Citations

Abstract Asthma is a heterogeneous disease with variable presentation and characteristics. There is a critical need to identify underlying molecular endotypes of asthma. We performed the largest transcriptomic analysis of 808 bronchial epithelial cell samples across 11 independent cohorts, including 3 cohorts from the Severe Asthma Research Program. Using seven datasets (218 patients with asthma, 148 healthy control subjects) as discovery cohorts, we identified 505 differentially expressed genes, which we validated in the remaining four datasets. Unsupervised clustering using the 505 differentially expressed genes identified four reproducible clusters of patients with asthma across all datasets, corresponding to healthy control subjects, patients with mild/moderate asthma, and patients with severe asthma with significant differences in several clinical markers of severity, including pulmonary function, Type 2 inflammation, fractional exhaled nitric oxide, and maximum bronchodilator reversibility. Importantly, we found the same clusters in pediatric patients using nasal lavage fluid cells, demonstrating the gene signature and clusters are not confounded by age and are conserved in both lower and upper airways. The four asthma clusters may represent a unifying framework for understanding the molecular heterogeneity of asthma. Further study could potentially enable a precision medicine approach of matching therapies with patients with asthma most likely to benefit.

Background and Aims: Biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary cancer, exhibit poor prognosis. This study examined temporal trends in mortality due to BTCs and their major subtypes at international, regional, and national levels. Approach and Results: This observational study used the World Health Organization mortality database. Locally weighted regression (LOESS) was used to produce a smoothed curve of long-term international and regional BTC and major subtype-related mortality rates in 2000–2022 based on available data from countries. Trends in age-standardized mortality rates (ASRs) during 2013–2022 for individual countries were examined using joinpoint regression analysis. Internationally, LOESS-smoothed ASRs per 100,000 population due to BTCs were 2.8 (95% CI: 2.5–3.1) in 2000, and 2.7 (2.3–3.1) in 2022. LOESS-smoothed BTC-related ASRs were the highest in the Western Pacific region at 4.2 (1.8–6.6) in 2022, compared with those in the European and American regions at 2.6 (2.3–2.9) and 2.2 (1.8–2.6), respectively. Among major subtypes, LOESS-smoothed ASRs due to iCCA increased by 120.0%, those due to gallbladder cancer decreased by 45.5%, and those due to extrahepatic cholangiocarcinoma remained stable between 2000 and 2022. Disparities in BTC and major subtype-related ASR trends were observed between countries during 2013–2022, with iCCA-associated ASRs showing increasing trends in many countries. Conclusions: Although internationally estimated BTC-associated ASRs showed a stable trend over the last 2 decades, a large increase in estimated iCCA-associated ASRs necessitates developing effective screening for high-risk individuals and disease management strategies.

Abstract Pituitary tumors require a diverse, multidisciplinary approach in their management. Stereotactic radiosurgery (single or hypofractionated) and fractionated radiotherapy are integral parts of the armamentarium. With the introduction of highly conformal, stereotactic ionizing radiation approaches, the reported tumor control rates and clinical outcomes have improved significantly. This review details the indications, risks, and outcomes of pituitary radiosurgery and radiation therapy, and presents in brief the differences in treatment approaches between stereotactic radiosurgery, fractionated radiation therapy, and proton therapy.

ABSTRACTBackgroundCellulite is a localized skin condition that affects many women, particularly after puberty. It results from a complex interplay of several factors that lead to the characteristic dimpled appearance of the skin. Cellulite may cause psychological stress and negatively impact quality of life. Additionally, body skin laxity may further exacerbate cosmetic concerns in these patients. Consequently, multiple therapeutic options, including topical treatments, have been explored to address both cellulite and skin laxity.ObjectivesTo review the pathophysiology of cellulite and skin laxity, as well as topical skincare options for their management.MethodsA literature search from 2000 to 2024 was conducted using the databases PubMed, EBSCOhost, Scopus, and Google Scholar, with the key terms “cellulite,” “cellulite management,” “cellulite topical treatment,” “skin sagging,” “skin laxity,” and “loose skin.” The search included clinical trials, observational studies, book chapters, and review articles in English and Spanish.ResultsThe pathophysiologic mechanisms underlying cellulite involve a combination of histological, hormonal, genetic, and lifestyle factors. Several topical agents, including retinoids and methylxanthines, have shown potential in improving the cosmetic appearance of cellulite and may contribute to localized fat reduction. Emerging botanical extracts hold promise as topical treatments for cellulite and skin tightening.ConclusionsCellulite and skin laxity are prevalent cosmetic concerns with multifactorial and complex pathophysiologic origins. Topical treatments for cellulite and skin tightening require further investigation. Although some studies have demonstrated positive outcomes with skincare products and topicals, robust evidence and studies with extended follow‐up are still lacking. Additional research is necessary to evaluate the long‐term efficacy of topical treatments as standalone therapies for cellulite and skin tightening.

Background: Venous thromboembolism (VTE) poses a major risk after abdominal contouring surgery, impacting morbidity and mortality. Despite various preventative strategies, surgeons are cautious about using enoxaparin for extended postoperative periods. This study aims to determine if a 7-day postoperative course of enoxaparin increases bleeding risks compared with a single dose of intraoperative unfractionated heparin in patients undergoing abdominal contouring surgery. Methods: A retrospective cohort analysis was performed on patients who underwent abdominoplasty or panniculectomy from August 2017 to October 2023. Patients were split into 2 groups: Group 1 received 5000 units of intraoperative unfractionated heparin in addition to 7 days of postoperative enoxaparin (40 mg daily); group 2 received only the intraoperative heparin dose. Primary outcomes included bleeding events and VTE incidence. Secondary outcomes were seroma, infection, surgical site dehiscence, necrosis, drain duration, and reoperation rates. Results: The study included 121 patients (111 women, 10 men), with 61 patients in group 1 and 60 in group 2. The average age was 49 ± 12 years, and the average body mass index was 29.8 ± 5 kg/m². No cases of VTE were reported. Postoperative bleeding occurred in 3 patients (4.9%) in group I and 2 patients (3.3%) in group 2, showing no statistically significant difference (P = 0.66). Secondary outcomes also showed no significant differences between the groups. Conclusions: Our study of 121 patients undergoing either abdominoplasty or panniculectomy demonstrated that administering enoxaparin for 7 days postoperatively is safe and does not increase the risk of bleeding.

Radiologists play a key role in the management of renal masses, and it is important to understand the nonsurgical treatment options for solid renal masses, typical imaging findings after treatment, common complications, and methods to avoid pitfalls.

Abstract Introduction COVID-19 infection is associated with an increased risk of complications, prolonged hospitalization, and mortality despite vaccination in patients with cancer. Evusheld (tixagevimab-cilgavimab) was granted emergency use approval in December 2021 for pre-exposure prophylaxis based on preliminary results from the PROVENT trial. However, studies evaluating the impact of Evusheld in cancer patients in the real-world are limited. In this study, we assessed the impact of Evusheld on the incidence and severity of COVID-19 infection in cancer patients at our institution. Methods and Materials We conducted a retrospective descriptive study at our institution on patients with current and prior history of cancer diagnosis regardless of treatment history who received Evusheld between December 2021 and March 2022. The primary outcome was incidence of COVID-19 during a 6 month follow up period. Secondary outcomes included rate of hospitalization related to COVID-19 and associated mortality. Results A total of 228 patients were included, 43% of which received 2 doses of Evusheld during the study period. Twenty-nine patients (12.7%, 95% CI 9.4% – 18.7%) developed COVID-19, with an average time to diagnosis of 2.5 months (SD 1.6) from receiving Evusheld. Most had hematologic malignancies (68.4%) and were receiving active chemotherapy (71.5%) at the time of diagnosis. Five (17.2%) patients were hospitalized for COVID-19, of whom 4 had hematological malignancy. One patient with hematological malignancy required mechanical ventilation and died. Conclusion Overall, the incidence of COVID-19 following Evusheld was higher than in the PROVENT trial. Infections appeared to be more common and severe in patients with hematologic malignancies.

Purpose: We report the first multicenter, prospective, randomized noninferiority controlled trial of steerable ureteroscopic renal evacuation (SURE) for nephrolithiasis treatment. Materials and Methods: Candidates for laser lithotripsy ≥18 years with ≥1 renal stone ≥7 mm and 7–20 mm stone burden were randomized 1:1 SURE vs ureteroscopy (URS). SURE was performed using the CVAC Aspiration System, a novel steerable irrigation–aspiration catheter. The primary efficacy end point was noninferiority in stone-free rate (SFR) based on zero residual fragments (RFs) 30 days postprocedure on noncontrast computed tomography. Secondary end points were superiority tests, stone clearance (percent stone volume reduction), residual stone volume (RSV), SFR (no RF >2 mm), and SFR (no RF >4 mm) 30 days postprocedure. Results: Of the subjects, 123 were randomized and 101 qualified for efficacy analysis (SURE 46 vs URS 55). Despite randomization, baseline URS stone volume was higher (SURE 485.0 ± 432.5 mm 3 vs URS 713.3 ± 558.5 mm 3 ). The primary noninferiority end point was achieved (SURE SFR 48% vs URS SFR 49%, p = 0.027, −1.3% [90% confidence interval; −18%, 15%]). Stone clearance was significantly higher for SURE vs URS subjects (SURE 96.9 ± 5.6% vs URS 92.9 ± 11.6%, p = 0.036); RSV was significantly lower (SURE 14.3 ± 3 0.9 mm 3 vs URS 70.2 ± 144.9 mm 3 , p = 0.012). SURE stone clearance and RSV were independent of baseline stone volume, but for URS degraded with increasing baseline stone volume. Safety was comparable between groups. Conclusions: SFR for SURE subjects was noninferior compared with URS subjects; stone clearance and RSV were significantly better with SURE, independent of baseline stone volume.

Background: Bucket-handle meniscal tears (BHMTs) are a common subtype of meniscal tears that represent a clinical challenge. Arthroscopic inside-out repair has been considered the gold standard in treatment; however, an all-inside approach has gained widespread popularity, with limited long-term evidence. Purpose/Hypothesis: The purpose of this study was to (1) compare long-term clinical outcomes and rates of failure after surgical repair of BHMTs using the all-inside versus inside-out technique, and 2) identify risk factors for failure at long-term follow-up. It was hypothesized that clinical outcomes and rates of failure would be similar between the 2 techniques. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who had undergone surgical repair of BHMTs between 2003 and 2013 at a single institution were identified. Patient-reported outcome measures (PROMs) were assessed preoperatively and at the latest follow-up using the Tegner scale, International Knee Documentation Committee questionnaire, and visual analog scale pain at rest and with activity. A univariate Cox proportional hazards model was used to identify predictors for repair failure, defined as revision meniscal surgery and/or documented meniscal retear. Results: In total, 63 patients were included (37 with inside-out repair, 26 with all-inside repair). At a mean follow-up of 11.2 years, the survival rate for BHMT repair was 63% overall, 70% for all-inside repairs, and 60% for inside-out repairs ( P = .37). The mean time to failure was 2.6 years for all-inside repairs and 2.5 years for inside-out repairs ( P = .98). PROM scores were not significantly different between the 2 repair groups ( P > .22). Univariate Cox proportional hazards model for failure demonstrated that increasing age at surgery was associated with lower failure rates (hazard ratio, 0.91 change per 1-year increase in age; 95% CI, 0.84-0.98) and medial meniscus repair was associated with higher failure rates (hazard ratio, 3.12; 95% CI, 1.14-8.77). Conclusion: Long-term follow-up of BHMT repair demonstrated satisfactory clinical outcomes and failure rates. In appropriately selected patients, the all-inside technique did not compromise outcome as compared with the inside-out repair techniques. For both methods, older age was associated with lower failure rates and medial meniscus repair was associated with increased failure.