IntroductionIn Mexico, delays in pediatric cancer diagnosis remain a major barrier to timely care and are partly driven by inefficiencies in referral pathways. This study aimed to evaluate the impact of a direct pathway on referral intervals for patients with suspected childhood cancer treated at a high-specialty hospital in Mexico.MethodsWe conducted a retrospective observational cohort study based on a comprehensive review of medical records of patients referred to a high-specialty hospital in Mexico between 2017 and 2022. Patients' characteristics, along with dates from symptom recognition to diagnosis, were collected. The exposure was the referral pathway: standard versus direct (Golden Code strategy) pathway, which enables access to pediatric oncology through a zero-rejection policy. The primary outcome was the time attributable to oncological referral (TAOR), analyzed as a continuous variable and a dichotomous outcome. Secondary intervals were calculated using standardized definitions. Regression models were used to evaluate factors associated with untimely (>7 days) referral.ResultsA total of 399 patients were included. The direct pathway was associated with a shorter TAOR compared to the standard pathway (median 2.0 vs. 7.0 days; p<0.001). The proportion of timely referrals was substantially higher in the direct pathway (91.3%) than in the standard (50.6%) and reduced the likelihood of an untimely referral (OR = 0.098, 95% CI: 0.055-0.173; p<0.001). No differences were observed in other diagnostic intervals.ConclusionThe direct referral pathway improves the timeliness and consistency of access to pediatric oncology care by reducing referral delays and increasing the proportion of patients evaluated within recommended referral intervals. However, the absence of changes in the secondary intervals, such as time to oncological diagnosis, highlights the need for complementary actions targeting downstream diagnostic processes. Strengthening referral systems represents a feasible and impactful strategy to address delays in pediatric cancer care in middle-income settings. In Mexico, many children and adolescents with suspected cancer experience delays before seeing a cancer specialist. These delays can occur for various reasons, including the organization of the health system. When referrals move slowly through several levels of care, diagnosis and treatment may be postponed. This study examined a program called the Golden Code, which is designed to help children with possible cancer access a pediatric cancer specialist more quickly. The program allows doctors to refer patients directly to a specialized hospital, reducing administrative steps and speeding up appointments. Researchers reviewed the medical records of 399 children and adolescents treated between 2017 and 2022. They compared those referred through the Golden Code program with those referred through the usual system. The results showed that children referred through the Golden Code were seen by a cancer specialist much faster. On average, they had their specialist visit within two days, compared to seven days under the standard referral system. The program greatly reduced the chances of a delayed specialist visit. These findings show that improving how patients are referred within the health system can make an important difference in how quickly children with suspected cancer receive expert evaluation. Although Mexico performs better than some countries with fewer resources, further improvements in referral processes and access to care could help ensure children receive timely diagnosis and treatment.
A 13-year-old neutered female domestic shorthair cat was referred for weight loss, polyphagia, polyuria, polydipsia and intermittent vomiting. Blood work demonstrated diabetes mellitus; abdominal ultrasonography revealed a hypoechoic, thickened pancreas with two large fluid-filled cavities within the body and right limb. Cytology of the aspirated fluid indicated suppurative inflammation with bacterial infection, which cultured Pasteurella multocida. Medical management for diabetes mellitus and pancreatic abscessation was initiated. After approximately 4 months of antimicrobial therapy and five percutaneous drainages, clinical signs improved; nevertheless, serial abdominal ultrasonography demonstrated persistent pancreatic abscessation, while repeated cultures and antibiograms documented progressively resistant bacterial infections. The condition culminated in abscess rupture and septic peritonitis, prompting surgical drainage and omentalisation. Histopathological examination of the pancreatic parenchyma revealed severe lymphoplasmacytic pancreatitis with glandular atrophy, while evaluation of the pancreatic tissue associated with the abscess demonstrated a suspected pancreatic exocrine neoplasm, most compatible with a well-differentiated adenocarcinoma. This case highlights the need for earlier consideration of surgical intervention in cases of recurrent pancreatic abscessation and underscores the importance of including concurrent pancreatic neoplasia as a differential diagnosis in chronic, non-resolving presentations.
Scrub typhus has nonspecific symptoms, making it easy to miss or underdiagnose. This retrospective study evaluated targeted next-generation sequencing (tNGS) for the early diagnosis of acute Orientia tsutsugamushi infection in terms of feasibility and application value. This retrospective study included 49 patients with suspected scrub typhus as the case group. Among them, 28 patients with eschar or ulcers were assigned to the clinical diagnosis group. The remaining 21 patients without eschar or ulcers formed the clinically suspected group. Additionally, 48 patients with nonscrub typhus bloodstream infections during the same period were included in the negative control group. Clinical data and tNGS results were collected for all the patients. No significant differences were found between the clinical diagnosis group and the clinically suspected group in sex, age, time from onset to sampling, season of onset, complications, or clinical prognosis (p > 0.05). The sensitivity of tNGS for diagnosing scrub typhus was 91.8% (45/49), and the specificity was 100.0% (48/48). No significant differences were observed between the clinically diagnosed group and the clinically suspected group regarding the positivity rate of O. tsutsugamushi detected by tNGS or the therapeutic response to doxycycline (p > 0.05). Significant changes were observed in the median eosinophil count (EOS), platelet count (PLT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) before and after doxycycline treatment in the case group (p < 0.001). TNGS demonstrated high sensitivity and specificity for the detection of O. tsutsugamushi. It facilitates the early diagnosis of scrub typhus, particularly in suspected cases without eschars. However, prospective studies are needed for validation.
Predictive biomarkers for symptomatic tuberculosis (TB) progression would transform targeted prevention efforts. Although interferon-gamma release assays (IGRAs), including QuantiFERON® TB-Gold Plus (QFT-Plus), have been studied for this purpose, systematic evaluation of the QFT-Plus TB1 and TB2 Interferon-Gamma (IFNγ) concentrations remains limited, particularly in high-burden TB settings. Baseline TB1 and TB2 IFNγ concentrations from 5246 participants (ages 15-34 years) in TB-endemic regions were analyzed in relation to subsequent TB outcomes over a median of 525 days follow-up (NCT05190146). Participants were categorized as controls (no TB), suspected TB (no microbiological confirmation), or laboratory-confirmed TB, including a subset meeting a stringent case definition (≥2 positive microbiologic tests). Associations between baseline IFNγ concentrations and progression to symptomatic TB were assessed. In the full cohort (IGRA+/- participants), baseline TB2 IFNγ concentrations were significantly higher compared with controls among participants who developed suspected TB (P = .01), laboratory-confirmed TB (P = .01), or met the stringent case definition (P < .0001). In IGRA+ participants, baseline TB2 concentrations were significantly higher than controls in suspected (P = .01) and laboratory-confirmed (P = .02) groups. Associations with baseline TB1 IFNγ concentrations and TB progression were observed for participants meeting the stringent case definition within the full cohort (P = .001). Among stringent definition cases, TB2 concentrations achieved an area under the receiver operating characteristic curve of 0.84, with sensitivity of 80% and specificity of 78%. Quantitative IFNγ concentrations from QFT-Plus, particularly TB2, were associated with progression to symptomatic TB, met or exceeded WHO-recommended sensitivity and specificity thresholds for predictive biomarkers, and may support biomarker-based stratification in TB clinical research.
Diagnosing facioscapulohumeral muscular dystrophy (FSHD) requires integrated evaluation of D4Z4 repeat size, permissive haplotype status, epigenetic context and alternative molecular aetiologies, particularly in borderline, non-contracted or structurally complex cases. We evaluated 135 unrelated referrals with suspected FSHD at a tertiary referral centre in Türkiye between 2019 and 2026. First-line testing included single-molecule D4Z4 repeat sizing, haplotyping and structural analysis using molecular combing or optical genome mapping. DR1 methylation profiling and whole-exome sequencing (WES) were used as second-line tests in unresolved, borderline, non-contracted or clinically atypical cases. FSHD was confirmed in 121/135 referrals (89.6%): FSHD1 in 109/121 (90.1%), FSHD1+2 in 4/121 (3.3%) and FSHD2 in 8/121 (6.6%). Of the remaining referrals, two had confirmed alternative molecular diagnoses, one had a candidate DES-related myopathy, six were FSHD excluded and five remained unresolved. Single-molecule analysis identified mosaicism, allelic imbalance, homozygous contracted genotypes and complex 4q configurations. Second-line DR1 methylation refined borderline and non-contracted cases, while WES identified six SMCHD1 variants, including four identified in this study, and candidate alternative or dual diagnoses. Exploratory analyses showed that age-corrected severity captured repeat length and age-at-onset-related gradients better than raw severity scores. These findings support the real-world diagnostic value of combining established structural, epigenetic and sequencing-based methods for suspected FSHD, particularly in diagnostically challenging referrals. The study further provides cohort-level data from Türkiye, an under-represented population in the FSHD literature, and may inform future diagnostic interpretation of borderline, non-contracted and complex locus configurations.
Two rescued juvenile cats with unilateral severe shoulder deformities (SDs) suspected to be secondary to septic arthritis were referred for further management. Comprehensive diagnostic evaluations confirmed SD with suspected septic arthritis in both cases. Because of the poor prognosis for preserving shoulder joint function, shoulder arthrodesis was performed to relieve pain and restore forelimb weightbearing ability. At 6 and 8 years postoperatively, both cats exhibited normal motor function in the affected limbs, no signs of lameness and maintained a good quality of life. No evidence of osteomyelitis or implant failure was noted. These findings suggest that arthrodesis may be a viable and effective long-term treatment option for irreparable shoulder joint disorders in cats. Shoulder joint injuries and disorders are less common in cats than in dogs, and only a limited number of reports exist in the small animal orthopaedic literature. In clinical practice, SD in small animals is rarely documented, with few references regarding its aetiology and pathophysiology. This report presents two cases of SD in rescued cats, demonstrating that shoulder arthrodesis can be an effective treatment for irreparable feline shoulder joint disorders. To the best of our knowledge, this is the first report to describe long-term clinical and radiographic outcomes of shoulder arthrodesis in cats with SD. Surgical fusion of the shoulder joint to treat severe shoulder deformity caused by infection in two cats Two young rescued cats were referred for treatment of severe deformities of one shoulder, likely caused by infection in the joint at an early age. Because the shoulder joints could not be repaired, a surgical procedure called shoulder arthrodesis (joint fusion) was performed to reduce pain and allow the cats to use their front legs normally. Both cats recovered well and were able to walk and use their affected limbs without lameness. Long-term follow-up at 6 and 8 years after surgery showed stable implants, successful bone fusion, and no signs of infection, with both cats maintaining a good quality of life. Shoulder joint problems are less common in cats than in dogs, and there are very few reports describing this condition or its treatment in cats. This case report shows that shoulder arthrodesis can be an effective long-term treatment option when the shoulder joint cannot be preserved. To our knowledge, this is the first report to describe long-term clinical and imaging outcomes of this procedure in cats with severe shoulder deformity.
The accurate and timely diagnosis of inherited retinal diseases (IRDs) represents an unmet clinical need in ophthalmology, as the current pathways rely on resource-intensive phenotyping, multidisciplinary expertise and genetic testing. Here we developed Retina4IRD, an artificial intelligence (AI)-based clinician decision support system (CDSS) that predicts 17 genotype categories from retina images. Retina4IRD uses a Vision Transformer model pretrained with RETFound. We then trained and validated Retina4IRD using multimodal data with color fundus photographs and optical coherence tomography scans from 1,843 genetically confirmed patients (3,376 eyes) across China, South Korea and Poland. The top-5 prediction accuracy was 0.904 (95% confidence interval (CI): 0.896-0.912) and 0.856 (95% CI: 0.850-0.863) for internal and external validation, respectively. We conducted a randomized controlled trial with 300 participants with suspected IRD randomized 1:1 to either Retina4IRD-assisted specialist arm or specialist-only arm. Of these, 295 participants (median age 33 years, 114 (38.6%) females) with available next-generation sequencing reports were included in the final analysis. The primary outcome was met: top-5 genetic accuracy was significantly higher in the Retina4IRD-assisted specialist arm versus the specialist-only arm (88.5% versus 67.3%, P < 0.001). For secondary endpoints, top-1 to top-4 accuracies all favored the Retina4IRD-assisted specialist arm, with top-1 accuracy of 37.8% versus 22.4% and top-4 accuracy of 81.8% versus 53.1%, respectively. Post hoc analyses demonstrated that, with Retina4IRD assistance, clinicians made better management decisions, and the composite downstream management score indicated significantly higher scores relative to the control group (37.7 versus 28.5, P < 0.001). Our study shows that Retina4IRD is a CDSS tool prior to genetic testing and aligns with clinical workflow for patients with suspected IRDs. ClinicalTrials.gov identifier: NCT06839170 .
Post-surgical pyoderma gangrenosum (PSPG) is a challenging diagnosis associated with significant morbidity, often misidentified as postoperative infections, leading to inappropriate management. This systematic review aims to elucidate the characteristics, management strategies, and outcomes of PSPG in the context of foot and ankle surgery to improve diagnostic accuracy and patient care. A systematic literature search was conducted across multiple databases, including PubMed, Scopus, and Embase, for cases of PSPG following foot and ankle surgery published up to January 2023. Data on demographics, clinical presentation, management, and outcomes were extracted and analyzed. Ten cases met the inclusion criteria, predominantly females presenting with rapidly worsening and painful postoperative ulcers. A high rate of negative cultures was observed during the patients' treatment period. Dermatology consults initially suspected 83.33% of the cases. Notably, 30% of patients underwent amputation of various parts of the lower extremity, all diagnosed more than 35 days after symptom onset, and were female. The mainstream treatment for PSPG involved systemic immunosuppressants, with corticosteroids being the most common, effectively resolving symptoms in the majority of instances. PSPG should be suspected in patients with unexplained, worsening postoperative wounds. Early recognition and appropriate treatment with immunosuppressants are crucial to prevent severe outcomes. Multidisciplinary management involving dermatologists and surgeons is recommended to optimize patient outcomes. Further research is needed to establish robust diagnostic and management protocols for PSPG in the surgical context.
Ultrasound (US) is currently the primary modality for assessing acute appendicitis in children. However, as rapid abdominal magnetic resonance imaging (MRI) protocols become more readily available, using MRI as a first-line modality in certain patients may decrease the need for additional studies and reduce time to diagnosis. This study evaluates imaging utilization patterns for suspected appendicitis at a large pediatric emergency department and identifies clinical scenarios where MRI may serve as a more efficient first-line imaging modality. We retrospectively analyzed 5856 pediatric and young adult patients who underwent US, MRI, or both for suspected appendicitis (2016-2023), focusing on imaging utilization, demographics, and examination timing. US was used as the primary modality in 86% of cases, with 22% of these patients requiring subsequent MRI. 7% of patients underwent MRI first. Time from imaging order to completion was significantly longer for the US + MRI group (217.72 min) compared to US-only (101.82 min) or MRI-only (120.75 min) (p < 0.001). Age, weight, and female sex correlated with increased US examination duration (p < 0.001), whereas MRI times remained consistent. MRI use increased from day (20.3%) to evening (23.4%) to night (29.5%), while US use declined but remained the dominant modality (p < 0.001). Nearly a quarter of patients undergoing US for appendicitis evaluation ultimately proceed to MRI, resulting in diagnostic delays. MRI may be underutilized as a first-line modality in this subset of patients.
Pulmonary infections are common and potentially life-threatening in critically ill patients. Conventional microbiological tests (CMTs) often show limited sensitivity, particularly in the setting of prior antimicrobial exposure. Targeted next-generation sequencing (tNGS) has emerged as an alternative approach for broad pathogen detection; however, data describing pathogen spectrum, mixed infection patterns, and diagnostic performance in critically ill populations remain limited. This retrospective study included 217 critically ill patients with suspected pulmonary infection who underwent tNGS testing of respiratory specimens. Baseline clinical characteristics were summarized. The pathogen spectrum and mixed detection patterns identified by tNGS were analyzed, including mixed microbial codetection. Diagnostic performance of tNGS was compared with that of CMTs using clinical diagnosis as the reference standard. Sensitivity, specificity, accuracy, agreement indices, and McNemar's test were applied. tNGS detected at least one microorganism in 208 of 217 patients, yielding a significantly higher overall detection rate than CMTs. A broad spectrum of bacterial, viral, and fungal pathogens was identified, and mixed detections were common, frequently involving organisms from different pathogen categories. Co-occurrence network analysis highlighted recurrent patterns of mixed microbial detection in this cohort. Compared with CMTs, tNGS demonstrated substantially higher sensitivity and overall diagnostic accuracy, whereas conventional methods showed higher specificity. tNGS provides a comprehensive overview of the pathogen spectrum and mixed detection patterns in critically ill patients with suspected pulmonary infection. Compared with CMTs, tNGS offers a markedly higher detection rate and sensitivity. However, careful clinical interpretation remains essential, particularly in the context of frequent mixed microbial detections, to ensure appropriate integration of sequencing results into clinical decision-making.
Timely transfer of patients with suspected LVO remains critical in acute stroke systems. Artificial intelligence (AI)-based imaging tools are increasingly implemented to support triage in non-thrombectomy centres. We assessed whether integrating an AI algorithm within established tele-stroke centres reduces time to transfer decision. We conducted a prospective, multicentre, quasi-experimental study comparing consecutive cohorts in 2 tele-stroke centres referring to a single comprehensive stroke centre, before and after implementation of the Methinks Stroke Suite, an AI algorithm for LVO detection on non-contrast CT (NCCT) and CTA. Consecutive transferred patients with suspected acute ischaemic stroke were included. Remote vascular neurologists retained responsibility for final transfer decisions. Each phase spanned approximately 15 months. The primary outcome was time from arrival at the local centre to emergency medical services activation. Secondary outcomes included workflow intervals, imaging utilisation and algorithm performance. We included 265 patients (136 in the post-implementation cohort; 129 in the pre-implementation cohort). Adjusted median time from arrival to transfer request did not differ (median difference - 2.40 min; 95% CI, -6.16 to 4.48). Post-implementation, time from imaging to transfer request (-7.16 min; 95% CI, -13.02 to -1.85) and arrival to groin puncture (-31.28 min; 95% CI, -60.89 to -13.74) decreased. Computed tomography angiography acquisition at referring centres increased (28%-81%), reducing repeat imaging at the comprehensive centre (79%-42%). Non-contrast CT-based AI prediction yielded a positive predictive value of 66% for endovascular treatment. Artificial intelligence implementation was not associated with a shorter time to transfer decision. Fewer redundant imaging examinations were associated with a shorter time to reperfusion.
Phenotypic presentations and aetiologies of disorders/differences of sex development (DSD) are variable. While postnatal management is well described, no consensus exists regarding prenatal care, despite increasingly frequent detection. To describe prenatal management practices of isolated ultrasound suspicion of DSD referred to the Multidisciplinary Center for Prenatal Diagnosis (MCPD) of Lyon over a 10-year period. Retrospective study of pregnancies referred to MCPD between January 2013 and December 2022 for isolated ultrasound suspicion of DSD. Foetuses referred for family history risk were not included. DSD were considered isolated when no additional malformation was suspected at referral, except minor cardiac anomalies, renal pelvis or ureteral dilation and intrauterine growth restriction (IUGR). 71 patients were referred for suspected isolated DSD, 57 were confirmed by experts. At birth, 52.3% newborn were preterm and 52.3% had IUGR. Among the 57 prenatally suspicion, 41 children presented a DSD phenotype. SRY testing on maternal blood was performed in 17.5% of cases and invasive examination in 59.6% of cases. Amniotic fluid analyses included steroid profile (76.5%), biochemical analyses for SLO (64.7%) and genetic analyses (100%). Genetic analyses comprised karyotype (100%), CGH array (67.6%), DSD panel (14.7%), targeted gene analysis (35.3%). A molecular diagnosis was obtained in 13 cases, including 5 prenatally. Three fetuses were ultimately diagnosed with severe neurological condition. Prenatal assessment may support counselling and care planning for families expecting a child with DSD. Further prospective studies are necessary to confirm these findings and formulate recommendations for prenatal management of DSD.
Background Maternal sepsis remains a major cause of maternal morbidity and mortality, particularly in resource-limited settings where early recognition is often delayed. However, conventional sepsis scoring systems have limited applicability in pregnancy because physiological adaptations of gestation can mimic features of sepsis and affect score performance, highlighting the potential role of pregnancy-specific tools, such as the Sepsis in Obstetrics Score (SOS), for risk stratification. Materials and methods This analytical cross-sectional study was conducted at a tertiary care center in Bhopal, India, from January 2022 to January 2023. A total of 450 antenatal women with suspected infection were included. The SOS was calculated at admission using pregnancy-adjusted physiological and laboratory parameters and categorized as low risk (SOS <6) or high risk (SOS ≥6), indicating increased risk of severe sepsis-related adverse outcomes. Associations between clinical variables and elevated SOS were assessed using the chi-square test with odds ratios (OR). Continuous variables were compared using the independent samples t-test. Multivariable logistic regression analysis identified independent predictors of elevated SOS. Results Among the 450 participants, 50 (11.1%) were categorized as high risk (SOS ≥6). Significant predictors of elevated SOS included ≥4 vaginal examinations, premature rupture of membranes (PROM), PROM lasting >24 hours, and abnormal vaginal discharge. Multivariable analysis identified PROM >24 hours (adjusted OR (aOR) 3.48), ≥4 vaginal examinations (aOR 3.05), and abnormal vaginal discharge (aOR 2.21) as independent predictors. Women with elevated SOS scores demonstrated significant physiological derangements. Conclusions The SOS may be useful as a bedside risk-stratification tool among antenatal women with suspected infection. Elevated SOS was primarily associated with modifiable intrapartum and infection-related factors, highlighting potential opportunities for preventive obstetric interventions.
To compare the diagnostic efficacy of white light endoscopic (WLE), narrow band imaging (NBI), and iodine staining, both individually and in combination, for the detection of early esophageal cancer (EC) and precancerous lesions. A retrospective analysis was conducted on 55 patients with suspected early EC or precancerous lesions who were treated at Wuxi Second People's Hospital between January 2022 and June 2023. All patients underwent simultaneous endoscopic examination using WLI, NBI, and iodine staining. A total of 63 lesions were identified. Surgical histopathological results and/or follow-up confirmation served as the gold standard. The diagnostic performance (including accuracy, sensitivity, and negative predictive value) of each method individually and in combination was observed and compared. Among the 63 suspected lesions, 5 cases of early EC and 37 cases of precancerous lesions were confirmed by histopathology or follow-up. The combined diagnostic and iodine staining approach demonstrated significantly higher accuracy and sensitivity for early EC compared to WLI or NBI alone (P < 0.05). Agreement with pathological findings was poor for WLI (Kappa = 0.327), fair for NBI (Kappa = 0.476), fair for iodine staining (Kappa = 0.577), and substantial for the combined method (Kappa = 0.715). Among negative lesions, the false positive rate for mucosal staining was lower than that for background coloration. Both endoscopic NBI and iodine staining exhibit relatively high clinical detection rates for early EC and precancerous lesions. Their combined use can further enhance the detection rate of these conditions.
This prospective randomized study protocol is designed to determine whether low-concentration iodine contrast media can maintain coronary enhancement on coronary computed tomography angiography (CCTA) compared with high-concentration iodine contrast media under standardized acquisition conditions. Dynamic stress computed tomography perfusion (CTP)-derived myocardial blood flow (MBF) will be assessed as a key secondary quantitative endpoint. Exploratory diagnostic performance analyses using invasive coronary angiography (ICA) and fractional flow reserve (FFR) will be performed only in clinically indicated invasive testing subgroups. The trial plans to enroll 258 adults (age ≥ 40 years) with known or suspected coronary artery disease referred for clinically indicated cardiac computed tomography, including CCTA with planned dynamic stress CTP. Participants will be randomized 1:1 to receive low-concentration iodine contrast media (270 mg I/mL) or high-concentration iodine contrast media (350 mg I/mL). The primary endpoint is quantitative coronary enhancement on CCTA. Dynamic stress CTP-derived MBF will be evaluated as a key secondary endpoint focused on quantitative comparability. ICA/FFR-based diagnostic performance analyses will be considered prespecified exploratory analyses in participants who undergo invasive testing as part of routine clinical care. The primary endpoint will be analyzed using linear mixed-effects models with a prespecified noninferiority margin, and MBF will be analyzed using mixed-effects models without claiming formal equivalence or noninferiority. This study protocol is expected to clarify whether low-concentration iodine contrast media can maintain CCTA coronary enhancement and support quantitative dynamic stress CTP assessment while reducing iodine exposure. Because ICA and FFR are clinically driven rather than protocol mandated, diagnostic performance analyses will be interpreted cautiously and regarded as exploratory. CRIS identifier: KCT0011418. Registered on January 7, 2026.
Interstitial lung disease (ILD) is a toxicity of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). We characterized agent-specific fatality and timing patterns in the Japanese Adverse Drug Event Report database (JADER). We analyzed March 2026 JADER reports accepted from 2004 Q4 through 2025 Q2. Eligible reports involved single-agent osimertinib, gefitinib, erlotinib, or afatinib as the suspected drug for non-small cell lung cancer-related indications and were coded with the core ILD term. Fatal outcome, time to onset (TTO), and operationally defined pre-existing lung disease were evaluated. Logistic regression adjusted for agent, pre-existing lung disease, sex, age group, and report year. Among 3206 reports, fatal outcomes were reported in 10.8% of osimertinib, 33.1% of gefitinib, 32.2% of erlotinib, and 21.0% of afatinib cases. Among 2534 reports with evaluable TTO, median TTO were 55, 28, 22, and 35.5 days, respectively. Compared with osimertinib, adjusted odds of fatal outcome were higher for gefitinib (odds ratio (OR) 2.64, 95% confidence interval (CI) 1.80-3.86), erlotinib (OR 2.66, 95% CI 1.88-3.76), and afatinib (OR 1.87, 95% CI 1.22-2.88). Pre-existing lung disease showed an imprecise association (OR 1.30, 95% CI 1.00-1.70). ILD reports showed apparent agent-specific differences in timing and fatality. Osimertinib showed a later, less fatal pattern; gefitinib and erlotinib earlier, more fatal patterns; and afatinib an intermediate profile. These findings describe pharmacovigilance reporting patterns, not incidence, causal comparative safety, or treatment-selection guidance.
Esophageal varices (EV) need monitoring in patients with portal hypertension. In 2022, a single-use ultra-slim (3.5 mm) gastroscope was approved for use in children and adults. This study evaluated if an ultra-slim gastroscope could evaluate, grade, and corroborate the presence of EV in sedated pediatric patients as compared to standard oral gastroscopes (>8.6 mm). Ten pediatric subjects with suspected or known EV underwent surveillance endoscopy using the ultra-slim endoscope followed by the standard gastroscope under sedation. Esophageal findings were analyzed using images from both procedures by two independent endoscopists. Visual findings for the presence or absence of EV had 100% congruence. EV were identified in 8/10 subjects (Grade I (4), Grade II (3), and Grade II/III (1)). Endoscopic grading matched between both endoscopes in 7/8 (87.5%) cases. Ultra-slim and standard gastroscopes showed reliable visual agreement and could be used similarly in certain clinical settings to evaluate EV.
Postoperative pneumonia significantly prolongs mechanical ventilation (MV) and intensive care unit (ICU) stay after pediatric cardiac surgery. Lung ultrasound (LUS) offers superior diagnostic accuracy compared with chest radiography, but its longitudinal impact on clinical outcomes remains unclear. We evaluated the effect of structured LUS implementation on pneumonia detection, antibiotic stewardship, and ventilatory outcomes in a pediatric cardiac surgical ICU (PCSICU). This retrospective three-era study included all bronchoalveolar lavage (BAL) episodes performed for suspected postoperative pneumonia between 2019 and 2025. Patients were grouped as pre-LUS (2019-2020), LUS introduction (2021-2022), and established LUS (2023-2025). Outcomes included BAL positivity, antibiotic escalation, reintubation, and MV duration. In the established LUS era, pneumonia severity was classified using a structured 12-zone protocol into low-, moderate-, and high-yield categories. Categorical variables were compared using Chi-square tests and MV duration using Kruskal-Wallis with Bonferroni correction. A total of 313 BAL episodes were analyzed (48, 125, and 140 across the three eras). BAL positivity declined significantly from 70.8% in the pre-LUS era to 42.4% and 43.6% in the later eras (P = 0.0018). Among BAL-positive cases, antibiotic escalation increased progressively (52.9%, 62.3%, and 88.5%; P = 0.00027), while blind escalation among BAL-negative patients decreased markedly (50.0%, 20.8%, and 8.9%; P = 0.00060). Median MV duration decreased significantly from 95.5 h to 46.5 h across three eras (P = 0.00030). Higher LUS yield categories were strongly associated with BAL positivity (P < 0.001), reintubation (P = 0.0336), and Tier-3 antibiotic escalation. Structured LUS adoption improved early pneumonia detection, antibiotic stewardship, and postoperative ventilatory outcomes. Routine LUS integration may significantly improve multidomain outcomes in PCSICUs.
To evaluate the additive value of a zero echo time (ZTE) sequence to standard brachial plexus MR neurography (MRN) for detecting and characterizing osseous anomalies in patients with suspected neurogenic thoracic outlet syndrome (nTOS). In this retrospective, case-control study (January 2022-March 2025), unilateral brachial plexus MRN examinations with ZTE and reference imaging (radiographs and/or CT) were included. Two board-certified radiologists determined case status and osseous anomaly subtype (cervical rib, rib synostosis, or elongated C7 transverse process) on the reference imaging. Age- and sex-matched controls were randomly selected. Three musculoskeletal radiologists independently reviewed each examination in 3 rounds (MRN-only, ZTE-only, MRN + ZTE). Inter-reader agreement was assessed, and diagnostic performance was compared with reference standard. Thirty examinations from 27 subjects (20 female; median age 31 years) were analyzed, including 15 case examinations (elongated C7 transverse process n = 7, cervical rib n = 4, rib synostosis n = 4) and 15 control examinations. Accuracy for osseous anomaly detection was highest in ZTE-only (0.90; sensitivity 0.80; specificity 1.00), followed by MRN + ZTE (0.87; 0.73; 1.00) and MRN-only (0.73; 0.53; 0.93). MRN + ZTE identified anomaly-related nerve impingement more frequently than MRN-only. MRN + ZTE showed the highest agreement for osseous anomaly detection and subtype (κ = 0.68 and 0.61), compared with MRN-only (κ = 0.53 and 0.56) and ZTE-only (κ = 0.59 and 0.54). Agreement for nerve impingement improved from fair with MRN-only (κ = 0.40) to substantial with MRN + ZTE (κ = 0.62). ZTE improves detection of osseous anomalies in brachial plexus MRN and increases inter-reader agreement and diagnostic confidence, supporting its incorporation into MR protocols for nTOS evaluation.
Mamushi (Gloydius blomhoffii) bite is the most common type of snakebite in Japan. However, clinical information on pediatric patients remains limited. This study aimed to clarify the clinical characteristics of pediatric cases of mamushi envenomation by making comparisons with adult cases. This secondary analysis used data from the OROCHI study, a multicenter prospective observational study conducted at 24 hospitals in Japan, of patients hospitalized for confirmed or suspected mamushi envenomation. The primary outcome was hospital stay. Secondary outcomes included adverse events, pain scores, and the grade of swelling. Patients were classified into pediatric (< 18 years) and adult (≥ 18 years) groups. Of the 106 patients enrolled in the OROCHI study, 99 met the inclusion criteria for this analysis (7 pediatric cases; 92 adult cases). There was no significant difference in median (interquartile range) hospital stay between the pediatric and adult groups (4 days; p = 0.375). Among patients who received antivenom, no adverse reactions were observed in the pediatric group, whereas four adults experienced adverse reactions, including one case of anaphylaxis. The pain scores at antivenom administration were higher in pediatric patients (median 10 vs. 5), but no significant differences were observed after 6 h. The grade of swelling did not differ significantly between the groups at any time point. The clinical course and outcomes of pediatric patients with mamushi envenomation appear similar to those of adult patients. Further accumulation of pediatric cases is warranted to strengthen these findings.