Search Results (988)

Background and Clinical Significance: Carbimazole is a widely used medication to treat Graves’ disease, although it can rarely cause acquired aplastic anemia, a complication that happens in less than 0.01% of people. Case Presentation: We report a 36-year-old woman treated with supratherapeutic dose carbimazole who, after approximately six months of treatment, developed high grade fever, severe menorrhagia, spontaneous epistaxis, and pancytopenia. Her bone marrow biopsy showed severe bone marrow failure with only 5% cellularity and trilineage hypoplasia. Other potential causes were ruled out. Immediate discontinuation of carbimazole was done, and supportive care, including blood transfusions, broad-spectrum antibiotics, G-CSF, and eltrombopag, was started. The patient deteriorated during her hospital stay, developed neutropenic sepsis and acute respiratory failure from diffuse alveolar hemorrhage, which required intubation and pulse steroid therapy. She was stabilized and discharged, with a referral to a tertiary medical center for starting antithymocyte globulin (ATG) immunosuppressive therapy, which she subsequently completed; two months after discharge she was transfusion independent with near-normalization of her blood counts. Conclusions: This case serves as a stark reminder of how lethal thionamide-induced bone marrow failure can be, highlighting the vital need for immediate drug cessation, swift intensive care, and thorough patient education on early warning signs. Full article

Machine learning (ML) applied to pediatric intensive care data could enable earlier risk stratification and more precise decision support, but limited shareable pediatric datasets have constrained progress. The Pediatric Intensive Care database (PIC) on PhysioNet provides a de-identified, bilingual electronic health record resource spanning 2010–2018. In this narrative review we synthesize ten PIC-based ML studies identified through forward citation tracking on the original PIC publication and PhysioNet dataset record in PubMed, Web of Science, and Google Scholar. For each study we abstracted the clinical question, cohort, label construction, feature engineering, model class, validation design, calibration reporting, and release of reproducibility artifacts. The reviewed studies addressed catheter-associated thrombosis, sepsis, in-hospital mortality, and organ-dysfunction phenotyping. We organize the synthesis around four substrate properties of PIC: irregular time series, constructed labels, single-center temporal drift, and bilingual identifier semantics. The review advances three claims. First, upstream design choices appear to drive performance at least as much as classifier selection across the studies reviewed. Second, within-site discrimination metrics are insufficient without calibration, decision-curve analysis, and deployment-realistic validation. Third, PIC should be viewed as the seed for a collaborative pediatric ICU data ecosystem. Full article

Viral infections are a widely recognized cause of mortality. Recently it has been demonstrated that vitamin D plays an important immuno-modulatory role in both innate and adaptive immune responses against infections, by reducing excessive inflammation and enhancing defense mechanisms. Specifically, exacerbation of infections may cause sepsis, characterized by a dysregulated immune response with hyperinflammation and immune exhaustion. Vitamin D can modulate these processes through various mechanisms, such as enhancing antiviral protection, promoting anti-inflammatory responses, protecting endothelial barriers, and modulating T-cells. This has been demonstrated for various viral infections, including influenza viruses, respiratory syncytial virus, and severe acute respiratory syndrome coronavirus. Although vitamin D deficiency has been associated with increased susceptibility to viral infections and immune cells of infected patients are highly responsive to vitamin D, the clinical benefits of its supplementation to vitamin D-deficient infected individuals are uncertain and, most importantly, direct evidence linking vitamin D to viral sepsis specifically remains particularly limited, with most mechanistic inference extrapolated from non-septic viral infection and bacterial sepsis literature. Based on these assumptions, this review will outline the present understanding about vitamin D regulatory effects on immune system and the possible connection between its serum levels and viral infections, while also addressing controversial issues. Full article

Background/Objectives: To quantify the adjusted association of obesity with in-hospital outcomes in adult scoliosis hospitalizations involving spine deformity corrective surgery. Methods: A retrospective cohort study was conducted using the National Inpatient Sample (2016–2021), including adult hospitalizations for scoliosis undergoing corrective spine surgery. Obesity was the primary exposure. The primary outcome was a composite of in-hospital complications. Secondary outcomes included individual complications, length of stay, total hospital charges, and discharge disposition. Weighted multivariable regression models adjusted for patient- and hospital-level factors were used. Sensitivity analysis was performed excluding severity adjustment to assess potential overadjustment, as the All Patient Refined Diagnosis Related Group (APR-DRG) severity score may partially reflect in-hospital complications. Results: Among 9323 unweighted hospitalizations (representing a national estimate of 46,610 weighted hospitalizations) included (16.6% obese), obesity was associated with a 22% increase in the odds of total in-hospital complications (Odds Ratio (OR) 1.22; 95% Confidence Interval (CI) 1.04–1.43). Among individual complication categories, obesity was associated with higher odds of renal complications (OR 1.69; 95% CI 1.29–2.21), whereas no significant differences were observed in pulmonary, cardiac, Venous Thromboembolism (VTE), or sepsis complications. Additionally, obesity was associated with increased odds of non-home discharge (OR 1.28; 95% CI 1.12–1.46). In sensitivity analysis, these associations were more pronounced, with additional complication categories reaching statistical significance. Conclusions: Obesity is associated with increased in-hospital morbidity in adult scoliosis surgery, particularly higher odds of renal complications and non-home discharge. These population-level findings help optimize preoperative risk communication and anticipate post-acute discharge resource needs. Full article

Sepsis-associated acute lung injury (SALI) is characterized by disruption of the alveolar–capillary barrier, uncontrolled inflammation, oxidative stress, and impaired tissue repair. Ferroptosis and cellular senescence have emerged as potentially interacting stress-response programs that may jointly shape the progression of septic lung injury. Ferroptosis promotes epithelial and endothelial damage through iron-dependent lipid peroxidation, glutathione depletion, and impaired GPX4-mediated lipid repair. In parallel, senescence-associated remodeling may contribute to persistent cell-cycle arrest, senescence-associated secretory phenotype (SASP) production, endothelial dysfunction, and defective regenerative capacity. This review summarizes current evidence on the molecular and cellular crosstalk between ferroptosis and cellular senescence in SALI. Candidate regulatory intersections include context-dependent mitochondrial dysfunction, reactive oxygen species accumulation, iron dyshomeostasis, metabolic reprogramming, lysosomal dysfunction, DNA-damage responses, and stress-responsive pathways involving p53, NRF2, ATF4, STAT3, and FOXO1. Direct SALI evidence is currently strongest for ferroptosis-induced senescence-associated remodeling in pulmonary endothelial cells, whereas senescence-associated ferroptosis resistance is supported mainly by non-pulmonary models. Likewise, SASP-mediated paracrine ferroptosis in neighboring pulmonary cells remains insufficiently validated. We therefore propose an evidence-informed, temporally and cell-type-dependent ferroptosis–senescence framework in SALI, in which acute senescence-associated responses may coexist with ferroptotic injury, whereas persistent senescence-associated remodeling may contribute to defective repair and microenvironmental injury amplification. Targeting this axis through ferroptosis inhibition, restoration of endogenous antioxidant defenses, senotherapeutic modulation, and regenerative strategies may offer stage-informed therapeutic opportunities. Further time-resolved and cell-specific studies are required to define causal relationships and clinically actionable therapeutic windows. Full article

Background/Objectives: This study aimed to evaluate the associations of adding oXiris hemoadsorption therapy to standard sepsis treatment with inflammatory markers, organ dysfunction, hemodynamic parameters, respiratory function, and overall survival (OS) in patients with sepsis and septic shock managed in the intensive care unit (ICU). In our ICU, oXiris was used as adjunctive hemoadsorption for endotoxin and cytokine removal, delivered on a continuous venovenous hemodiafiltration (CVVHDF) platform and initiated independently of acute kidney injury (AKI). Methods: This retrospective comparative cohort study included 83 adult patients with sepsis or septic shock admitted to the Internal Medicine ICU. Patients were allocated to either the oXiris group (n = 33), which received oXiris hemoadsorption for 72 h in addition to standard sepsis therapy, or the control group (n = 50), which received standard sepsis therapy without oXiris or another adsorptive CRRT membrane. Conventional intermittent hemodialysis for independent renal indications was permitted and recorded in both groups. C-reactive protein (CRP), procalcitonin (PCT), white blood cell count, updated Sequential Organ Failure Assessment (SOFA-2) score, PaO₂/FiO₂ ratio, serum lactate, norepinephrine dose, and renal parameters were recorded at baseline, 48 h, and 72 h. Between-group differences in temporal changes were evaluated using adjusted generalized estimating equation models, and robustness was assessed with a propensity-score-based inverse-probability-of-treatment-weighted (IPTW) sensitivity analysis. Survival analysis was performed using the Kaplan–Meier method and log-rank test. Results: The oXiris group had significantly greater baseline clinical severity, including a higher burden of renal dysfunction. This marked baseline imbalance was considered important when interpreting the unadjusted findings and supported the use of adjusted and IPTW analyses. In the oXiris group, CRP, PCT, SOFA-2 score, and norepinephrine requirement showed greater reductions over time, whereas the PaO₂/FiO₂ ratio improved significantly. After IPTW adjustment, the between-group differences in SOFA-2 score, norepinephrine requirement, and PaO₂/FiO₂ ratio remained statistically significant, whereas the CRP and PCT differences were no longer statistically significant. Serum lactate levels showed an increasing trend in the oXiris group compared with the control group (p = 0.042). No significant difference in overall survival was observed between the two groups (p = 0.897). Conclusions: The addition of oXiris hemoadsorption to standard sepsis therapy was associated with favorable early temporal changes in organ dysfunction, norepinephrine requirement, and oxygenation. However, the observed CRP and PCT differences were not preserved after IPTW adjustment, and no survival association was identified. These findings should therefore be interpreted as associations rather than evidence of a causal treatment effect. Full article

Background: Sex-based differences in complications after venoarterial extracorporeal membrane oxygenation (VA-ECMO) for cardiogenic shock are not well defined. We compared 30-day coded acute kidney injury and other short-term outcomes between female and male patients receiving ECMO. Methods: We performed a retrospective multicenter cohort study using the TriNetX U.S. Collaborative Network from 2012 through 2025. Adults with cardiogenic shock supported with VA-ECMO were identified. Patients with a diagnosis-coded AKI (ICD-10-CM N17) recorded on or before the index ECMO procedure were excluded, and female and male cohorts were then matched 1:1 by propensity score on 23 characteristics. The primary endpoint was diagnosis-coded AKI between day 1 and day 30 after ECMO initiation. Secondary endpoints were all-cause mortality, newly diagnosis-coded sepsis, and newly diagnosis-coded ischemic stroke. Results: Among 11,229 adults meeting cohort criteria, 3773 were women, and 7456 were men. After exclusion of 8272 patients with previously coded AKI, 1152 women and 1805 men were eligible, and 1100 patients were matched in each group. Diagnosis-coded AKI occurred in 222 women (20.2%) and 276 men (25.1%) (risk ratio, 0.80; 95% confidence interval [CI], 0.69–0.94; hazard ratio [HR], 0.78; 95% CI, 0.65–0.93; p = 0.005). All-cause mortality was identical between groups (29.5% vs. 29.5%; risk ratio, 1.00; 95% CI, 0.88–1.14). Newly coded sepsis (5.1% vs. 6.3%) and newly coded ischemic stroke (4.0% vs. 3.2%) did not differ significantly. In an unadjusted Aalen–Johansen analysis performed in the unmatched eligible cohorts, the 30-day cumulative incidence of coded AKI was 21.6% among women and 27.8% among men. Conclusions: In this propensity-matched federated electronic health record cohort of adults with cardiogenic shock receiving VA-ECMO and without previously coded AKI, recorded female sex was associated with a lower 30-day risk of diagnosis-coded AKI. Mortality, newly coded sepsis, and newly coded ischemic stroke were similar. These findings are hypothesis-generating and support further investigation of sex-associated differences in datasets with granular renal and ECMO-specific variables. Full article

Background: Trauma-induced coagulopathy is associated with a high rate of hemorrhagic complications and with increased mortality after major trauma. Viscoelastic techniques have been demonstrated to be useful for early diagnosis and appropriate management in these patients. Methods: This prospective observational study included patients who underwent major trauma (ISS (injury severity score) > 15) and were referred to hospital within the first hour. All underwent early ROTEM evaluation. Results: The study included 100 patients (80 males, 20 females, mean age 52.41 years). Twenty-three had bleeding, requiring transfusion (mean age of 57.3 years and ISS 21.7). According to accepted criteria of hypocoagulability, 10/23 (43.5%) had at least one abnormality in one of the ROTEM parameters. EXTEM CT was significantly longer in transfused patients. Four had symptomatic VTE (venous thromboembolism), and Doppler examination showed DVT (deep venous thrombosis) in 14 (14%) of the population. Sepsis, pneumonia, and acute renal failure were statistically more frequent in patients with thrombosis, while no relation was found with ROTEM. Finally, 3 out of 5 patients who died showed a severe hypocoagulable condition at initial ROTEM evaluation. Conclusions: In patients with major trauma referred to hospital within the first hour, early qualitative ROTEM examination at admission may be useful in identifying patients at bleeding risk. Sepsis, pneumonia, and acute renal failure, but not ROTEM parameters, were associated with the risk of thromboembolic events. Full article

Background/Objectives:This study aimed to evaluate whether early renal perfusion scintigraphy is associated with sepsis severity and short-term mortality in an experimental polymicrobial sepsis model. Methods: A total of 90 female Wistar albino rats were divided into Control, mild sepsis, and severe sepsis groups using a cecal ligation and puncture (CLP) model. Renal perfusion was evaluated 5 h after sepsis induction using technetium-99m-labeled erythrocyte scintigraphy, expressed as the kidney-to-aorta (R/A) activity ratio. Survival was monitored for 5 days. Histopathological and biochemical analyses were also performed. Results: The kidney-to-aorta (R/A) activity ratio decreased progressively with increasing sepsis severity (all p < 0.001). Kaplan–Meier analysis demonstrated significantly reduced survival in septic animals (log-rank p < 0.001). The R/A ratio showed high discrimination for 5-day mortality (AUC = 0.944, 95% CI 0.902–0.986; p < 0.001). Univariable Cox proportional hazards analysis demonstrated that a lower R/A ratio was significantly associated with an increased hazard of death (HR = 0.005, 95% CI 0.001–0.036; p < 0.001). Histopathological injury scores and biochemical markers (TNF-α, VEGF, STAT3, NGAL, BUN, creatinine, and MDA) increased significantly with sepsis severity. Conclusions: Early Tc-99m-labeled erythrocyte renal perfusion scintigraphy was associated with sepsis severity and short-term mortality in experimental polymicrobial sepsis. These findings support further investigation of this imaging approach as an experimental marker of sepsis severity and outcome; however, external validation is required before clinical translation. Full article

Mucosal microbiota contribute broadly to host defense and immune homeostasis, while the lung and gut microbiota form a particularly important bidirectional ecological and immunological network that shapes pulmonary host defense, inflammatory injury, and tissue repair. In pneumonia, loss of colonization resistance and altered microbial metabolite production may weaken innate and adaptive immunity; respiratory infection, antibiotics, and critical-care exposures can, in turn, remodel both microbial communities. In acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), intestinal barrier failure, circulating microbial products, immune cell trafficking and, in selected settings, lymphatic or hematogenous dissemination of gut-derived organisms may aggravate alveolar–capillary injury. Alveolar macrophages integrate these signals through pattern-recognition, metabolic, and epigenetic pathways, linking microbial ecology to pathogen clearance and inflammatory resolution. The evidence, however, remains uneven. Mechanistic causality rests largely on animal studies, most human data are associative, and trials of microbiota-directed interventions are heterogeneous and strain-specific. This Review examines bacterial and viral pneumonia, sepsis-associated ALI and ventilator-associated injury; separates mechanistic, observational, and interventional evidence; and evaluates probiotics, live biotherapeutic products, microbial metabolites, and dietary approaches. Translation will depend on longitudinal sampling, source-resolved microbial tracking, metabolite-informed patient stratification, and adequately powered trials with clinically relevant endpoints. Full article

Arguably, the most vital function of the cardiovascular system (CVS) is its ability to facilitate the oxygenation of blood in the lungs, and to deliver that oxygen to the rest of the body. This relies on the ability of oxygen to diffuse in and out of the bloodstream, as well as for the CVS to maintain adequate perfusion of body tissues. The CVS also plays a key role in immune responses, particularly in initiating an acute inflammatory reaction in response to infection or injury. Changes in vascular function, such as vasodilation, increased vascular permeability, and initiation of coagulation, are critical elements of this inflammatory response. Normally, the regulated nature of immune responses helps to limit any potential detrimental effects. However, in cases of severe, dysregulated inflammation, as seen in conditions such as sepsis, the vascular responses that form a normal part of the inflammatory reaction may start to impact upon tissue oxygenation. Increased microvascular permeability and the development of edema can impact upon oxygen diffusion, whilst tissue perfusion can be impacted at the level of both the micro- and macrocirculation. In severe cases, impaired perfusion and oxygen delivery to vital organs may lead to multiple organ system failure. An increased understanding of the impact of inflammation on vascular function may help elucidate novel therapeutic approaches to manage these critical care situations. Full article

Background/Objectives: We aimed to analyse the development of acute kidney injury (AKI), its association with mortality, and mortality-associated factors in patients admitted to the intensive care unit (ICU) with sepsis. Methods: This retrospective cohort study was conducted on adult patients with sepsis admitted to the ICU of a tertiary-care hospital between January 2023 and December 2023. Demographic, clinical, and laboratory data within the first 24 h of admission to the ICU were recorded. These data were compared between patients with and without sepsis-associated acute kidney injury (SA-AKI). Results: Among 1163 admissions, 185 met the study criteria, and the incidence of SA-AKI was 45.4%. The overall 28-day mortality was 38.4%. Patients with SA-AKI had significantly higher mortality than those without SA-AKI (63.1% vs. 17.8%, p < 0.001). In the multivariable Cox regression analysis, SA-AKI was independently associated with a higher risk of 28-day mortality (HR = 2.87, 95% CI 1.51–5.45, p = 0.001). Among patients with SA-AKI, elevated lactate showed a borderline association with mortality (HR = 1.06 per mmol/L, 95% CI 1.00–1.13, p = 0.053); first-day vasopressor use was not independently associated with mortality after adjustment for illness severity. Conclusions: SA-AKI was independently associated with higher 28-day mortality. Within the SA-AKI subgroup, lactate showed only a borderline association with mortality, whereas first-day vasopressor use appeared to reflect illness severity. Full article

Enolase-1 (ENO-1) is classically known as a highly conserved glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in the final steps of glycolysis. This enzyme, however, is being increasingly implicated as a multifunctional moonlighting protein with compartment-specific roles in inflammation. Within the cytosol, ENO-1 regulates macrophage inflammation during sepsis; on the cell surface, it functions as a plasminogen receptor, and extracellularly, it can participate in innate immune signaling. Across innate and adaptive immunity, ENO-1 has been implicated in macrophage activation, neutrophil recruitment, endothelial cell dysfunction, fibroblast remodeling, and autoantigenicity. These functions have been linked to sepsis, acute respiratory distress syndrome, acute organ injury, hemorrhagic shock, rheumatoid arthritis, and cancer-associated inflammation in the tumor microenvironment. Therapeutic targeting of ENO-1 includes small-molecule inhibitors and monoclonal antibodies. ENO-1, with its compartment-specific functions in disease pathogenesis, serves as a significant therapeutic target for inflammatory diseases. In this review, we discuss the novel compartment-specific roles of ENO-1 in inflammatory diseases, defining its functions beyond its role in glycolysis. We conclude that both the metabolic and moonlighting functions of ENO-1 contribute to inflammation, and future studies should delineate its compartment-specific roles in inflammatory pathophysiology, as compartment-specific targeting may represent the future of ENO-1-directed therapy. Full article

Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening, chronic cutaneous inflammatory disease characterized by unpredictable, recurrent acute flares of painful sterile pustules on a widespread erythematous background. In addition to cutaneous manifestations, patients may experience fever, pruritus, pain, chills, and general malaise, which may be further complicated by secondary infection, sepsis, and organ failure, thus requiring urgent medical treatment and, in some cases, hospitalization. Prompt therapeutic management of the acute phase is crucial for severe cases, and proactive treatment to prevent flares should always be considered. However, early recognition of acute flares can be challenging due to the low frequency of the disease, the rapid onset of flares, the lack of hematological biomarkers and the absence of standardized diagnostic criteria. Moreover, despite the approval of new targeted therapies, there are still several unmet needs, as these treatments are highly expensive, not always readily available, and may have limited efficacy in patients with advanced or complicated disease. For these reasons, multidisciplinary round-table discussions and shared diagnostic and therapeutic algorithms involving dermatologists, who are responsible for diagnosing and treating GPP, and other medical specialists are desirable to facilitate prompt referral to dermatologists for accurate diagnosis and appropriate treatment. We report the updated literature discussed during a multidisciplinary meeting with the aim of providing practice recommendations for clinicians involved in GPP management. Full article

Sepsis is a life-threatening syndrome characterized by severe immune dysregulation, frequently culminating in acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). Current supportive therapies fail to reverse the underlying pathophysiological damage. However, mesenchymal stromal cells (MSCs) have emerged as a promising therapeutic frontier due to their robust immunomodulatory, anti-inflammatory, and tissue-regenerative properties. Despite compelling preclinical evidence, translating these benefits into consistent clinical efficacy remains a major challenge. This review critically examines the biological and anatomical barriers limiting the efficacy of MSCs, particularly the pulmonary first-pass effect, which restricts the systemic delivery of viable cells to distant organs such as the kidneys. To overcome these physical limitations, we highlight the recent paradigm shift toward nanoscale, cell-free therapies, specifically MSC-derived extracellular vesicles (MSC-EVs). EVs effectively bypass pulmonary sequestration and thromboembolic risks, exerting their potent therapeutic effects through the horizontal transfer of bioactive cargo, notably microRNAs, to reprogram cellular fate and restore immune homeostasis. We also discuss the critical need for rigorous clinical trial designs, scalable good manufacturing practice protocols, and the integration of a precision medicine approach. Ultimately, incorporating validated biomarkers for targeted patient stratification will be the decisive step in unlocking the full therapeutic potential of MSCs and their derivatives in critical care. Full article