Metformin-associated lactic acidosis: Bridging pharmacokinetic determinants, metabolic pathways, and clinical outcomes.

Impact of Adverse Events on Costs and Length of Stay Following Transcatheter Tricuspid Valve Replacement.

Vasopressin and Major Adverse Kidney Events in Patients Requiring Vasopressor Support After Cardiac Surgery: A Multicenter Retrospective Cohort Study.

The management and clinical course of patients admitted to the intensive care unit with leptospirosis in a referral hospital in Far North Queensland, Tropical Australia.

Human infection with Andes hantavirus: an update for the general physician.

Sepsis is a recognized risk factor for upper gastrointestinal bleeding, yet sepsis-specific randomized evidence informing stress ulcer prophylaxis remains limited. This protocol describesthe rationale, methods, and statistical analysis plan for a post hoc subgroup analysis evaluating pantoprazole versus placebo in invasively ventilated critically ill adults with septic shock enrolled in the REVISE trial (NCT03374800). This study will be a post hoc extended subgroup analysis of the international, blinded, randomized REVISE trial, which enrolled 4821 mechanically ventilated adults in 68 ICUs across 8 countries. Patients were randomized to intravenous pantoprazole 40 mg once daily or placebo during invasive mechanical ventilation. Septic shock will be defined as receipt of vasopressors or inotropes at baseline together with an admitting diagnosis of infection according to APACHE III diagnostic categories. The primary efficacy outcome will be clinically important upper gastrointestinal bleeding in the ICU within 90 days after randomization, and the primary safety outcome will be all-cause mortality within 90 days. Additional trial outcomes will include patient-important upper gastrointestinal bleeding, ventilator-associated pneumonia, Clostridioides difficile infection during hospitalization, new renal replacement therapy, mortality in the ICU and hospital, and duration of ICU and hospital stay. Analyses will be adjusted for prehospital acid suppression; the mortality analyses will be additionally adjusted for APACHE II score. This protocol and statistical analysis plan describes an evaluation of the efficacy and safety of pantoprazole in patients with septic shock within a large randomized trial dataset. Trial Registration: ClinicalTrials.gov identifier: NCT03374800.

Design and rationale of the Impella®-protected cardiac surgery trial (IMPACT): A multicenter, single-arm pilot study in high-risk cardiac surgery patients.

Effects of tocilizumab on neutrophil gelatinase-associated lipocalin following out-of-hospital cardiac arrest, and its prognostic value.

Erratum for Li et al., "Pharmacokinetics/pharmacodynamics of ceftazidime-avibactam in critically ill adult patients receiving continuous renal replacement therapy".

Individual differences exist in the recovery of muscle strength in critically ill patients with intensive care unit (ICU)-acquired weakness, but the characteristics of patients who do not recover muscle strength are unclear. To elucidate the factors associated with the nonrecovery of muscle strength in patients with ICU-acquired weakness. This prospective cohort study involved critically ill patients with ICU-acquired weakness. The patients' outcomes were categorized as recovery (Medical Research Council Sum Score [MRC-SS] ≥48 until hospital discharge or the time of stroke, death, or ICU readmission) or nonrecovery (MRC-SS <48). Separate logistic regression analyses adjusted for age and sex were performed for each candidate factor to identify factors associated with nonrecovery of muscle strength. A total of 111 patients were included in the analysis. Thirty patients were classified as having nonrecovery. Analysis using a logistic regression model showed that septic shock, duration of deep sedation, corticosteroid use, total amount of corticosteroids used, duration of mechanical ventilation, duration of renal replacement therapy, day of first out-of-bed mobilization, initial evaluation of MRC-SS, and length of ICU stay were age- and sex-adjusted predictors of nonrecovery of muscle strength. Patients with ICU-acquired weakness with the predictors identified in this study may not recover muscle strength. Future multicenter interventional studies should assess not only the timing of rehabilitation but also its intensity and the muscle groups specifically targeted.

Continuous renal replacement therapy (CRRT) is the preferred method of kidney support for critically ill children with severe acute kidney injury (AKI) or fluid overload (FO). The number of survivors after pediatric CRRT is increasing, but there are insufficient data describing the risk of developing chronic kidney disease (CKD) in these patients. A register-based study from a tertiary multidisciplinary hospital, 2008-2021. PICU patients 18 years or younger treated with CRRT due to AKI or FO at Karolinska University Hospital from 2008 to 2021 were included. Detailed PICU data from PICU survivors were combined with data from the Swedish National Patient Register aiming to investigate the long-term risk of CKD development. Secondary outcomes included risk of hypertension, end-stage renal disease and mortality. None. We identified and included 156 PICU survivors with a mean follow-up time of 6.4 years ( sd 3.2). CKD developed in 19 of 156 (12.2%) patients, resulting in an incidence of 18.9 (95% CI, 11.4-29.6) cases per 1000 person-years. Median time to CKD diagnosis was 11.5 months (interquartile range 3-62.5). Hypertension occurred in 17 of 156 patients (10.9%), and the composite outcome of CKD or hypertension in 28 of 156 patients (17.9%). The incidence of post-PICU mortality was 6 per 1000 person-years (95% CI, 2.2-13.1). In multivariable analysis, CRRT duration ( p = 0.02) and estimated glomerular filtration rate (eGFR) at hospital discharge ( p = 0.02) were associated with CKD development. We failed to identify an association between age at CRRT initiation or PICU illness and subsequent development of CKD. In our center in Sweden, 2008-2021, we found that a significant proportion of children surviving critical illness requiring CRRT are subsequently diagnosed with CKD or hypertension over time, demonstrating that rigorous follow-up of PICU patients undergoing CRRT is warranted.

Major adverse cardiovascular events (MACE) are a leading cause of morbidity and mortality in patients with end-stage renal disease (ESRD). However, risk stratification and prognostic prediction remain limited. To assess the incremental prognostic value of combined left atrial (LA) and left ventricular (LV) strain in predicting MACE among ESRD patients receiving renal replacement therapy. Prospective. Three hundred thirteen ESRD patients (mean age: 53.8 ± 14.0 years; 202 males) undergoing maintenance dialysis. Balanced steady-state free precession (bSSFP) cine sequence at 3.0 T. Myocardial strain was analyzed from bSSFP cine images using feature-tracking software (CVI42). LA strain components were reservoir (LARS), conduit (LAScd), and contractile (LASct) strain, and LV strain included global longitudinal (GLS), radial (GRS), and circumferential (GCS) strain. Patients were followed up via clinical records and MACE were documented. Prognostic models were constructed using multivariable Cox proportional hazards regression. The baseline prediction model of conventional cardiovascular risk factors was then compared with models incorporating LARS and GLS to assess incremental prognostic value. Cox proportional hazards regression identified predictors of MACE, and model performance was evaluated using C-index, Akaike and Bayesian information criteria (AIC/BIC), and Kaplan-Meier analysis. p < 0.05 was considered significant. During a median follow-up of 16.93 months, 61 patients developed MACE. LARS (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.87-0.94) and LV GLS (HR 1.21, 95% CI 1.08-1.36) were independent predictors. The Cox model incorporating both LARS and LV GLS showed improved discrimination compared with the clinical risk factor model (C-index 0.79 vs. 0.70). Stratification by both LA and LV strain markers significantly improved MACE prediction (log-rank: p < 0.001). The integration of LA and LV strain offered superior prognostic value for MACE prediction in ESRD patients, enabling refined risk stratification beyond traditional measures. 2. Stage 3.

Antifouling and antimicrobial coating with intelligent pH-responsive charge-switching capability prevents catheter-associated obstructions and infection.

Continuous renal replacement therapy (CRRT) is a complex, high-risk life-sustaining intervention in intensive care units (ICUs). Despite its widespread use, understanding of how nurses navigate 'human-machine' interactions to develop professional competence remains limited. To describe the clinical experiences of critical care nurses in caring for patients receiving CRRT and to explore their professional growth trajectory from technical anxiety to autonomy. A descriptive qualitative study design was employed. Ten registered nurses with at least 1 year of ICU experience were recruited from a tertiary medical centre using purposeful sampling. Data from semi-structured interviews were analysed using inductive content analysis. The study was reported in accordance with the Consolidated Criteria for Reporting Qualitative Research (COREQ). Methodological rigour was ensured using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research. A dynamic growth trajectory from 'technical anxiety' to 'professional mastery' emerged, consisting of four core themes: (1) navigating uncertainty, (2) battling the machine, (3) beyond the numbers: developing clinical judgement and (4) the safety net of interprofessional collaboration. A critical turning point occurred when nurses integrated machine data with physiological responses to see the 'patient behind the machine'. Caring for patients on CRRT involves a complex psychological and professional maturation process. Through accumulated practice and interprofessional support, nurses overcome initial fears and develop 'technological competency as caring'. Healthcare institutions should implement simulation-based education focusing on clinical troubleshooting and establish robust interprofessional support systems to reduce cognitive load and foster professional resilience among nurses.

Background: Sepsis management in elderly populations presents unique challenges due to age-related physiological changes and comorbidities. Current guidelines remain conflicted regarding optimal antibiotic timing. We conducted a retrospective, multicenter study to evaluate the association between antibiotic administration timing and short-term and long-term outcomes in elderly sepsis patients. Methods: This retrospective cohort study analyzed data from the MIMIC-IV (v3.1) database. Patients were categorized into the early group (antibiotics initiated within 1 h) and the late group (antibiotics initiated >1 h after diagnosis). Further analyses were stratified by shock status (septic shock vs non-septic shock) and pathogen type (Gram-positive vs Gram-negative bacteria). Multivariable Cox regression assessed associations between antibiotic administration timing and 28-/180-/365-day hospital mortality. Restricted cubic spline models evaluated dose-response relationships. The primary outcome was 28-day hospital mortality. Secondary outcomes included 180-day and 365-day mortality rates, along with the incidence of continuous renal replacement therapy (CRRT) and mechanical ventilation requirements. Results: A total of 12,425 patients met the inclusion criteria from the MIMIC-IV database. The multivariable-adjusted analysis demonstrated that delayed antibiotics administration was significantly associated with a 35% increased risk of 28-day all-cause hospital mortality (HR = 1.35, 95% CI 1.22-1.52; P < 0.001), a 43% elevated 180-day hospital mortality risk (HR = 1.43, 95% CI 1.30-1.56; P < 0.001), and a 45% higher 365-day mortality risk (HR = 1.45, 95% CI 1.33-1.56; P < 0.001). Stratified analyses revealed mortality benefits persisted in non-shock patients (28-day HR = 1.31, P < 0.001) and Gram-positive infections (28-day HR = 1.63, P < 0.001), whereas no significant associations emerged in septic shock (28-day HR = 0.82, 95%CI 0.65-1.03; P = 0.081) or Gram-negative infections (HR = 1.04, 95%CI 0.87-1.24; P = 0.692). A linear relationship was observed between antibiotic delay and mortality (Nonlinear P = 0.88). Conclusions: Early antibiotic administration improves survival in elderly sepsis patients, particularly non-shock cases and Gram-positive infections. These insights advocate the importance of individualized selection based on patients' clinical context in critical care practice.

Anemia is less prevalent in autosomal dominant polycystic kidney disease (ADPKD) owing to preserved erythropoietin production. However, its impact on kidney prognosis remains unclear. Given sex-related differences in hemoglobin (Hb) levels, we hypothesized that the prognostic relevance of anemia may vary by sex and age. Therefore, we aimed to identify subgroup-specific risk patterns using an attribute-based cross-classification approach to support individualized anemia management in ADPKD. We analyzed 552 Japanese patients with ADPKD from a single-center cohort. The primary outcome was a ≥ 30% decline in the estimated glomerular filtration rate (eGFR) or initiation of renal replacement therapy. Cox regression analysis was used to assess the association between Hb and kidney outcomes. Subgroup analyses were performed using cross-classification by sex and age (< 50 or ≥ 50years). Anemia was defined using multiple Hb thresholds (< 11, < 12, and < 13g/dL). Lower Hb levels were independently associated with worse renal outcomes (hazard ratio [HR] per 1g/dL increase: 0.83). Cross-classified analyses revealed distinct risk patterns. Anemia (Hb level < 13.0g/dL) significantly increased the risk in young (HR: 2.92) and old men (HR: 3.84). In women, anemia defined as a Hb level < 12.0g/dL was associated with adverse outcomes in both age groups (HR: 1.98 in < 50years; HR: 2.08 in ≥ 50years). Anemia is a significant prognostic marker for kidney disease progression in ADPKD. Its prognostic impact differs by sex and age, suggesting the need for attribute-based, individualized hemoglobin thresholds rather than uniform cutoffs, to optimize risk stratification and clinical assessment.

Aggressive joint pharmacokinetic/pharmacodynamic target attainment of TDM-guided continuous infusion meropenem-vaborbactam monotherapy: A valuable strategy for maximizing the microbiological outcome of documented KPC-producing Enterobacterales infections?

Dihydropyridine Calcium Channel Blocker Therapy and Risk of CKD Progression in Type 2 Diabetes Treated With Renin Angiotensin System Inhibitors and SGLT2 Inhibitors: A Real-World Retrospective Cohort Study.

Model-informed cefepime dosing in paediatric patients receiving continuous renal replacement therapy.

Adsorption within continuous renal replacement therapy (CRRT) circuits may reduce exposure to echinocandins. Because micafungin is highly protein bound, the behavior of its unbound fraction during CRRT remains difficult to characterize. We assessed unbound micafungin disappearance from a central compartment and late release/desorption in a protein-free in vitro CRRT model. Micafungin stability was assessed in a 5-L bag of Hemosol™ B0 over 8h. In the NeckEpur model, a 5-L protein-free central compartment was circulated at 200mL/min for 6h through either a polyacrylonitrile hemofilter (ST™150; post-dilution continuous veno-venous hemofiltration [CVVH], 2.5L/h) or a polysulfone hemofilter (AV™1000). For AV™1000, one run used CVVH (2.5L/h) and one used continuous veno-venous hemodiafiltration (CVVHDF; dialysis 1.5L/h plus filtration 1.0L/h). Initial micafungin concentrations in the central compartment were 2.18mg/L or approximately 6.8mg/L. Concentrations were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with a lower limit of quantification (LLOQ) of 0.1mg/L. Apparent central-compartment clearance (Cl_CC), sieving coefficient (Sc), and extraction coefficient (EC) were used to describe disappearance from the circuit, filtration, and late release. Sensitivity analyses replaced values < LLOQ by LLOQ/2 or LLOQ/√2. Segmental sampling and within-filter mass balance were used descriptively to localize loss within the extracorporeal system. Micafungin was stable in Hemosol™ B0 over 8h (- 5.2 ± 0.5%). With ST™150 at 2.18mg/L, C_CC reached the LLOQ by 200min and was below the LLOQ thereafter; apparent Cl_CC was approximately 6L/h, effluent concentrations were not measurable, and limited late release was estimated over 120-200min. With ST™150 at approximately 6.8mg/L, elimination from the central compartment was 92 ± 4% at 6h (apparent Cl_CC 4.9 ± 0.2L/h), with within-filter contributions from measurable effluent removal (54 ± 6%) and non-effluent loss (46 ± 6%); small late release was compatible with negative EC values during 180-360min. For AV™1000, two exploratory runs-one CVVH and one CVVHDF-showed rapid disappearance from the central compartment, with C_CC below the LLOQ by 120min, no measurable effluent concentrations, and no negative EC values. Sensitivity analyses for values < LLOQ changed the numerical Cl_CC estimates but not the overall pattern. Segmental concentration data and within-filter mass-balance analysis localized the dominant loss to the filter module, with only limited upstream inlet-segment contribution. In this exploratory protein-free in vitro model, unbound micafungin rapidly disappeared from the CRRT circuit with both tested filter systems. ST™150 showed measurable effluent removal at higher concentrations and limited late release, whereas both exploratory AV™1000 runs showed rapid disappearance without detectable late release. Segmental concentration data and within-filter mass-balance analysis localized the dominant loss to the filter module, with only limited upstream inlet-segment contribution. These findings characterize unbound micafungin-circuit interactions under the tested conditions; their clinical translation will depend on in vivo protein binding and rebinding kinetics.