Citations

Inferior vena cava (IVC) pathology is often underrecognized on non-dedicated imaging examinations, yet it carries significant diagnostic and clinical implications, particularly in acute emergency settings. This review highlights the complementary roles of ultrasound (US) and computed tomography (CT) in the assessment of IVC abnormalities. The US provides real-time, bedside evaluation of IVC patency, caliber, and hemodynamics, whereas CT offers detailed anatomic and structural characterization critical for diagnosis and management. The review aims to systematically discuss congenital variants, thrombotic, traumatic, systemic conditions, and neoplastic involvement of the IVC, emphasizing their imaging features and clinical relevance.

Objective: To gain firsthand accounts from female physician leaders in academic medicine to better understand the challenges and success factors they have encountered in order to provide insights to early-career female physicians and inform organizations about the challenges faced by female physicians to build better systems and processes to support them in achieving more satisfying and fulfilling careers within an academic setting. Method: This qualitative research study is based on interviews with female physician leaders. Participants were selected based on their scores in multi-rater leadership assessments taken within the past three years, all ranking in the top 30% across four capabilities: Inspiring Values, Engaging Colleagues, Bold and Forward Thinking, and Driving Results. Coding and thematic analysis were used to categorize the challenges and success factors. Results: Data analysis revealed challenges experienced by these female physician leaders, including gender bias, time constraints, family responsibilities, change and innovation, self-doubt, and exclusion from networking. The strategies identified for navigating these challenges and achieving high performance included support from family and colleagues, building relationships and networking, maintaining a positive attitude, making powerful choices, seizing opportunities, finding value, meaning, and purpose, continuous learning, strategic planning, and gaining recognition. Conclusion: Challenges for female leaders in academic medicine are prevalent and evolve alongside changes in health care. Success factors can be generated at an individual level, such as attitudes, making powerful choices, and networking. However, societal and organizational support, including assistance with family responsibilities and providing opportunities, feedback, and mentorship, has also been identified as crucial.

Abstract Background Gastrointestinal (GI) cancer remains a major global health challenge. This study provides updated 2022 estimates of GI cancer incidence and mortality worldwide, along with projections of incident cases and deaths through 2050 to inform cancer control strategies. Methods In this population‐based study, data from the GLOBOCAN 2022 database were used to examine incidence and deaths associated with GI cancer. By using global demographic projections, this study estimated the projected number of incident cases and deaths until the year 2050. Results By 2050, the global burden of GI cancer is projected to reach 9.06 million incident cases (+85%) and 6.42 million deaths (+93%) from 2022. Increases in incidence are projected for both females (+87%) and males (+83%), as are increases in mortality for both females (+97%) and males (+91%). Whereas the Western Pacific region will have the highest absolute burden, with 3.88 million new cases and 2.79 million deaths, the greatest relative increase is expected in Africa, with incidence and deaths rising by 157% and 160%, respectively. As measured by the Human Development Index (HDI), the steepest increases are projected in low (+151% incidence; +152% deaths) and medium (+112% incidence; +114% deaths) HDI countries. Overall, all GI cancer types are projected to increase, led by pancreatic cancer in incidence (+95%) and colorectal cancer in deaths (+103%). Conclusions GI cancer incidence and deaths are expected to nearly double by 2050, with increases across sexes, cancer types, and regions, especially in lower HDI countries.

Artificial intelligence (AI) is revolutionizing interventional pulmonology (IP) by enhancing diagnostics, procedural precision, and patient outcomes. AI-powered tools improve lung nodule detection, radiomics-based risk stratification, and bronchoscopic navigation. Machine learning (ML) algorithms aid in lung cancer screening by analyzing imaging data, reducing false positives, and improving early diagnosis. AI-driven robotic-assisted bronchoscopy enhances navigation and biopsy accuracy, particularly for peripheral lung lesions. Endobronchial ultrasound (EBUS) and cytopathology benefit from AI’s ability to assess lymph node malignancy and optimize rapid on-site evaluation (ROSE). AI applications extend to phenotyping chronic obstructive pulmonary disease (COPD) and identifying candidates for bronchoscopic lung volume reduction (BLVR). Deep learning (DL) models analyze computed tomography (CT) imaging and spirometry data to optimize patient selection. AI-driven algorithms are also advancing pleural effusion detection, differentiation, and classification, supporting clinical decision-making. Education and research in IP are also transforming with AI-driven simulation, virtual reality, and automated assessment tools that enhance procedural training and competency evaluation. The integration of AI into clinical work and procedural training accelerates advancements while presenting challenges in ethical AI implementation, data security, and bias mitigation. As AI continues to evolve, its role in IP will expand, improving procedural efficiency, personalizing treatment plans, and optimizing patient selection for interventions. Future developments will focus on refining AI-driven predictive analytics, enhancing robotic-assisted procedures, and integrating AI seamlessly into clinical workflows. The responsible implementation of AI in IP holds the potential to transform patient care, reduce complications, and advance precision medicine.

ABSTRACT A prevailing model holds that human cytomegalovirus (HCMV) spreads cell-to-cell spread upon initial culturing from clinical specimens and that de novo mutations in the UL128-131 genes reduce expression of glycoprotein complex gH/gL/UL128-131 (pentamer) relative to gH/gL/gO (trimer), which in turn enhances virion infectivity and favors cell-free spread. The clone Merlin-BAC (ME) expresses far more pentamer than trimer and is highly cell-associated, whereas clone TB40-BAC4 (TB) expresses mostly trimer and spreads predominantly cell-free. A single G>T polymorphism in TB relative to ME was shown to impair UL128 mRNA splicing, reducing pentamer expression and enhancing infectivity and cell-free spread. However, enhanced cell-free spread of ME due to pentamer suppression did not come at the expense of efficient cell-to-cell spread, and cell-to-cell spread of TB was especially poor despite highly infectious intracellular virus. Most of the nucleotide diversity in the HCMV genome is due to 17 genes that have up to 14 alleles each, and TB and ME match at only two of the 17. Here, we report a set of recombinant HCMV generated by coinfecting cells with TB and ME. Trimer:pentamer ratio and virion infectivity largely aligned with the TB or ME UL128, with “TB-like” recombinants displaying more trimer and higher infectivity and “ME-like” recombinants displaying more pentamer and lower infectivity. Strikingly, some recombinants had shifts in preference for cell-free vs cell-to-cell spread without predicted changes to trimer:pentamer ratio or virion infectivity, demonstrating uncoupling of these phenotypes. IMPORTANCE The emerging picture of HCMV genetic diversity in vivo prompts a reevaluation of how in vitro -characterized phenotypes, such as the abundance of different viral envelope glycoproteins, virion infectivity, and tendency toward cell-free or direct cell-to-cell spread, reflect viral characteristics in vivo . Laboratory examination of HCMV phenotypes has included a limited sampling of the apparent in vivo genetic diversity. A widely held model that directly links cell-free and cell-to-cell spread characteristics to glycoprotein display and virion infectivity also presumes that HCMV is predominantly cell-associated in vivo . These have implications for intervention strategies, such as calling into question the therapeutic benefit of neutralizing antibodies. Our finding that spread characteristics can be uncoupled from glycoprotein display and virion infectivity suggests a model that includes both cell-free and cell-associated spread as bona fide wild-type phenotypes for different allelic haplotypes. This model would allow a broader examination of neutralizing antibodies as correlates of protection.

Objectives: To evaluate evolving management, ICU admission, and outcomes for critically ill chimeric antigen receptor (CAR) T-cell patients over a 6-year period. Design: Multicenter retrospective cohort study from January 2018 to September 2023. Setting: Eight U.S. centers. Patients: Adult CAR T-cell patients requiring ICU admission. Interventions: None. Methods: Summary statistics included mean, sd , median, and interquartile range (IQR). Fisher exact test or chi-square test were used to evaluate association between year treated and other categorical variables. Cochran-Armitage test was performed to assess significance of trends across years. Multivariable logistic regression was performed to assess covariates associated with mortality. Measurements and Main Results: Demographics, toxicity management, ICU admission, support modalities, toxicity severity, and survival (ICU, hospital, and 3-mo) were compared year-to-year. From 2018 to 2023, 2238 patients received CAR T cells, with increasing number of patients treated yearly; 398 (17.8%) required ICU care. Of those admitted to the ICU, 66.1% were male, 89.2% had lymphoma, and median age was 64 years (53–71 yr). ICU admission rates declined from 38.5% (95% CI, 31.6–45.8%) in 2018 to 16.4% in 2023 (95% CI, 13.5–19.7%; p < 0.0001). Cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome was the reason for ICU admission in 87.9%. In 2023 vs. 2018, ICU patients were older (median, 65 yr [IQR, 55–73 yr] vs. 58 yr [48–67 yr]; p = 0.003) with higher comorbidity indices (4 [4–6] vs. 3 [2–4]; p = 0.005) and more severe toxicities (≥ grade 3: 90.1% vs. 69.9%; p = 0.004). Corticosteroid use for less severe toxicities (≤ grade 2 toxicity: 73.8% vs. 40.6%; p = 0.0001) and anakinra use (56% vs. 5.5%; p < 0.0001) increased throughout the years. Mortality from cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome remained low (5.5%). Age, Sequential Organ Failure Assessment greater than or equal to 10 at ICU admission, and ICU admission for noncytokine release/neurotoxicity syndrome reasons were associated with hospital mortality (odds ratios, 1.02 [95% CI, 1–1.04; p = 0.046], 4.69 [2.44–9.01; p < 0.0001], and 3.74 [1.91–7.3; p = 0.0001], respectively). Conclusions: ICU admission rates after CAR T-cell treatment are declining. Although ICU patients are older with higher severity of illness and toxicity grades, ICU mortality after CAR T-cell therapy remains low.

Abstract Study Objectives This study examined whether basal electromyographic (EMG) amplitude during sleep is altered in patients with isolated REM sleep behavior disorder (iRBD) and its relationship to disease progression, as well as changes across the sleep cycle. Methods Baseline polysomnograms collected from 95 iRBD patients (15 converters, 80 non-converters) and matched 24 controls were analyzed. EMG amplitude was calculated from submentalis recordings across all sleep stages using 3-s mini-epochs, with REM sleep further classified as REM sleep without atonia (RWA) and non-RWA (RA) according to the presence of “any” RWA events. Kaplan–Meier analysis assessed phenoconversion risk, and EMG amplitude was compared between early and late sleep cycles within each group. Results Group comparisons with post-hoc adjustment showed that EMG amplitude in RA and RWA was higher in non-converters than controls (adj-p &lt; .001), while converters showed further increases of EMG amplitude in N2 and N3 (adj-p &lt; .045). RA amplitude was higher in converters than non-converters (adj-p = .02). Increased EMG amplitude in N2, N3, and RA was associated with higher phenoconversion risk (p &lt; .05). EMG amplitude remained stable between early and late cycles during RA in both iRBD and controls. In contrast, iRBD patients showed a significant decrease in EMG amplitude during late cycles in N2 (p &lt; .009). Conclusions Elevated basal EMG amplitude during both REM and NREM sleep in iRBD patients shows potential as a prognostic marker, indicating muscle tone dysregulation beyond REM atonia loss and underscoring the need to consider broader sleep stages in iRBD evaluation. Statement of Significance This study provides compelling evidence that increased basal electromyographic amplitude during both REM and NREM sleep in isolated REM sleep behavior disorder (iRBD) patients serves as a marker of prodromal alpha-synucleinopathy. By showing that electromyographic abnormalities extend beyond discrete REM events to affect global muscle tone, our findings challenge the conventional view that iRBD pathophysiology is limited to REM-specific activity. Furthermore, the predictive value of these changes appears linked to muscle tone regulation across the sleep–wake cycle. These insights not only deepen our understanding of iRBD pathophysiology but also underscore the potential for refining diagnostic criteria.

Abstract Cockayne Syndrome is an ultra-rare premature aging condition associated with UV sensitivity, neurocognitive decline, retinopathy, metronidazole-induced lethality, and sensorineural hearing loss. In 70% of affected patients, bi-allelic pathogenic variants in ERCC6 are identified. Although the role of ERCC6 in DNA damage repair has been studied, little is known about the mechanism for defective ERCC6 function in clinical findings, particularly hearing loss. To identify the mechanism of disease caused by pathogenic variants in ERCC6, we developed a zebrafish (Danio rerio) ercc6 loss of function model. We assessed survival after UV and metronidazole exposure, measured basal respiration rates, and evaluated mechanoelectrical transduction function and counts of lateral line hair cells. We found that UV exposure significantly reduces ercc6−/− larval viability. Metronidazole treatment results in complete lethality; wildtype controls show nearly complete survival. ercc6−/− embryos have significantly increased oxygen consumption, suggesting abnormal mitochondrial function. Phalloidin staining of lateral line hair cells with and without UV treatment shows no difference in hair cell counts per neuromast between treatment groups. Mechanoelectrical transduction function after UV exposure, measured by FM1–43 uptake, is reduced. Metronidazole lethality is reduced, oxygen consumption rates are restored, and mechanoelectrical transduction function is preserved by treatment with Mn(III)tetrakis(4-benzoic acid)porphyrin Chloride (MnTBAP), a superoxide dismutase mimetic. We propose that defective mitochondrial function and increased reactive oxygen species levels provide a mechanism for hair cell dysfunction in this model of Cockayne Syndrome. These results provide a foundation for further experiments to explore disease mechanisms and treatment modalities for this premature aging condition.