The study evaluated clinical and health economic consequences of two diagnostic strategies, standard of care (SOC) and SOC plus MeMed BV (MMBV; a host-response test designed to discriminate between bacterial and viral infections), for suspected community-acquired pneumonia (CAP) in adults from a French and Spanish healthcare perspective. A cost-consequence analysis using a decision tree for adults presenting to the emergency department with suspected CAP. The time horizon was less than one year, modeling a hypothetical cohort of 1,000 patients with low-to-moderate disease severity. Clinical outputs were derived from published studies; unit costs were sourced from national or regional tariffs and cost studies. Deterministic one-way sensitivity analyses accounted for uncertainty in model parameters. In the base case analysis, SOC + MMBV was cost-saving versus SOC alone in both countries. The total cost per 1,000 patients decreased from €523,557 to €304,064 in France and from €467,356 to €267,786 in Spain, resulting in savings of approximately €220 and €200 per patient, respectively. The cost of MMBV was offset by reductions in other diagnostic tests and hospital admissions. Per 1,000 patients, SOC + MMBV correctly identified 181 more viral infections than SOC alone, resulting in 181 fewer unnecessary antibiotic prescriptions and almost 600 fewer additional diagnostic tests performed. Key limitations include use of a simplified patient pathway, assuming correctly diagnosed patients are not admitted due to clinical deterioration, and a short-term time horizon focused on immediate clinical and economic outcomes. Conclusion Adding MMBV to SOC for adults with suspected CAP in EDs may be cost-saving for public payers in France and Spain. Adding MMBV to SOC for adults with suspected CAP in EDs can be cost-saving for public payers in France and Spain. Respiratory tract infections are among the leading causes of illness and death worldwide, with community-acquired pneumonia (CAP) being responsible for many hospital admissions in adults. When people arrive at the emergency department with suspected CAP, it is not always clear whether the illness is caused by bacteria or a virus. When the underlying cause is uncertain, patients may receive unnecessary antibiotics, undergo additional diagnostic tests, or be admitted to the hospital for observation without a clear clinical need.This study evaluated the clinical and health economic consequences of two diagnostic strategies: standard of care (SOC) and SOC plus MMBV. MMBV is a host-response test designed to distinguish between bacterial and viral infections. A decision-tree model was developed with 1,000 adults with suspected CAP and low-to-moderate disease severity, from French and Spanish healthcare system perspectives.SOC plus MMBV was projected to reduce costs by about €220 per patient in France and €200 per patient in Spain. Although MMBV adds an upfront test cost, this is offset by fewer other diagnostic tests, fewer unnecessary antibiotic courses, and fewer hospital admissions. Per 1,000 patients, SOC plus MMBV correctly identified 181 more viral infections than SOC alone.These results suggest that adding MMBV to SOC could support more targeted antibiotic use and reduce short-term healthcare costs for adults with suspected CAP in emergency departments. Real-world studies are needed to confirm effects on decisions and patient outcomes.
Neighborhood socioeconomic disadvantage, measured by Area Deprivation Index (ADI), is associated with disparities in health care and child welfare responses following evaluation for suspected child physical abuse. We sought to determine whether historical redlining and contemporary spatial social polarization strengthen associations between neighborhood disadvantage and caregiver exclusion at discharge, a system-level outcome reflecting child welfare involvement. This multicenter retrospective cohort study included children (age <18 y) admitted with suspected/ confirmed physical abuse at 7 New York pediatric trauma centers (2011-2023). Home addresses were linked to neighborhood disadvantage measures, including ADI, Social Vulnerability Index, Child Opportunity Index, Index of Concentration at the Extremes for race, income, and racialized economic segregation, and a Historic Redlining Score (HRS). The primary outcome was caregiver exclusion at discharge (legal removal from the home environment). Univariable and multivariable mixed-effects models adjusted for age, Injury Severity Score, and admission year. Of 1,242 patients, 517 (41.6%) experienced caregiver exclusion. These children were more often Black (29.6% vs. 20.0%, p < 0.001) and lived in neighborhoods with greater disadvantage [median (interquartile range); ADI: 78.0 (52.3 to 93.0) vs 52.5 (18.0 to 84.0); Child Opportunity Index: 26.0 (5.0 to 51.0) vs 31.0 (8.0 to 62.5), p < 0.001], compared with those without caregiver exclusion. Compared with ADI Quartile 1, children in the most disadvantaged neighborhoods (ADI: Q4) had 4.93-fold higher odds of caregiver exclusion (95% CI: 2.75 to 8.85). Inclusion of HRS improved model performance (area under the curve: 0.825 → 0.833); each unit increase in HRS increased the odds of caregiver exclusion by 38% (p = 0.045). Neighborhood deprivation is strongly associated with caregiver exclusion following hospitalization for suspected child physical abuse. This relationship is strengthened by incorporating historical redlining measures. These findings highlight the intersection of structural neighborhood disadvantage and system-level responses to child safety concerns, suggesting that historic patterns of disinvestment may continue to shape child welfare involvement. (J Trauma Acute Care Surg 2026;00:000-000. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). Prognostic/Epidemiological; Level III. Multicenter Retrospective Cohort Study.
Morbidity of placenta accreta spectrum (PAS) increases with increasing severity of placental attachment. PAS with only a focal area of invasion or focal PAS based on magnetic resonance imaging (MRI) has been defined in a previous study as the greatest dimension of involvement of 25 mm or less. The objective of this study was to describe maternal and neonatal outcomes in patients with prenatally suspected focal PAS as defined by MRI imaging. This is a retrospective cohort study evaluating prenatally suspected focal PAS between 2020 and 2024. Focal PAS was defined based on MRI. Delivery and neonatal outcomes were described for the entire cohort and these outcomes were then compared between patients who delivered at <37 weeks (preterm) or at ≥37 weeks (term). A neonatal composite of cord pH < 7, cord base excess <-12, APGARs ≤3, continuous positive airway pressure/ventilator support, hypoxic ischemic encephalopathy, birthweight <3rd percentile, neonatal intensive care unit admission (NICU), and hypoglycemia was compared. Of 40 cases of prenatally suspected focal PAS, 21 (52%) cases delivered preterm and 19 (48%) delivered at term. Six (15%) met International Federation of Gynecology and Obstetrics (FIGO) clinical criteria for PAS. Hysterectomy was performed in 3 (8%) cases. Pathology was negative in 33 (85%) patients, not sent in 1 patient, and positive for PAS in 6. The neonatal composite occurred in 11 (28%) neonates. Median APGARs at 1 min were 6 (6-8), no neonate had a pH < 7, and median birthweight was 2905 g (2721-3108 g). Ten (25%) infants were admitted to the NICU. Patients delivered preterm were more likely to have a placenta previa (76% vs. 42%, p = 0.0115) and were more likely to stay for more than 3 days in the hospital (24% vs. 0%, p = 0.049). Neonatal length of stay was longer (6 [4-14] vs. 4 [4-4] days, p = 0.003), and the rate of the neonatal composite outcome was higher in patients delivered preterm (43% vs. 11%, p = 0.034). Delivery and neonatal outcomes were favorable in cases of prenatally suspected focal PAS with low overall hysterectomy rates. Term delivery did not impact maternal outcomes, improved neonatal outcomes, and can be considered in an otherwise uncomplicated patient.
Early diagnosis of hematologic malignancies can be challenging when initial diagnostic studies are discordant, particularly because flow cytometry, although central to evaluation, may be non-diagnostic in evolving disease. We report the case of a 33-year-old female who presented with leukocytosis, systemic symptoms, and progressive hematologic abnormalities, including circulating blasts identified on peripheral blood analysis. Initial diagnostic evaluation included laboratory studies, peripheral smear review, and flow cytometry, followed by cross-sectional imaging that demonstrated an anterior mediastinal mass, lymphadenopathy, and hepatosplenomegaly concerning for lymphoproliferative malignancy. Despite strong clinical suspicion, early flow cytometric findings were insufficient for definitive classification, prompting escalation to bone marrow biopsy with comprehensive immunophenotypic and cytogenetic analysis. Bone marrow examination ultimately demonstrated T-lymphoblastic leukemia/lymphoma with an abnormal immature T-cell population and isolated ABL1 copy number gain in the absence of BCR::ABL1 fusion. The hospital course was further complicated by catheter-associated upper extremity thrombosis. This case highlights the limitations of isolated diagnostic modalities in early hematologic malignancy and underscores the importance of integrating clinical, laboratory, morphologic, immunophenotypic, and imaging findings. Persistent clinical suspicion should prompt timely tissue-based evaluation despite initially inconclusive studies to avoid delays in definitive diagnosis and management.
To evaluate the safety and effectiveness of the pregnancy-adapted YEARS guideline at a major referral emergency department. This was a single-centre, retrospective cohort study of the impact of pregnancy-adapted YEARS guideline at Townsville University Hospital Emergency Department. Pregnant women who presented between July 2018 and June 2025 (2 years before to 5 years after) and were investigated for possible pulmonary embolism (PE) were eligible. Safety was defined as the rate of venous thromboembolism (VTE) at 90 days, and effectiveness as the proportion of women who did not undergo imaging. A total of 532 pregnant women were identified, 76 in the 2 years pre-guideline and 456 in the 5 years post-guideline. Pre-guideline, 24 out of 76 (32%) had D-dimers with no imaging, 36 (47%) had both D-dimers and imaging, 16 (21%) had imaging without D-dimers and there was 1 diagnosed with PE (1.3%). Of the 456 women who presented after guideline introduction, 168 (37%) were evaluated with D-dimers alone, 276 (61%) had D-dimers and imaging, 12 (3%) had imaging without D-dimers and 4 (0.9%) were diagnosed with PE. Of the 168 women post-guideline assessed with D-dimers only, outcome data were available for 150 (89%), none of whom had VTE. The introduction of the pregnancy-adapted YEARS guideline was associated with increased investigation for PE. Over 5 years, there were no known cases of missed PE.
Fungal laryngitis is an uncommon clinical entity that may radiographically and symptomatically mimic laryngeal malignancy, posing diagnostic challenges. We present the case of a 62-year-old male with a 40-pack-year smoking history, inhaled corticosteroid use, hypertension, diabetes mellitus, hepatitis C, and substance and alcohol abuse who presented with progressive hoarseness, sore throat, and dyspnea. Computed tomography (CT) revealed a laryngeal mass causing supraglottic airway narrowing, initially suggestive of carcinoma. Fiberoptic laryngoscopy demonstrated extensive white patches of the oropharynx, hypopharynx, and larynx. The patient showed significant clinical improvement following intravenous fluconazole and steroid therapy. Subsequent microsuspension laryngoscopy with biopsy revealed acute/chronic mucositis with reactive epithelial changes but no malignancy. Special stains (Periodic acid-Schiff (PAS), Grocott's Methenamine Silver (GMS), and Acid-Fast Bacilli (AFB)) were negative for fungi, though prior antifungal response supported the diagnosis. This case underscores the importance of considering isolated fungal laryngitis in high-risk patients with laryngeal masses to avoid misdiagnosis and unnecessary interventions.
Pleural effusions are common in the ICU, often requiring drainage. Although fluid cultures are frequently obtained, pleural microbial findings in ICU patients remain poorly characterized. The current study aimed to assess prevalence and microbial characteristics of positive pleural fluid cultures in ICU patients, assessing positive cultures' associations with clinical assessments and 90-day mortality. Retrospective population-based cohort study of pleural fluid cultures in ICU. The primary outcome was the proportion of first pleural fluid cultures yielding positive microbial growth, secondary outcome was 90-day all-cause mortality. Using multiple regression, we assessed associations between suspected pleural infection and parapneumonic effusion, respectively, and the risk of a positive culture, as well as associations between a positive culture and 90-day mortality. Data from eight ICUs comprising the entire North Denmark Region from March 1, 2013, to February 28, 2023, were obtained from the regional microbiological database, administrative databases, and through review of electronic medical records. All adult patients who underwent pleural fluid culturing in any of the eight ICUs within the inclusion period. None. A total of 1251 patients were included, of whom 51 (4.1%) had a positive first pleural culture. Suspected pleural infection was associated with a higher positive culture risk (adjusted risk ratio [RR]: 4.88; 95% CI, 2.70-8.83). No such association was observed for parapneumonic effusions (adjusted RR: 1.41; 95% CI, 0.83-2.38). A positive culture was associated with increased 90-day mortality (adjusted RR: 1.35; 95% CI, 1.04-1.73). In this 10-year cohort study of ICU patients undergoing pleural drainage, the risk of positive pleural fluid cultures was low. Suspected pleural infection significantly increased the likelihood of a positive culture, suggesting that culturing may be most useful in these cases. A positive pleural culture was associated with increased 90-day mortality underscoring its potential clinical significance.
Mucormycosis is an invasive mold disease (IMD) caused by fungi in the order Mucorales. Early initiation of active antifungal therapy is critical for optimal outcomes, and molecular diagnostics can speed up the time to critical results. We reviewed 6 years of Mucorales polymerase chain reaction (PCR) testing to assess agreement with culture, histopathology, and/or pan-fungal sequencing across different specimen types. Medical record review was also performed to adjudicate cases of suspected IMD from our institution. A total of 5,779 PCRs and 2,017 fungal cultures from the same patients were performed during the study period. PCR results were issued approximately 7 days sooner than Mucorales-positive cultures. The overall PCR positivity rate was 2.9%. Sinus and other fresh tissue specimens had the highest diagnostic yield (23.8% and 19.4% PCR positive, respectively). PCR cycle thresholds (Cts) were significantly earlier for culture-positive specimens and for tissue versus other sample types, while serum had the latest Cts (all comparisons P < 0.005). Among 315 specimens with shared testing, PCR detected all culture- or sequencing-positive samples (n = 13), and negative percent agreement across methods was high (97.3%). Twenty-one cases of proven/probable mucormycosis were identified from our hospitals; 67% had at least one positive PCR. False-negative PCRs came from serum (n = 6) or cerebrospinal fluid (n = 1), while false positives were rare (PCR specificity: 99%). In conclusion, Mucorales PCR is a useful adjunct to routine testing for suspected IMD, given its relatively rapid turnaround time and high specificity. Testing should ideally be performed using fresh tissue from the primary site of infection when possible. This work addresses a critical gap in the diagnosis of mucormycosis, a rapidly progressive and frequently fatal invasive mold disease for which timely, accurate laboratory confirmation is essential but often difficult to achieve. By evaluating over 6 years of real-world Mucorales polymerase chain reaction (PCR) testing in a national reference laboratory and tertiary-care setting, this study provides robust evidence that targeted PCR offers substantially faster turnaround times than culture while maintaining high specificity across multiple specimen types. The findings underscore the diagnostic value of molecular testing, particularly from fresh tissue obtained at the site of infection, and highlight important limitations of serum testing that can inform optimal test utilization. In the context of increasing mucormycosis incidence, absence of reliable antigen-based diagnostics, and the need for early antifungal therapy, these data support the incorporation of Mucorales PCR as a complementary tool to conventional methods.
Among adults with mild traumatic brain injury (mTBI), only a minority develop clinically significant intracranial hemorrhage requiring neurosurgical intervention or causing death. The Quebec Brain Injury Categories (QueBIC) stratifies risk based on computed tomography (CT) morphology, with complications occurring mainly in moderate/high-risk categories. Identifying pre-CT clinical predictors of these categories could help prioritize imaging and monitoring. We aimed to identify such predictors in complicated mTBI and assess concordance between QueBIC and the Canadian CT Head Rule (CCHR). We conducted a retrospective multicenter cohort study of adults ≥18 years with complicated mTBI (GCS 13-15 plus intracranial hemorrhage and/or skull fracture) who underwent head CT between January 2020 and December 2022. QueBIC categories were assigned from radiology reports by two radiologists and two emergency physicians. Multivariable logistic regression identified independent pre-CT predictors of moderate/high QueBIC risk. Diagnostic performance metrics were estimated, and QueBIC-CCHR concordance was described. Among 2,253 patients (median age 66.3 y [IQR: 47.9-80.6]; 65.6% male), 42.6% were classified as moderate/high by QueBIC. Antithrombotic medication independently increased the risk of moderate/high QueBIC: antiplatelet therapy, OR: 1.41 (95% CI: 1.06-1.88); anticoagulants, OR: 2.25 (1.40-3.60); and dual therapy, OR: 2.49 (1.11-5.55). Older age was associated with higher risk: 65-74 years, OR: 1.52 (1.11-2.08); ≥75 years, OR: 1.66 (1.24-2.22). Confusion was the strongest clinical correlate, with an OR of 18.67 (13.06-27.33). Suspected skull vault fracture was also associated, OR: 2.09 (1.61-2.72). CCHR frequently assigned high risk where QueBIC remained low or moderate: among CCHR-high patients, 48.5% were QueBIC-low, 36.3% QueBIC-moderate, and 15.2% QueBIC-high. Conversely, among CCHR-low patients, 79.6% were QueBIC-low. In complicated mTBI, pre-CT risk per QueBIC is mainly driven by antithrombotic exposure, older age, confusion, and suspected skull fracture. CCHR shows moderate concordance and tends to overestimate risk compared with morphology-based stratification. These findings support using QueBIC-informed pathways to guide imaging and monitoring. (J Trauma Acute Care Surg 2026;00:000-000. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.). Prognostic and Epidemiological Study, Level III.
Oral tyrosine kinase inhibitors and poly (adenosine diphosphate-ribose) polymerase inhibitors are widely used across solid tumors and hematologic malignancies and are typically administered at fixed doses. However, substantial interindividual pharmacokinetic variability results in heterogeneous systemic exposure, potentially leading to underexposure with reduced antitumor efficacy or overexposure with preventable toxicity. Therapeutic drug monitoring and model-informed precision dosing have emerged as complementary strategies to individualize dosing and optimize the exposure-response balance in routine oncology practice. This narrative problem-oriented review evaluates the clinical applicability of therapeutic drug monitoring and model-informed precision dosing for selected oral targeted agents, including epidermal growth factor receptor, anaplastic lymphoma kinase, BCR-ABL, vascular endothelial growth factor receptor, mitogen-activated protein kinase kinase, and multi-kinase inhibitors, as well as poly(adenosine diphosphate-ribose) polymerase inhibitors. For each agent, we assessed the presence of clinically meaningful exposure-response or exposure-toxicity relationships, the availability of validated assays, and the existence of actionable concentration thresholds. We also integrated an updated therapeutic drug monitoring usefulness score to contextualize the strength of recommendation. High-level evidence, including prospective interventional studies, supports exposure-guided dosing for imatinib and sunitinib, demonstrating improved molecular or clinical outcomes when predefined trough concentration targets are achieved. For alectinib, cabozantinib, trametinib, and lenvatinib, consistent exposure-response or exposure-toxicity relationships and pragmatic concentration thresholds support selective implementation, although randomized validation remains limited. For agents such as osimertinib, brigatinib, olaparib, and niraparib, monitoring appears most clinically relevant in toxicity-driven scenarios rather than for efficacy optimization. In contrast, lorlatinib currently lacks a clearly defined therapeutic window, limiting routine applicability. Across drugs, steady-state trough concentration remains the default sampling strategy. Clinical scenarios warranting measurement include early or unexpected disease progression, recurrent or severe adverse events, suspected drug-drug interactions, altered absorption, organ dysfunction, or concerns regarding adherence. Model-informed precision dosing extends conventional monitoring by integrating patient-specific covariates with pharmacokinetic models to simulate individualized dosing regimens. In conclusion, therapeutic drug monitoring and model-informed precision dosing are ready for selective clinical adoption in a subset of oral targeted therapies. Future prospective trials integrating pharmacometric tools with patient-centered outcomes are required to refine exposure targets and expand evidence-based implementation.
Calprotectin, a neutrophil activation marker, is a promising diagnostic biomarker for infection and sepsis, but its usefulness in the emergency department (ED) is unclear. The aim of this study was to investigate the diagnostic value of calprotectin for sepsis and the source of infection in the ED. A total of 583 prospectively included patients presenting with suspected sepsis to the ED of a university hospital in southern Sweden were analyzed. Calprotectin was measured in plasma samples obtained at admission. Mean age was 69 years and 49% were female. Calprotectin discriminated between sepsis and noninfectious systemic inflammatory response syndrome with an area under the curve (AUC) of 0.63, but was not an independent predictor in multivariable analysis including C-reactive protein (CRP). The Modified Early Warning Score did not show any discriminatory ability. Calprotectin and CRP discriminated between lower respiratory tract infection and (1) upper respiratory tract infection, (2) urinary tract infection, and (3) other sources of infection. Addition of calprotectin to CRP significantly increased the AUC for lower versus upper respiratory tract infection and lower respiratory tract infection versus urinary tract infection. Calprotectin was an independent predictor for all outcomes while CRP was only an independent predictor of lower versus upper respiratory tract infection. Calprotectin may improve differentiation of lower respiratory tract infections from upper respiratory tract infections and urinary tract infections in patients presenting to the ED with sepsis. Further research is needed to clarify if calprotectin adds diagnostic value to standard clinical assessment.
Inborn errors of immunity (IEI) comprise a heterogeneous, and growing, group of over 550 disorders linked to over 500 genes. Current diagnostic rates for IEI range from 15-70%, with missed diagnoses likely explained by variants of uncertain significance that lack evidence for reclassification and/or variants undetectable with current methods. To overcome these limitations, we developed a structured, RNA-guided approach to reanalyze unsolved IEI patients and increase the diagnostic yield of genetic testing. In a multidisciplinary team, we analyzed a cohort of 22 patients suspected to have an IEI for whom standard diagnostic genetic testing was inconclusive. We systematically evaluated whether aberrant expression, aberrant splicing or mono-allelic expression, based on the detection of expression outliers, splicing outliers and allele-specific read counts at heterozygous single nucleotide variants could reveal potentially causative variants that aligned with the clinical phenotype and expected mode of inheritance. In one male patient, we detected a splice variant in IKBKG (NM_001099857.5: c.671 + 2T>G) that causes exon 5 skipping, which explains his phenotype. In one female patient, we detected a pathogenic splice variant in the X-linked recessive gene CYBB (NM_000397.4: c.45 + 5G>A) that, in combination with skewed X-inactivation, caused a significant decrease in functional transcripts. We also detected a deep-intronic variant (NM_003998.4: c.1495 + 506T>C) that activates a cryptic splice site, leading to a pseudo-exon in NFKB1 in a patient with a phenotype consistent with NFKB1 haploinsufficiency. We could provide a conclusive diagnosis for 2 out of 22 patients, underscoring how RNA-guided variant interpretation can improve genetic diagnostic yield in IEI patients. With advances in interpretation technologies, integrating RNA-sequencing into routine diagnostics could be a pivotal step toward achieving more comprehensive and precise genetic diagnoses of IEI.
Androgen receptor (AR) gene mutations are a common cause of 46, XY disorders of sex development (DSD), resulting in varying degrees of androgen insensitivity. This study aims to comprehensively evaluate the clinical features, hormone profiles, and AR gene variants of patients diagnosed with Androgen Insensitivity Syndrome (AIS), and to analyze the distribution of these variants across different functional domains. This retrospective, single-center study analyzed 16 cases of 46, XY DSD, all of whom were found to have AR variants from a single tertiary center in Turkey. Patients were evaluated based on their complaints, hormonal measurements, clinical features, and genetic diagnoses. Patients were classified as having Complete, Partial, or Mild AIS. The variants were categorized based on their location within the functional domains: The Ligand Binding Domain (LBD) and the N-terminal Domain (NTD). Patients were classified as having CAIS (8/16), PAIS (6/16), MAIS (1/16), and suspected diagnosis (1/16). The most common clinical finding was cryptorchidism (11/16). Ten different AR variants were detected: eight missense (p.Pro392Ser, p.Ala749Val, p.Val890Met, p.Asp733Asn, p.Arg856His, p.Arg856Cys, p.Glu494Ala, and p.Glu710Lys), one nonsense (p.Lys659Ter), and with p.Lys659Ter, p.Glu494Ala and being novel. A CAIS associated with p.Pro392Ser has been reported, and intrafamily variability has been documented in variants such as p.Arg856His and p.Pro392Ser. Most variants (10/16 patients) localized to the LBD. Individuals harboring LBD variants demonstrated lower external genital scores and shorter phallus lengths compared to those with NTD variants. T/DHT ratio was available in 11 patients and did not yield false-positive AIS diagnoses. Marked intrafamilial phenotypic variability was observed. This study expands the AR variant spectrum in AIS and represents one of the more comprehensively characterized cohorts from our country. While LBD variants were more often associated with severe phenotypes and NTD variants with milder presentations, marked phenotypic variability was observed. Nevertheless, considerable phenotypic variability, including marked intrafamilial heterogeneity, was evident. The T/DHT ratio provided supportive biochemical information but did not replace the need for molecular confirmation. Molecular confirmation remains essential, and multidisciplinary, patient-centered management is warranted.
Aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) is a clinical concern. Echocardiography is routinely used to assess AR but relies on semiquantitative and operator-dependent measures, while cardiovascular magnetic resonance (CMR) allows direct quantification of regurgitant flow. This study compared transthoracic echocardiography (TTE) and CMR in assessing AR after TAVI using standardized Valve Academic Research Consortium-3 (VARC-3) criteria. In this prespecified substudy of the multicenter COMPARE-TAVI 1 trial, patients were randomized to treatment with Sapien 3/Sapien 3 Ultra or Myval/Myval Octacor transcatheter heart valves. TTE and CMR were performed in 327 participants 4-6 weeks post-TAVI, and AR severity was graded according to VARC-3 criteria. TTE was evaluated by core laboratory consensus, whereas CMR-derived regurgitant fraction was quantified by phase-contrast velocity mapping. Agreement, diagnostic accuracy, and clinical predictors of discordance were evaluated. By TTE, AR was none-trace-mild in 88.4% (n = 289), mild-moderate in 10.1% (n = 33), moderate in 0.9% (n = 3), and moderate-severe in 0.6% (n = 2) of patients. Corresponding CMR results were 92.7% (n = 303), 7.0% (n = 23), 0.3% (n = 1) and 0%, with a median [IQR] AR fraction of 5% [3-9]. Overall agreement between modalities was 86%, with TTE overestimating AR in 9% and underestimating in 5% as compared with CMR. Using CMR as the reference for detecting moderate or greater AR (AR fraction ≥30%), TTE did not identify the one patient who had moderate AR by CMR. Of five patients graded as moderate or greater by TTE, all were downgraded by CMR to less than moderate AR (sensitivity 0.00, 95% CI 0.00-0.98; specificity 0.99, 95% CI 0.97-1.00). Discordance was more frequent with extensive aortic valve calcification and those receiving Myval/Myval Octacor valves. In this multicenter study, current-generation transcatheter valves exhibits low rates of moderate or greater AR. One patient with moderate AR by CMR was not detected by TTE. CMR reclassified all five patients classified with moderate or greater AR by TTE to lower severity categories, underscoring the complementary value of CMR to TTE, when moderate or severe AR is suspected.
Blunt thoracic aortic injury (BTAI) is the second leading cause of mortality in patients with trauma, closely following head injuries, which remain a significant concern in trauma care. Thoracic endovascular aortic repair (TEVAR) is the preferred treatment for BTAI; however, insufficient proximal sealing zone length poses a significant challenge for successful TEVAR. This study aimed to investigate the outcomes of TEVAR in patients with BTAI, including those with short proximal sealing zones (≤ 15 mm). This retrospective study included 52 consecutive patients who underwent TEVAR for BTAI in the authors' institution between January 2018 and December 2023. Patient demographics, BTAI grade, adverse events, and endoleak were assessed. Proximal sealing zone length was measured on pre-procedural computed tomography (CT). Subgroup analysis was used to compare outcomes between patients with proximal sealing zones ≤ 15 and > 15 mm. The average injury severity score was 44.1 ± 15.8, with 88.5% of patients sustaining grade 3 BTAI. One technical failure occurred owing to an acute aortic arch angle. A total of 29 patients had proximal sealing zones ≤ 15 mm, with 5 of them undergoing left subclavian artery coverage. Endoleak occurred in three patients (5.9%), resulting in the death of one patient. The remaining two patients had suspected type 4 endoleaks that resolved on follow-up CT. No significant differences were observed in aortic-related mortality and endoleak between the two groups. TEVAR is an effective treatment option for BTAI, even in patients with short proximal sealing zones ≤ 15 mm.
Hepatitis E virus genotype 3 (HEV-3) is a major cause of acute hepatitis in Europe. However, the clinical burden of symptomatic infection in routine practice and the relative contribution of host and viral factors to disease severity remain incompletely defined. We aimed to characterise the clinical burden, molecular epidemiology and determinants of adverse outcomes in patients with symptomatic HEV-3 infection. Prospective multicentre study including patients with suspected HEV infection from ten hospitals in southern Spain between 2022 and 2025. Samples were analysed at a central laboratory using a standardised diagnostic algorithm based on HEV IgM and HEV RNA testing, with molecular characterisation of viraemic cases. Demographic, clinical and outcome data were extracted from medical records. Multivariable logistic regression analyses were performed to identify factors associated with hospital admission and severe acute hepatitis. Among 1124 tested patients, 267 HEV infections were diagnosed (23.7%). Overall diagnostic positivity remained consistently high throughout the study period. Of the 267 patients, 111 (41.6%) required hospital admission, 14 (5.2%) developed severe acute hepatitis and three died (overall mortality 1.1%), all of whom had major comorbidities. Major comorbidity was independently associated with hospital admission and severe acute hepatitis, whereas HEV-3 clade was not. Symptomatic HEV-3 infection in southern Spain was associated with a substantial clinical burden. Adverse outcomes were driven primarily by host comorbidity rather than by the viral features assessed in this cohort, while molecular surveillance provided useful epidemiological context on circulating strains.
With the widespread use of antiretroviral therapy, the clinical spectrum among people with HIV has evolved significantly. This study aims to investigate the dynamic changes in the primary indications and final diagnostic spectrum of bone marrow examinations in this population. We conducted a retrospective analysis of 154 hospitalized individuals with HIV who underwent bone marrow examination at Mengchao Hepatobiliary Hospital of Fujian Medical University, the largest designated HIV/AIDS care hospital in Southeast China, from September 2019 to December 2025. Demographic, laboratory, and pathological data were collected, and participants were stratified into tumor and nontumor groups based on final diagnosis for comparative analysis. Among the indications for bone marrow examination, the proportion of procedures performed due to cytopenia decreased from 55.55% in 2019 to 17.86% in 2025. Conversely, the proportion performed for suspected hematological malignancy or to assess tumor marrow infiltration increased significantly from 11.11% to 60.71%. Final diagnoses revealed that the proportion of malignant tumors increased from 11.11% to 53.57%, whereas the proportion of opportunistic infections showed a declining trend. The Cochran-Armitage trend test confirmed that the proportion of opportunistic infections decreased significantly (p = .002), while the proportion of malignancies increased significantly (p = .002). Compared to the nontumor group, individuals in the tumor group were older, had significantly higher proportions receiving antiretroviral therapy, higher rates of HIV RNA suppression, as well as significantly higher CD4+ T-cell counts, CD8+ T-cell counts, lymphocyte counts, platelet counts, and lactate dehydrogenase levels. Our findings demonstrate that the clinical indications for bone marrow examination in people with HIV have shifted from the evaluation of traditional opportunistic infections and unexplained cytopenia toward the diagnosis and staging of malignant tumors, particularly hematological malignancies. These results suggest that in the contemporary management of HIV, greater emphasis should be placed on screening for malignancies.
The incidence and imaging characteristics of non-neoplastic sulcal enhancement on contrast-enhanced T2-weighted fluid-attenuated inversion recovery (CE-T2FLAIR) imaging in routine neuro-oncologic magnetic resonance imaging (MRI) were investigated. Contrast-enhanced T1-T2FLAIR sequence matching was used to differentiate benign contrast leakage from leptomeningeal metastasis (LMS). This retrospective, single-center study included 337 patients who underwent contrast-enhanced brain MRI for evaluation of suspected intracranial metastasis. Sulcal enhancement on CE-T2FLAIR was classified as absent, contrast leakage, or LMS based on imaging and clinical criteria. Two neuroradiologists independently determined T1-T2FLAIR matching status. Overall, 271 showed no leptomeningeal enhancement; 55 patients demonstrated contrast leakage and were older than the other groups; 11 were accurately diagnosed with LMS. Using match positivity as the cutoff, sensitivity and specificity were 90.9% and 94.8%, respectively for the LMS diagnosis. Mismatch patterns were common in contrast leakage and associated with older age, higher cerebral microbleed burden, cortical superficial siderosis, and prior radiotherapy. Non-neoplastic sulcal enhancement on CE-T2FLAIR is a common finding in contemporary neuro-oncologic MRI, particularly with delayed post-contrast acquisition. Assessing agreement between CE-T2FLAIR and contrast-enhanced T1-weighted imaging provides a simple and robust method for distinguishing benign contrast leakage from LMS.
We report a case of meningeal carcinomatosis (MC) presenting with bilateral optic disc edema and an absence of symptoms of intracranial hypertension, such as headache or vomiting. A 54-year-old woman presented with a 2-week history of bilateral blurred vision and new-onset floaters in the left eye. She had a history of surgeries for both ovarian and gastric cancer while undergoing chemotherapy for recurrent ovarian cancer. Fundoscopic examination revealed bilateral optic disc edema. Although intracranial hypertension was suspected, non-contrast computed tomography and non-contrast magnetic resonance imaging showed no intracranial lesions or enlarged ventricles. Cerebrospinal fluid examination revealed normal opening pressure and cytology demonstrated adenocarcinoma cells, confirming MC. The cell morphology suggested that the metastasis likely originated from her previous gastric cancer. Two weeks after the initial ophthalmologic examination, the patient developed headache and vomiting, and her general condition deteriorated rapidly. Radiation therapy was considered, but the patient died 1 month after the initial presentation. A diagnosis of MC should be considered in patients with a history of malignancy who present with bilateral optic disc edema, even in the absence of typical symptoms of intracranial hypertension.
Parvovirus B19 typically causes mild symptoms in healthy adults, including fever, rash, and arthralgias. Certain immunocompromised adult populations, including those with immunodeficiencies or hematologic disease, are at risk of clinically significant complications, including transient aplastic crisis. Further, in pregnant patients, there is a risk of transplacental viral transmission, which may lead to severe fetal anemia, nonimmune hydrops fetalis, and intrauterine fetal demise. The clinical course of parvovirus B19 in pregnant patients with underlying hematologic disease has not been well reported. In this case report, we present a 27-year-old pregnant patient with sickle cell beta thalassemia who was infected with parvovirus B19 at 20 weeks of gestation. She experienced a prolonged hospitalization characterized by persistent maternal vaso-occlusive crisis with concomitant transient aplastic crisis. There was suspected vertical transmission of the virus, leading to concern for severe fetal anemia and termination of the pregnancy. The patient continued to have cyclic fevers, bicytopenia, and a constellation of laboratory findings leading to a diagnosis of postviral hemophagocytic lymphohistiocytosis (HLH). She was successfully treated with pulse dose corticosteroids and an Interleukin-1 receptor antagonist with subsequent improvement of her symptoms and laboratory markers. This report highlights the distinct diagnostic and management challenges of parvovirus B19 in pregnant patients with comorbid hematologic disease, including a rare but serious sequela of the infection, and the risk for severe maternal and fetal complications.