Early identification of gram-negative bacteremia in intensive care units (ICUs) remains challenging at the time of blood culture sampling, when clinical signs are often nonspecific and existing diagnostic approaches typically rely on single-timepoint measurements. We conducted a retrospective cohort study of adult ICU patients admitted between July 2022 and January 2024 to investigate whether short-term longitudinal patterns in routinely collected clinical and laboratory data contain diagnostically relevant information for gram-negative bacteremia. Clinical and laboratory variables were extracted at three consecutive timepoints (Day -2, -1, and 0 relative to blood culture collection), and diagnostic models incorporating this temporal information were developed using complementary statistical and machine-learning approaches. Model performance was evaluated on a held-out test set using discrimination, calibration, and decision curve analysis. Among 568 patients, models incorporating short-term longitudinal data demonstrated good and consistent discrimination for gram-negative bacteremia (AUC range 0.81-0.83) with good calibration after recalibration. Diagnostic performance was stable across modeling approaches, indicating robustness of the underlying signal rather than dependence on a specific algorithm. Decision curve analysis suggested higher net benefit for model-based risk stratification compared with treat-all or treat-none strategies across clinically relevant threshold probabilities. Hemoglobin, creatinine, and albumin consistently emerged as influential contributors. These findings indicate that short-term longitudinal clinical trajectories contain diagnostically meaningful information for gram-negative bacteremia at the time of blood culture sampling and support further external validation and prospective evaluation prior to clinical implementation.
The Lynch syndrome INtegrative Epidemiology And GEnetics (LINEAGE) consortium was established to address gaps in understanding genotype-specific cancer risks and risk-modifiers in contemporary North American Lynch syndrome (LS) populations. LINEAGE is a multi-center, longitudinal cohort to systematically collect data on risk factors, adherence to care, quality of surveillance, and patient-, provider-, and system-level factors associated with incident LS-associated cancers. LINEAGE recruits individuals with confirmed pathogenic or likely pathogenic variants in LS-associated genes from participating institutions. Data includes retrospective and prospective collection, encompassing clinical abstraction (demographics, surgical history, endoscopic data, treatments), patient-reported surveys (behavioral/lifestyle factors, quality of life, procedures), endoscopist-level data, and biosample metadata. A standardized REDCap database, data harmonization protocols, and a virtual biobank support reproducibility and linkage of clinical data and biosamples. Rigorous quality assurance/quality control processes are embedded for data integrity. Participating centers will contribute data to determine gene-specific risks, and gene-environment interactions for Lynch-associated, and other cancers. We will evaluate associations with exposure to, and quality of cancer risk-reduction care, including endoscopic surveillance, risk-reduction surgery, and chemoprevention. The inclusion of provider-level variables, such as endoscopist training and experience, enables unique research into modifiers of post-endoscopy cancer risk. The linked biosample resources will further facilitate mechanistic studies and biomarker discovery. LINEAGE provides a robust platform for advancing LS research by integration of clinical, pathological, epidemiological and genetic data across institutions. Its standardized, collaborative framework enhances the validity and generalizability of risk estimates that will guide decision-making and policy for surveillance to ultimately reduce morbidity and mortality for individuals with Lynch syndrome.
CapsoCam provides a 360° panoramic-view in capsule endoscopy (CE). This study aimed to conduct the initial systematic review and meta-analysis on the diagnostic efficacy and clinical aspects of CapsoCam in patients with Suspected small bowel bleeding (SSBB), potentially comparing it to forward-view CE. A systematic search of PubMed, Embase, and Scopus databases was performed for human studies reporting outcomes of interest up to January 2025. Titles and abstracts were screened, and full-texts were selected based on predefined inclusion criteria by two reviewers. The quality assessment used Joanna Briggs Institute checklist. Meta-analysis used a random-effects model with a 95% confidence interval (CI). Publication bias was evaluated using Egger and Begg's tests. A leave-one-out sensitivity analysis was performed. Five studies met the inclusion criteria. The meta-analysis revealed no statistically significant difference in diagnostic yield between the two CE types in cases of SSBB (p = 0.89, 95% CI: -0.08 to 0.09). Egger's test and Begg's test showed no significant publication bias. Comparative analysis between panoramic and forward-view CEs demonstrated similar performance for small bowel transit time (p = 0.58, 95% CI: -0.33 to 0.59), although evaluation time was significantly longer with CapsoCam (p = 0.001, 95% CI: 0.42 to 1.60). The risk difference in completion rates was not statistically significant (p = 0.91, 95% CI: -0.13 to 0.15). Subgroup analyses showed no significant differences in diagnostic yield or other outcomes between CapsoCam PLUS and SV-1, or by study design. Our analysis suggests that CapsoCam demonstrates comparable performance to forward-view CE in terms of diagnostic reliability, clinical efficacy, and safety profile, except for reading time. However, the limited number of studies underscores the need for further research to validate CapsoCam's usability in routine clinical practice for SSBB patients compared to forward-view CE.
Timely diagnosis and effective management are critical for improving outcomes in neonatal bloodstream infections (BSIs), particularly in resource-limited settings. This study aimed to determine clinical signs and laboratory markers associated with BSIs among neonates at Tertiary hospital in Mwanza, Tanzania. A hospital-based cross-sectional study was conducted, among neonates treated for suspected BSI from January 2023 to June 2024. Clinical signs of sepsis were systematically documented. Blood samples were collected for culture, serial C-reactive protein (CRP), and complete blood count at admission, 24 h, and 72 h. Data were analyzed using R software version 4.4. A total of 327 neonates with suspected BSI were enrolled, with a median age of 1 day [interquartile range (IQR): 1-5 days]. The case-fatality rate was 9.2% (30/327). BSIs were confirmed in 53/327 (16.2%) neonates. Among confirmed cases, 39/53 (73.5%) were caused by Gram-negative bacteria, predominantly Klebsiella pneumoniae and Acinetobacter spp. Neonates with confirmed BSI had a significantly longer mean hospital stay than those with culture-negative sepsis (10.1 ± 8.0 days vs. 6.6 ± 6.6 days; p < 0.001). Elevated CRP was an independent predictor of BSI (p < 0.001). BSIs remain a significant cause of neonatal morbidity and mortality in this setting. Gram-negative organisms predominated and were associated with worse outcomes. A combination of clinical features, early warning signs, and CRP may aid in the early identification of neonates at high risk of BSIs and support timely initiation of appropriate management in resource limited settings.
Randomized trials established the safety of omitting axillary lymph node dissection (ALND) among patients with clinically node-negative breast cancer and less than 3 positive sentinel lymph nodes (+SLNs) having upfront surgery and adjuvant radiation. Patients with palpable mobile level I/II axillary adenopathy (cN1) were not eligible for these studies. Presently, more than 80% of patients with HR+/HER2- cN1 disease undergo ALND either at upfront surgery or after neoadjuvant therapy, despite evidence that 50% to 60% will have only 1 or 2 positive nodes. To determine upfront sentinel lymph node biopsy (SLNB) feasibility and evaluate ALND rate among patients with HR+/HER2- cN1 breast cancer selected with axillary ultrasound (AUS). This nonrandomized clinical trial involved patients with cTx/cT1-2 cN1 HR+/HER2- breast cancer with 3 or fewer morphologically abnormal nodes on AUS at 4 centers. The trial began on April 20, 2021, and the database for this report was frozen on September 26, 2024. Patients underwent upfront lumpectomy/mastectomy and SLNB, with single/dual-tracer mapping. ALND was indicated for 3 or more positive SLNs. The primary outcome was ALND rate. Secondary outcomes were frequency of palpable nodes being radioactive/blue and locoregional recurrence. Among 78 enrolled patients, the median (IQR) age was 58 (49.0-66.5) years. Most tumors were cT1 (37 [47%]) or cT2 (40 [51%]), 56 patients (72%) had ductal histology, and 59 tumors (76%) were moderately differentiated. On AUS, 39 patients (50%) had 1 abnormal-appearing node, 33 (42%) had 2, and 6 (8%) had 3. Median (IQR) pathologic tumor size was 2.3 (1.6-3.3) cm, 50 patients (64%) had lymphovascular invasion, and 54 (69%) had extracapsular extension. SLNB was performed with dual tracer in 68 (87%), and 3 or more SLNs were retrieved in 75 (96%). The palpable diseased nodes were blue and/or radioactive in 107 of 161 instances (66.5%). Overall, 24 patients (31%) had 1 +SLN, 30 patients (38%) had 2 +SLNs, and 24 patients (31%) had 3 or more +SLNs. SLNB alone was performed in 59 patients (76%), while 19 (24%) had ALND; indicated ALND was deferred in 5 cases. Among those with 12 months or more follow-up (n = 68; median, 25 months), there have been no isolated axillary or locoregional recurrences. This study found that SLNB is feasible among patients with cN1 HR+/HER2- disease and that resection of palpable nodes is necessary to minimize false-negative rates. This approach affords the opportunity to omit ALND and minimize morbidity among patients with cN1 cancer and limited nodal burden. ClinicalTrials.gov Identifier: NCT04854005.
Posttraumatic stress disorder (PTSD) is a mental health condition with widespread effects on mental and physical health and mortality. In this paper, we present the current state of research on the epidemiology of PTSD, including its prevalence, risk factors, and impact. The U.S. lifetime prevalence of PTSD is estimated to be 6.1%-8.3%, and the global prevalence is estimated at 3.9%. PTSD prevalence has been consistently found to be higher among certain subgroups, including women and military veterans. Risk factors for PTSD include pretrauma variables, preexisting mental health conditions, sociodemographic characteristics, and features of the traumatic event itself. Consequences of PTSD include effects on psychiatric comorbidity, physical health conditions, and all-cause and cause-specific mortality. Points of consideration and challenges affecting the study of PTSD epidemiology are noted, including debates on specifying a trauma criterion for diagnosis, the validity of complex PTSD as a diagnosis, and the dearth of recent population-based longitudinal data to understand this disorder. Suggestions for future research and clinical implications are discussed.
Carbapenemase-producing Klebsiella pneumoniae (CPK) is a major threat in North Africa, yet long-term genomic surveillance efforts remain scarce. To address this, we analyzed 1,013 CPK clinical isolates collected at Habib Bourguiba Hospital (Sfax, Tunisia) from 2009 to 2022. Given limited genomic resources, clinical microbiologic and pulse-field gel electrophoresis (PFGE) profiles identified representative isolates for genomic analyses to resolve transmission dynamics and plasmid dissemination over time. Hospital-acquired CPK increased >10-fold, from 0.95 to 9.59 per 10,000 patient-days. OXA-48-like enzymes predominated, followed by NDMs and dual producers. Genomic analyses identified 23 sequence types, with ST101, ST147, and ST383 accounting for 70% of isolates. ST383 strains carrying blaOXA-204 on IncC plasmids occurred first, followed by ST101 with blaOXA-48 on IncL replicons and ST147 with blaNDM-1 on IncFIB/IncFII multi-replicons. Since 2019, epidemic ST383 co-harboring blaOXA-48 on IncL plasmids and blaNDM-5 with rmpA/iuc on hybrid IncFIB/IncHI1B plasmids became dominant. Comparison with 80,252 global genomes in NCBI Pathogen Detection showed that 82% of study isolates clustered with Mediterranean/global lineages, demonstrating frequent international dissemination. Findings reveal both local and international reservoirs driving CPK introductions, informing targeted infection-control strategies in regional hospitals.
Human epidermal growth factor receptor 2 (HER2) mutations in non-small cell lung cancer (NSCLC) are associated with aggressive disease and poor prognosis. Improved understanding of patient characteristics is vital to advance personalized treatment and improve outcomes. In this structured protocol-based targeted literature review, we assessed the epidemiology and 'real-world' outcomes in patients with HER2-mutant NSCLC by region, and by mutation category (tyrosine kinase domain [TKD] and non-TKD). Across 64 studies, the frequency of HER2 mutations ranged from 1% to 5%. Patients with HER2-mutant NSCLC were more frequently female, never smokers, and exhibited a high burden of central nervous system involvement. The HER2 mutational landscape differed between TKD and non-TKD groups, with non-TKD mutations associated with higher frequencies of concomitant mutations and higher tumor mutational burden. Few studies systematically assessed HER2 mutation oncogenicity; however, TKD mutations appear to be more commonly oncogenic than non-TKD mutations. Further information regarding the oncogenicity of uncommon HER2 mutations is required. Most patients received first-line platinum-doublet chemotherapy or chemoimmunotherapy, with no clear second-line standard of care. Clinical outcomes were modest. There is a clear unmet need for HER2-directed agents. Three such agents have gained accelerated US Food and Drug Administration (FDA) approval for use in previously treated HER2-mutant NSCLC: the antibody-drug conjugate, trastuzumab deruxtecan; the HER2-specific tyrosine kinase inhibitor (TKI), zongertinib; and the HER2/EGFR TKI, sevabertinib. Zongertinib has also been granted accelerated FDA approval in a first-line setting. The emergence of multiple treatment options highlights the importance of early HER2 mutation testing to guide treatment sequencing and maximize patient benefit.
Scalable interventions are urgently needed to mitigate the adverse effects of heat on pregnancy and newborn health. To evaluate whether low-dose aspirin modifies the association between heat exposure and preterm birth. This secondary analysis of the Global Network for Women's and Children's Health Research Aspirin Supplementation for Pregnancy Indicated Risk Reduction in Nulliparas (ASPIRIN) randomized, double-blinded, placebo-controlled clinical trial was conducted from March 2016 to June 2018. Statistical analyses were performed from June 2024 to June 2025. The study settings included the Democratic Republic of Congo, Zambia, Kenya, Guatemala, Pakistan, and Belagavi and Nagpur, India. Participants included nulliparous individuals between 6 and 13 weeks' gestation recruited through local clinics and communities, with delivery at 20 or more weeks' gestation. Prenatal care site-specific daily maximum humid heat averaged across gestation and by gestational week, and randomization to aspirin or placebo. The main outcome was preterm birth (delivery between 20 and <37 weeks' gestation) with gestational age confirmed by enrollment ultrasonography. Of 11 558 participants (mean [SD] age, 20.9 [3.3] years), 5787 were randomized to receive aspirin and 5771 to receive placebo. Preterm birth occurred among 754 placebo recipients (13.1%) and 668 aspirin recipients (11.6%). In mixed-effects pooled logistic regression, each 1 °C increase in mean daily maximum shaded wet-bulb globe temperature across gestation was associated with a 5% increased odds of preterm birth (adjusted odds ratio, 1.05; 95% CI, 1.01-1.10). In stratified analyses, this increased risk was observed only among placebo recipients (adjusted odds ratio [AOR], 1.07; 95% CI, 1.02-1.13), not among aspirin recipients (AOR, 1.03; 95% CI, 0.97-1.10). In pooled mixed-effects logistic distributed lag models, increased odds of preterm birth were observed 17 to 19 weeks before delivery among individuals whose daily maximum shaded wet-bulb globe temperature exceeded the site-specific 75th percentile compared with the lowest 3 quartiles. This vulnerability was not observed among aspirin recipients. In contrast, the association of heat with perinatal mortality was observed only among those receiving aspirin (AOR, 1.15; 95% CI, 1.05-1.26) and not among those receiving placebo (AOR, 1.03; 95% CI, 0.96-1.11). The findings of this secondary analysis of the Global Network ASPIRIN trial suggest that low-dose aspirin initiated early in pregnancy among nulliparous individuals may mitigate the effects of heat exposure on preterm birth. The increasing global prevalence of heat stress warrants testing its efficacy more broadly among pregnant people as well as its safety with respect to perinatal mortality. ClinicalTrials.gov Identifier: NCT02409680.
Background: Substance misuse is a commonly cited reason for the initiation of child protection proceedings. Additionally, posttraumatic stress disorder (PTSD) shows a higher prevalence in both mothers and fathers involved in child protection services compared to the general population. Complex PTSD (CPTSD), recently included in the International Classification of Diseases 11th revision (ICD-11), has yet to be formally investigated in child protection systems using a validated tool.Objective: We aimed to identify the observed rates of PTSD and CPTSD in parents subject to child protection proceedings using the International Trauma Questionnaire (ITQ) and to examine associated demographic (age, gender, ethnicity) and clinical (depression, anxiety, substance/alcohol misuse, and domestic abuse) factors.Methods: As a cross-sectional, observational study, we used routinely collected ITQ data pertaining to 93 parents accessing a Family Drug and Alcohol Court service in England between August 2022 and June 2024. We used multivariable logistic regression models to explore associations between demographic and clinical variables and presence of PTSD or CPTSD.Results: We found that over half of the parents met criteria for PTSD or CPTSD (N = 52, 55.9%), with CPTSD being more prevalent (N = 34, 36.6%) than PTSD (N = 18, 19.4%). Anxiety and depression were significantly associated with presence of PTSD or CPTSD, and 90.1% of parents assessed had histories of substance misuse.Conclusion: These findings show high rates of CPTSD and high levels of trauma and substance misuse difficulties in CP contexts, highlighting the need for integrating trauma-informed treatments and whole person care services for parents subject to CP proceedings to produce better outcomes for families. This study is the first to assess complex PTSD (CPTSD) in parents subject to child protection proceedings, using a validated tool.Over half of parents (55.9%) met the criteria for PTSD or CPTSD, with CPTSD more prevalent than PTSD. Significant associations were seen with anxiety and depression, and 90.1% of parents had substance misuse histories.Findings support the need for trauma informed courts and whole person care services within child protection proceedings to improve outcomes for both parents and children.
Children with acute gastroenteritis-associated vomiting discharged from emergency departments (EDs) have improved outcomes when provided with ondansetron for home use. However, only one-third of children who present with significant vomiting experience ongoing vomiting after discharge. To identify characteristics associated with 3 or more vomiting episodes among pediatric patients within 24 hours of ED discharge. This nonprespecified secondary analysis of a randomized clinical trial of children aged 6 months to less than 18 years presenting to EDs between September 14, 2019, and June 27, 2024, with acute gastroenteritis-associated vomiting and who were followed up for 7 days. A prognostic score was derived using generalized linear mixed models across 10 imputed datasets. Data analysis was performed between May 9, 2025, and February 13, 2026. The primary outcome was 3 or more episodes of vomiting within 24 hours of ED discharge. Secondary outcomes included unscheduled health care revisits, intravenous fluid administration, and hospitalization within 7 days after the ED visit. Of 1030 children enrolled, 977 had follow-up data available and were included in this analysis (median age, 47.0 months [IQR, 22.1-80.1 months]; 493 [50.5%] girls; 925 [89.8%] with complete follow-up data). Eighty of 927 children (8.6%) had 3 or more episodes of vomiting in the 24 hours after ED discharge. In unadjusted analysis, only age 6 months to less than 2 years was associated with ongoing vomiting after discharge (odds ratio [OR], 2.17; 95% CI, 1.37-3.43). In multivariable regression analysis, variables associated with postdischarge vomiting included age 6 months to less than 2 years, symptom duration of 24 to 48 hours, or 10 or more vomiting episodes in the 24 hours preceding the ED visit. In a predictive model, a score of 4 points or more was associated with a 13.6% (95% CI, 9.9%-18.1%) probability of 3 or more vomiting episodes within 24 hours of ED discharge, with a sensitivity of 0.50 (95% CI, 0.39-0.61) and specificity of 0.70 (95% CI, 0.67-0.73). Children with 3 or more vomiting episodes within 24 hours of discharge, compared with those without, were more likely to have an unscheduled health care visit (33 of 80 [41.3%] vs 65 of 846 [7.7%]; difference, 33.6%; 95% CI, 22.6%-44.5%), receive intravenous fluids (9 of 80 [11.3%] vs 15 of 846 [1.8%]; difference, 9.5%; 95% CI, 2.5%-16.5%), and be hospitalized (5 of 80 [6.2%] vs 9 of 846 [1.1%]; difference, 5.2%; 95% CI, -0.2% to 10.5%) within 7 days of discharge. In this analysis of children presenting for ED care with vomiting, younger children and those unwell for 24 to 48 hours with 10 or more episodes of vomiting at presentation were more likely to have persistent vomiting after discharge. Based on these findings, these children are most likely to benefit from being provided ondansetron for home administration. ClinicalTrials.gov Identifier: NCT03851835.
Metabolic syndrome substantially elevates venous thromboembolism (VTE) risk, increasing health care burdens. The Metabolic Score for Visceral Fat (METS-VF) offers a novel, simplified approach to assess visceral fat. This study evaluates METS-VF's association with VTE risk and its utility for risk stratification in patients with metabolic syndrome. Using UK Biobank data, we included 118 619 participants with metabolic syndrome free of VTE at baseline. Time-dependent area under the curve analysis with bootstrap validation identified the strongest VTE predictor. Multivariable Cox models assessed associations of METS-VF, a VTE-specific polygenic risk score, and their combination with incident VTE. Mediation analysis evaluated potential mediators. Robustness was assessed through subgroup and sensitivity analyses, including competing risk of death. Over a median 12-year follow-up, 5162 participants developed VTE. METS-VF demonstrated stronger association with VTE than traditional metabolic indicators. Highest quartile participants showed significantly increased risks of VTE (hazard ratio [HR], 1.46 [95% CI, 1.33-1.61]), pulmonary embolism (HR, 1.50 [95% CI, 1.33-1.70]), deep vein thrombosis (HR, 1.52 [95% CI, 1.34-1.73]), and lower-extremity deep vein thrombosis (HR, 1.59 [95% CI, 1.38-1.82]). Stratified analysis revealed synergistic interaction between METS-VF and genetic susceptibility. CRP (C-reactive protein) and estimated glomerular filtration rate significantly mediated the METS-VF-VTE association. METS-VF is a significant, independent risk indicator for VTE in patients with metabolic syndrome, demonstrating synergistic effects with genetic risk. The CRP- and estimated glomerular filtration rate-mediated association supports METS-VF's clinical utility in VTE risk stratification.
We compared health care spending and utilization associated with semaglutide relative to bariatric surgery in patients with obesity and type 2 diabetes (T2D). Using MarketScan insurance claims of patients with BMI ≥ 35 and T2D from 2016 to 2021, we examined associations between choice of semaglutide, sleeve gastrectomy, or gastric bypass; 3-year health care spending (out-of-pocket [OOP] and total); and clinical outcomes (ED visits, hospital admissions, and major adverse cardiovascular events [MACE]). Analyses were adjusted using generalized linear models, inverse probability weighting, and instrumental variables. Among 6748 patients (2797 semaglutide, 2300 sleeve gastrectomy, 1651 gastric bypass), bariatric surgery patients had higher BMI and more comorbidities. In IPTW-adjusted analysis, semaglutide was associated with the highest 3-year OOP costs ($7752 vs. $5980 [sleeve gastrectomy] vs. $6591 [gastric bypass], p < 0.001), but total spending was not statistically different across the groups. Relative to semaglutide, the gastric bypass group showed higher observed ED visits (hazard ratio relative to semaglutide [95% CI]: 1.36 [1.28-1.45]) and inpatient admissions (1.25 [1.13-1.37]) and fewer MACE (0.71 [0.59-0.88]). Sleeve gastrectomy was associated with fewer long-term admissions (0.79 [0.72-0.86]) and MACE (0.79 [0.66-0.93]). For patients with T2D and obesity, compared with semaglutide, bariatric surgery is associated with lower OOP spending and similar total spending at 3 years, as well as lower long-term MACE rates.
To analyze the epidemiology, clinical characteristics, surgical outcomes, and risk factors for incarceration and recurrence in a large cohort of children undergoing inguinal hernia repair, and to evaluate differences across sex, laterality, and surgical approaches. We retrospectively reviewed the children who underwent inguinal hernia repair at a tertiary pediatric center over ten years. Demographic characteristics, perioperative outcomes, and postoperative complications were analyzed. Subgroup comparisons were performed by sex, laterality, and surgical approach. Multivariate logistic regression models were used to identify independent predictors of incarceration and recurrence. Of 9590 children, 72.2% were male, and the median age was 2 years and 10 months. Laparoscopic surgery was performed in 93.1% of cases. Incarceration occurred in 4.2% of children and recurrence in 1.4%. Females, children ≤1 year, and unilateral hernias were independently associated with higher risk of incarceration. Male sex and age >1 year predicted recurrence, while laparoscopic technique served as a protective factor. Laparoscopy identified synchronous contralateral hernias in 39.2% of children initially diagnosed with unilateral hernia, compared with only 0.9% detected during open repair. Laparoscopic approach was also associated with shorter operative time, fewer complications, and faster recovery. This large cohort study highlights the epidemiology and surgical outcomes of pediatric inguinal hernia. Age, sex, and hernia laterality were associated with clinical presentation and complication risk. Laparoscopic surgery showed favorable perioperative outcomes and facilitated detection of contralateral hernias. Because surgical approach selection was not randomized, comparisons between techniques should be interpreted cautiously. These findings emphasize the importance of individualized risk stratification and surgical decision-making.
Trichophyton indotineae is an emerging dermatophytic pathogen causing severe infections that are frequently resistant to standard antifungals. Since 2015, this species has spread intercontinentally. To highlight the clinical characteristics and challenges in managing T. indotineae infections in the United States and to introduce the utility of rapid real-time PCR (qPCR) diagnosis. Records from a molecular diagnostics laboratory (Bako Diagnostics, GA, USA) were retrospectively reviewed for T. indotineae detections between May 2025 and January 2026. Cases were identified using a novel single-plex qPCR assay and confirmed by sequencing of the internal transcribed spacer region. The squalene epoxidase gene (SQLE) was sequenced to assess terbinafine resistance. A survey was distributed to treating physicians to collect information on recent international travel, household transmission, clinical features, immunosuppressive medications or conditions, and treatment history. All patients (median age: 54; 3 males and 2 females) reported recent travel to India or Nepal, except one, who was the spouse of a patient who had traveled to India. Two different SQLE substitutions were detected, F397L (N = 2) and L393F (N = 1), which are common among terbinafine-resistant T. indotineae isolates found globally. Potential gaps in clinical management - attributed to treatment initiation prior to confirmatory diagnosis of T. indotineae - were identified. These gaps include the use of topical corticosteroids, lack of itraconazole use (100-200 mg/day for 6-8 weeks or longer) as first-line treatment, and prescribing fixed, short treatment durations. In T. indotineae cases, these practices may increase the risk of disease recurrence and domestic spread. Current clinical recommendations are summarized herein, highlighting the utility of this novel qPCR assay for real-time treatment decision-making.
In 2024, a comprehensive framework for the screening, diagnosis, and management of metabolic dysfunction-associated steatotic liver disease (MASLD) was incorporated in the EASL-EASD-EASO clinical practice guidelines. However, physicians often face barriers applying these recommendations in routine clinical care, especially in the Southeastern Europe, Middle East, and Africa (SEEMEA) region. As a multidisciplinary group of physicians involved in MASLD and metabolic dysfunction-associated steatohepatitis (MASH) management, our objective is to provide a practice-oriented roadmap including practical and educational considerations beyond the hepatology field that could improve patient care and support implementation of clinical guidance within the SEEMEA region. This work is informed by a narrative review and expert input obtained through structured discussions, to examine the status quo and identify key gaps in the MASLD/MASH management, unravelling the patient journey from screening and diagnosis to treatment and follow-up. Furthermore, we advise on priorities on screening triggers and, considering the limited availability of vibration-controlled transient elastography (VCTE), discuss alternative approaches to achieve accurate and timely diagnosis. Finally, following the approval of resmetirom and semaglutide 2.4 mg for MASH treatment, we review the evolving pharmacotherapy landscape and propose a "blueprint" for a specialised MASLD clinic, suggesting mandatory and optional facilities for optimised care.
Andexanet alfa is a reversal agent for factor Xa (FXa) inhibitors (rivaroxaban and apixaban) and is available for the treatment of severe FXa inhibitor-associated bleeding. However, an increase in thrombotic events after administration has been reported. This multicenter Dutch observational study aimed to provide insights into the characteristics, usage patterns, and clinical outcomes of the Dutch patient population treated with andexanet alfa. We included all patients treated with on- and off-label andexanet alfa from 6 of the 11 hospitals in the Netherlands that prescribed andexanet alfa between June 2019 and December 2023. Data were collected by LOGEX, a Dutch healthcare data company, using healthcare administrative data and questionnaires completed by clinicians at participating centers. Patient characteristics, details related to andexanet alfa administration, and 30-day clinical outcomes, including thrombotic events and all-cause mortality, were collected. A total of 217 patients received andexanet alfa, including 192 treated on-label and 25 off-label. In the on-label group, the median age was 77 years (IQR, 69-82 years), and intracranial hemorrhage was the most common indication for reversal (61%). Most patients received a low dose (≤1000 mg) and were administered andexanet alfa within 4 hours of hospital admission (79%). The overall 30-day cumulative incidence of thrombotic events was 4.6%, and no thrombotic events occurred after anticoagulation was reinitiated. All-cause mortality was 34%, with similar rates between the on- and off-label groups. Andexanet alfa was primarily prescribed for the reversal of FXa inhibitors in patients with intracerebral hemorrhage. We observed a lower incidence of thrombotic events than reported in clinical trials.
Intravenous immunoglobulin (IVIg) is the standard of care for the treatment of Kawasaki disease (KD) and should be administered within 10 days of the onset of fever. Management guidelines for children with KD who defervesce spontaneously are not clear. In this study, we analysed patients with KD diagnosed between 1994 and 2024 at our centre who had defervesced spontaneously, had normal acute-phase reactants, and underwent echocardiographic examination, and in whom IVIg had not been administered. We reviewed the records of patients with KD from January 1994 - December 2024. The diagnosis of KD was based on standard guidelines. Patients with KD were said to be in spontaneous defervescence when they remained afebrile for ≥ 48 h, had normal acute-phase reactants [C-reactive protein (CRP), Erythrocyte sedimentation rate (ESR)] and no coronary artery abnormalities (CAAs) on echocardiography at presentation, and when IVIg was not administered. Patients with spontaneous defervescence were subdivided into (i) early defervescence (Ed-KD), if the interval between onset of symptoms and defervescence was < 10 days, and (ii) late defervescence (Ld-KD), if the duration between onset of symptoms and defervescence was ≥ 10 days, respectively. Details of the clinical profile, laboratory investigations, and echocardiography findings were obtained from the records. Of the 1499 patients with KD enrolled during the study period, 115 patients (7.7%; 86 boys) defervesced spontaneously. The median age at disease onset was 6 years (mean, 5.6 years; range, 0.8-15 years). The median duration of fever, defined as the total duration of the febrile episode before spontaneous defervescence, was 5 days (range, 1-21 days). The median interval between illness onset (defined as fever onset) and diagnosis of KD was 15 days (range, 4-40 days), indicating that diagnosis was often made after fever had already subsided. The most common clinical feature was periungual desquamation, followed by rash, oral-mucosal changes, cervical lymphadenopathy, and conjunctival injection. Incomplete presentation was noted in 73.9% (n = 85/115) of patients. No patient has developed CAAs or other cardiac sequelae over a median follow-up of 9 months (range 2 months-156 months). The cumulative follow-up for the cohort was 235 patient-years. The 'low-risk' subgroup of patients with KD who defervesce spontaneously, and have normal acute phase reactants with no CAAs at presentation, have good clinical and coronary outcomes.
Strongyloidiasis is a neglected soil-transmitted helminthiasis caused by Strongyloides stercoralis, affecting an estimated 300-600 million people worldwide. Due to its ability to cause autoinfection, the parasite may persist lifelong and lead to severe complications. While gastrointestinal symptoms are common, presentation as gastric outlet obstruction (GOO) is rare and can mimic malignancy. A 42-year-old male presented with several months of non-projectile vomiting, epigastric pain, indigestion, anorexia, and significant weight loss. Examination revealed dehydration, hypotension, and tachycardia. Laboratory tests showed mild microcytic anemia and mild hyponatremia, with normal eosinophil counts. Abdominal ultrasonography suggested gastric outlet obstruction. Upper gastrointestinal endoscopy demonstrated a circumferential ulcerated duodenal lesion with pyloric deformity, initially suspicious for malignancy. Histopathological examination of duodenal biopsies revealed S. stercoralis. After correction of hypovolemia and electrolyte imbalance, the patient was treated with ivermectin, resulting in complete resolution of symptoms. Strongyloidiasis has a broad clinical spectrum, ranging from asymptomatic infection to disseminated disease. Gastric outlet obstruction is an uncommon manifestation and poses diagnostic challenges, particularly in endemic regions. Endoscopy with histopathological confirmation is essential for diagnosis when clinical and laboratory findings are non-specific. Prompt treatment with ivermectin is highly effective and prevents serious complications. Strongyloidiasis should be considered in the differential diagnosis of gastric outlet obstruction, especially in endemic areas. Early diagnosis and timely antiparasitic treatment are crucial to reduce morbidity and prevent life-threatening complications.
Kidney transplantation faces organ shortages, underscoring the need for early risk stratification of graft loss. We developed and validated a 12-month prediction model that treats death as a competing event. We conducted a retrospective cohort study of 2030 adult kidney transplant recipients (2008-2023) from Colombia's largest transplant network. Models included a random survival forest for competing risks (RSF-CR) and Fine-Gray (FG) regression. Internal validation used stratified cross-validation. Model performance was evaluated via discrimination (C-index), calibration and clinical utility (decision curve analysis). Key predictors included donor type, stroke cause of death (deceased donor), recipient age, donor creatinine, panel reactive antibodies (PRA) class I >20, expanded criteria donor, donor age, years on dialysis, PRA class II >20, donor hypertension, donor-recipient compatibility and retransplantation. The RSF-CR model outperformed the FG, achieving a C-index of 0.87 (versus 0.72) and high sensitivity (88%). It accurately identified low-risk candidates (negative predictive value 98%) and showed a positive net benefit. We developed and validated a predictive model for first-year graft loss in kidney transplant recipients using a machine learning for competing risks model. The model showed strong discriminative ability and moderate calibration. Further temporal validation in our population and external validation in other clinical contexts is required to ensure its applicability.