Contemporary TAVR for Patients With Bicuspid Aortic Valve: Importance of Specific Bicuspid Phenotypes, Raphe, Calcification, and a Lifetime Management Intention
Cardiac Computed Tomography for Prosthetic Heart Valve Assessment. An Expert Consensus Document of the Society of Cardiovascular Computed Tomography (SCCT), the American College of Cardiology (ACC), the European Soci
ImportanceEffective treatments for advanced or metastatic non–small cell lung cancer (NSCLC) are limited. Understanding clinical treatment patterns is critical for understanding unmet medical needs.ObjectiveTo describe clinical treatment patterns and outcomes, including time to treatment discontinuation, progression-free survival, and overall survival, in patients who received platinum-based chemotherapy and anti–programmed cell death 1 protein or programmed cell death ligand 1 (PD-[L]1) regimens.Design, Setting, and ParticipantsThis retrospective cohort study used data from 2018 to 2023 from a US nationwide, electronic health record–derived, deidentified database with median duration of follow-up of 7.8 (range, 0-65.0) months. Patients 18 years or older with advanced or metastatic NSCLC in second- and third-line treatment settings were included. Eligible patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, received platinum-based chemotherapy and anti–PD-(L)1 therapy in 1 (combination) or 2 (sequential) lines, and initiated at least 1 subsequent treatment between January 1, 2018, and June 30, 2023. Exclusion criteria included disease progression within 8 weeks after anti–PD-(L)1 treatment initiation. Follow-up was until death or last available data through June 30, 2023.ExposuresAntineoplastic drugs following platinum-based chemotherapy and anti–PD-(L)1 treatment.Main Outcomes and MeasuresTime to treatment discontinuation, progression-free survival, and overall survival were analyzed overall and by initial treatment. Exploratory subgroup analyses were stratified by patient characteristics and index treatment without adjustment for group differences.ResultsIn the 1793 patients (974 [54.3%] male) included in the analysis, mean (SD) age at index treatment was 67.4 (9.4) years and median time from advanced diagnosis to index treatment was 10.5 (range, 1.1-103.8) months. The most common index treatments were docetaxel plus ramucirumab (314 [17.5%]), docetaxel monotherapy (158 [8.8%]), and carboplatin plus paclitaxel (136 [7.6%]). Overall, median time from index treatment to treatment discontinuation was 3.71 (95% CI, 3.48-3.94) months; median progression-free survival, 5.29 (95% CI, 5.03-5.52) months; and median overall survival, 11.20 (95% CI, 10.48-11.93) months. In exploratory analyses, these outcomes were numerically shorter in patients who received chemotherapy monotherapy as index treatment vs the overall group; medians were numerically longer in patients who received index treatments of immuno-oncology monotherapy or chemotherapy plus immuno-oncology combination therapy.Conclusions and RelevanceIn this retrospective cohort study of patients with advanced or metastatic NSCLC, results underscored a significant need for novel treatments, including immuno-oncology combinations.
Link Between Cardiac Allograft Vasculopathy and Metabolic Syndrome: A Systematic Review and Meta-Analysis
Summary: Breast cancer is a common malignancy, and treatment often involves mastectomy. For oncological safety, the anterior and lateral cutaneous branches of the third through fifth intercostal nerves are routinely resected during nipple-sparing mastectomies, leading to loss of nipple sensation. The current gold standard for nipple neurotization uses nerve allografts to connect the nipple with a remaining stump of an intercostal nerve. Despite the convenience of off-the-shelf solutions, this study explored a novel approach using intercostal nerves as autografts or for direct repair to restore nipple sensation. Six patients underwent nipple-sparing mastectomy and opted for nipple neurotization. Three patients underwent neurotization with an intercostal nerve autograft, whereas in 3 patients, long intercostal nerves allowed nipple neurotization directly without the need for an autograft. Meticulous dissection of the intercostal nerves enabled a length of approximately 9 cm (±1.5) per nerve. The acquired nerve length allowed tension-free coaptation of direct nipple neurotization in 3 patients and utilization as an autograft in the other 3 patients. No postoperative complications were observed, whereas sensory outcomes are yet to be evaluated. The study highlighted the feasibility of using intercostal nerves either as autologous intercostal nerve grafts or for direct neurotization. Using an intercostal nerve as an autograft is a cost-effective and time-efficient strategy to avoid the need for an allograft without additional donor-site morbidity. This technique offers a practical and globally accessible solution for improving patient access to state-of-the-art postmastectomy breast reconstruction.
Molecular Insights into Outer Dynein Arm Defects in Primary Ciliary Dyskinesia: Involvement of ZMYND10 and GRP78
Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by recurrent sinopulmonary infections due to motile cilia defects. The disease is genetically heterogeneous, with abnormalities in structural ciliary proteins. Zinc finger MYND-type containing 10 (ZMYND10) is essential for the assembly of outer dynein arms (ODA), with chaperones like Glucose-regulated protein 78 (GRP78) facilitating protein folding. This study investigates ZMYND10 and Dynein axonemal heavy chain 5 (DNAH5) mutations in individuals with PCD. Methods: Eight individuals aged 14–22 with clinical PCD symptoms and confirmed DNAH5 mutations were included. We analyzed the correlation between DNAH5 abnormalities and preassembly/chaperone proteins using immunofluorescence labeling. Nasal swabs were double-labeled (DNAH5–β-tubulin, β-tubulin–ZMYND10, β-tubulin–GRP78) and examined via fluorescence microscopy. Serum metabolomics and proteomics were also assessed. Results: The corrected total cell fluorescence (CTCF) levels of DNAH5, ZMYND10, and GRP78 were significantly different between PCD individuals and controls. Metabolomic analysis showed reduced valine, leucine, and isoleucine biosynthesis, with increased malate and triacylglycerol biosynthesis, malate-aspartate and glycerol phosphate shuttles, and arginine/proline metabolism, suggesting mitochondrial and ER stress. Conclusions: The altered expression of DNAH5, ZMYND10, and GRP78, along with metabolic shifts, points to a complex link between ciliary dysfunction and cellular stress in PCD. Further studies are needed to clarify the underlying mechanisms.
Metabolic Dysfunction–Associated Steatotic Liver Disease—The New Epidemic of Chronic Liver Disease
Background: Outcomes after arthroscopic rotator cuff repair (RCR) are frequently measured through clinically significant outcomes (CSOs) such as the minimal clinically important difference, the substantial clinical benefit, and the Patient Acceptable Symptom State. Global achievement of CSOs is challenging to predict. Purpose: To determine if unsupervised machine learning can identify distinct patient subgroups based on CSO achievement after elective arthroscopic RCR. Study Design: Case-control study; Level of evidence, 3. Methods: A prospectively collected database was analyzed to identify patients who underwent elective arthroscopic RCR from 2015 to 2017. Tear dimensions were measured on magnetic resonance imaging utilizing a validated technique. CSO achievements on the American Shoulder and Elbow Surgeons, the Single Assessment Numeric Evaluation, and the Constant-Murley subjective score at 2-year follow-up were calculated. An unsupervised random forest algorithm was utilized to develop and internally validate patient subgroups with significantly different rates of CSO achievement. Patient subgroup membership, along with a total of 30 demographic and clinical variables, as well as preoperative patient-reported outcomes, were incorporated into a stepwise multivariable logistic regression to identify factors predictive of optimal CSO achievement. Results: A total of 346 patients (192 male; mean ± SD age, 57.2 ± 9.1 years; body mass index, 30.1 ± 5.4 kg/m 2 ) were eligible for inclusion and followed for a mean of 3.8 years (range, 2.0-6.2 years) Of these, a total of 333 patients were partitioned by the random forest algorithm into 2 subgroups (stability, 0.16; connectivity: 180.8; Dunn: 0.16; silhouette: 0.05), with 176 patients in the optimal achievement subgroup and 157 patients in the suboptimal achievement subgroup. The 2 subgroups differed significantly (all P ≤ .004) in the likelihood of achievement of all CSOs. Stepwise multivariable logistic regression identified an increase of 1 mm in tear size in the sagittal dimension beyond 1.9 cm to predict a 10% increase in the probability of suboptimal achievement. Additional risk factors for suboptimal CSO achievement included increasing number of tendons involved (odds ratio [OR], 14.07; 95% CI, 4.50-44.02; P < .001), subscapularis involvement (OR, 8.67; 95% CI, 2.45-30.71; P = .01), and increased preoperative CMS score (OR, 1.11; 95% CI, 1.04-1.18; P = .001). Protective factors included performance of a subpectoral biceps tenodesis compared with biceps tenotomy (OR, 0.22; 95% CI, 0.05-0.92; P = .03). Conclusion: Clinically meaningful subgroups were uncovered using an unsupervised machine learning algorithm in patients undergoing arthroscopic RCR. Tear size, number of tendons involved, and subscapularis involvement were significant and additive predictors of suboptimal CSO achievement at 2-year minimum follow-up. Treatment of concurrent biceps pathology with tenodesis conferred 78% increased likelihood of CSO achievement compared with tenotomy.