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.

Exosomal mediators in sepsis and inflammatory organ injury: unraveling the role of exosomes in intercellular crosstalk and organ dysfunction.

Sepsis, a severe systemic inflammatory response to infection, remains a leading cause of morbidity and mortality worldwide. Exosomes, as mediators of intercellular communication, play a pivotal role in the pathogenesis of sepsis through modulating immune responses, metabolic reprogramming, coagulopathy, and organ dysfunction. This review highlights the emerging significance of exosomes in these processes. Initially, it provides an in-depth insight into exosome biogenesis and characterization, laying the groundwork for understanding their diverse and intricate functions. Subsequently, it explores the regulatory roles of exosomes in various immune cells such as neutrophils, macrophages, dendritic cells, T cells, and B cells. This analysis elucidates how exosomes are pivotal in modulating immune responses, thus contributing to the complexity of sepsis pathophysiology. Additionally, this review delves into the role of exosomes in the regulation of metabolism and subsequent organ dysfunction in sepsis. It also establishes a connection between exosomes and the coagulation cascade, which affects endothelial integrity and promotes thrombogenesis in sepsis. Moreover, the review discusses the dual role of exosomes in the progression and resolution of sepsis, exploring their complex involvement in inflammation and healing processes. Furthermore, it underscores their potential as biomarkers and therapeutic targets. Understanding these mechanisms presents new opportunities for novel interventions to mitigate the severe outcomes of sepsis, emphasizing the therapeutic promise of exosome research in critical care settings.

The physiology of venoarterial extracorporeal membrane oxygenation - A comprehensive clinical perspective.

Venoarterial extracorporeal membrane oxygenation (VA ECMO) has become a standard of care for severe cardiogenic shock, refractory cardiac arrest and related impending multiorgan failure. The widespread clinical use of this complex temporary circulatory support modality is still contrasted by a lack of formal scientific evidence in the current literature. This might at least in part be attributable to VA ECMO related complications, which may significantly impact on clinical outcome. In order to limit adverse effects of VA ECMO as much as possible an indepth understanding of the complex physiology during extracorporeally supported cardiogenic shock states is critically important. This review covers all relevant physiological aspects of VA ECMO interacting with the human body in detail. This, to provide a solid basis for health care professionals involved in the daily management of patients supported with VA ECMO and suffering from cardiogenic shock or cardiac arrest and impending multiorgan failure for the best possible care.

Facial appearance associates with longitudinal multi-organ failure: an ICU cohort study.

BACKGROUND: Facial appearance, whether consciously or subconsciously assessed, may affect clinical assessment and treatment strategies in the Intensive Care Unit (ICU). Nevertheless, the association between objective clinical measurement of facial appearance and multi-organ failure is currently unknown. The objective of this study was to examine whether facial appearance at admission is associated with longitudinal evaluation of multi-organ failure. METHODS: This was a sub-study of the Simple Intensive Care Studies-II, a prospective observational cohort study. All adult patients acutely admitted to the ICU between March 26, 2019, and July 10, 2019, were included. Facial appearance was assessed within three hours of ICU admission using predefined pictograms. The SOFA score was serially measured each day for the first seven days after ICU admission. The association between the extent of eye-opening and facial skin colour with longitudinal Sequential Organ Failure Assessment (SOFA) scores was investigated using generalized estimation equations. RESULTS: SOFA scores were measured in 228 patients. Facial appearance scored by the extent of eye-opening was associated with a higher SOFA score at admission and follow-up (unadjusted 0.7 points per step (95%CI 0.5 to 0.9)). There was no association between facial skin colour and a worse SOFA score over time. However, patients with half-open or closed eyes along with flushed skin had a lower SOFA score than patients with a pale or normal facial skin colour (P-interaction < 0.1). CONCLUSIONS: The scoring of patients' facial cues, primarily the extent of eye-opening and facial colour, provided valuable insights into the disease state and progression of the disease of critically ill patients. The utilization of advanced monitoring techniques that incorporate facial appearance holds promise for enhancing future intensive care support.

Hepatic portal venous gas initially manifesting as severe shock: a case series.

Hepatic portal venous gas is often referred to as the "sign of death" because it signifies a very poor prognosis if appropriate treatments are not promptly administered. The etiologies of hepatic portal venous gas are diverse and include severe complex abdominal infections, mesenteric ischemia, diving, and complications of endoscopic surgery, and the clinical manifestations are inconsistent among individual patients. Thus, whether emergency surgery should be performed remains controversial. In this report, we present three cases of hepatic portal venous gas. The patients initially exhibited symptoms consistent with severe shock of unknown etiology and were treated in the intensive care unit upon admission. We rapidly identified the cause of each individual patient's condition and selected problem-directed intervention measures based on active organ support, antishock support, and anti-infection treatments. Two patients recovered and were discharged without sequelae, whereas one patient died of refractory infection and multiple organ failure. We hope that this report will serve as a valuable reference for decision-making when critical care physicians encounter similar patients.

A woman in her fifties with a post-operative infection, generalised rash and organ failure. / En kvinne i 50-årene med postoperativ infeksjon, generalisert utslett og organsvikt.

Background: Toxic shock syndrome (TSS) is a rare but potentially life-threatening disease caused by superantigen-producing Gram-positive bacteria such as Staphylococcus aureus and Streptococcus pyogenes. Staphylococcal TSS received special attention from 1978 to 1981, when an epidemic was observed associated with the use of hyper-absorbent tampons. Today the disease is rare and generally not related to menstruation, but can occur postpartum or in post-surgical wounds, intrauterine devices (IUDs), burns or other soft tissue injuries, mastitis or other focal infections. The annual incidence of staphylococcal TSS is around 0.5/100 000 and around 0.4/100 000 for streptococcal TSS. The mortality in menstrual-related cases is < 5 % and up to 22 % in non-menstrual related cases. Case presentation: This article presents a case of a middle-aged woman who developed symptoms of toxic shock syndrome five days after elective breast cancer surgery, with high fever, multiorgan failure and a characteristic desquamation of the palms. Interpretation: Toxic shock syndrome is a potentially lethal, toxin-mediated disease. Symptoms develop quickly, within hours. Early recognition and appropriate surgical management, intensive care and antibiotics are therefore important to reduce mortality and sequelae.

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.

[Research progress on the organ-protective effect of Maresin-1 in sepsis].

Sepsis is a fatal organ dysfunction caused by the uncontrolled inflammatory response of the host to infection. Excessive inflammatory reaction is the core factor in the occurrence and development of sepsis, the degree of organ dysfunction is directly related to the prognosis of sepsis. Timely intervention of excessive inflammatory response and alleviation of organ function damage are essential to improve the prognosis of sepsis. Maresin-1 (MaR-1) is a newly discovered endogenous specific pro-inflammatory resolution mediator, which plays a role of anti-inflammatory, pro-inflammatory regression and organ protection in sepsis, and may be a new target for the treatment of sepsis. This article reviews the research progress of the role of MaR-1 in the regulation of inflammation and organ protection in sepsis, in order to provide reference for the clinical development of new drugs for the treatment of sepsis.

[Molecular mechanisms underlying the pathogenesis of septic multiple organ failure].

Sepsis is defined as the body's overwhelming and life-threatening response to infection that can lead to tissue damage, organ failure, and death. Since bacterial infection is one of the main causes of sepsis, appropriate antimicrobial therapy remains the cornerstone of sepsis and septic shock management. However, since sepsis is a multifaceted chaos involving inflammation and anti-inflammation disbalance leading to the unregulated widespread release of inflammatory mediators, cytokines, and pathogen-related molecules leading to system-wide organ dysfunction, the whole body control to prevent the progression of organ dysfunction is needed. In sepsis and septic shock, pathogen-associated molecular patterns (PAMPs), such as bacterial exotoxins, cause direct cellular damage and/or trigger an immune response in the host. PAMPs are recognized by pattern recognizing receptors (PRRs) expressed on immune-reactive cells. PRRs are also activated by host nuclear, mitochondrial, and cytosolic proteins, known as damage-associated molecular patterns (DAMPs) that are released from cells during sepsis. Thus, most PRRs respond to PAMPs or DAMPs by triggering activation of transcriptional factors, NF-κB, AP1, and STAT-3. On the other hand, sepsis leads to immune (lymphocytes and macrophages) and nonimmune (endothelial and epithelial cells) cell death. Apoptosis has been the major focus of research on cell death in sepsis, but autophagy, necrosis, necroptosis, pyroptosis, NETosis, and ferroptosis may also play an important role in this critical situation. The recent development in our understanding regarding the cellular pathogenesis of sepsis will help in developing new treatment of sepsis.

Case report of scrub typhus complicated by hypokalemia and multiple organ dysfunction syndrome.

CONTEXT: Scrub typhus, caused by Orientia tsutsugamushi, has a wide range of clinical manifestations, including meningoencephalitis, acute renal failure, pneumonitis, myocarditis, and septic shock. However, there are no documented cases of scrub typhus with hypokalemia. In this report, we present a case of scrub typhus with hypokalemia and multiple organ failure syndrome, highlighting the importance of electrolyte imbalance in patients with scrub typhus. CASE REPORT: A 59-year-old woman presented to the emergency department with abdominal pain that had been present for 1 day. On admission, the physical examination and laboratory test results indicated that the patient had renal, liver, and circulatory failure, and hypokalemia. She developed meningitis and disseminated intravascular coagulation during hospitalization. She recovered with appropriate management, and was discharged on day 17. CONCLUSION: This report highlights the potential for atypical presentations of scrub typhus, including a previously undocumented association with hypokalemia. Although the contribution of hypokalemia to the patient's clinical course remains uncertain, this case underscores the importance of considering electrolyte imbalance in the management of patients with scrub typhus. Further research is warranted to better understand the relationship between scrub typhus and electrolyte imbalance.

Ward monitoring 4.0: real-time metabolic insights from continuous glucose monitoring into perioperative organ dysfunction.

The now-routine clinical deployment of continuous glucose monitoring has demonstrated benefit in real-world settings. We make the case that continuous glucose monitoring can help re-examine, at scale, the role that (stress) hyperglycaemia plays in fuelling organ dysfunction after tissue trauma. Provided robust perioperative data do emerge, well-established continuous glucose monitoring technology could soon help transform the perioperative landscape.

Unraveling the role of HIF-1α in sepsis: from pathophysiology to potential therapeutics-a narrative review.

Sepsis is characterized by organ dysfunction resulting from a dysregulated inflammatory response triggered by infection, involving multifactorial and intricate molecular mechanisms. Hypoxia-inducible factor-1α (HIF-1α), a notable transcription factor, assumes a pivotal role in the onset and progression of sepsis. This review aims to furnish a comprehensive overview of HIF-1α's mechanism of action in sepsis, scrutinizing its involvement in inflammatory regulation, hypoxia adaptation, immune response, and organ dysfunction. The review encompasses an analysis of the structural features, regulatory activation, and downstream signaling pathways of HIF-1α, alongside its mechanism of action in the pathophysiological processes of sepsis. Furthermore, it will delve into the roles of HIF-1α in modulating the inflammatory response, including its association with inflammatory mediators, immune cell activation, and vasodilation. Additionally, attention will be directed toward the regulatory function of HIF-1α in hypoxic environments and its linkage with intracellular signaling, oxidative stress, and mitochondrial damage. Finally, the potential therapeutic value of HIF-1α as a targeted therapy and its significance in the clinical management of sepsis will be discussed, aiming to serve as a significant reference for an in-depth understanding of sepsis pathogenesis and potential therapeutic targets, as well as to establish a theoretical foundation for clinical applications.

Severe Sepsis During Treatment for Childhood Leukemia and Sequelae Among Adult Survivors.

Importance: Children undergoing treatment for leukemia are at increased risk of severe sepsis, a dysregulated immune response to infection leading to acute organ dysfunction. As cancer survivors, they face a high burden of long-term adverse effects. The association between sepsis during anticancer therapy and long-term organ dysfunction in adult survivors of childhood cancer has not been examined. Objective: To determine whether severe sepsis during therapy for leukemia in childhood is associated with subsequent chronic health conditions in adult survivors. Design, Setting, and Participants: This cohort study included 644 adult survivors of childhood leukemia who were diagnosed between January 1, 1985, and July 19, 2010, and participated in the St Jude Lifetime Cohort Study. Participants were excluded if they received hematopoietic cell transplant or had relapsed leukemia. Data collection ended June 30, 2017. Data were analyzed from July 1, 2020, to January 5, 2024. Exposures: Severe sepsis episodes, defined according to consensus criteria as septic shock, acute respiratory distress syndrome, or multiorgan dysfunction associated with infection occurring during anticancer therapy, were abstracted by medical record review for all participants. Main Outcomes and Measures: Common Terminology Criteria for Adverse Events-defined chronic health condition outcomes were independently abstracted. Associations between sepsis and cumulative incidence of chronic health conditions (eg, cardiovascular, pulmonary, kidney, neurological, and neurocognitive outcomes) were compared by adjusted hazard ratios from Cox proportional hazards logistic regression. Inverse propensity score weighting was used to adjust for potential confounders, including age, year of diagnosis, and leukemia type. Results: The study sample consisted of 644 adult survivors of pediatric leukemia (329 women [51.1%] and 315 men [48.9%]; including 56 with a history of acute myeloid leukemia and 585 with a history of acute lymphoblastic leukemia) who were most recently evaluated at a median age of 24.7 (IQR, 21.2-28.3) years at a median time after leukemia diagnosis of 17.3 (IQR, 13.7-21.9) years. Severe sepsis during treatment of acute childhood leukemia occurred in 46 participants (7.1%). Participants who experienced severe sepsis during treatment were more likely to develop moderate to severe neurocognitive impairment (29 of 46 [63.0%] vs 310 of 598 [51.8%]; adjusted hazard ratio, 1.86 [95% CI, 1.61-2.16]; P < .001) significantly affecting attention, executive function, memory and visuospatial domains. Sepsis was not associated with long-term risk of cardiovascular, pulmonary, kidney, or neurological chronic health conditions. Conclusions and Relevance: In this cohort study of long-term outcomes in survivors of pediatric leukemia, severe sepsis during anticancer therapy for leukemia was associated with a selectively increased risk for development of serious neurocognitive sequelae. Efforts to reduce the effects of anticancer therapy on long-term function and quality of life in survivors might include prevention of severe sepsis during therapy and early detection or amelioration of neurocognitive deficits in survivors of sepsis.

Microcirculation-driven mitochondrion dysfunction during the progression of experimental sepsis.

Sepsis is accompanied by a less-known mismatch between hemodynamics and mitochondrial respiration. We aimed to characterize the relationship and time dependency of microcirculatory and mitochondrial functions in a rodent model of intraabdominal sepsis. Fecal peritonitis was induced in rats, and multi-organ failure (MOF) was evaluated 12, 16, 20, 24 or 28 h later (n = 8/group, each) using rat-specific organ failure assessment (ROFA) scores. Ileal microcirculation (proportion of perfused microvessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI)) was monitored by intravital video microscopy, and mitochondrial respiration (OxPhos) and outer membrane (mtOM) damage were measured with high-resolution respirometry. MOF progression was evidenced by increased ROFA scores; microcirculatory parameters followed a parallel time course from the 16th to 28th h. Mitochondrial dysfunction commenced with a 4-h time lag with signs of mtOM damage, which correlated significantly with PPV, while no correlation was found between HI and OxPhos. High diagnostic value was demonstrated for PPV, mtOM damage and lactate levels for predicting MOF. Our findings indicate insufficient splanchnic microcirculation to be a possible predictor for MOF that develops before the start of mitochondrial dysfunction. The adequate subcellular compensatory capacity suggests the presence of mitochondrial subpopulations with differing sensitivity to septic insults.

Should Glucokinase be Given a Chance in Diabetes Therapeutics? A Clinical-Pharmacological Review of Dorzagliatin and Lessons Learned So Far.

Despite advances in the management of type 2 diabetes mellitus (T2DM), one-third of patients with diabetes do not achieve the desired glycemic goal. Considering this inadequacy, many agents that activate glucokinase have been investigated over the last two decades but were withdrawn before submission for marketing permission. Dorzagliatin is the first glucokinase activator that has been granted approval for T2DM, only in China. As overstimulation of glucokinase is linked with pathophysiological disturbances such as fatty liver and cardiovascular issues and a loss of therapeutic efficacy with time. This review aims to highlight the benefits of glucokinase activators vis-à-vis the risks associated with chronic enzymatic activation. We discuss the multisystem disturbances expected with chronic activation of the enzyme, the lessons learned with glucokinase activators of the past, the major efficacy and safety findings with dorzagliatin and its pharmacological properties, and the status of other glucokinase activators in the pipeline. The approval of dorzagliatin in China was based on the SEED and the DAWN trials, the major pivotal phase III trials that enrolled patients with T2DM with a mean glycosylated hemoglobin of 8.3-8.4%, and a mean age of 53-54.5 years from multiple sites in China. Patients with uncontrolled diabetes, cardiac diseases, organ dysfunction, and a history of severe hypoglycemia were excluded. Both trials had a randomized double-blind placebo-controlled phase of 24 weeks followed by an open-label phase of 28 weeks with dorzagliatin. Drug-naïve patients with T2DM with a disease duration of 11.7 months were enrolled in the SEED trial while the DAWN trial involved patients with T2DM with a mean duration of 71.5 months and receiving background metformin therapy. Compared with placebo, the decline in glycosylated hemoglobin at 24 weeks was more with dorzagliatin with an estimated treatment difference of - 0.57% in the SEED trial and - 0.66% in the DAWN trial. The desired glycosylated hemoglobin (< 7%) was also attained at more than two times higher rates with dorzagliatin. The glycemic improvement was sustained in the SEED trial but decreased over 52 weeks in the DAWN trial. Hyperlipidemia was observed in 12-14% of patients taking dorzagliatin versus 9-11% of patients receiving a placebo. Additional adverse effects noticed over 52 weeks with dorzagliatin included an elevation in liver enzymes, hyperuricemia, hyperlacticacidemia, renal dysfunction, and cardiovascular disturbances. Considering the statistically significant improvement in glycosylated hemoglobin with dorzagliatin in patients with T2DM, the drug may be given a chance in treatment-naïve patients with a shorter disease history. However, with the waning therapeutic efficacy witnessed in patients with long-standing diabetes, which was also one of the potential concerns with previously tested molecules, extended studies involving patients with chronic and uncontrolled diabetes are needed to comment upon the long-term therapeutic performance of dorzagliatin. Likewise, evidence needs to be generated from other countries, patients with organ dysfunction, a history of severe hypoglycemia, cardiac diseases, and elderly patients before extending the use of dorzagliatin. Apart from monitoring lipid profiles, long-term safety studies of dorzagliatin should involve the assessment of serum uric acid, lactate, renal function, liver function, and cardiovascular parameters.

[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.

Stevens-Johnson syndrome and toxic epidermal necrolysis in Hong Kong.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) [hereafter, SJS/TEN] are uncommon but severe mucocutaneous reactions. Although they have been described in many populations worldwide, data from Hong Kong are limited. Here, we explored the epidemiology, disease characteristics, aetiology, morbidity, and mortality of SJS/TEN in Hong Kong. METHODS: This retrospective cohort study included all hospitalised patients who had been diagnosed with SJS/TEN in Prince of Wales Hospital from 1 January 2004 to 31 December 2020. RESULTS: There were 125 cases of SJS/TEN during the 17-year study period. The annual incidence was 5.07 cases per million. The mean age at onset was 51.4 years. The mean maximal body surface area of epidermal detachment was 23%. Overall, patients in 32% of cases required burns unit or intensive care unit admission. Half of the cases involved concomitant sepsis, and 23.2% of cases resulted in multiorgan failure or disseminated intravascular coagulation. The mean length of stay was 23.9 days. The cause of SJS/TEN was attributed to a drug in 91.9% of cases, including 84.2% that involved anticonvulsants, allopurinol, antibiotics, or analgesics. In most cases, patients received treatment comprising either best supportive care alone (35.2%) or combined with intravenous immunoglobulin (43.2%). The in-hospital mortality rate was 21.6%. Major causes of death were multiorgan failure and/or fulminant sepsis (81.5%). CONCLUSION: This study showed that SJS/TEN are uncommon in Hong Kong but can cause substantial morbidity and mortality. Early recognition, prompt withdrawal of offending agents, and multidisciplinary supportive management are essential for improving clinical outcomes.

Mortality and associated factors among children admitted to an intensive care unit in muhimbili national hospital, from the time of admission to three months after discharge: a prospective cohort study.

BACKGROUND: Mortality of children admitted to Intensive Care Units (ICU) is higher in low-to-middle-income countries (LMICs) as compared to high-income countries (HICs). There is paucity of information on outcomes following discharge from ICU, especially from sub-Saharan Africa region. This study was conducted to determine mortality and its associated factors among children admitted to Pediatric ICU (PICU) at Muhimbili National Hospital, from admission to three months after discharge. METHODOLOGY: This was a hospital-based prospective cohort study conducted between July 2021 and May 2022, among children admitted to PICU who were followed up for 3-month after discharge. Structured questionnaires were used to collect data from their medical charts. Telephone interviews were made after discharge. Medical records and verbal autopsy were used to determine the cause of death after discharge. Cox regression analysis was performed to assess the association between variables. A p-value of < 0.05 was considered statistically significant. Survival after PICU discharge was estimated by Kaplan - Meier curve. RESULTS: Of 323 children recruited, 177(54.8%) were male, with a median age of 17 months (1-168). The leading cause of PICU admission was severe sepsis 90/323(27.9%). A total of 161/323 children died, yielding an overall mortality of 49.8%. Of 173 children discharged from PICU, 33(19.1%) died. The leading cause of death among children who died in the general ward or as readmission into PICU was sepsis 4/17(23.5%). Respiratory diseases 4/16(25.0%) were the commonest cause of death among those who died after hospital discharge. Independent predictors of overall mortality included single organ dysfunction with hazard ratio(HR):5.97, 95% confidence interval (CI)(3.05-12.26)] and multiple organ dysfunction [HR:2.77,95%CI(1.03-2.21)]. Chronic illness[HR:8.13,95%CI(2.45-27.02)], thrombocytosis [HR:3.39,95%CI(1.32-8.73)], single[HR:3.57,95%CI(1.42-9.03)] and multiple organ dysfunction[HR:3.11,95%CI(1.01-9.61)] independently predicted post-PICU discharge mortality. CONCLUSION: Overall mortality and post- PICU discharge mortality were high and more likely to affect children with organ dysfunction, chronic illness, and thrombocytosis. The leading causes of mortality post- PICU discharge were sepsis and respiratory diseases. There is a need for a focused follow up plan of children post- PICU discharge, further research on the long term survival and strategies to improve it.