Organ Dysfunction Syndrome Research Articles

Mitigating the Effects of 1-Palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol on Gastrointestinal Acute Radiation Syndrome after Total-Body Irradiation in Mice.

Total-body irradiation (TBI) with gamma rays can damage organisms in various unexpected ways and trigger several organ dysfunction syndromes, such as acute radiation syndrome (ARS). Hematopoietic cells and enterocytes are particularly sensitive to radiation due to their self-renewal ability and rapid division, which leads to hematopoietic ARS (H-ARS) and gastrointestinal ARS (GI-ARS). We previously showed that a lipid-based small molecule, 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), improved 30-day survival and alleviated H-ARS symptoms in BALB/c mice after a lethal dose (LD70/30) of gamma-ray TBI. In this study, we investigated the mitigating effects of PLAG on radiation-induced GI damage that occurs under the same conditions as H-ARS in BALB/c mice. Our study showed that PLAG facilitated the structural restoration of intestinal tissues by increasing villus height, crypt depth, crypt number, mucin-producing goblet cells, and proliferating cell nuclear antigen (PCNA)-positive crypt cells. PLAG significantly improved intestinal absorptive capacity and reduced intestinal injury-induced bacterial translocation. In addition, PLAG effectively inhibited radiation-induced necroptosis signaling activation in the intestinal crypt cells, which was responsible for sustained tissue damage and the release of high mobility group box 1 (HMGB1), a typical damage-associated molecular pattern. Overall, our findings support the radiation-mitigating potential of PLAG against GI-ARS after accidental radiation exposure.

Research Progress on Mechanisms and Treatment of Sepsis-Induced Myocardial Dysfunction.

Sepsis is a syndrome of organ dysfunction caused by a dysregulated immune response to infection, with high morbidity and mortality. At present, there have been many advances in the study of its pathogenesis, especially the cardiac dysfunction caused by sepsis, namely sepsis-induced myocardial dysfunction, SIMD, which has received widespread attention. The mechanisms of SIMD mainly include excessive release of inflammatory mediators, impaired mitochondrial function, autophagy, apoptosis and myocardial dysfunction. This article reviews the pathogenesis of SIMD and elaborates on the progress in its treatment, aiming to improve the prognosis of patients with SIMD and sepsis.

The preventative effects of Lactococcus Lactis metabolites against LPS-induced sepsis.

Sepsis is a syndrome of organ dysfunction caused by a dysregulated host response to infection and septic shock. Currently, antibiotic therapy is the standard treatment for sepsis, but it can lead to drug resistance. The disturbance of the gut microbiota which is affected by sepsis could lead to the development of organ failure. It is reported that probiotics could shape the gut microbiota, potentially controlling a variety of intestinal diseases and promoting whole-body health. In this study, we evaluated the preventive effects of intra- and extracellular products of probiotics on sepsis. The extracellular products of Lactococcus lactis (L. lactis) were identified through the in vivo cell experiments. The preventive effect and mechanism of L. lactis extracellular products on mouse sepsis were further explored through HE staining, mouse survival rate measurement, chip analysis, etc. L. lactis extracellular products increase cell survival and significantly reduce inflammatory factors secreted in a cellular sepsis model. In in vivo experiments in mice, our samples attenuated sepsis-induced pulmonary edema and inflammatory infiltrates in the lungs of mice, and reduced mortality and inflammatory factor levels within the serum of mice. Finally, the mechanism of sepsis prevention by lactic acid bacteria is suggested. Extracellular products of L. lactis could effectively prevent sepsis episodes. In animal experiments, we reported that extracellular products of L. lactis can effectively prevent sepsis, and preliminarily discussed the pathological mechanism, which provides more ideas for the prevention of sepsis. In the future, probiotics may be considered a new way to prevent sepsis.

Optimizing the connection of CRRT and ECMO lines with additional pressure regulator on the therapeutic effect, filter life, and incidence of complications.

Extracorporeal membrane oxygenation (ECMO) is used for severe cardiopulmonary failure, with veno-arterial ECMO for cardiogenic shock and veno-venous ECMO for acute respiratory failure. ECMO's application has expanded to ICUs, emergency departments, and operating rooms. ECMO patients are at high risk for complications, including acute kidney injury (AKI), often requiring renal replacement therapy (RRT), posing significant management challenges. From August 2015 to June 2022, 120 patients were cured with veno-venous ECMO (n = 60) or veno-arterial ECMO (VA-ECMO, n = 60) combined with CRRT in our hospital. In the control group (n = 60), the input end (arterial end) of CRRT was connected to the ECMO oxygenator. The reinfusion end (venous end) of CRRT was connected to the oxygenator of ECMO for CRRT + ECMO treatment. In the experimental group (n = 60), the input end (arterial end) of CRRT was connected to the oxygenator of ECMO, and an additional pressure regulating device was installed on the connection of the 2 lines. The observation indexes including clinical therapeutic effect, clinical therapeutic effect, the incidence of complications, and the incidence of complications were compared. There was a notable decrease in serum creatinine, and the differences in blood urea nitrogen, procalcitonin, and C-reactive protein after operation were statistically significant (P < .05). The filter use time in the study group was notably longer (P < .01). There exhibited no remarkable difference in the incidences of bleeding, thrombosis, numbness of hands and feet, metabolic alkalosis, disseminated intravascular coagulation, organ dysfunction syndrome, hyperbilirubinemia, and infection. This study demonstrates that additional pressure regulation devices are installed at the line connection between the CRRT input end and the CRRT return end to ensure that the flow rate of ECMO does not affect the CRRT treatment. ECMO and CRRT provide a safe pressure range so that the ECMO line can be safely connected to the CRRT machine at physiological pressure, reducing the occurrence of complications related to CRRT machine interruption and improving the efficiency of CRRT without affecting the efficiency of ECMO, ensuring patient safety.

Recent advances in the pathogenesis, diagnosis, and treatment of sepsis‐associated encephalopathy

AbstractSepsis is a life‐threatening organ dysfunction syndrome caused by the host's dysregulated response to infection. The leading causes of death in critically ill patients are sepsis‐associated encephalopathy (SAE), respiratory dysfunction, circulatory dysfunction, and other multi‐organ dysfunctions. SAE is among the most common serious complications of sepsis and is associated with a poor prognosis and long‐term cognitive dysfunction. Its clinical manifestations vary, and there are still no unified diagnostic criteria. The incidence of SAE varies from 9% to 71% in critically ill patients due to therapeutic interventions such as sedation, mechanical ventilation, and muscle relaxants. Advances in medical technology have significantly increased the survival rate of patients with sepsis, but up to 21% now experience long‐term sequelae or cognitive impairment. The lack of specific early diagnostic and treatment methods leads to increased SAE‐associated mortality and complications in patients, which also impose heavy economic burdens. This article reviews the pathogenesis and diagnostic methods of SAE and progress in its treatment, aiming to reduce the mortality and hospitalization lengths of patients with SAE and improve their survival rate and quality of life through early detection, diagnosis, and effective treatment.

Unlocking the Potential: Quercetin and Its Natural Derivatives as Promising Therapeutics for Sepsis.

Sepsis is a syndrome of organ dysfunction caused by an uncontrolled inflammatory response, which can seriously endanger life. Currently, there is still a shortage of specific therapeutic drugs. Quercetin and its natural derivatives have received a lot of attention recently for their potential in treating sepsis. Here, we provide a comprehensive summary of the recent research progress on quercetin and its derivatives, with a focus on their specific mechanisms of antioxidation and anti-inflammation. To obtain the necessary information, we conducted a search in the PubMed, Web of Science, EBSCO, and Cochrane library databases using the keywords sepsis, anti-inflammatory, antioxidant, anti-infection, quercetin, and its natural derivatives to identify relevant research from 6315 articles published in the last five years. At present, quercetin and its 11 derivatives have been intensively studied. They primarily exert their antioxidation and anti-inflammation effects through the PI3K/AKT/NF-κB, Nrf2/ARE, and MAPK pathways. The feasibility of these compounds in experimental models and clinical application were also discussed. In conclusion, quercetin and its natural derivatives have good application potential in the treatment of sepsis.

Computerized tomography-guided therapeutic percutaneous puncture catheter drainage-combined with somatostatin for severe acute pancreatitis: An analysis of efficacy and safety.

Severe acute pancreatitis (SAP), a condition with rapid onset, critical condition and unsatisfactory prognosis, poses a certain threat to human health, warranting optimization of relevant treatment plans to improve treatment efficacy. To evaluate the efficacy and safety of computerized tomography-guided therapeutic percutaneous puncture catheter drainage (CT-TPPCD) combined with somatostatin (SS) in the treatment of SAP. Forty-two SAP patients admitted to The Second Affiliated Hospital of Fujian Medical University from June 2020 to June 2023 were selected. On the basis of routine treatment, 20 patients received SS therapy (control group) and 22 patients were given CT-TPPCD plus SS intervention (research group). The efficacy, safety (pancreatic fistula, intra-abdominal hemorrhage, sepsis, and organ dysfunction syndrome), abdominal bloating and pain relief time, bowel recovery time, hospital stay, inflammatory indicators (C-reactive protein, interleukin-6, and procalcitonin), and Acute Physiology and Chronic Health Evaluation (APACHE) II score of both groups were evaluated for comparison. Compared with the control group, the research group had a markedly higher total effective rate, faster abdominal bloating and pain relief and bowel recovery, shorter hospital length of stay, fewer complications, and lower posttreatment inflammatory indices and APACHE-II scores. CT-TPPCD in combination with SS is effective for SAP patients, which can reduce complications, accelerate symptom resolution, inhibit inflammation, and improve patient condition, with promising prospects for clinical promotion.

A new hematological parameter model for the diagnosis and prognosis of sepsis in emergency department: A single-center retrospective study.

Sepsis, a syndrome of organ dysfunction caused by an unregulated host response to infection. This study aimed to develop a novel sepsis diagnostic model of hematological parameters and evaluate its effectiveness in the early identification and prognosis of sepsis in emergency departments. A retrospective study was conducted in Emergency Department. Cell population data parameters related to monocytes and neutrophils were obtained using the Mindary BC-6800 plus hematology analyzer. Receiver operating characteristic (ROC) curve analysis, logistic regression analysis was performed to assess the performance of the parameters and establish a diagnostic and prognostic model of sepsis, which was then verified with a validation cohort. Mon_XW exhibited the best diagnostic performance (area under the ROC curve [AUC] = 0.848, 95% confidence interval [CI]: 0.810-0.885, p < 0.001), followed by Neu_Y and Neu_YW (AUC = 0.777 95% CI: 0.730-0.824, p < 0.001). Logistic regression analysis identified Mon_XW and Neu_Y as independent predictors, which were used to establish a diagnostic model named hematological parameter for sepsis (HPS). HPS demonstrated the best diagnostic performance with an AUC of 0.862 (95% CI: 0.826-0.898, p < 0.001), sensitivity of 70.0%, and specificity of 87.1%, compared to C-reactive protein (CRP) and procalcitonin (PCT). The validation cohort also found that the positive predictive value of HPS was 70.4% and the negative predictive value was 92.2%. The developed HPS model showed promising diagnostic efficacy for sepsis in the emergency department, which outperformed CRP and PCT in terms of sensitivity and specificity. By enabling early identification and prognosis of sepsis, that contributes to reducing sepsis-related mortality.

Diagnostic and predictive values of pyroptosis-related genes in sepsis.

Sepsis is an organ dysfunction syndrome caused by the body's dysregulated response to infection. Yet, due to the heterogeneity of this disease process, the diagnosis and definition of sepsis is a critical issue in clinical work. Existing methods for early diagnosis of sepsis have low specificity. This study evaluated the diagnostic and predictive values of pyroptosis-related genes in normal and sepsis patients and their role in the immune microenvironment using multiple bioinformatics analyses and machine-learning methods. Pediatric sepsis microarray datasets were screened from the GEO database and the differentially expressed genes (DEGs) associated with pyroptosis were analyzed. DEGs were then subjected to multiple bioinformatics analyses. The differential immune landscape between sepsis and healthy controls was explored by screening diagnostic genes using various machine-learning models. Also, the diagnostic value of these diagnosis-related genes in sepsis (miRNAs that have regulatory relationships with genes and related drugs that have regulatory relationships) were analyzed in the internal test set and external test. Eight genes (CLEC5A, MALT1, NAIP, NLRC4, SERPINB1, SIRT1, STAT3, and TLR2) related to sepsis diagnosis were screened by multiple machine learning algorithms. The CIBERSORT algorithm confirmed that these genes were significantly correlated with the infiltration abundance of some immune cells and immune checkpoint sites (all P<0.05). SIRT1, STAT3, and TLR2 were identified by the DGIdb database as potentially regulated by multiple drugs. Finally, 7 genes were verified to have significantly different expressions between the sepsis group and the control group (P<0.05). The pyroptosis-related genes identified and verified in this study may provide a useful reference for the prediction and assessment of sepsis.

Rhein ameliorates septic lung injury and intervenes in macrophage metabolic reprogramming in the inflammatory state by Sirtuin 1

AimsSepsis is an organ dysfunction syndrome caused by the maladjustment of response to infection. Acute lung injury (ALI) appears the earliest, with urgent onset and limited treatments. Previous pharmacological studies have found that rhein (RH), an active ingredient rich in rhubarb, has multiple pharmacological activities such as anti-inflammatory, anti-infection and metabolic regulation. This research aimed to explore whether RH alleviates septic acute lung injury and probe possible mechanisms. Main methodsIn this study, the septic ALI mouse model was established by cecal ligation and perforation (CLP). LPS-induced RAW264.7 model was selected to further explore the protective mechanism of RH. H&E staining, Western blot, qRT-PCR, and 1H NMR analysis were used to verify the protective effect of RH on ALI in vivo and vitro. Key findingsRH could relieve pathological lung injury and pulmonary edema, reduce the serum LPS and inhibit inflammatory response in CLP mice. Further studies displayed that RH affected the metabolism in vivo, with significant changes in serum and lung metabolomics. In vitro results demonstrated that RH inhibited the expression of inflammatory mediators and factors in macrophages by affecting metabolic reprogramming and upregulating the expression of Sirtuin 1. SignificanceRH improved the overall metabolic condition of sepsis mice by up-regulating and activating SIRT1, and inhibited the over activation of macrophages by regulating metabolism. These findings reveal the therapeutic mechanism of RH on sepsis ALI from the perspective of metabolism.

Direct autotransfusion in the management of acute pericardial tamponade during catheter ablation for atrial fibrillation: An imperfect but practical method.

BackgroundAcute pericardial tamponade (APT) is one of the most serious complications of catheter ablation for atrial fibrillation (AF-CA). Direct autotransfusion (DAT) is a method of reinjecting pericardial blood directly into patients through vein access without a cell-salvage system. Data regarding DAT for APT are rare and provide limited information. Our present study aims to further investigate the safety and feasibility of DAT in the management of APT during the AF-CA procedure.Methods and resultsWe retrospectively reviewed 73 cases of APT in the perioperative period of AF-CA from January 2014 to October 2021 at our institution, among whom 46 were treated with DAT. All included patients successfully received emergency pericardiocentesis through subxiphoid access guided by X-ray. Larger volumes of aspirated pericardial blood (658.4 ± 545.2 vs. 521.2 ± 464.9 ml), higher rates of bridging anticoagulation (67.4 vs. 37.0%), and surgical repair (6 vs. 0) were observed in patients with DAT than without. Moreover, patients with DAT were less likely to complete AF-CA procedures (32/46 vs. 25/27) and had a lower incidence of APT first presented in the ward (delayed presentation) (8/46 vs. 9/27). There was no difference in major adverse events (death/disseminated intravascular coagulation/multiple organ dysfunction syndrome and clinical thrombosis) (0/0/1/0 vs. 1/0/0/0), other potential DAT-related complications (fever/infection and deep venous thrombosis) (8/5/2 vs. 5/3/1), and length of hospital stay (11.4 ± 11.6 vs. 8.3 ± 4.7 d) between two groups.ConclusionDAT could be a feasible and safe method to deal with APT during AF-CA procedure.

Intra-Abdominal Pressure Monitoring in Acute Severe Pancreatitis—A Boon or Bane?

Background Intra-abdominal hypertension (IAH) is increasingly reported in patients with acute pancreatitis, and is caused by visceral edema, massive fluid resuscitation, paralytic ileus, and retroperitoneal inflammation. Patients with acute severe pancreatitis actually suffer from abdominal compartment syndrome (ACS)/IAH and since there is a strong correlation between early organ dysfunction and mortality in these patients, IAH appears to be an active and attractive target for early analysis and intervention.[1] Aim The study is undertaken to estimate the significance of intra-abdominal pressure monitoring in acute severe pancreatitis. Objectives The objective of this study is to evaluate relationship between intra-abdominal pressure (IAP) and severity of acute pancreatitis and measure outcome in the form of intensive care unit (ICU) stay, hospital stay, treatment modality, and condition on discharge. Methodology A total of 50 patients diagnosed as acute severe pancreatitis were enrolled in this observational study. IAP monitoring was started on admission, once after controlling pain and then every 4 hours. IAP was measured via transvesical route. Data were collected on the length of the hospital stay, the development of systemic inflammatory response syndrome (SIRS), multiorgan failure, the extent of necrosis, the presence of infection, and mortality. Results IAH was present in 86% of patients with acute severe pancreatitis, which shows IAP monitoring is essential in managing these patients. Severity estimation by IAP monitoring is consistent with alternative laboratory parameters like Ranson’s score (p = 0.002), SIRS (p = 0.013), organ failure/multiple organ dysfunction syndrome (p = 0.009). Two deaths were incurred during the study period. Conclusions IAP measurement in acute severe pancreatitis is a cost-effective and prognostic marker. Timely diagnosis and management of IAH/ACS through IAP monitoring can prevent major comorbidity (ICU/hospital stay) and mortality.

Serum proteomics reveals disorder of lipoprotein metabolism in sepsis.

Sepsis is defined as an organ dysfunction syndrome and it has high mortality worldwide. This study analysed the proteome of serum from patients with sepsis to characterize the pathological mechanism and pathways involved in sepsis. A total of 59 patients with sepsis were enrolled for quantitative proteomic analysis. Weighted gene co-expression network analysis (WGCNA) was performed to construct a co-expression network specific to sepsis. Key regulatory modules that were detected were highly correlated with sepsis patients and related to multiple functional groups, including plasma lipoprotein particle remodeling, inflammatory response, and wound healing. Complement activation was significantly associated with sepsis-associated encephalopathy. Triglyceride/cholesterol homeostasis was found to be related to sepsis-associated acute kidney injury. Twelve hub proteins were identified, which might be predictive biomarkers of sepsis. External validation of the hub proteins showed their significantly differential expression in sepsis patients. This study identified that plasma lipoprotein processes played a crucial role in sepsis patients, that complement activation contributed to sepsis-associated encephalopathy, and that triglyceride/cholesterol homeostasis was associated with sepsis-associated acute kidney injury.

Mortality Review of Children Admitted in Pediatric Intensive Care Unit Over One Year in a Tertiary Care Hospital

Introduction: Childhood mortality is still high in developing countries. This can be reduced with good preventive and curative services especially with critical care. The treatment of critically ill children must be focused for better outcome. The pediatrics deaths audit and review provide feedback to health workers and to the institution. The outcome measures of critical care medicine include mortality, morbidity and disability rate.&#x0D; Objectives: The aim of this study is to review the causes and mode of death in children and length of PICU (pediatric intensive care unit) stay.&#x0D; Methodology: A retrospective study was conducted of the patients who were admitted and died within the period of 16 July 2019 to 15 July, 2020 at PICU of Kanti Children Hospital (KCH). Variables recorded were patient's demography, diagnosis, co- morbidities, complications, length of PICU stay (LOS), mode and time of death. Data were tabulated into MS Excel and analyzed using SPSS version 23.&#x0D; Result: Out of 718 admitted children, 99 (13.78%) died with male to female ratio of 1.8:1. The maximum death (75%) was observed in less than five year of age and most of them were from outside the Kathmandu valley. The leading causes of death were pneumonia (28%), sepsis (20%) and congenital heart diseases (21%). The common complications seen were disseminated intravascular coagulation (DIC), multi- organ dysfunction syndrome (MODS), acute kidney injury (AKI) (5.1 %) and acute respiratory distress syndrome (ARDS) (6.1%) and co- morbidities were congenital heart disease (CHD) (18.2%) and global developmental delay (GDD) (9.1%). Mechanical ventilation was needed in 80.8%. Most of the cases (86%) died despite active treatment and (75%) during off hours (4pm-9am).&#x0D; Conclusion: Pneumonia, sepsis and CHD were the main reason of death and most of them were from outside the valley.

Wogonin alleviates liver injury in sepsis through Nrf2-mediated NF-κB signalling suppression.

Sepsis is a life‐threatening organ dysfunction syndrome, and liver is a susceptible target organ in sepsis, because the activation of inflammatory pathways contributes to septic liver injury. Oxidative stress has been documented to participate in septic liver injury, because it not only directly induces oxidative genotoxicity, but also exacerbates inflammatory pathways to potentiate damage of liver. Therefore, to ameliorate oxidative stress is promising for protecting liver in sepsis. Wogonin is the compound extracted from the medicinal plant Scutellaria baicalensis Geogi and was found to exert therapeutic effects in multiple inflammatory diseases via alleviation of oxidative stress. However, whether wogonin is able to mitigate septic liver injury remains unknown. Herein, we firstly proved that wogonin treatment could improve survival of mice with lipopolysaccharide (LPS)‐ or caecal ligation and puncture (CLP)‐induced sepsis, together with restoration of reduced body temperature and respiratory rate, and suppression of several pro‐inflammatory cytokines in circulation. Then, we found that wogonin effectively alleviated liver injury via potentiation of the anti‐oxidative capacity. To be specific, wogonin activated Nrf2 thereby promoting expressions of anti‐oxidative enzymes including NQO‐1, GST, HO‐1, SOD1 and SOD2 in hepatocytes. Moreover, wogonin‐induced Nrf2 activation could suppress NF‐κB‐regulated up‐regulation of pro‐inflammatory cytokines. Ultimately, we provided in vivo evidence that wogonin activated Nrf2 signalling, potentiated anti‐oxidative enzymes and inhibited NF‐κB‐regulated pro‐inflammatory signalling. Taken together, this study demonstrates that wogonin can be the potential therapeutic agent for alleviating liver injury in sepsis by simultaneously ameliorating oxidative stress and inflammatory response through the activation of Nrf2.

Study of factors associated with COVID-19 mortality in a rural tertiary health care center

Background: COVID-19 has swiftly spread to emerge as a global pandemic with no visible signs of decline. It is imperative to identify the parameters contributing toward COVID-19 mortality to facilitate prompt evaluation and control measures. Materials and Methods: A total of 1754 patients with confirmed COVID-19 infection were admitted at MVJMC and RH, Bangalore, from July 1, 2020 to December 12, 2020. Various parameters such as demographical profile, symptomatology, risk factors, laboratory profile, and complications of 75 patients (4.27%) who succumbed were studied. Results: About 45.33% of the patients who died were older than 65 years. 77% of patients who died were males. About 61.33% had severe illness at the time of presentation. 84% of the patients who died had comorbid illnesses. Respiratory failure secondary to acute respiratory distress syndrome and bilateral pneumonia was the leading cause of mortality followed by sepsis/multiple organ dysfunction syndrome, myocarditis, coagulopathy, and acute cardiovascular event. The presence of lymphopenia elevated inflammatory markers, and comorbid conditions were identified as risk factors for the requirement of oxygen, mechanical ventilation, and death. Conclusion: Elderly patients (>65 years of age) and middle-age patients (45–65 years of age) comprised the highest and second-highest proportion of mortality respectively. The increasing proportion of deaths among the middle-aged patients and the narrowing gap of the same between these two groups are alarming. Old age, male gender, underlying chronic illnesses, and elevated inflammatory markers are some of the factors attributed to these trends. Hence, stringent preventive measures, early detection, and initiation of treatment pose a greater impact on reducing the burden of morbidity and mortality.

A Review on Current Scenario of 2019-nCoV and Its Treatments

The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly from Wet Market of Wuhan City, Hubei ProVince, People’s Republic of China, caused a highly contagious disease, Novel Coronavirus Disease or COVID-19. World Health Organisation (WHO) declared Coronavirus Disease (COVID-19) outbreak as pandemic on 12th March, 2020. Reproduction Number (Ro) of SARS-CoV-2 virus ranges from 2.47-2.86. Incubation period of nCoV varies from 2-14 days based on age, gender, and other physiological conditions. Based on current published evidence, the most common symptoms of COVID-19 are fever (87.9%), cough (67.7%), fatigue (38.1%), diarrhoea (3.7%), and vomiting (5.0%) but Pneumonia, Multi Organ Dysfunction and Acute Respiratory Distress Syndrome (ARDS) or Death may occur in severe stages of infection.A study on phylogenetic analysis from Wuhan Institute of Virology showed 96.2% similarity in genome sequencing between SARS-CoV-2 and Bat Coronavirus (SARS-CoV-RaTG13).Coronaviruses are single-stranded RNA viruses (having 60-140 nm diameter) with four different types (α, β, δ, γ Coronavirus Strains). Usually, β-Coronavirus Strains are responsible for human to human transmission during COVID-19 infection. At present no specific antiviral drugs or vaccines are available for 2019-nCoV except some supportive cares but scientists are constantly struggling to develop. This review systematically summarizes the epidemiology, clinical characteristics, diagnosis, isolation, treatment, prevention, controlof COVID-19and its future perspective also. It is hoped that this review will help the public to recognize and deal with SARS-CoV-2, and provide a reference for future studies.

Gasdermin E-derived caspase-3 inhibitors effectively protect mice from acute hepatic failure.

Programmed cell death (PCD), including apoptosis, apoptotic necrosis, and pyroptosis, is involved in various organ dysfunction syndromes. Recent studies have revealed that a substrate of caspase-3, gasdermin E (GSDME), functions as an effector for pyroptosis; however, few inhibitors have been reported to prevent pyroptosis mediated by GSDME. Here, we developed a class of GSDME-derived inhibitors containing the core structure of DMPD or DMLD. Ac-DMPD-CMK and Ac-DMLD-CMK could directly bind to the catalytic domains of caspase-3 and specifically inhibit caspase-3 activity, exhibiting a lower IC50 than that of Z-DEVD-FMK. Functionally, Ac-DMPD/DMLD-CMK substantially inhibited both GSDME and PARP cleavage by caspase-3, preventing apoptotic and pyroptotic events in hepatocytes and macrophages. Furthermore, in a mouse model of bile duct ligation that mimics intrahepatic cholestasis-related acute hepatic failure, Ac-DMPD/DMLD-CMK significantly alleviated liver injury. Together, this study not only identified two specific inhibitors of caspase-3 for investigating PCD but also, more importantly, shed light on novel lead compounds for treating liver failure and organ dysfunctions caused by PCD.

FDA analysis of ECOG performance status and safety outcomes.

12024 Background: Patients with poor performance status are often excluded from clinical trials. The FDA has published several guidances on modernizing oncology clinical trial eligibility criteria to more accurately reflect the patient population. Many patients receiving novel oncology therapeutics are heavily pretreated, and often have comorbidities, organ dysfunction, and frailty syndromes. Little is known about the safety of novel therapeutics in patients with poor performance status. Methods: Data from six randomized trials (n=4465) leading to registration for several solid tumor and malignant hematologic cancers, including multiple therapeutic mechanisms of action, such as EGFR TKI’s, immune checkpoint inhibitors (ICI), and chemotherapy, were pooled. Cumulative incidence of Grade 3-5 adverse events and serious adverse events at Days 30, 90, and 180 were evaluated based on ECOG 0-2. Rates of treatment discontinuation by ECOG was also examined. Results: Cumulative incidence of toxicity events at days 30, 90, and 180 are shown in Table. Patient dropout rates due to death were 3.9%, 6.7%, and 10.9%; dropout rates due to disease progression were 66.5%, 66.6% and 56.9%; and dropout rates due to reasons other than progression or death were 29.7%, 26.7% and 32.1% for ECOG PS 0, 1 and 2, respectively. Conclusions: This FDA exploratory analysis of safety outcomes in registration trials based on ECOG suggests increasing rates of adverse events and rates of treatment discontinuation due to death with worsening performance status. Discontinuation rates due to disease progression and other reasons did not appear to be worse for ECOG 2 compared to 0-1. These findings were consistent across therapies (targeted therapy, ICI, chemotherapy). All trials in the analysis led to FDA approval, thus inclusion of patients with ECOG 2 did not adversely affect the trial outcome for this set of FDA approved agents. ECOG performance status eligibility criteria should be evaluated and modified on a frequent basis during drug development. Additional analysis of trials which enroll patients with ECOG 2 is needed. [Table: see text]

Research progress on neutrophil dysfunction during sepsis

Sepsis is a syndrome of life-threatening organ dysfunction caused by a dysregulated host response to infection. Neutrophils are essential players in the host defense against invading pathogens. This review provides an overview of neutrophils dysfunction and the underlying mechanism in the sepsis. Several investigations have shown that impairment of neutrophil migration to the site of infection occurs during sepsis, resulting in an inability of the host to eliminate the infection. On the other hand, the neutrophil accumulation contributes to tissue damage and organ dysfunction during sepsis. This review summarizes the role and the potential mechanism of neutrophils in the sepsis. Neutrophils play an important role in the development of sepsis. Thus, its specific mechanisms need to be further studied and explored to give full play to its proper medical value. Key words: Sepsis; Neutrophil migration; Organ dysfunction