, 67% were female, and 56% were Hispanic. The most common disease associated with ICU admission was systemic lupus erythematosus (42%), followed by rheumatoid arthritis (26%), and 12% of patients had systemic vasculitis. Sepsis was the leading cause of ICU admission, accounting for 31%, followed by respiratory failure due to pneumonia (10%) and congestive heart failure (10%). Twenty percent of patients died in the ICU, 5% died 30 days after ICU admission, and 7.5% died within 1 year after the ICU stay, resulting in overall mortality of 33% by the end of 1 year. Nonsurvivors were more likely to need mechanical ventilation (p = 0.001), vasopressor support (p < 0.001), had renal (p = 0.041) or cardiovascular (p < 0.001) involvement on admission, APACHE II score higher than 19 (p = 0.001), and 4 days or longer stay in the ICU (p = 0.001). Our findings indicated that systemic lupus erythematosus is the most common ARD associated with ICU admission, and sepsis was the most frequent cause. Predictors associated with higher mortality were the requirement for mechanical ventilation, vasopressor support, increase length of ICU stay, and renal and cardiovascular involvement on admission.

Assessment of features of morphometric structural changes in the testes at conditions of postresection portal hypertension

Introduction. Postresection portal hypertension leads to complex general biological processes that occur and develop in the organs and systems of the body during its adaptation to a new level of life [10]. It should be noted that detailed and objective knowledge of compensatory-adaptive processes in the testes during resection of various volumes of the liver, their role in the development of organ failure to date have been insufficiently studied and need to be addressed.Objective of the research: to study morphometric structural changes of testes in the conditions of postresection portal hypertension and multiorgan failure.Materials of the research and their discussion. The testes of 40 white male rats were divided into 3 groups studied morphologically. Group 1 consisted of 12 intact animals, 2 - 18 rats with postresection portal hypertension, 3 - 10 animals with postresection portal hypertension and poliorganic failure. Euthanasia of rats was performed by bloodletting under thiopental anesthesia a month after the start of the experiment. Micropreparations from the testes stained hematoxylin-eosin, toluidine blue, using the Weigert method, van Gieson, Mallory, Morphometrically, on the testicular micropreparations, the diameters of the testicles tubules, the thickness of their walls, the number of cells of the epithelio-spermatogenic layer in the tubule, the number of Sertoli cells per tubule, the tubulo-interstitial index, the stromal-parenchymal ratio, the Leydigas index, the sperm index, were determined. Quantitative morphological parameters were processed statistically.Results of the research and their discussion. It was found that the investigated morphometric indices of the testes in the 2 and 3 groups of observations varied markedly in comparison with the control values. Thus, the diameter of the seminile tubules in the conditions of postresection portal hypertension was statistically significantly (p˂0.001) decreased by 11.8 %, with the development of multiple organ failure - by 34.0 % (p&lt;0.001), and the number of cells of the epithelio-spermatogenic layer in tubules respectively by 11.3 % and 32.9 % (p˂0.001), which indicated the presence of atrophy of the studied structures.The wall thickness of the tubules in the 2 group increased by 8.8 %, in the 3 group - by 26.9 % (р&lt;0.001), and the Leydig index - by 22.9 % and 57.8 %, respectively (р&lt;0.001). The number of Sertoli cells in one testicle tubule in the 2nd group decreased by 1.6 % and in the 3rd by 8.06 % (p &lt;0.001).Stromal-parenchymal ratios in the testes with simulated pathology statistically significantly increased (р&lt;0.001) by 11.3 % (р˂0.01) and 31.8 % (р˂0.001), while the tubulo-interstitial index decreased respectively by 8.9 % (p&lt;0.001) and 31.8 % (p&lt;0.001). The revealed changes of the investigated morphometric parameters showed a pronounced increase in the number of stroma in the testes. The spermatogenesis intensity index also decreased by 2.9 % (p&lt;0.05) and 38.8 % (p&lt;0.001), respectively.Obtained morphometric parameters indicate that the simulated pathology leads to a decrease in the diameter of the tubules and the thickening of their walls. In the latter, optically sclerosis was observed. In the lumen of the seminiferous tubules, histologic examination revealed spermatocytes of the first order and spermatogonia, rarely observed spermatocytes of the second order. Protein detritus and rarely sperm were detected in the tubules.Conclusions. So postresection portal hypertension and multiorgan failure lead to pronounced structural restructuring of the vascular, interstitial and endocrine components of the testes, characterized by dilatation, plethora, varicose extensions, stasis, hemorrhage, perivasal swelling of the vessels gemomicrocirculatory bad and, hyperplasia, moderate hypertrophy Leydig cell dystrophy. The detected morphological changes dominate in multiple organ failure.

Clinical Efficacy of Enteral Saline Solution When Used as Part of Combined Treatment for Various Forms of Acute Pancreatitis

The article presents the results of a retrospective study of the effectiveness of intestinal lavage with enteral saline solution for the treatment of dynamic intestinal obstruction in acute forms of pancreatitis and pancreonecrosis. The objective of this study is to improve treatment results in patients with intestinal paresis with various forms of acute pancreatitis with the use of intestinal lavage with enteral saline solution.Materials and methods. The study included 81 patients, 56 (69.1 %) males and 25 (30.9 %) females, the age averaging at 59.3 ± 13.4 years. These patients were hospitalized at different time intervals counting from the onset of the disorder, ranging from 24 hours to 7 days. Patients were divided in two groups depending on hospitalisation prior to the first procedure of intestinal lavage providing there was no counterindications.Results and discussion. Prokinetic effect of intestinal lavage in patients with gastrostasis and dynamic bowel obstruction help improve the quality of conservative treatment (up to 78.3 % in 1st group and 37.1 % in 2nd group); avoid open surgical procedures (up to 6.5 % in 1st group, up to 37.1 % in 2nd group), perform minimally invasive procedures to drain confined lesions (15.2 % of patients in 1st group, 42.9 % in 2nd group); eliminate manifestations of gastrostasis within 3 days following IL in both groups. The reduction/elimination of dynamic intestinal obstruction within 24 hours following IL (up to 73.8 % in 1st group, up to 97.1 % in 2nd group) made it possible to start early enteral nutrition within 48 hours (73.9 % in 1st group, up to 42.8 % in 2nd group).Conclusions. Early use of intestinal lavage in the complex therapy of acute forms of pancreatitis is safe and effective. It reduces the number of purulent-septic complications, prevents the development of multiple organ failure, reduces the overall mortality, prepares the intestine for early enteral nutrition.

Hematopoietic Cell Transplantation (HCT) Followed By Solid Organ Transplantation (SOT) and SOT Followed By HCT: A Descriptive Analysis of Patients Undergoing Sequential Transplantation in the United States

<h3>Background</h3> Survival after solid organ transplantation(SOT) and hematopoietic cell transplantation(HCT) has increased over time. Despite these improvements, recipients of SOT are at increased risk for conditions leading to bone marrow failure, necessitating HCT. Moreover, recipients of HCT are at increased risk of developing organ failure, necessitating SOT. Complications of SOT and HCT have led the SOT and HCT communities to consider so-called, "sequential transplantation"; however, little data exists to inform outcomes and guide management decisions. We utilized data from the Center for International Blood and Marrow Transplant Research(CIBMTR) and the United Network for Organ Sharing(UNOS) to describe the characteristics and outcomes of patients with sequential transplantation in the United States. <h3>Methods</h3> A descriptive analysis of patients with sequential transplantation(SOT followed by HCT, HCT followed by SOT, HCT followed by SOT waitlist[WL]) was conducted. Analyses focused on SOT and HCT characteristics, outcomes including overall survival(OS) from first transplant and complications(graft-versus-host disease[GVHD] and SOT failure). <h3>Results</h3> We identified 258 patients registered with the CIBMTR and UNOS that had undergone sequential transplantation or been placed on the WL. Among patients who received a SOT followed by HCT(n=84), 50% underwent allogeneic HCT. In this group, there were 15 thoracic, 43 kidney, and 26 liver transplants performed prior to HCT, with living donation accounting for 23(54%) kidney and 2(8%) liver transplants. Five-year OS among recipients of SOT followed by HCT was 34%. Among patients who received an HCT followed by SOT(n=87) or HCT followed by WL(n=73), 45% underwent allogeneic HCT. Plasma cell disorder or multiple myeloma was the most common indication for HCT(48%).(Figure 1) There were 26 thoracic, 49 kidney, and 5 liver SOT procedures performed after initial HCT. Living donation accounted for 27(55%) kidney and 2(40%) liver transplants in this group. Five-year OS among recipients of HCT followed by SOT was 82%. Among all patients who underwent HCT, acute GVHD occurred in 47% and chronic GVHD in 53%. SOT graft failure occurred in 81(44%): 26(30%) SOT failures among HCT followed by SOT and 55(56%) SOT failures among SOT followed by HCT. <h3>Conclusion</h3> Sequential transplantation poses an enormous clinical challenge for members of the transplant community. OS among recipients of SOT followed by HCT is considerably less than OS among recipients of HCT followed by SOT. Additional analyses further characterizing outcomes of sequential transplantation and investigating potential factors associated with these outcomes are planned to assist SOT and HCT care providers in the management of these challenging clinical scenarios.

Reperfusion syndrome: state of the art

Reperfusion syndrome is a complex series of clinical manifestations resulting from restoration of blood flow to previously ischaemic tissues. It is accompanied by damage to cells, tissues and organs at various levels, followed by the development of multiple organ failure. This review deals with the main pathophysiological mechanisms of the development of reperfusion syndrome in lesions of cardiac, cerebral and lower-limb vessels. Oxidative stress is considered to be the most important marker of ischaemia-reperfusion injury irrespective of the type of tissues affected. Presented herein are the data on contemporary possibilities of influencing various stages and components of the development of reperfusion injury by means of drug therapy, demonstrating that due to the importance of oxidative stress as a key link of reperfusion injury, antioxidant therapy should be the main component of prevention and treatment of reperfusion injury.

Management of patients with enterocutaneous fistulae

Enterocutaneous fistula (ECF) is the most serious postoperative life-threating complication of various abdominal surgical interventions. Treatment of patients with ECF is associated with life-threatening complications including sepsis and septic shock, intestinal failure and severe water-electrolyte disorders that causes high mortality rates (35-75% according to national authors and 6-33% according to foreign colleagues). This issue is especially relevant in the cases of enteroatmospheric fistulae and high ECF with loss of intestinal contents of more than 500 ml per day. In the absence of correct conservative therapy, this quickly results progression of sepsis and development of multiple organ failure. Surgery without complex preoperative preparation in this period may be fatal and lead to clinical aggravation and death of patient in early postoperative period. Each patient requires an individual approach. However, there are general principles of treatment too. This literature review describes the main aspects of conservative treatment of patients with enteric fistulae.

Prognostic factors Influencing Necrotizing Soft tissue lesions in North India

Background: Severe skin or soft tissue (SST) infections can involve fascia planes, thereby constitution necrotizing fascitis. Such infections are characterized by extensive necrosis and systemic toxicity [1,2]. Early clinical diagnosis of necrotizing fascitis and superficial SST infection (erysipelas or cellulitis),may be difficult [3,4]. Method: At the time of admission a detailed clinical history were taken, clinical examination was done, patients were admitted and stabilized in emergency ward, aggressive debridement of infected and necrotizing tissue. All necrotic skin, subcutaneous tissue, fascia and nonviable muscle were removed, the excised tissue was sent for culture and sensitivity in microbiology laboratory. All the viable skin and soft tissues were saved to aid later closure. Result: the survival rate was 86.5% in patients who underwent surgical debridement in early stage of disease as compared to 61.5% mortality in patients who presented late. Septicemic shock and multiple organ failure was less in patients who presented at early stage of disease. Early and adequate nutritional support along with prompt recognition and treatment reduces the development of multiple organ failure and improves the outcome. Conclusion: Mortality rate is decreased in those patients who are treated in early cause of disease by means of surgical and medical approach. The mortality rate is directly proportional to involved body surface area in patients of Necrotizing soft tissue lesion. Site of lesion and extent of lesion influences the mortality.

A Prospective study of BISAP score in Acute Pancreatitis.

Background: Acute pancreatitis is defined as an inflammatory process of the pancreas with possible peri pancreatic tissue and multi-organ involvement inducing Multi-Organ Dysfunction Syndrome (MODS) with an increased mortality rate.The underlying mechanism of injury in pancreatitis is thought to be premature activation of pancreatic enzymes within the pancreas, leading to a process of auto digestion. Due to the risk of rapid deterioration in severe acute pancreatitis, the assessment of severity becomes crucial to a clinician. Multiple risk stratification tools for acute pancreatitis have been developed, but their clinical usefulness is limited. In Ranson's criteria and modified Glasgow score there are multiple parameters, of which some of them are not available in majority of hospitals in India. In addition, both are assessed after 48hrs, thereby missing potentially valuable early therapeutic window. The APACHE II score (Acute Physiology and Chronic Health Evaluation) is the most widely used prediction system currently, but it requires the collection of large number of parameters some of which may not be relevant to prognosis. APACHE II was originally developed as an intensive care instrument. For this purpose, a simple and accurate clinical scoring system that is, Bedside Index for Severity in Acute Pancreatitis (BISAP) scoring system was developed. This scoring system is used for stratifying patients according to their risk of mortality and is able to identify patientsat increased risk of mortality prior to the onset of organ failure. More over the data for BISAP score is collected within the first 24hrs of hospitalization. The ability tostratify patients early in their course is a major step in improving future management strategies in acute pancreatitis. Methods: A prospective study was done in cases of acute pancreatitis with the effectiveness of Bedside Index for Severity in Acute Pancreatitis (BISAP) scoring system is used for stratifying patients according to their risk of mortality and is able to identify patients at increased risk of mortality prior to the onset of organ failure Results: A total of 50 cases were taken and the Bedside Index for Severity in Acute Pancreatitis (BISAP) scoring system was calculated in assessing mortality and intermediate markers of severity in acute pancreatitis in 24 hours of presentation. It is observed that individuals with BISAP score ≥3 were 4.5 times more likely to develop organ failure and 6 times more likely to develop pancreatic necrosis, than those with BISAP score

Двусторонний острый гнойно-деструктивный пиелонефрит после выполнения контактной уретеролитотрипсии

The problem of urinary stone disease and acute destructive pyelonephritis remains to be relevant in the current urologic practice. The acute pyelonephritis is the most common infectious and inflammatory complication after retrograde ureteroscopy. According to data of leading urologists in Russian Federation and worldwide, the incidence of acute purulent pyelonephritis ranges from 0.1 to 0.2%. Infectious and inflammatory complications of retrograde ureteroscopy often require urgent interventions. Acute pyelonephritis can result in destructive changes in the renal parenchyma. In case of ineffective conservative measures, pyelonephritis can progress into sepsis with the development of multiple organ failure. Therefore, infectious and inflammatory complications require to start combined antibacterial, anti-inflammatory and detoxification therapy, as well as to resolve any upper urinary tract obstruction. If acute pyelonephritis leads to destructive phase with a formation of a carbuncle or an abscess in the kidney, an open surgery is indicated. Despite being minimally-invasive, retrograde ureteroscopy can lead to serious complications requiring an open surgical intervention. In some cases, the severity of the patients condition may require nephrectomy.

Ведення вагітних з прееклампсією після пологів

Pre-eclampsia found only in humans during the second half of pregnancy or the postpartum period, is known to be featured by the development of arterial hypertension and multiple organ failure syndrome. Almost a third of eclampsia is known to occur in the postpartum period. The pre-eclamptic patients require thorough monitoring of blood pressure and administration of antihypertensive drugs in the puerperium. The pathogenesis and tactics of the developed de novo postpartum pre-eclampsia have not been sufficiently studied. The greatest risk of stroke after delivery remains for 10 days. In the case of postpartum pre-eclampsia, it is very important to start using antihypertensives in a timely manner. First-line drugs should be used not later than 30-60 minutes from the time of severe pre-eclampsia diagnosing to prevent intracranial hemorrhage. Labetalol or hydralazine should be used in order to reduce blood pressure. Sublingual administration of nifedipine may also be considered as first-line therapy. The use of magnesium sulfate is necessary for the prevention of seizures in patients with severe preeclampsia. In the case of eclampsia, a solution of magnesium sulfate is administered intravenously at a loading dose of 4-5 g for 15-20 minutes and then continued infusion at a dose of 1 g per hour throughout the day. Uterine curettage is also a possible measure of reducing blood pressure in women with pre-eclampsia. Uterine curettage reduced blood pressure in pre-eclamptic patients, but without adequate reporting of harms of perforation and infection dissemination, so it cannot currently be recommended. However, curettage should be done during a caesarean section of women with preeclampsia. The own case of a systemic inflammatory response syndrome that occurred in a postpartum woman with mild pre-eclampsia is given. Postpartum endomyometritis, which was caused by group B streptococcus, should have played a triggering role in the progression of preeclampsia. The problem of polychemical resistance has led to the inability of traditional antimicrobial agents to prevent the dissemination of infection after curettage. The systemic inflammatory response syndrome has contributed to the increased severity of preeclampsia and the development of multiple organ failure. Key words: preeclampsia, postpartum period, antihypertensive drugs.

Blood metabolomics uncovers inflammation-associated mitochondrial dysfunction as a potential mechanism underlying ACLF

Acute-on-chronic liver failure (ACLF), which develops in patients with cirrhosis, is characterized by intense systemic inflammation and organ failure(s). Because systemic inflammation is energetically expensive, its metabolic costs may result in organ dysfunction/failure. Therefore, we aimed to analyze the blood metabolome in patients with cirrhosis, with and without ACLF. We performed untargeted metabolomics using liquid chromatography coupled to high-resolution mass spectrometry in serum from 650 patients with AD (acute decompensation of cirrhosis, without ACLF), 181 with ACLF, 43 with compensated cirrhosis, and 29 healthy individuals. Of the 137 annotated metabolites identified, 100 were increased in patients with ACLF of any grade, relative to those with AD, and 38 comprised a distinctive blood metabolite fingerprint for ACLF. Among patients with ACLF, the intensity of the fingerprint increased across ACLF grades, and was similar in patients with kidney failure and in those without, indicating that the fingerprint reflected not only decreased kidney excretion but also altered cell metabolism. The higher the ACLF-associated fingerprint intensity, the higher the plasma levels of inflammatory markers, tumor necrosis factor α, soluble CD206, and soluble CD163. ACLF was characterized by intense proteolysis and lipolysis; amino acid catabolism; extra-mitochondrial glucose metabolism through glycolysis, pentose phosphate, and D-glucuronate pathways; depressed mitochondrial ATP-producing fatty acid β-oxidation; and extra-mitochondrial amino acid metabolism giving rise to metabotoxins. In ACLF, intense systemic inflammation is associated with blood metabolite accumulation and profound alterations in major metabolic pathways, in particular inhibition of mitochondrial energy production, which may contribute to the development of organ failures. Acute-on-chronic liver failure (ACLF), which develops in patients with cirrhosis, is characterized by intense systemic inflammation and organ failure(s). Because systemic inflammation is energetically expensive, its metabolic costs may result in organ dysfunction/failure. We identified a 38-metabolite blood fingerprint specific for ACLF that revealed mitochondrial dysfunction in peripheral organs. This may contribute to organ failures.

Associations between clinical characteristics and the development of multiple organ failure after severe burns in adult patients

To determine the association between potential risk factors and multiple organ failure (MOF) in severe burn adult patients, we performed a secondary analysis of data from the “Inflammation and the Host Response to Injury” database, which included patients from six burn centers in the United States between 2003 and 2009. Three hundred twenty-two adult patients (aged ≥16 years) with severe burns (≥20.0% total body surface area [TBSA]) were included. MOF was defined according to the Denver score. Potential risk factors were analyzed for their association with MOF. Models were built using multivariable logistic regression analysis. Eighty-eight patients (27.3%) developed MOF during the study period. We found that TBSA, age, and inhalation injury were significant risk factors for MOF. This predictive model showed good performance, with the total area under the receiver operating characteristic curve being 0.823. Moreover, among patients who developed MOF, inhalation injury was significantly associated with the development of MOF in the acute phase (within three days of injury) (adjusted odds ratio 3.1; 95% confidence interval 1.1–8.3). TBSA, age, lactate, and Denver score within 24h were associated with the late phase development of MOF. Thus, we have identified key risk factors for the onset of MOF after severe burn injury. Our findings contribute to the understanding of individualized treatment and will potentially allow for efficient allocation of resources and a lower threshold for admission to an intensive care unit, which can prevent the development of MOF and eventually reduce mortality.