OBJECTIVE: To identify distinct phenotypes of critically ill leptospirosis patients upon ICU admission and their potential associations with outcome.
METHODS: Retrospective observational study including all patients with biologically confirmed leptospirosis admitted to the ICU between January 2014 and December 2022. Subgroups of patients with similar clinical profiles were identified by unsupervised clustering (factor analysis for mixed data and hierarchical clustering on principal components).
METHODS: All patients admitted to the ICU of the University Hospital of Guadeloupe on the study period.
METHODS: One hundred thirty critically ill patients with confirmed leptospirosis were included.
METHODS: None.
RESULTS: At ICU admission, 34% of the patients had acute respiratory failure, and 26% required invasive mechanical ventilation. Shock was observed in 52% of patients, myocarditis in 41%, and neurological involvement in 20%. Unsupervised clustering identified three clusters-\"Weil\'s Disease\" (48%), \"neurological leptospirosis\" (20%), and \"multiple organ failure\" (32%)-with different ICU courses and outcomes. Myocarditis and neurological involvement were key components for cluster identification and were significantly associated with death in ICU. Other factors associated with mortality included shock, acute respiratory failure, and requiring renal replacement therapy.
CONCLUSIONS: Unsupervised analysis of critically ill patients with leptospirosis revealed three patient clusters with distinct phenotypic characteristics and clinical outcomes. These patients should be carefully screened for neurological involvement and myocarditis at ICU admission.

We report a severe case of a 25-year-old girl presented with complaints of weakness, diarrhoea, vomiting, pain in abdomen and hypotension at Infectious Diseases and Clinical Immunology Research Center. From history on 25 February till 29 February she was in India and on 1 march this problem started with watery diarrhoea followed by vomiting. She ate pizza with mushroom following which her condition worsened. Stool culture revealed salmonella nontyphi (nonthyphodal Salmonella)and this is leading cause for gastroenteritis, bacteremia and affects several other bodily system. Her condition deteriorated due to the development of ARDS (acute respiratory distress syndrome) and for this she was on mechanical ventilation. Vitec machine was performed, which identified Salmonella typhi murium. Our goal is to manage and treat this patient well by early diagnosis. She was given ceftriaxone, iv fluids and symptomatic treatment but due to resistance meropenem was started and the patient\'s condition improved. From serology there was no evidence of immunocompromised state so being a severe case of immunocompetent patient this case reflects the importance of timely diagnosis and management together with food safety practices in population. On follow up she was stable and discharged after 3 weeks. Future research studies need to be continued regarding newer strains, effective treatment strategies and diagnostics to prevent morbidity and mortality.

A 19-year-old male patient with high-risk acute B-cell lymphoblastic leukemia received haploidentical stem cell transplantation. He developed anemia repeatedly and parvovirus B19 nucleic acid was positive in blood plasma. The patient was diagnosed with cold agglutinin syndrome and multiple organ dysfunction including respiratory failure and hepatitis. In the conflict between viral infection and the treatment of cold agglutinin syndrome, we provided supportive treatment, complement inhibitors to control hemolysis, and antiviral therapy. After timely glucocorticoid and immunosuppressant therapy, the patient had achieved a good response.
患者男性，19岁，高危急性B淋巴细胞白血病行单倍体异基因造血干细胞移植，移植后多次出现贫血，检测血细小病毒B19核酸阳性，随后出现冷凝集素综合征、多器官功能障碍（呼吸衰竭、肝脏损害等）。在病毒感染和冷凝集素综合征治疗矛盾情况下充分给予支持治疗、应用补体抑制剂控制溶血、坚持抗病毒治疗，适时加用糖皮质激素及免疫抑制剂，最终获得了较好的治疗效果。.

Background and Objectives: Prolidase deficiency (PD) is a rare, life-threatening, genetically determined disease with an incidence of 1-2 cases per 1 million births. The disease inhibits collagen synthesis, which leads to organ and systems failure, including hepato- and splenomegaly, immune disorders, chronic ulcerative wounds, respiratory infections, and pulmonary fibrosis. The complexity of the problems associated with this disease necessitates a comprehensive approach and the involvement of an interdisciplinary team. The objective was to present the treatment and care plan, as well as complications of PD, in a young woman following admission to an intensive care unit (ICU). Materials and Methods: A retrospective observational single-case study. Results: A 26-year-old woman with PD was hospitalized in the ICU for acute respiratory failure. The presence of difficult-to-heal extensive leg ulcers and the patient\'s immunocompromised condition resulted in the development of sepsis with multiple organ failure (respiratory and circulatory, liver and kidney failure). Complex specialized treatment consisting of wound preparation, limb amputation, the minimization of neuropathic pain, mechanical ventilation, renal replacement therapy, circulatory stabilization, and the prevention of complications of the disease and of therapy were applied. On the 83rd day of hospitalization, the patient expired. Conclusions: Despite the use of complex treatment and care, due to the advanced nature of the disease and the lack of therapies with proven efficacy, treatment was unsuccessful. There is a need for evidence-based research to develop effective treatment guidelines for PD.

OBJECTIVE: While cytokine response patterns are pivotal in mediating immune responses, they are also often dysregulated in sepsis and critical illness. We hypothesized that these immunological deficits, quantifiable through ex vivo whole blood stimulation assays, may be indicative of subsequent organ dysfunction.
METHODS: In a prospective observational study, adult septic patients and critically ill but nonseptic controls were identified within 48 hours of critical illness onset. Using a rapid, ex vivo assay based on responses to lipopolysaccharide (LPS), anti-CD3/anti-CD28 antibodies, and phorbol 12-myristate 13-acetate with ionomycin, cytokine responses to immune stimulants were quantified. The primary outcome was the relationship between early cytokine production and subsequent organ dysfunction, as measured by the Sequential Organ Failure Assessment score on day 3 of illness (SOFAd3).
METHODS: Patients were recruited in an academic medical center and data processing and analysis were done in an academic laboratory setting.
METHODS: Ninety-six adult septic and critically ill nonseptic patients were enrolled.
METHODS: None.
RESULTS: Elevated levels of tumor necrosis factor and interleukin-6 post-endotoxin challenge were inversely correlated with SOFAd3. Interferon-gamma production per lymphocyte was inversely related to organ dysfunction at day 3 and differed between septic and nonseptic patients. Clustering analysis revealed two distinct immune phenotypes, represented by differential responses to 18 hours of LPS stimulation and 4 hours of anti-CD3/anti-CD28 stimulation.
CONCLUSIONS: Our rapid immune profiling technique offers a promising tool for early prediction and management of organ dysfunction in critically ill patients. This information could be pivotal for early intervention and for preventing irreversible organ damage during the acute phase of critical illness.

Coagulopathy, microvascular alterations and concomitant organ dysfunctions are hallmarks of sepsis. Attempts to attenuate coagulation activation with an inhibitor of tissue factor (TF), i.e. tissue factor pathway inhibitor (TFPI), revealed no survival benefit in a heterogenous group of sepsis patients, but a potential survival benefit in patients with an international normalized ratio (INR) < 1.2. Since an increased TF/TFPI ratio determines the procoagulant activity specifically on microvascular endothelial cells in vitro, we investigated whether TF/TFPI ratio in blood is associated with INR alterations, organ dysfunctions, disseminated intravascular coagulation (DIC) and outcome in septic shock. Twenty-nine healthy controls (HC) and 89 patients with septic shock admitted to a tertiary ICU were analyzed. TF and TFPI in blood was analyzed and related to organ dysfunctions, DIC and mortality. Patients with septic shock had 1.6-fold higher levels of TF and 2.9-fold higher levels of TFPI than HC. TF/TFPI ratio was lower in septic shock compared to HC (0.003 (0.002-0.005) vs. 0.006 (0.005-0.008), p < 0.001). Non-survivors had higher TFPI levels compared to survivors (43038 (29354-54023) vs. 28041 (21675-46582) pg/ml, p = 0.011). High TFPI levels were associated with acute kidney injury, liver dysfunction, DIC and disease severity. There was a positive association between TF/TFPI ratio and troponin T (b = 0.531 (0.309-0.754), p < 0.001). A high TF/TFPI ratio is exclusively associated with myocardial injury but not with other organ dysfunctions. Systemic TFPI levels seem to reflect disease severity. These findings point towards a pathophysiologic role of TF/TFPI in sepsis-induced myocardial injury.

A 71-year-old male had disseminated multiple organ dysfunction syndrome (MODS). Following treatment with cefotaxime and piperacillin-tazobactam, his symptoms have worsened instead. Multiple organ failure caused by Japanese Spotted Fever (JSF) was diagnosed based on metagenomic next-generation sequencing (mNGS), we rapidly treated the patient with doxycycline. Thereafter, his symptoms gradually improved. In this report, we emphasized the importance of rapid microbial diagnostic tools and the early use of tetracyclines for the treatment of JSF.

UNASSIGNED: Acute pancreatitis (AP) scores need a battery of tests that are not helpful at an early stage. Can a single test predict Complicated Acute Pancreatitis (CAP) which includes moderate and severe AP, local complications, and need for intensive care unit (ICU).
UNASSIGNED: 30 patients of AP. D-dimer, C-reactive protein levels done within 3 days of AP onset. APACHE II, Ranson\'s score, CT severity index were done. Inhospital disease course for development of organ failure and need for ICU care was followed daily.
UNASSIGNED: D-dimer in CAP was 2732 ng/L (MAP 567 ng/L), in abnormal computed tomography (CT) was 1916 ng/L (normal CT 363 ng/L), and in organ failure was 4776 ng/L (776.5 ng/L absent organ failure). D-dimer increases as the severity of organ failure increases (P = 0.04). D-dimer in ICU patients was significantly elevated (P = 0.021). D-dimer correlates with APACHE II score well, with an increase in predictive mortality rate (P = 0.01). On receiver operator characteristics, D-dimer >933.5 ng/L predicts CAP, >827.5 ng/L predicts positive CT findings (local complications), and >1060.5 ng/L predicts the development of organ failure.
UNASSIGNED: Coagulopathy and microthrombi play a significant role in early pathogenesis. D-dimer test acts at the level of this core pathogenesis, even before the complications set in. D-dimer within 72 h of AP correlates well with the CT findings after 72 h. This is the first study that correlates D-dimer levels with CT scores, ICU requirement. D-dimer can guide primary care physicians in selecting AP patients for referral to a higher center in a resource-limited setting.

The kidney injury molecule (KIM)-1 is shed from proximal tubular cells in acute kidney injury (AKI), relaying tubular epithelial proliferation. Additionally, KIM-1 portends complex immunoregulation and is elevated after exposure to lipopolysaccharides. It thus may represent a biomarker in critical illness, sepsis, and sepsis-associated AKI (SA-AKI). To characterise and compare KIM-1 in these settings, we analysed KIM-1 serum concentrations in 192 critically ill patients admitted to the intensive care unit. Irrespective of kidney dysfunction, KIM-1 serum levels were significantly higher in patients with sepsis compared with other critical illnesses (191.6 vs. 132.2 pg/mL, p = 0.019) and were highest in patients with urogenital sepsis, followed by liver failure. Furthermore, KIM-1 levels were significantly elevated in critically ill patients who developed AKI within 48 h (273.3 vs. 125.8 pg/mL, p = 0.026) or later received renal replacement therapy (RRT) (299.7 vs. 146.3 pg/mL, p < 0.001). KIM-1 correlated with markers of renal function, inflammatory parameters, hematopoietic function, and cholangiocellular injury. Among subcomponents of the SOFA score, KIM-1 was elevated in patients with hyperbilirubinaemia (>2 mg/dL, p < 0.001) and thrombocytopenia (<150/nL, p = 0.018). In univariate and multivariate regression analyses, KIM-1 predicted sepsis, the need for RRT, and multi-organ dysfunction (MOD, SOFA > 12 and APACHE II ≥ 20) on the day of admission, adjusting for relevant comorbidities, bilirubin, and platelet count. Additionally, KIM-1 in multivariate regression was able to predict sepsis in patients without prior (CKD) or present (AKI) kidney injury. Our study suggests that next to its established role as a biomarker in kidney dysfunction, KIM-1 is associated with sepsis, biliary injury, and critical illness severity. It thus may offer aid for risk stratification in these patients.

OBJECTIVE: This comparative analysis aimed to investigate the efficacy of Sivelestat Sodium Hydrate (SSH) combined with Ulinastatin (UTI) in the treatment of sepsis with acute respiratory distress syndrome (ARDS).
METHODS: A control group and an observation group were formed with eighty-four cases of patients with sepsis with ARDS, with 42 cases in each group. The control group was intravenously injected with UTI based on conventional treatment, and the observation group was injected with SSH based on the control group. Both groups were treated continuously for 7 days, and the treatment outcomes and efficacy of both groups were observed. The Murray Lung Injury Score (MLIS), Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II) were compared. Changes in respiratory function, inflammatory factors, and oxidative stress indicators were assessed. The occurrence of adverse drug reactions was recorded.
RESULTS: The total effective rate in the observation group (95.24%) was higher than that in the control group (80.95%) (P < 0.05). The mechanical ventilation time, intensive care unit (ICU) hospitalization time, and duration of antimicrobial medication in the observation group were shorter and multiple organ dysfunction syndrome incidence was lower than those in the control group (P < 0.05). The mortality rate of patients in the observation group (35.71%) was lower than that in the control group (52.38%), but there was no statistically significant difference between the two groups (P > 0.05). MLIS, SOFA, and APACHE II scores in the observation group were lower than the control group (P < 0.05). After treatment, respiratory function, inflammation, and oxidative stress were improved in the observation group (P < 0.05). Adverse reactions were not significantly different between the two groups (P > 0.05).
CONCLUSIONS: The combination of SSH plus UTI improves lung injury and pulmonary ventilation function, and reduces inflammation and oxidative stress in patients with sepsis and ARDS.