Citations

ABSTRACTEndobronchial valves have a variety of potential applications, from lung volume reduction in patients with severe emphysema to closing cavities in those with drug‐resistant tuberculosis. This report presents two cases in which endobronchial valves were effectively used to treat pneumomediastinum.

Abstract Objectives The aim of this study was to compare the measured physiological factors that limit running performance with real marathon results from world-class distance runners, evaluating the compatibility between measured data and predicted results based on the previously suggested model. Methods Four world-class East African marathon runners (three male, one female) underwent physiological running assessments to predict marathon performance times using a model based on V ˙ $\dot {\mathrm{V}}$ O 2 peak, percentage of V ˙ $\dot {\mathrm{V}}$ O 2 peak at the second ventilatory threshold, and running economy. Predictions were then compared to participants’ best marathon times. Results The measured V ˙ $\dot {\mathrm{V}}$ O 2 peak of the world-class runners was 75.1 ± 2.7 mL/kg/min. The second ventilatory threshold occurred at 85 ± 3 % of the peak, with a running economy of 63.7 ± 2.4 mL/kg/min at 19.6 ± 0.9 km/h. The predicted marathon performance time was 2:06:51 ± 0:03:17 h:min:s for the males and 2:17:36 h:min:s for the female. Comparing these predictions to their personal best times, the average difference was 00:55 ± 00:51 min:s (range: 00:20-02:08). Conclusions This research provides laboratory data on world-class road running athletes, reinforcing the link between marathon performance and V ˙ $\dot {\mathrm{V}}$ O 2 peak, the percentage of V ˙ $\dot {\mathrm{V}}$ O 2 peak at the second ventilatory threshold, and running economy. The examined athletes had lower V ˙ $\dot {\mathrm{V}}$ O 2 peak compared to predicted values, highlighting the importance of running economy and fractional utilization of V ˙ $\dot {\mathrm{V}}$ O 2 peak in achieving such performances. Future studies should continue to advance the field by including additional bioenergetic parameters measured during race conditions and expanding the participant cohort of elite marathoners, encompassing both sexes.

Abstract Introduction: Periacetabular osteotomy (PAO) is a complex procedure historically requiring inpatient stay. There is increased emphasis for these to be performed on an outpatient basis by insurance companies. The purpose of this study was to investigate the proportion of various surgical listing classifications (outpatient, outpatient-overnight, inpatient), the incidence of subsequent denial/request for additional documentation for approval of inpatient stay, and to characterize the average length of stay (LOS) following PAO. Methods: A retrospective chart review was performed to identify all PAOs, performed by four participating surgeons, at a single academic institution over a two-year period. The initial listing status as an outpatient-overnight or inpatient procedure was identified. Whether a preoperative peer review was required for approval of inpatient listings as well as if additional documentation was necessary to convert outpatient-overnight listings to inpatient stays were also recorded. Results: A total of 140 PAOs amongst 117 patients were performed with 25 (17.9%) initially listed as an inpatient stay and 115 (82.1%) listed as outpatient-overnight. Of the 25 PAOs listed as inpatient, 2 (8.0%) required a preoperative peer review process to justify or clarify listing status. The average LOS was 1.9 ± 1.4 days with 55.7% (78/140) of PAOs staying two or more nights in the hospital. Only 6 PAOs (4.3%) went home the same day as surgery. Of the 115 PAOs listed as an outpatient-overnight, 53 (46.1%) converted to an inpatient stay. Conclusion: Over half of PAOs performed required inpatient stay beyond outpatient-overnight status. Preoperative peer-to-peer review for inpatient stay approval was modestly frequent (8% of inpatient listings), and all conversions to inpatient required additional service documentation to support status conversion. Understanding trends in postoperative hospitalizations and LOS might allow for better informed partnerships between surgeons and insurance companies creating more efficient pre-authorizations, billing practices, and expected patterns of patient care and discharge.

ImportanceCutaneous squamous cell carcinoma (CSCC) risk stratification is central to management, and physicians rely on tumor staging systems to estimate risk. The Brigham and Women’s Hospital (BWH) T staging system predicts risk based on 4 tumor risk factors (RFs). However, stage is not precisely associated with the number of RFs, as BWH stage T2b includes CSCCs with 2 and 3 RFs.ObjectiveTo determine how RF number is associated with the risk of recurrence, metastasis, and disease-related death.Design, Setting, and ParticipantsThis retrospective multination cohort study of CSCCs diagnosed between October 1, 1991, and July 19, 2023, was conducted at 12 centers in the US (10), Spain (1), and Brazil (1). Invasive CSCCs with confirmed negative margins longer than 14 days were included. Tumors were excluded if they were metastatic at presentation or received adjuvant therapy. Data were analyzed from October 2023 to August 2024.Interventions or ExposuresCSCCs were stratified by the number of the following RFs (0, 1, 2, 3, or 4): a diameter of 2 cm or larger, poorly differentiated histology, tumor extension beyond subcutaneous fat, and large caliber nerve invasion.Main Outcomes and MeasuresFive-year cumulative incidences of local recurrence, nodal metastasis, distant metastasis, and disease-specific death.ResultsA total of 16 844 CSCCs were included (5978 female individuals [35.5%]; median [IQR] age, 73.9 [65.7-81.8] years), with 0 (12 657 [75.1%]), 1 (2892 [17.2%]), 2 (1015 [6.0%]), 3 ( 225 [1.3%]) or 4 (55 [0.3%]) RFs. Median (IQ) follow up time was 33.6 (14.5-60.3) months. For local recurrence, the risk increased as the number of RF increased from 0 (1.7%; 95% CI, 1.5%-2.0%) to 1 (5.0%; 95% CI, 4.1%-5.9%) to 2 (8.8%; 95% CI, 7.0%-11.0%) to 3 (16.0%; 95% CI, 11.0%-22.0%) to 4 (33.0%; 95% CI, 19.0%-47.0%; P < .001 for between-group differences). This increase was also observed for nodal metastasis (0.6% [95% CI, 0.4%-0.7%] vs 3.6% [95% CI, 2.9%-4.4%] vs 11.0% [95% CI, 9.2%-13.0%] vs 20.0% [95% CI, 15.0%-26.0%] vs 28.0% [95% CI, 15.0%-42.0%], respectively; P < .001), distant metastasis (0.2% [95% CI, 0.1%-0.3%] vs 1.1% [95% CI, 0.7%-1.6%] vs 2.3% [95% CI, 1.4%-3.4%] vs 7.9% [95% CI, 4.6%-12.0%] vs 8.4% [95% CI, 2.6%-19.0%], respectively; P < .001), and disease-specific death (0.3% [95% CI, 0.2%-0.4%] vs 1.9% [95% CI, 1.4%-2.7%] vs 5.4% [95% CI, 4.0%-7.0%] vs 11.0% [95% CI, 6.7%-16.0%] vs 25% [95% CI, 12%-39%], respectively; P < .001). CSCCs with 3 RFs had higher cumulative incidences of local recurrence (1.6-fold), nodal metastasis (1.9-fold), distant metastasis (4.3-fold), and disease-specific death (1.9-fold) compared with those with 2 RFs.Conclusions and RelevanceThe results of this cohort study suggest that the number of RFs is an indicator of risk, and among BWH T2b tumors, those with 3 RFs represent a higher risk subset.

Abstract Human immune system (HIS) mice constructed in various ways are widely used for investigations of human immune responses to pathogens, transplants and immunotherapies. In HIS mice that generate T cells de novo from hematopoietic progenitors, T cell-dependent multisystem autoimmune disease occurs, most rapidly when the human T cells develop in the native NOD.Cg- Prkdcscid Il2rgtm1Wjl (NSG) mouse thymus, where negative selection is abnormal. Disease develops very late when human T cells develop in human fetal thymus grafts, where robust negative selection is observed. We demonstrate here that PD-1+CD4+ peripheral (Tph) helper-like and follicular (Tfh) helper-like T cells developing in HIS mice can induce autoimmune disease. Tfh- like cells were more prominent in HIS mice with a mouse thymus, in which the highest levels of IgG were detected in plasma, compared to those with a human thymus. While circulating IgG and IgM antibodies were autoreactive to multiple mouse antigens, in vivo depletion of B cells and antibodies did not delay the development of autoimmune disease. Conversely, adoptive transfer of enriched Tfh- or Tph-like cells induced disease and autoimmunity-associated B cell phenotypes in recipient mice containing autologous human APCs without T cells. Tfh/Tph cells from mice with a human thymus expanded and induced disease more rapidly than those originating in a murine thymus, implicating HLA-restricted T cell-APC interactions in this process. Since Tfh, Tph, autoantibodies and lymphopenia-induced proliferation (LIP) have all been implicated in various forms of human autoimmune disease, the observations here provide a platform for the further dissection of human autoimmune disease mechanisms and therapies.

ABSTRACTBackgroundInsomnia and substance use disorders (SUD) are common comorbidities of bipolar disorder (BD). Genome‐wide association studies (GWAS) have uncovered shared genetic contributions to insomnia and BD as well as SUDs and BD. Electronic health record (EHR) derived phenotypes (phecodes) and questionnaire data were used to examine the relationship between insomnia genetic liability and SUDs in BD.Methods40,839 participants from the Mayo Clinic Bipolar Disorder Biobank (BD Biobank; n = 774) and Mayo Clinic Biobank (n = 485 BD cases, n = 39,580 controls) were included in the analyses of diagnosis (phecode) outcomes (insomnia, SUD, alcohol use disorder [AUD] and tobacco use disorder [TUD]). Analyses of specific SUD outcomes obtained through the BD Biobank questionnaire included 1789 cases and considered BD subtype. Logistic regression was used to test for associations between insomnia polygenic risk scores (PRS) and insomnia and SUD outcomes in BD cases and controls.ResultsInsomnia PRS was associated with having an insomnia diagnosis (phecode) in the EHR in controls (OR = 1.19, p = 9.64e‐33) but not in BD cases (OR = 1, p = 0.95). Associations between insomnia PRS and SUD diagnoses were significant in BD cases and controls, with the association being stronger in BD cases (interaction p = 0.024). In the BD Biobank data, the insomnia PRS was associated with increased odds of AUD (OR = 1.19, p = 4.26e‐04), TUD (OR = 1.21, p = 1.25e‐05) and cannabis use disorder (OR = 1.16, p = 4.19e‐03).ConclusionThe effect of genetic predisposition to insomnia on SUD risk may be stronger in BD cases than in controls, which could have clinical care implications for individuals with BD and comorbid SUD.

Abstract Clostridiodes difficile’s epidemiology has evolved over the past decades, being recognized as an important cause of disease in the community setting. Even so, there has been heterogeneity in the reports of CA-CDI. Therefore, the aim of this study was to assess the epidemiologic profile of CA-CDI. This systematic review and meta-analysis were conducted according to PRISMA checklist and Cochrane guidelines (CRD42023451134). Literature search was performed by an experienced librarian from inception to April 2023, searching in databases like MEDLINE, Scopus, Web of Science, EMBASE, CCRCC, CDSR, and ClinicalTrials. Observational studies that reported prevalence, incidence of CA-CDI, or indicators to calculate them were included. Pool analysis was performed using a binomial-normal model via the generalized linear mixed model. Subgroup analysis and publication bias were also explored. A total of 49 articles were included, obtaining a prevalence of 5% (95% CI 3–8) and an incidence of 7.53 patients (95% CI 4.45–12.74) per 100,000 person-years. In conclusion, this meta-analysis underscores that among the included studies, the prevalence of CA-CDI stands at 5%, with an incidence rate of 7.3 cases per 100,000 person-years. Noteworthy risk factors identified include prior antibiotic exposure and age.

Objectives While extracorporeal shockwave therapy (ESWT) may be an efficacious adjunctive treatment option for musculoskeletal injuries, current research is limited by significant heterogeneity within treatment protocols. This study aims to establish international expert consensus recommendations on ESWT terminology, parameters, procedural considerations, contraindications and side effects in the application of ESWT to sports injuries. Methods A systematic literature search was performed on the use of ESWT for musculoskeletal and sports medicine injuries to identify potential panellists, followed by the development of a steering committee-led questionnaire. A three-stage, modified Delphi questionnaire was provided to a panel of 41 international clinical and research experts across 13 countries. Panellists had the opportunity to suggest edits to existing statements or recommend additional statements in Round 1. Consensus was defined as≥75% agreement. Results All 41 panellists completed Rounds 1, 2 and 3. Consensus was reached on 69/118 statements (58.5%), including recommendations on terminology and fundamental concepts, indications for use, procedural aspects for tendinopathy and bone pathologies, treatment correlations with imaging, periprocedural and postprocedural considerations, absolute and relative contraindications and potential side effects. Of the 49 statements that did not reach consensus, 17/49 (34.7%) were related to procedural aspects of bone pathology. Conclusion This international panel presents recommendations on ESWT terminology, indications and treatment considerations to guide ESWT use and decision-making by sports medicine clinicians. While our panel supported the use of ESWT in the treatment of bone pathologies, certain procedural aspects of ESWT specific to these injuries did not reach consensus and require further investigation.

Intratumoral heterogeneity and clonal evolution are pivotal in the progression and metastasis of melanoma. However, when combined with variable tumor cellularity, intratumoral heterogeneity limits the sensitivity and accuracy of uncovering a cancer’s clonal evolution. In this study, we combined fluorescence-activated cell sorting (FACS) with whole-exome sequencing (WES) to investigate the clonal composition and evolutionary patterns in seven melanoma biopsies obtained from three patients, each having both primary site and metastatic samples. We employed a multiparameter ploidy sorting approach to isolate tumor populations based on DNA ploidy and melanoma biomarkers (SOX10 or S100), enabling us to investigate clonal evolution with high resolution. Our approach increased the mean tumor purity from 70% (range 19–88%) in unsorted material to 91% (range 87–96%) post-sorting. Our findings revealed significant inter- and intratumor heterogeneity, with one patient exhibiting two genomically distinct clonal tumor populations within a single primary site biopsy, each giving rise to different metastases. Our findings highlight the critical role of intratumoral heterogeneity and clonal evolution in melanoma, especially when analyzing tumor trajectories. The unique combination of multiparameter FACS and WES provides a powerful method for identifying clonal populations and reconstructing clonal evolution. This study provides valuable insights into the clonal architecture of melanoma and lays the groundwork for future research with larger patient groups.

ABSTRACTBronchial dehiscence is a known complication following lung transplantation. In cases involving extensive airway necrosis and air leaks, bronchoscopic placement of self‐expanding metallic stents provides an effective and safe management strategy. These stents facilitate granulation and tissue reepithelialization. We present a case of bronchial anastomotic dehiscence size mismatch after a lung transplant. This complication was successfully managed using three stents placed via a telescoping technique with flexible bronchoscopy.