Citations

Objective: Analyzing textbook outcome (TO) following rectal cancer resection and its association with long-term survival when compared to hospital case volume alone. Background: TO is a quality metric representing the ideal result following complex cancer surgery. Prior studies have suggested improved long-term survival for rectal cancer patients undergoing surgery at HV institutions. Methods: Patients undergoing surgery for rectal adenocarcinoma from 2014 to 2015 were identified using the National Cancer Database. Low (LV), medium (MV), and high-volume (HV) hospital strata were defined by quartile cutoffs (low <25th, high >75th, and 25–75th medium volume). TO was achieved with adequate lymph node count (≥12), negative margins (R0 resection), length of stay <75th percentile, absence of 30-day readmission/mortality event, and appropriate plus timely systemic therapy. Adjusted analyses for long-term survival were performed using a hierarchical multivariable Cox regression model. Results: TO was achieved in 28.5% of 48,484 patients. LV or MV hospital patients were more likely to be older, uninsured/Medicaid, and less likely to achieve a TO (HV 31.2% vs MV 29.6% vs LV 23.2%, P < 0.001). TO was associated with improved 5-year survival (84.0% vs 72.0%, P < 0.001). On multivariable analyses, TO was the strongest protective factor against mortality (HR 0.60, 95% confidence interval = 0.56–0.64), even after controlling for case volume. Conclusions: Only 28.5% of patients undergoing resection for rectal cancer achieve TO. However, they had a 40% reduction in long-term mortality independent of hospital volume. Optimizing long-term survival in patients with rectal cancer can be achieved by TO criteria rather than increasing surgical case volume.

Platelet-rich plasma (PRP) therapy is a non-invasive, autologous treatment with regenerative potential in gynaecology beyond fertility applications. This review evaluates PRP in non-fertility-related gynaecological conditions affecting women’s quality of life (QoL). Methods: Following PRISMA-ScR guidelines, we searched Embase, CINAHL, Web of Science, Scopus, CENTRAL, and MEDLINE for studies on PRP in conditions such as vulvar lichen sclerosus (VLS), vulvovaginal atrophy (VVA), sexual dysfunction (SD), stress urinary incontinence (SUI), and interstitial cystitis/bladder pain syndrome (IC/BPS). Of 3660 records screened, 43 studies (randomised controlled trials, quasi-experimental, cohort, and case series) were included. Results: PRP improved symptoms and QoL in several conditions, particularly VLS and SD, and was generally well tolerated with minor adverse effects (e.g., injection-site pain, transient discomfort). Evidence for abnormal uterine bleeding (AUB) and pelvic organ prolapse (POP) was inconclusive. Considerable heterogeneity in preparation protocols and outcome measures limited cross-study comparison. Conclusions: PRP shows promise as a minimally invasive therapy for certain gynaecological conditions. Standardisation of preparation and administration, along with large-scale RCTs, is needed to determine long-term efficacy and safety.

While anatomic total shoulder arthroplasty is a successful procedure that provides reliable pain relief and restoration of function in most patients, its success has been limited by glenoid component loosening. While series reporting the outcomes of inlay glenoid components have demonstrated excellent clinical outcomes with low rates of component loosening and need for revision, surgeons have been hesitant to adopt these implants due to concerns of inadequate pain relief secondary to the remaining glenoid rim contacting the humeral head implant. The inset glenoid component, a variant of the traditional inlay components, has gained interest because its design aims to achieve similar stability to traditional inlay components through implantation within strong subchondral bone, reduce the amount of glenoid vault removed compared to inlay components, and has a glenoid face designed to limit the rocking-horse phenomenon. In limited series, the inset glenoid component has demonstrated superior biomechanical and clinical performance compared to traditional onlay glenoid components. Although there have been minimal clinical studies investigating the inset glenoid in comparison to onlay and inlay components to date, a subset of case series with short-term follow-up have demonstrated favorable outcomes. The purpose of this article was to review the design rationale, biomechanical evidence, and clinical performance of the inset glenoid component.

This cross-sectional study analyzes patient-reported outcome findings from the Enhanced, Electronic Health Record–Facilitated Cancer Symptom Control (E2C2) trial to investigate level of symptom burden in adolescents and young adults with cancer.

ImportanceBurnout remains prevalent among physicians and can negatively affect quality, safety, and cost of patient care. Few randomized studies on interventions to address burnout have been conducted to date.ObjectiveTo determine whether wearing a smartwatch and having access to its physiological data (eg, sleep, step count, and heart rate) improves physician well-being (and if so, which dimensions of well-being).Design, Setting, and ParticipantsThis randomized clinical trial included physicians at 2 US medical centers (Mayo Clinic and the University of Colorado School of Medicine) who volunteered to wear a provided smartwatch beginning June 7, 2023. The study concluded on June 27, 2024.InterventionSix months of wearing a smartwatch.Main Outcomes and MeasuresBurnout, resilience, quality of life, depressive symptoms, stress, and sleepiness were measured using validated scales. Participants completed electronic surveys at baseline and 3, 6, 9, and 12 months. An intention-to-treat analysis was conducted.ResultsThis study included 184 physicians (mean [SD] age, 37.5 [9.3] years; 107 females [58.8%]). A total of 83 of 183 physicians (45.4%) were residents or fellows, 103 of 184 (56.0%) lived in Colorado, and 99 of 182 (54.4%) worked in non–primary care settings. Baseline levels of well-being across the measured dimensions were similar for the 2 study arms. At 6 months, 35 of 85 physicians (41.2%) in the intervention arm had burnout compared with 46 of 91 (50.5%) in the control arm (P = .21). Mean (SD) resilience scores at 6 months were 31.9 (5.0) and 29.5 (6.2) among physicians in the intervention and control arms, respectively (P = .01). In multivariable analysis adjusting for baseline score, demographics, specialty, and work hours, the prevalence of burnout was lower (odds ratio, 0.46 [95% CI, 0.21-0.99]; P = .046) and mean resilience score was higher (parameter estimate [scale, 0-40], 1.20 points [95% CI, 0.11-2.28 points]; P = .03; Cohen d = 0.17) among physicians in the intervention arm vs the control arm after 6 months.Conclusions and RelevanceIn this randomized clinical trial to evaluate the effect of wearing a smartwatch and having access to its physiological data on physician well-being, physicians who wore a smartwatch experienced improvements in burnout and resilience. Future research should explore whether engagement with smartwatch data leads to actual behavior change (eg, adaptive coping or reflective habits) that reduces burnout risk and enhances resilience.Trial RegistrationClinicalTrials.gov Identifier: NCT05463250

Background: Type IV Hereditary Sensory and Autonomic Neuropathy (HSAN IV) is an exceedingly rare autosomal recessive disease classically characterized by generalized loss of temperature/pain sensation, intellectual disability, and anhidrosis. HSAN IV patients are subject to repeated orthopaedic injuries and complications. There is some data on the clinical presentation, but limited data on the diagnostic and treatment challenges, and functional outcomes with HSAN IV. Methods: This is a retrospective case series of 4 siblings with HSAN IV. Medical records were reviewed for data regarding presentation, diagnosis, and management. Functional outcomes were assessed using the Pediatric Outcomes Data Collection Instrument, with historical normative data used as a control. The 2 populations were evaluated with a Welch-modified 2-sample t test to explore the alternative hypothesis that HSAN IV patients are significantly functionally impaired. Results: Our study included 4 siblings, 2 males and 2 females, aged 3, 8, 12, and 21 years, respectively. The average time to diagnosis was 53 months, and each diagnosis was confirmed through whole-exome sequencing. The challenges faced included delayed diagnosis, diverse clinical presentations, unestablished treatment guidelines, and unnecessary healthcare utilization before definitive diagnosis. The comparison of means between the normative population and the HSAN IV patients revealed a significant difference in sports/play ( T -score =−4.14, P =0.025) and global function ( T -score =−3.19, P =0.049) but no significant difference in upper extremity function ( P =0.216), transfer mobility ( P =0.164), pain/comfort ( P =0.955), and happiness ( P =0.995). Conclusions: HSAN IV is a rare genetic condition with protean clinical manifestations that can result in significant deficits in play and global function. The clinical manifestations are varied, including multiple fractures, delayed/abnormal fracture healing, bone deformity, osteomyelitis, and various other non-orthopaedic manifestations. Whole-exome sequencing is a useful tool that, when combined with a high index of clinical suspicion, can expedite the diagnostic process for HSAN IV. Patients can benefit from earlier diagnosis and earlier access to education to prevent functional deterioration and repeat medical interventions. Level of Evidence: IV—case series.

Abstract The effectiveness of T cell–based immunotherapy depends on durable T-cell responses that can efficiently eliminate tumor cells. NKG7 was discovered three decades ago as a protein associated with lytic granules. However, only studies published over the past 5 years have contributed substantially to our understanding of NKG7 in T-cell biology. NKG7 has been recognized as an important T-cell functional marker in responses to immune checkpoint inhibitor therapy and in the prognosis of certain cancers. Besides its role in the generation, trafficking, and release of lytic granules, which is critical for efficient T-cell cytotoxicity against tumor cells, NKG7 has been identified as a key negative regulator of mTORC1 activity. By restraining mTORC1 activity, NKG7 promotes T-cell longevity and memory generation after infection. Importantly, NKG7 upregulation has demonstrated therapeutic potential in preclinical T-cell therapy for cancer. Collectively, NKG7 is emerging as a promising biomarker and therapeutic addition to T cell–based immunotherapies.

ABSTRACT Herpes simplex virus type 1 replicates in the nucleus of the host cell and utilizes many cellular proteins to facilitate DNA replication. HSV-1 DNA replication is closely linked with homologous recombination, and HSV-1 encodes a two-subunit recombinase consisting of an exonuclease (UL12) and a single-strand DNA-binding protein (ICP8). We identified the cellular deubiquitinating enzyme USP15 as a new UL12-binding partner. USP15 is one of the most enriched proteins on viral DNA and has recently been implicated in regulating cellular homologous recombination. Utilizing isolation of proteins on nascent DNA (iPOND) to compare the proteins on wild-type and UL12-deficient viruses, we observed that USP15 is not recruited to newly replicated DNA in the absence of UL12. We also observed that UL12 and USP15 interact directly in vitro using purified proteins. Together, these data suggest that UL12 directly recruits USP15 to viral DNA. UL12 stimulates a type of homology-directed repair called single-strand annealing (SSA). We generated a USP15 knockout cell line with an integrated GFP-based SSA reporter and observed that UL12 and USP15 both contribute to the maximal induction of SSA. In addition to the reporter cell line, there is a 10-fold reduction in the frequency of marker rescue, and individual replication forks move slower in the absence of USP15. These data support a role for USP15 in facilitating recombination during the virus life cycle and the maintenance of replication fork stability. IMPORTANCE HSV-1 is a ubiquitous pathogen in the global population that causes lifelong latent infection with sporadic reactivation in the host. It has long been appreciated that HSV-1 DNA replication exhibits high rates of recombination and is linked to the host DNA damage response. In this study, we show a novel interaction between UL12, a member of the HSV recombinase, and the deubiquitinating host enzyme USP15. We show that USP15 physically interacts with UL12 and is required for UL12 to maximally stimulate recombination. In the absence of USP15, we also observe an overall reduction in virus growth. This work demonstrated that host proteins facilitate viral-induced recombination. The interaction of USP15 with UL12 represents a potential target for intervention against HSV-1 infection and associated disease.