Proteome characterization of liver-kidney comorbidity after microbial sepsis.

Sepsis is a life-threatening condition that occurs when the body responds to an infection but subsequently triggers widespread inflammation and impaired blood flow. These pathologic responses can rapidly cause multiple organ dysfunction or failure either one by one or simultaneously. The fundamental common mechanisms involved in sepsis-induced multiple organ dysfunction remain unclear. Here, employing quantitative global and phosphoproteomics, we examine the liver's temporal proteome and phosphoproteome changes after moderate sepsis induced by cecum ligation and puncture. In total, 4593 global proteins and 1186 phosphoproteins according to 3275 phosphosites were identified. To characterize the liver-kidney comorbidity after sepsis, we developed a mathematical model and performed cross-analyses of liver and kidney proteome data obtained from the same set of mice. Beyond immune response, we showed the commonly disturbed pathways and key regulators of the liver-kidney comorbidity are linked to energy metabolism and consumption. Our data provide open resources to understand the communication between the liver and kidney as they work to fight infection and maintain homeostasis.

Clinical characteristics and prognosis of patients with COVID-19 on mechanical ventilation undergoing continuous renal replacement therapy.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has significantly strained global healthcare, particularly in the management of patients requiring mechanical ventilation (MV) and continuous renal replacement therapy (CRRT). This study investigated the characteristics and prognoses of these patients. METHODS: This multicenter retrospective cohort study gathered data from patients with COVID-19 across 26 medical centers. Logistic analysis was used to identify the factors associated with CRRT implementation. RESULTS: Of the 640 patients with COVID-19 who required MV, 123 (19.2%) underwent CRRT. Compared to the non-CRRT group, the CRRT group was older and exhibited higher sequential organ failure assessment scores. The incidence of hypertension, diabetes, cardiovascular disease, chronic neurological disease, and chronic kidney disease was also higher in the CRRT group. Moreover, the CRRT group had higher intensive care unit (ICU) (75.6% vs. 26.9%, p < 0.001) and in-hospital (79.7% vs. 29.6%, p < 0.001) mortality rates. CRRT implementation was identified as an independent risk factor for both ICU mortality (hazard ratio [HR]:1.833, 95% confidence interval [CI]:1.342-2.505, p < 0.001) and in-hospital mortality (HR: 2.228, 95% CI: 1.648-3.014, p < 0.001). Refractory respiratory failure (n = 99, 19.1%) was the most common cause of death in the non-CRRT death group, and shock with multi-organ failure (n = 50, 40.7%) was the most common cause of death in the CRRT death group. Shock with multi-organ failure and cardiac death were significantly more common in the CRRT death group, compared to non-CRRT death group. CONCLUSION: This study indicates that CRRT is associated with higher ICU and in-hospital mortality rates in patients with COVID-19 who require MV. Notably, the primary cause of death in the CRRT group was shock with multi-organ failure, emphasizing the severe clinical course for these patients, while refractory respiratory failure was most common in non-CRRT patients.

[Prolonged spinal and sacral neurostimulation in children with pelvic organ dysfunction: preliminary analysis]. / Dlitel'naya spinal'naya i sakral'naya neirostimulyatsiya u detei pri narusheniyakh funktsii tazovykh organov: predvaritel'nyi analiz.

OBJECTIVE: To evaluate the clinical efficacy of long-term spinal and sacral programmable neurostimulation for pelvic organ dysfunction in patients with myelodysplasia and chronic dysfunction of the bladder and rectum. MATERIAL AND METHODS: A retrospective study included 32 children aged 1-17 years (mean 10.7) with myelodysplasia, pelvic organ dysfunction and ineffective therapy including botulinum therapy and exclusion of tethered spinal cord syndrome. All children underwent comprehensive urodynamic examination with analysis of bladder and residual urine volume, mean flow rate, intravesical pressure and total urine volume, as well as electromyographic examination. Examination was carried out before surgery, after 6, 12 and 36 months. We applied urinary diary, NBSS questionnaire and urodynamic examination data. All patients underwent neurological examinations (neurological status, magnetic resonance imaging of the spinal cord, computed tomography and radiography of the spine, electroneuromyography). The study was conducted at the neurosurgical department of the Republican Children's Clinical Hospital in Ufa between 2014 and 2022. There were 32 implantations of epidural neurostimulators for pelvic organ dysfunctions. RESULTS: Patients used epidural spinal and sacral stimulation up to 6 times a day for 10-15 min turning on the pulse generator. This method significantly increased urinary volume, decreased episodes of urinary leakage and fecal incontinence, residual volume after urination and number of periodic catheterizations compared to baseline data. Sixteen patients were very satisfied, 10 ones were moderately satisfied, and 2 patients were not satisfied with therapy. The number of bladder catheterizations per day decreased by 51.1%. Urine volume significantly increased from 131.5±16.1 to 236±16.7 ml, intravesical pressure decreased from 23.5±4.2 to 18.5±2.1 cm H2O (by 20.3%). CONCLUSION: Chronic epidural spinal and sacral stimulation can improve the quality of life in patients with pelvic organ dysfunction. This technique may be effective for pelvic organ dysfunction caused by myelodysplasia.

Proteomic analysis of multiple organ dysfunction induced by rhabdomyolysis.

Rhabdomyolysis (RM) leads to dysfunction in the core organs of kidney, lung and heart, which is an important reason for the high mortality and disability rate of this disease. However, there is a lack of systematic research on the characteristics of rhabdomyolysis-induced injury in various organs and the underlying pathogenetic mechanisms, and especially the interaction between organs. We established a rhabdomyolysis model, observed the structural and functional changes in kidney, heart, and lung. It is observed that rhabdomyolysis results in significant damage in kidney, lung and heart of rats, among which the pathological damage of kidney and lung was significant, and of heart was relatively light. Meanwhile, we analyzed the differentially expressed proteins (DEPs) in the kidney, heart and lung between the RM group and the sham group based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). In our study, Serpina3n was significantly up-regulated in the kidney, heart and lung. Serpina3n is a secreted protein and specifically inhibits a variety of proteases and participates in multiple physiological processes such as complement activation, inflammatory responses, apoptosis pathways, and extracellular matrix metabolism. It is inferred that Serpina3n may play an important role in multiple organ damage caused by rhabdomyolysis and could be used as a potential biomarker. This study comprehensively describes the functional and structural changes of kidney, heart and lung in rats after rhabdomyolysis, analyzes the DEPs of kidney, heart and lung, and determines the key role of Serpina3n in multiple organ injury caused by rhabdomyolysis. SIGNIFICANCE: This study comprehensively describes the functional and structural changes of kidney, heart and lung in rats after rhabdomyolysis, analyzes the DEPs of kidney, heart and lung, and determines the key role of Serpina3n in multiple organ injury caused by rhabdomyolysis.

A DNA-based and bifunctional nanomedicine for alleviating multi-organ injury in sepsis under diabetic conditions.

Sepsis, defined as a life-threatening organ dysfunction, is associated with increased mortality in individuals with diabetes mellitus. In sepsis under diabetic conditions (SUDC), the superimposed inflammatory response and excessive production of reactive oxygen species (ROS) can cause severe damage to the kidney and liver, making it challenging to effectively repair multi-organ injury. In this study, we report the development of a DNA-based bifunctional nanomedicine, termed IL10-rDON, generated by assembling interleukin 10 (IL10) with rectangular DNA origami nanostructures (rDON) to address multi-organ dysfunction in SUDC. IL10-rDON was shown to predominantly accumulate in the kidney and liver of diabetic mice in vivo and effectively alleviate inflammatory responses through its anti-inflammatory IL10 component. In addition, the consumption of rDON itself significantly reduced excessive ROS in the liver and kidney. Serum and histological examinations further confirmed that IL10-rDON treatment could effectively improve liver and kidney function, as well as the survival of mice with SUDC. This study demonstrates an attractive antioxidant and anti-inflammatory nanomedicine for addressing acute liver and renal failure. The integration of rDON with therapeutic agents using DNA nanotechnology is a promising strategy for generating multifunctional nanomedicine to treat multi-organ dysfunction and other complicated diseases. STATEMENT OF SIGNIFICANCE: Sepsis under diabetic conditions (SUDC) leads to high mortality due to multiple organ failure such as acute liver and kidney injury. The anti-inflammatory cytokine interleukin 10 (IL10) holds great potential to treat SUDC, while disadvantages of IL-10 such as short half-life, non-specific distribution and lack of antioxidant activities limit its wide clinical applications. In this study, we developed a DNA-based, bifunctional nanomedicine (IL10-rDON) by assembling IL10 with rectangular DNA origami nanostructures (rDON). We found that IL10-rDON preferentially accumulated and sufficiently attenuated the increased levels of ROS and inflammation in the kidney and liver injury sites, and eventually improved the survival rate of mice with SUDC. Our finding provides new insights into the application of DNA-based nanomedicine in treating multi-organ failure.

Biochemical profiles and organ dysfunction in neonates with hypoxic-ischemic encephalopathy post-hoc analysis of the THIN trial.

BACKGROUND: Therapeutic hypothermia for infants with moderate to severe hypoxic-ischemic encephalopathy is well established as standard of care in high-income countries. Trials from low- and middle-income countries have shown contradictory results, and variations in the level of intensive care provided may partly explain these differences. We wished to evaluate biochemical profiles and clinical markers of organ dysfunction in cooled and non-cooled infants with moderate/severe hypoxic-ischemic encephalopathy. METHODS: This secondary analysis of the THIN (Therapeutic Hypothermia in India) study, a single center randomized controlled trial, included 50 infants with moderate to severe hypoxic-ischemic encephalopathy randomized to therapeutic hypothermia (n = 25) or standard care with normothermia (n = 25) between September 2013 and October 2015. Data were collected prospectively and compared by randomization groups. Main outcomes were metabolic acidosis, coagulopathies, renal function, and supportive treatments during the intervention. RESULTS: Cooled infants had lower pH than non-cooled infants at 6-12 h (median (IQR) 7.28 (7.20-7.32) vs 7.36 (7.31-7.40), respectively, p = 0.003) and 12-24 h (median (IQR) 7.30 (7.24-7.35) vs 7.41 (7.37-7.43), respectively, p < 0.001). Thrombocytopenia (< 100 000) was, though not statistically significant, twice as common in cooled compared to non-cooled infants (4/25 (16%) and 2/25 (8%), respectively, p = 0.67). No significant difference was found in the use of vasopressors (14/25 (56%) and 17/25 (68%), p = 0.38), intravenous bicarbonate (5/25 (20%) and 3/25 (12%), p = 0.70) or treatment with fresh frozen plasma (10/25 (40%) and 8/25 (32%), p = 0.56)) in cooled and non-cooled infants, respectively. Urine output < 1 ml/kg/h was less common in cooled infants compared to non-cooled infants at 0-24 h (7/25 (28%) vs. 16/23 (70%) respectively, p = 0.004). CONCLUSIONS: This post hoc analysis of the THIN study support that cooling of infants with hypoxic-ischemic encephalopathy in a level III neonatal intensive care unit in India was safe. Cooled infants had slightly lower pH, but better renal function during the first day compared to non-cooled infants. More research is needed to identify the necessary level of intensive care during cooling to guide further implementation of this neuroprotective treatment in low-resource settings. TRIAL REGISTRATION: Data from this article was collected during the THIN-study (Therapeutic Hypothermia in India; ref. CTRI/2013/05/003693 Clinical Trials Registry - India).

[Patients with Cirrhosis:Key Points for Management Before and After Use of a Cardiopulmonary Bypass].

Patients with cirrhosis have increased mortality and complication rates with increasing severity. The hyperdynamic circulatory state is associated with vasodilatation, and drastic changes in circulatory dynamics can induce multiple organ failures, including renal failure. Intensive perioperative systemic management is essential.

Novel Therapeutic Approaches in Treatment of Acute-on-Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF), a clinical syndrome that can develop at any stage in the progression of cirrhotic liver disease, is characterized by an acute decompensation in liver function with associated multiorgan failure and high short-term mortality. Current evidence points to ACLF being reversible, particularly in those at the lower end of the severity spectrum. However, there are no specific treatments for ACLF, and overall outcomes remain poor. Expedited liver transplantation as a treatment option is limited by organ shortage and a lack of priority allocation for this indication. Other options are therefore urgently needed, and our improved understanding of the condition has led to significant efforts to develop novel therapies. In conclusion, this review aims to summarize the current understanding of the pathophysiological processes involved in the onset, progression, and recovery of ACLF and discuss novel therapies under development.

Sepsis­induced cardiac dysfunction and pathogenetic mechanisms (Review).

Sepsis is a manifestation of the immune and inflammatory response to infection, which may lead to multi­organ failure. Health care advances have improved outcomes in critical illness, but it still remains the leading cause of death. Septic cardiomyopathy is heart dysfunction brought on by sepsis. Septic cardiomyopathy is a common consequence of sepsis and has a mortality rate of up to 70%. There is a lack of understanding of septic cardiomyopathy pathogenesis; knowledge of its pathogenesis and the identification of potential therapeutic targets may reduce the mortality rate of patients with sepsis and lead to clinical improvements. The present review aimed to summarize advances in the pathogenesis of cardiac dysfunction in sepsis, with a focus on mitochondrial dysfunction, metabolic changes and cell death modalities and pathways. The present review summarized diagnostic criteria and outlook for sepsis treatment, with the goal of identifying appropriate treatment methods for this disease.

Antitubercular therapy causing drug reaction with eosinophilia and systemic symptoms manifesting multi-organ dysfunction syndrome and death in an elderly patient: A case report with review of literature.

We present the case of a drug reaction with eosinophilia and systemic symptoms (DRESS) manifesting multi-organ dysfunction syndrome (MODS) that led to death in an elderly patient during the intensive phase of antitubercular therapy (ATT). A 74-year-old male developed skin rash (morbilliform), patchy erythematous macules, pustular-purpuric nonblanching spots, fever, lymphadenopathy, liver dysfunction, leukocytosis, and eosinophilia during intensive phase of ATT (ATT: day 45). Laboratory tests revealed hypereosinophilia (eosinophils; 10500/µL), hyperacute fulminant hepatic failure (aspartate transaminase/alanine transaminase; 1444/1375 IU/L, total bilirubin; 11.3 mg/dL), hepatic encephalopathy (Child-Pugh score: 15), coagulopathy (international normalized ratio; 3.0 and activated partial thromboplastin time; 52 s), and acute renal failure (serum creatinine; 2.6 mg/dL). The patient was diagnosed with DRESS with a RegiSCAR score of 7 (definite). ATT was discontinued. Despite immediate treatment with pulse methylprednisolone, N-acetylcysteine and sustained low-efficiency dialysis, the patient's clinical condition evolved to shock due to MODS (sequential organ failure Assessment: 15 points), and on day 51, he succumbed. Concluding, an elderly patient with high-dose antitubercular drugs needs a clinical management review. Clinical symptoms pertaining to DRESS may paradoxically worsen after 3-4 days of discontinuation of the offending drug.

Impaired microvascular circulation in distant organs following renal ischemia.

Mortality in acute kidney injury (AKI) patients remains very high, although very important advances in understanding the pathophysiology and in diagnosis and supportive care have been made. Most commonly, adverse outcomes are related to extra-renal organ dysfunction and failure. We and others have documented inflammation in remote organs as well as microvascular dysfunction in the kidney after renal ischemia. We hypothesized that abnormal microvascular flow in AKI extends to distant organs. To test this hypothesis, we employed intravital multiphoton fluorescence imaging in a well-characterized rat model of renal ischemia/reperfusion. Marked abnormalities in microvascular flow were seen in every organ evaluated, with decreases up to 46% observed 48 hours postischemia (as compared to sham surgery, p = 0.002). Decreased microvascular plasma flow was found in areas of erythrocyte aggregation and leukocyte adherence to endothelia. Intravital microscopy allowed the characterization of the erythrocyte formations as rouleaux that flowed as one-dimensional aggregates. Observed microvascular abnormalities were associated with significantly elevated fibrinogen levels. Plasma flow within capillaries as well as microthrombi, but not adherent leukocytes, were significantly improved by treatment with the platelet aggregation inhibitor dipyridamole. These microvascular defects may, in part, explain known distant organ dysfunction associated with renal ischemia. The results of these studies are relevant to human acute kidney injury.

Predictive performance of multiple organ dysfunction in asphyxiated newborns treated with therapeutic hypothermia on 24-month outcome: a cohort study.

BACKGROUND: Perinatal asphyxia may be followed by multiple organ dysfunction (MOD) and is often included in prognostication of the individual patient, but evidence of discriminating accuracy is lacking. The aim of this study was to assess whether MOD in asphyxiated neonates during therapeutic hypothermia (TH) predicts mortality or neurodevelopmental impairment (NDI) at 24 months of age and which peripartum variables are associated with the onset of MOD. METHODS: A retrospective analysis of a prospective cohort study of asphyxiated newborns undergoing TH was performed. MOD was defined as dysfunction of the brain (encephalopathy) combined with two or more organ systems. Outcome was routinely assessed by standardised developmental testing at the age of 24 months. The predictive accuracy of MOD on the combined outcome and its components (death and NDI) was expressed as areas under the receiver operating characteristic curves (AUROCs). The associations of peripartum variables and development of MOD were expressed as ORs and their CIs. RESULTS: 189 infants (median gestation 40 (range 36-42 weeks) with moderate to severe hypoxic ischaemic encephalopathy were included. 47% developed MOD. The prediction of the combined 24-month outcome or its components showed AUROCs <0.70. Associated with MOD were pH at birth (OR 0.97, CI 0.95 to 0.99), lactate at birth (OR 1.09, CI 1.04 to 1.15), Base Excess (BE) at birth (OR 0.94, CI 0.90 to 0.99) and epinephrine administration during resuscitation (OR 2.09, CI 1.02 to 4.40). CONCLUSION: MOD has a low discriminating accuracy in predicting mortality or NDI at 24 months age and might not be useful for prognostication. Signs of acid-base disturbance and adrenalin use at birth are associated with the development of MOD.

A 52-Year-Old Diabetic Man with Poor Dental Hygiene, Right Dental Abscess, and Parapharyngeal Abscess with Gas Gangrene Due to Klebsiella pneumoniae Infection, Presenting with Septic Shock and Multiorgan Failure, Who Recovered After Surgical Neck Debridement.

BACKGROUND Gas gangrene is a rapidly progressive and potentially fatal infection that is common in the extremities. Gas gangrene of the head and neck is a very rare condition, and non-clostridial gas-forming neck abscess caused by Klebsiella pneumoniae is unusual. This report is of a diabetic man with poor dental hygiene, a right dental abscess, and parapharyngeal abscess with gas gangrene due to Klebsiella pneumoniae infection, presenting with septic shock and multiorgan failure, who recovered after surgical neck debridement. CASE REPORT A 52-year-old man with diabetes mellitus lost consciousness and collapsed on a curbside. He presented with painful swelling of the right-side neck, associated with spiking fever, confusion, dyspnea, and stridor. He had right submandibular and supraclavicular swelling with crepitus, multiple dental caries, and multiorgan dysfunction, and was intubated. A computed tomography scan showed a gas-forming abscess in the right parapharyngeal, retropharyngeal, and paralaryngeal spaces and dense infiltration with pleural effusion in the upper lobes. Neck exploration was performed for drainage. Necrotic tissue and foul-smelling pus were debrided and drained. Gram stain showed gram-negative bacilli. Necrotic tissue, pus, and blood culture showed Klebsiella pneumoniae. He remained on intravenous meropenem for 14 days and was frequently debrided with irrigation until the infection subsided. Finally, normal physiologic functions of the failing organ system were restored. CONCLUSIONS We present a rare case of Klebsiella pneumoniae infection causing gas gangrene in the deep neck spaces, leading to septic shock and multiorgan failure, who recovered after surgical neck debridement. This is a potentially fatal condition that requires emergency drainage because of its high mortality rate.

IV Vitamin C in Adults With Sepsis: A Bayesian Reanalysis of a Randomized Controlled Trial.

OBJECTIVES: The Lessening Organ Dysfunction with Vitamin C trial showed a harmful effect of vitamin C on 28-day death or persistent organ dysfunction. To maximize interpretation, we present a post hoc Bayesian reanalysis. DESIGN: Bayesian reanalysis of a randomized placebo-controlled trial. SETTING: Thirty-five ICUs. PATIENTS: Adults with proven or suspected infection, vasopressor support, and no more than 24 hours of ICU admission. INTERVENTIONS: Patients were allocated to receive either vitamin C (50 mg/kg of body weight) or placebo every 6 hours for up to 96 hours. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the composite of death or persistent organ dysfunction (i.e., vasopressor use, invasive mechanical ventilation, or new renal replacement therapy) at 28 days. We used Bayesian log-binomial models with random effects for hospital site and varying informative prior beliefs for the effect of vitamin C to estimate risk ratios (RRs) with 95% credible intervals (Crls) in the intention to treat population (vitamin C, 435 patients; placebo, 437 patients). Using weakly neutral priors, patients allocated to vitamin C had a higher risk of death or persistent organ dysfunction at 28 days (RR, 1.20; 95% Crl, 1.04-1.39; probability of harm, 99%). This effect was consistent when using optimistic (RR, 1.14; 95% Crl, 1.00-1.31; probability of harm, 98%) and empiric (RR, 1.09; 95% Crl, 0.97-1.22; probability of harm, 92%) priors. Patients allocated to vitamin C also had a higher risk of death at 28 days under weakly neutral (RR, 1.17; 95% Crl, 0.98-1.40; probability of harm, 96%), optimistic (RR, 1.10; 95% Crl, 0.94-1.30; probability of harm, 88%), and empiric (RR, 1.05; 95% Crl, 0.92-1.19; probability of harm, 76%) priors. CONCLUSIONS: The use of vitamin C in adult patients with proven or suspected infection and vasopressor support is associated with high probability of harm.

Cachexia: A systemic consequence of progressive, unresolved disease.

Cachexia, a systemic wasting condition, is considered a late consequence of diseases, including cancer, organ failure, or infections, and contributes to significant morbidity and mortality. The induction process and mechanistic progression of cachexia are incompletely understood. Refocusing academic efforts away from advanced cachexia to the etiology of cachexia may enable discoveries of new therapeutic approaches. Here, we review drivers, mechanisms, organismal predispositions, evidence for multi-organ interaction, model systems, clinical research, trials, and care provision from early onset to late cachexia. Evidence is emerging that distinct inflammatory, metabolic, and neuro-modulatory drivers can initiate processes that ultimately converge on advanced cachexia.

Multi-organ dysfunction in infants with acidosis at birth in the absence of moderate to severe hypoxic ischemic encephalopathy.

INTRODUCTION: Infants with perinatal asphyxia are at risk for organ failure aside from the brain, regardless of the severity of the asphyxial insult. We aimed to evaluate the presence of organ dysfunction other than the brain in newborns with moderate to severe acidosis at birth, in the absence of moderate to severe hypoxic ischemic encephalopathy. MATERIALS AND METHODS: Data of 2 years were retrospectively recorded. Late preterm and term infants admitted to the intensive care unit with ph < 7.10 and BE < -12 mmol/l in the first hour were included in the absence of moderate to severe hypoxic ischemic encephalopathy. Respiratory dysfunction, hepatic dysfunction, renal dysfunction, myocardial depression, gastrointestinal problems, hematologic system dysfunction, and circulatory failure were evaluated. RESULTS: Sixty-five infants were included [39 (37-40) weeks, 3040 (2655-3380) grams]. Fifty-six (86 %) infants had one or more dysfunction in any system [respiratory: 76.9 %, hepatic: 20.0 %, coagulation: 18.5 %, renal: 9.2 %, hematologic: 7.7 %, gastrointestinal: 3.0 %, and cardiac: 3.0 %]. Twenty infants had at least two affected systems. The incidence of coagulation dysfunctions was higher in the infants with severe acidosis (n = 25, ph < 7.00) than the infants with moderate acidosis (n = 40: pH = 7.00-7.10); 32 % vs 10 %; p = 0.03. CONCLUSIONS: Moderate to severe fetal acidosis is associated with the development of extra-cranial organ dysfunctions in infants who do not require therapeutic hypothermia. A monitoring protocol is needed for infants with mild asphyxia in order to identify and manage potential complications. Coagulation system should be carefully evaluated.

Sepsis heterogeneity.

BACKGROUND: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, with extremely high mortality. Notably, sepsis is a heterogeneous syndrome characterized by a vast, multidimensional array of clinical and biologic features, which has hindered advances in the therapeutic field beyond the current standards. DATA SOURCES: We used PubMed to search the subject-related medical literature by searching for the following single and/or combination keywords: sepsis, heterogeneity, personalized treatment, host response, infection, epidemiology, mortality, incidence, age, children, sex, comorbidities, gene susceptibility, infection sites, bacteria, fungi, virus, host response, organ dysfunction and management. RESULTS: We found that host factors (age, biological sex, comorbidities, and genetics), infection etiology, host response dysregulation and multiple organ dysfunctions can all result in different disease manifestations, progression, and response to treatment, which make it difficult to effectively treat and manage sepsis patients. CONCLUSIONS: Herein, we have summarized contributing factors to sepsis heterogeneity, including host factors, infection etiology, host response dysregulation, and multiple organ dysfunctions, from the key elements of pathogenesis of sepsis. An in-depth understanding of the factors that contribute to the heterogeneity of sepsis will help clinicians understand the complexity of sepsis and enable researchers to conduct more personalized clinical studies for homogenous patients.

Perioperative Nutritional Status and Organ Dysfunction Following Surgery for Congenital Heart Disease.

Children with congenital heart disease (CHD) are at risk of malnutrition; however, there is limited information regarding the impact of nutritional status on organ dysfunction and outcomes after surgery for CHD. The study aim was to assess the association between malnutrition, organ dysfunction, and outcomes after surgery for CHD. Retrospective cohort study of patients aged 30 days to 18 years admitted to the cardiac intensive care unit (CICU) following cardiac surgery. Nutritional status (malnutrition defined as weight for age z-score < - 2) and validated organ dysfunction scores (pSOFA and PELOD-2) on CICU days 1 and 3 were collected. The cohort included 967 patients with a median age of 2.8 years (IQR 0.46, 7.12) and hospital survival of 98.86%. The prevalence of malnutrition was 18.5% (n = 179). By multivariable logistic regression analysis including age, malnutrition, cardiopulmonary bypass time, and duration of mechanical ventilation; High STAT category (OR 7.51 [1.03-54], p = 0.0462) and PSOFA score > 5 day 1 (OR 1.84 [1.25-2.72], p = 0.0021) were associated with mortality; in a similar model including the same variables; High STAT category (OR 9.12 [1.33-62], p = 0.0243) and PELOD-2 score > 5 day 1 (OR 1.75 [1.10-2.77], p = 0.0175) were associated with mortality. Malnutrition was associated with persistent or worsening organ dysfunction by pSOFA (p < 0.05) and PELOD-2 (p < 0.01) on day 3. Malnutrition was present in infants and children undergoing surgery for congenital heart disease. Organ dysfunction and high surgical risk were associated with mortality. Malnutrition was not associated with mortality but was associated with postoperative organ dysfunction.

Management of cardiovascular surgery in patients with systemic lupus erythematosus including thromboembolism and multiple organ failure prevention: A retrospective observational study.

Systemic lupus erythematosus is a chronic autoimmune disease that affects most tissues. Cardiovascular events are critical, life-threatening, long-term complications of systemic lupus erythematosus (SLE). We report our single-center experience of performing cardiovascular surgery in patients with SLE while avoiding postoperative complications. We also suggest a new approach for cardiopulmonary bypass and perioperative management. We applied the antiphospholipid antibody syndrome (APS) severity classification published by the Japan Intractable Disease Information Center to patients with SLE for perioperative management. Patients with Grade III or higher severity are treated with a slightly relaxed version of catastrophic APS therapy. This treatment modality includes glucocorticoids, anticoagulation, intravenous immunoglobulin, and plasma exchange. Between April 2010 and January 2021, 26 patients (2 males, 24 females) with SLE underwent cardiovascular surgery. The mean age was 74.2 ± 13.0 years (38-84 years). The primary outcomes were in-hospital mortality and long-term results, and the secondary outcomes were related to bleeding/embolization and coagulation function/platelet count. A subset analysis was performed to examine treatment efficacy in the APS Grade III or higher group. Of the 26 patients, 17 underwent valve surgery, 4 underwent isolated coronary artery bypass grafting, and 5 underwent thoracic aortic aneurysm surgery. There were no in-hospital deaths or associated bleeding/embolic complications. Postoperative antithrombin III decreased in patients who underwent valvular and aortic surgery, and platelet counts recovered to preoperative levels within 7 to 10 days. The 5- and 10-year survival rates were 80.5% and 53.7%, respectively. In addition, there were 10 patients with APS Grade III or higher, but there was no significant difference in the frequency of complications other than platelet recovery after treatment. The surgical outcome of open-heart surgery in patients with SLE was good. Surgical treatment of cardiovascular disease in these patients is difficult and complex. We focused on blood coagulation abnormalities and treated each patient by selecting the best individual treatment protocol according to the severity of the disease, taking into account the risk of bleeding and thrombosis. Management of blood coagulation function in these patients is essential, and careful therapeutic management should be considered during open-heart surgery.

Fatal complication caused by laxative suppository agent on pediatric patient with hydrocephalus on ventriculo-peritoneal shunt: a case report.

INTRODUCTION: Laxative suppository agent is oftenly used for patient with constipation due to its effectiveness and rapid onset. However, beside the benefit of the drugs, it could cause several side effects which could lead to life-threatening complication. In this report, we present a rare case of laxative's side effect that leads to fatal complication in pediatric patient with history of hydrocephalus and ventriculo-peritoneal (VP) shunt placement. CASE REPORT: An 11 years old boy admitted with general weakness, low nutrition intake, and constipation for 4 days. Patient had a history of VP shunt surgery at half months old due to congenital hydrocephalus. Abdominal X-ray found colon dilatation and fecal material collection. Laxative suppository agent was given to the patient. An hour after the treatment, patient had an abdominal pain followed by defecation, and 30 min after defecation, patient was unresponsive with irregular breathing followed by cardiac arrest. Code blue was activated and resuscitation was done for about 40 min, and patient did not respond to resuscitation and pronounced dead 2.5 h after drug's administration. DISCUSSION: The pathophysiology of this complication is related with elevated intraabdominal pressure that caused abdominal compartment syndrome (ACS), and this condition could lead to several organ dysfunction such as cardiopulmonary and abdominal organ dysfunction inducing central nervous system impairment through raised intracranial pressure (ICP). Pediatric patient with history of hydrocephalus on VP shunt could have a low brain compliance and very susceptible to fatal complication due to acute raised of ICP. CONCLUSION: Laxative suppository agent on pediatric patient with hydrocephalus on VP shunt could lead to fatal complication through ACS and acute elevated ICP pressure. Oral laxative agent should be chosen in constipated patient with neurologic preexisting condition, and patient should be closely monitored if suppository agent is given.