Citations

ABSTRACT Objective To identify and compare how patient perceptions contribute to Type 1 Delays, defined as delays in deciding to seek care, among individuals with head and neck cancer (HNC) in high‐income countries (HICs) and low‐ and middle‐income countries (LMICs). Methods We conducted a scoping review and systematic search of MEDLINE, Embase, Cochrane Library, and Scopus from inception through November 20, 2023. Eligible studies included patients with HNC in HICs or LMICs who reported patient perceptions contributing to Type 1 Delays. Data extraction was performed in duplicate, and barriers were categorized thematically. Fisher's exact test was used to compare the frequency of reported barriers between HIC and LMIC studies. Results Seventeen studies met inclusion criteria, of which 64.7% ( n = 11) were conducted in HICs and 35.3% ( n = 6) in LMICs, representing 9 countries and 1410 participants. The most frequently cited perceptions contributing to delay were symptom unawareness, misinterpretation, and minimization. Additional barriers included fear of diagnosis, stigma, alternative medicine use, financial challenges, and geographic barriers. Transport/geographic barriers showed a trend toward being more common in LMIC studies ( p = 0.05). Descriptive patterns suggested LMIC patients more often reported structural and sociocultural barriers, whereas HIC patients more commonly cited psychosocial or perceptual barriers. Conclusion Type 1 Delays in HNC are common across both HICs and LMICs, with overlapping and region‐specific contributors. Tailored interventions, such as patient education, stigma reduction, and improved access to diagnostic services, may promote earlier detection and improve global HNC outcomes. Level of Evidence 3.

Inverted sinonasal papilloma (ISP) and respiratory epithelial adenomatoid hamartoma (REAH) are sinonasal lesions with overlapping clinical, radiographic, and histologic features, making accurate diagnosis challenging. ISP is a benign but aggressive tumor with a propensity for local destruction, recurrence, and malignant transformation, whereas REAH is a hamartomatous lesion often arising in the olfactory cleft. We present four patients with lesions initially suspected to be ISP based on intraoperative frozen section but ultimately diagnosed as REAH on permanent pathology. All patients had polypoid sinonasal masses, frequently involving or adjacent to the olfactory cleft. Intraoperative frozen sections were often inconclusive or favored ISP, reflecting the difficulty of distinguishing these entities. Histologic analysis revealed that epithelial thickness served as a key morphologic feature differentiating ISP from REAH, with REAH exhibiting ciliated glandular proliferation and ISP characterized by hyperplastic epithelium with features of columnar and squamous differentiation. These patients underscore the diagnostic pitfalls of small biopsies and frozen sections, and highlight the importance of permanent specimens and collaboration with experienced pathologists. Accurate differentiation is critical, as management strategies differ substantially: ISP requires aggressive resection and long-term surveillance, while REAH may be treated with limited excision and minimal follow-up.

PURPOSE We sought to characterize outcome associations of poly ADP-ribose polymerase inhibitors (PARPi) in patients with ovarian cancer (OVCA) whose cancers contain homozygous loss (deletions) of homologous recombination repair (HRR) pathway genes, an alteration class not uniformly reported on clinical testing and not susceptible to acquired resistance via secondary reversion mutations. METHODS This study used US-based deidentified Flatiron Health-Foundation Medicine OVCA Clinico-Genomic Database. Patients with advanced OVCA and genomic profiling by Foundation Medicine were assembled into cohorts evaluating PARPi monotherapy use, and separately, PARPi maintenance therapy use, with outcomes associated with HRR gene alterations: BRCA1 / 2 , PALB2 , RAD51B/C/D , BARD1 , and BRIP1 . RESULTS 1.5% (82/5,404) had HRR gene homozygous loss, with BRCA1 and BRCA2 loss being most common. Among all OVCAs with BRCA1/2 alterations, 7.5% (63/836) were homozygous losses. Most BRCA1 (34/38, 89%) and BRCA2 (18/25, 72%) homozygous losses were intragenic, with breakpoints not spanning entire gene. Maintenance cohort: 22 patients had HRR gene homozygous loss, with strongly improved progression-free survival (PFS) for PARPi versus no PARPi use (HR, 0.06, 95% CI, 0.01 to 0.37). Monotherapy cohort: patients without HRR alterations (n = 198), HRR mutations or rearrangements (n = 93), and HRR homozygous loss (n = 8) had median PFS of 4.9, 10.6, and 25.4 months, and median overall survival of 18.5, 22.5, and 51.8 months, respectively. CONCLUSION We observe durable PARPi effectiveness for patients with OVCA and HRR gene homozygous loss in routine practice. We demonstrate the importance of detecting and reporting homozygous loss in HRR genes, an aspect not standard to all sequencing assays.

Abstract Objectives To examine the extent to which heat-related causes of death are recorded in fatal drug overdoses, how these patterns vary across states and over time, and how overdose characteristics differ between deaths with, versus without, heat involvement recorded. Methods Death certificate data for all drug overdose deaths in US residents from 2001 to 2024 (from the National Center for Health Statistics) were analyzed to identify whether a heat-related cause of death was also listed on the death certificate. Joinpoint regression, descriptive statistics, and nonparametric tests were used to examine temporal trends and compare overdose deaths with versus without recorded heat involvement. Results In 2001, fewer than 10 drug overdose deaths with recorded heat involvement were identified, but this number increased to 558 in 2024. From 2013 to 2024, mortality rates increased significantly, with an estimated annual percent change of 30.1 (95% Confidence Interval, 26.5–47.1). The highest mortality rates and numbers of deaths were observed in residents of Arizona and Nevada. American Indian/Alaska Native, Mexican-heritage, and foreign-born populations accounted for larger shares of overdose deaths with, compared to without, heat involvement recorded. A street or highway was more frequently identified as the place of injury in overdose deaths with (18.9%), versus without (2.2%) heat involvement reported. Psychostimulants such as methamphetamine were involved in 85.9% of overdose deaths with, compared to 28.9% without, recorded heat involvement. Conclusions Although representing only a fraction of all overdose deaths, fatal overdoses involving heat exposure have increased markedly over time and disproportionately impact certain states and demographic groups.

Background: Although donor and recipient characteristics are used to estimate graft failure risk, they remain limited in predicting early acute rejection. We developed and validated a next-generation sequencing (NGS) assay targeting the pre-transplant immunologic profile to predict early acute rejection following kidney transplantation. Methods: This prospective, international study enrolled 321 kidney transplant participants across 13 sites, forming discovery and validation cohorts. Peripheral blood was collected prior to transplant and at 1, 3, 6, 12, and 24 months post-transplant, with protocol biopsies performed at 3 and 12 months, as well as any indication biopsies. Biopsies were assessed by a blinded central pathologist according to the 2019 Banff criteria. The pre-transplant risk assessment (PTRA™) test to evaluate RNA expression of a 29-gene signature algorithm designed to predict early acute rejection risk was clinically validated utilizing 122 deceased donor kidney transplant recipients. Results: PTRA classified 31 of 122 participants (25%) as high-risk and 91 (75%) as low-risk. There were 9 early acute rejection events in the first 60 days post-transplant: 6/31 (19%) in the high-risk group and 3/91 (3%) in the low-risk group. PTRA discrimination for early acute rejection at 60 days post-transplant yielded an AUC of 0.78 (95% confidence interval [CI]: 64.4 to 91.5), p<0.001. A cut-off of ≤45 was defined as low-risk and >45 as high-risk for early acute rejection within 60 days post-transplant. Sensitivity 0.67 (95% CI: 0.36 to 0.97), specificity 0.78 (95% CI: 0.70 to 0.86), positive predictive value 0.19 (95% CI: 0.05 to 0.33), and negative predictive value 0.97 (95% CI: 0.93 to 1.00). The odds ratio comparing patients identified as high- vs low-risk by PTRA was 7.04 (95% CI: 1.64 to 30.2), p=0.009. Conclusions: This study validates the ability of PTRA to stratify kidney transplant recipients as high- or low-risk for early acute rejection using a pre-transplant transcriptomic profile, with implications for graft health and personalized treatment management.

Augmented cardiovascular responses to spontaneous nocturnal arousals were previously shown in chronic short-sleeping adults, without known sex differences. Sustained 4-h sleep restriction produced a sex-dependent alteration in heart rate responses to arousals and resulted in a prolonged reduction in postarousal pulse transit time in females only. These findings yield the first sex-specific characterization of nocturnal cardiovascular responses to spontaneous arousals following sleep restriction, and may place females at greater sleep truncation-related cardiovascular disease risk.

Abstract Background Breast cancer (BC) diagnosed during pregnancy or postpartum often presents with aggressive features, potentially influenced by hormonal, immunological, and tissue remodeling changes. Studies have suggested that postpartum BC may be associated with worse outcomes, though most evidence is retrospective and constrained by methodological limitations. This study evaluated associations between pregnancy history, recency of childbirth, and long-term outcomes in a prospective cohort of young patients with early-stage BC. Patients and Methods Patients aged ≤40 years with stage I–III BC enrolled in the Young Women’s Breast Cancer Study were categorized at diagnosis as nulligravid, nulliparous, pregnant, or parous (≤5 vs 5 to 10 years postpartum). Analyses were stratified by BC subtype (estrogen receptor-positive [ER+]/HER2−, HER2+, and triple-negative [TNBC]), with distant recurrence-free survival (DRFS) as the primary endpoint. Results Among 859 patients, 257 (29.9%) were nulligravid, 50 (5.8%) nulliparous, 37 (4.3%) pregnant, and 515 (60.0%) parous. Pregnant patients had proportionally more TNBC, nodal involvement, T3/T4, and grade 3 tumors. After 11.1 years median follow-up, pregnancy or postpartum status was not independently associated with DRFS in multivariable models adjusted for age, tumor characteristics, and treatment, with consistent findings across ER+/HER2−, HER2+, and TNBC subtypes. Sensitivity analyses, including further categorization of postpartum diagnoses (&lt;2 vs 2 to 5 years), yielded consistent results. Conclusions Pregnancy history and recency of childbirth were not independently associated with long-term DRFS. Despite more aggressive features at diagnosis, patients diagnosed during or after pregnancy had comparable outcomes after adjustment, suggesting no adverse prognostic impact. Clinical trial registration NCT01468246 (https://clinicaltrials.gov/study/NCT01468246? term=NCT01468246&rank=1).

Abstract Stromal tumor infiltrating lymphocytes (sTILs), quantified via hematoxylin and eosin (H&E) tumor slides, are associated with improved response to chemotherapy and better overall survival (OS) in triple-negative breast cancer (TNBC). Digitization of H&E slides offers the opportunity for image-based computational approaches to enumerate sTILs. We describe QuTILs, a research-based TIL enumeration approach using a multilayer perceptron-based framework trained on open-source H&E images using the QuPath software and executed on a standard computer. QuTILs was applied to H&E images from two phase III TNBC clinical trials, CALGB 40502 and 40603 (total n = 462 patients). In Cox proportional hazards models, QuTILs showed significant univariate association in CALGB 40502, with higher TIL% associated with reduced hazard (HR: 0.75, 95% CI: 0.63–0.91), which remained significant in multivariable models and validation CALGB 40603 TNBC clinical trial. In summary, QuTILs provides a computationally efficient, open-source workflow for sTIL identification from digital H&E images for research application.

Abstract Aims Trends in upright seated pulmonary artery pressure (PAP) with synchronous measurement of weight, blood pressure (BP), and heart rate (HR) have not been compared prior to heart failure events (HFE) and other causes of hospitalization during remote monitoring. Methods We analysed 24-month data from patients in the PROACTIVE-HF trial. Participants (N = 456) used the CordellaTM HF daily to measure seated PAP, weight, BP, and HR, all taken and transmitted within minutes. Events that were analysed included HFE, those potentially related to HF treatment (HF-TRE), and others (non-HFE). Parameters were trended from 60-days before (D-60) to 30-days after (D + 30) the day of the event (D = 0), and their concurrent changes were compared between D-60 and D = 0, and D = 0 and D + 30 using a mixed effects model. Results There were 196 HFE, 276 non-HFE, and 66 HF-TRE. Prior to HFE, average mean PAP (mPAP) increased from 27.8 ± 10.9 mmHg at D-60 to 32.6 ± 11.2 mmHg at D = 0 (P &lt; .001), and decreased to 30.0 ± 12.4 mmHg at D + 30 (P = .001). Kinetics of mPAP before HFE differed by left ventricular ejection fraction (LVEF); mPAP rose by 3.4 ± 6.8 mmHg in 2 weeks before HFE in those with LVEF &gt;40%, whereas a similar magnitude (3.1 ± 9.1 mmHg) of mPAP rise occurred over 6-weeks before HFE in those with LVEF ≤40%. No consistent changes in weight, SBP, or HR prior to HFE were observed (P &gt; .05). Changes in vital signs but not mPAP were noted prior to HF-TRE and non-HFE. Conclusion Seated mPAP increased weeks in advance of HFE and vital signs did not change consistently before HFE. Differential kinetics of mPAP prior to HFE by the LVEF suggest that an uptrend in seated mPAP may need to be addressed more rapidly in those with LVEF&gt;40%. Changes in vital signs with non-HFE and HF-TRE need further validation.