Citations

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a functional imaging modality that can quantify tissue permeability and blood flow. Due to vasculature changes resulting from radiation therapy (RT), DCE-MRI quantitative parameters should be significantly different in regions receiving a high radiation dose compared to regions receiving a low radiation dose. This study sought to determine whether a significant difference exists in post-head-and-neck-cancer (HNC)-RT DCE-MRI quantitative parameters (Ktrans and ve) between regions of the mandible receiving a high radiation dose and regions of the mandible receiving a low radiation dose. Methods: DCE-MRI was acquired from HNC subjects post-RT. The DCE-MRI quantitative parameters Ktrans and ve were obtained through Tofts model fitting. Four mandible sections (left ramus, left body, right ramus, and right body) were delineated on subject mandible contours. Two Friedman tests comparing the mean Ktrans and ve in low-dose (≤60 Gy) areas of the four mandible regions were computed. If the Friedman test determined that a significant difference for a parameter between mandible regions exists, post hoc Wilcoxon signed-rank tests were completed comparing the four mandible regions. If the Friedman test determined that there was no significant difference between mandible regions, a Wilcoxon signed-rank test was used to determine whether a significant difference exists in the parameter between high-dose (>60 Gy) and low-dose (≤60 Gy) mandible regions. Results: 48 HNC subjects were included in the analysis. The Friedman tests showed no significant difference in ve means between mandible regions (χ(3)2 = 1.63, p = 0.44) and a significant difference in Ktrans means between mandible regions (χ(3)2 = 10.29, p = 0.005). Post hoc testing between Ktrans mandible regions found that the left body and right body differed significantly from the left ramus and right ramus. The Wilcoxon signed-rank test comparing the mean ve between high- and low-dose mandible regions found a significant difference (W = 214, p = 0.00013). Conclusions: no inherent difference in the DCE-MRI quantitative parameter ve was observed within subject mandibles, but a significant difference was observed between ve means in high- and low-radiation-dose mandible regions. These results provide evidence of the utility of DCE-MRI to monitor mandible vasculature changes resulting from head and neck cancer radiation therapy. Monitoring post-HNC-RT mandible vasculature changes is important to initiate earlier toxicity management and ultimately improve HNC survivors’ quality of life.

Rationale Despite significant advances in patient care and outcomes, criteria for cardiopulmonary exercise testing (CPET) in risk stratification guidelines for lung resection have not been updated in over a decade. We hypothesised that CPET no longer holds additional predictive value for postoperative complications. Methods In this secondary analysis, we included lung resection candidates from two prospective, multicentre studies eligible for CPET and assessed with preoperative pulmonary function tests (PFTs) and arterial blood gas analysis. Postoperative pulmonary (PPCs) and cardiovascular complications (PCCs) were documented during hospitalisation. We trained five types of machine learning models applying nested cross-validation to predict complications and compared predictive performance based on four metrics, including area under the receiver operating characteristic curve (AUC-ROC). Results A total of 497 patients were included. PPCs developed in 71 (14%) patients. Adding CPET parameters to PFTs and baseline clinical data did not improve the ability of models to predict PPCs in unselected patients (AUC-ROC=0.72–0.78; p=0.47), nor in those meeting American College of Chest Physicians (ACCPs) (n=236; AUC-ROC=0.64–0.78; p=0.70) or European Respiratory Society/European Society of Thoracic Surgery (ERS/ESTS) criteria (n=168; AUC-ROC=0.59–0.76; p=0.92). PCCs developed in 90 (18%) patients. CPET parameters likewise did not improve model performance for the prediction of PCCs in unselected patients (AUC-ROC=0.65–0.73; p=0.96), nor in the ACCP (AUC-ROC=0.61–0.73; p=0.82) or ERS/ESTS subgroups (AUC-ROC=0.62–0.69; p=0.87). Conclusions In contemporary surgical practice, CPET did not improve the predictive performance of machine learning models for PPCs or PCCs in patients with an indication based on established guidelines or in those without. The role of CPET in preoperative risk stratification for lung resection should be re-evaluated. Trial registration number NCT03498352 , NCT04826575 .

Evaluation of T-cell receptor (TCR) β-chain constant region 1 (TRBC1) expression is an alternative T-cell clonality assessment method. However, evaluation of TRBC1 immunohistochemistry (IHC) for distinguishing mycosis fungoides (MF)/Sezary syndrome (SS) from reactive inflammatory infiltrates in skin is incomplete. We evaluated the utility of a novel dual TRBC1-CD3 IHC stain in skin biopsies with MF/SS (n=40), reactive (n=24), or atypical T-cell infiltrates indeterminant for MF/SS (n=9). Twenty of 24 reactive cases showed clear polytypic TRBC1 expression (median percent TRBC1 positivity among CD3-positive T cells [%TRBC1+] 50% in dermis, 42.5% in epidermis among all cases), while 34/40 MF/SS were clearly monotypic (%TRBC1+ either ≤20% or ≥85%) (sensitivity 85.0%, specificity 91.7%, positive predictive value 94.4%, negative predictive value 78.6%). Discordance between TRBC1 expression and diagnosis was associated with few neoplastic/monotypic T cells and/or lack of physical separation between neoplastic and non-neoplastic populations. Among patch/plaque MF/SS, TRBC1 showed similar diagnostic sensitivity (80.0% vs. 86.7%) and high categorical correlation (monotypic vs. not monotypic, 80%) with TCR gene rearrangement results. TRBC1 interpretation was reproducible, with ≥2/3 and 3/3 pathologists rendering identical interpretations in 100% and 86% of cases, respectively, after independent review and 100% agreement following collective review. Digital image analysis confirmed visual %TRBC1+ accuracy ( r =0.9749, P <0.0001). On the basis of these results, we propose %TRBC1+ cutoffs of <25% or >75% for establishing T-cell monotypia in skin. Considering such thresholds, TRBC1-CD3 evaluation facilitated diagnostic refinement in 7/9 (78%) atypical cases. Overall, TRBC1-CD3 IHC clearly and rapidly aids diagnosis of cutaneous T-cell proliferations.

Objective: To estimate the relative risk of meningitis after repair of spontaneous lateral skull base cerebrospinal fluid (CSF) leaks through meta-analysis of published studies. Databases Reviewed: PubMed, Medline, Embase, Cochrane, SCI-EXPANDED, ESCI, Epistemonikos, and WHO Global Index Medicus were queried for terms including and related to meningitis, CSF leak, surgery, and spontaneous from inception to April 02, 2024. Methods: Prospective and retrospective studies in any language reporting either preoperative or postoperative rates of meningitis in adults with spontaneous lateral skull base CSF leaks were included. Two reviewers independently screened 2,564 studies and extracted data and evaluated risk of bias in 57 studies that met inclusion criteria. A random effects generalized linear mixed model was used to pool and compare logit transformed risk of meningitis before and after repair. Results: Of 1,310 patients who met inclusion criteria, 1,239 underwent CSF leak repair. Fifty-two studies reported rates of preoperative meningitis, and 27 studies reported rates of postoperative meningitis. Twenty-two studies with a total of 511 patients reported both rates. The average follow-up period of 17 studies reporting duration of follow-up was 23.1 months. The preoperative pooled risk of meningitis was 0.16 (95% CI: 0.13–0.25, I 2 = 40.57%). The postoperative pooled risk was considerably lower at 0.01 (95% CI: 0.01–0.14, I 2 = 4.16%). With substantial heterogeneity (I 2 = 62.94%), we observed a relative risk of meningitis after repair of 0.02 (95% CI: 0.00–0.79, p = 0.04). Conclusion: Surgical repair of spontaneous lateral skull base CSF leaks may significantly reduce the risk of adult meningitis.

Objective: Assess the impact of adult cochlear implantation on the disability and quality of life (QOL) of communication partners (CP) of cochlear implant (CI) recipients. Databases reviewed: PubMed, MEDLINE, Embase, Cochrane CENTRAL, Science Citation Index Expanded, and Emerging Sources Citation Index were searched. Methods: This study was reported following the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Articles included reported on disability or QOL measures of CP of adult CI recipients. Study selection included retrospective, prospective, and randomized controlled studies in English language. Three reviewers independently screened studies for inclusion, extracted data, and evaluated risk of bias. Outcomes included both qualitative and quantitative pre-CI and post-CI measures of CP disability or QOL. Results: Of 1615 screened articles, 9 studies utilizing quantitative and qualitative measures with 504 CP met inclusion criteria. Four of 6 studies assessing only post-CI CP QOL, demonstrated self-reported improvement, while one demonstrated worse CP QOL compared with the general population and one identified CP and CI recipient qualities that correlated with CP QOL scores. Two studies assessing pre-CI to post-CI CP QOL also reported improvements. One study assessing only pre-CI CP QOL suggested that CPs had worse QOL than normal hearing controls. Duration of CI recipient hearing loss did not impact CP QOL in any study. Conclusions: Though homogenous data on the QOL of CPs of CI recipients and the relationship between CI recipient and CP factors is limited, studies suggest that CPs of CI recipients may have worse QOL than the general population but, cochlear implantation may improve CP QOL.

ABSTRACT Transgender and gender diverse (TGD) individuals face minority stress and often avoid the emergency department (ED) due to previous negative experiences. The goal of this review is to prepare the emergency medicine pharmacist to care for TGD patients, with the ultimate goal of improving the care TGD patients receive. This review summarizes interactions with TGD patients, trauma‐informed considerations, physical exam and organ inventory sensitivities, and gender‐affirming hormone therapy and complications that may arise and be seen in the ED. Additionally, this review discusses common complaints and considerations that may commonly arise when caring for TGD patients.

PURPOSE Public reporting of health care outcomes can have unintended effects such as inappropriate risk aversion in patient selection. METHODS The center-specific survival analysis annually assigns all hematopoietic cell transplantation (HCT) centers in the United States a +1, −1, or 0 score for observed outcomes that are above, below, or within a center-specific predicted range of outcome. For each index year (2012-2016), centers receiving a −1 score after 0 scores in the preceding 2 years were compared with contemporaneous centers with as-predicted outcomes (0 score). Changes in the patient population characteristics in the 3 years before versus the 3 years after the index years were compared between the newly below-expected centers (NBCs) and the controls. A multivariate model adjusted for baseline patient population characteristics and center volume. RESULTS No differences in patient selection behavior were identified when comparing the NBCs with the controls across eight key patient population characteristics. For the statistically modeled (predicted) 1-year overall survival (OS), reflecting a holistic measure of centers' patient population risk, we observed no statistically significant difference in change (−0.23% [95% CI, −1.4 to 0.9]; P = .70). The observed OS increased in both NBCs and controls by 0.9% and 4.5%, respectively, without statistically significant difference in change. CONCLUSION Centers receiving a −1 score were not observed to deviate significantly from patient selection trends in the HCT field. These findings suggest that public reporting of HCT outcomes in the United States does not result in unintended bias against HCT for high-risk patients.

ImportancePatients with metastatic castration–resistant prostate cancer (mCRPC) harboring BRCA1/2 alterations are eligible to receive poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors as single agents or in combination with an androgen receptor pathway inhibitor after these agents showed survival improvement in their landmark clinical trials. However, data are limited regarding the uptake of PARP inhibitors in these patients.ObjectiveTo investigate the use of PARP inhibitors in patients with mCRPC harboring BRCA1/2 alterations.Design, Setting, and ParticipantsThis retrospective cohort study used the deidentified Flatiron-Health electronic health record–derived database of US community and academic practices to extract patient-level data. The data cutoff date was May 31, 2024. Patients with mCRPC with evidence of harboring BRCA1/2 alterations and alive after August 15, 2020 (ie, 3 months after the approval of the first PARP inhibitor, rucaparib, in mCRPC) were included. Statistical analysis was performed from September 2024 to May 2025.ExposuresAge, race and ethnicity, insurance status, and practice type at the time of mCRPC diagnosis.Main Outcomes and MeasuresThe receipt of PARP inhibitors. Multivariable logistic regression was conducted to assess the association between the exposures and the main outcome.ResultsOf 24 105 patients with metastatic prostate cancer, 443 male patients (median [IQR] age, 72 [65-79] years) had mCRPC with BRCA1/2 alterations and were eligible and included in our analysis. Of these patients, 227 (51.2%) received a PARP inhibitor, whereas 216 (48.8%) did not. Compared with patients covered by a commercial health plan, those covered by Medicare were significantly more likely to receive a PARP inhibitor (odds ratio, 1.91; 95% CI, 1.02-3.66; P = .047). The odds of receiving a PARP inhibitor were not significantly higher in patients treated in community practice compared with those treated in academic centers (odds ratio, 1.64; 95% CI, 1.00-2.70; P = .05).Conclusions and RelevanceThis retrospective cohort study of patients with mCRPC and evidence of BRCA1/2 alterations found that approximately half of patients did not receive PARP inhibitors despite evidence of survival improvement in this population. These findings highlight the need to increase awareness of the survival data and access to life-prolonging therapies in patients with mCRPC.