Citations

Abstract Pain treatments have modest effects. Health outcomes might be improved if treatments are matched to mechanisms underlying the persistence and biopsychosocial impact of an individual's pain. The International Association for the Study of Pain (IASP) defines 3 mechanistic pain descriptors presumed to involve different mechanisms—nociceptive, neuropathic, and nociplastic. Although treatments to address each descriptor have been proposed, there is no consensus on how to assign descriptors to clinical presentations. A recent consensus identified candidate clinical features to discriminate between descriptors in clinical practice and research. These need refinement to progress towards a tool. This study aimed to determine the rank and relative weight of identified clinical features to aid discrimination between mechanistic pain descriptors. Candidate clinical features (n = 196) were refined by the IASP Terminology Task Force to converge similar and remove redundant features. The Task Force (n = 24) and an expert panel (n = 39) ranked features using 1000minds conjoint analysis software and assigned weights based on discrete pairwise choices. Participants nominated from pairs of scenarios, which most likely indicated that pain aligned predominantly to a descriptor. Highest ranked features for neuropathic and nociplastic pain were aligned with IASP Clinical Criteria. Criteria for nociceptive pain have not been established. A ranked list of features shared by 2 mechanisms (indicating mixed mechanisms) was also identified. This study identified expert consensus on the highest ranked clinical features with potential to discriminate between pain descriptors, reflective of different underlying mechanisms. This study extends current frameworks by identifying and refining key discriminators for future operationalisation and validation.

Abstract Introduction: Maintenance of donor lung pressure is recommended to maintain inflation pressures of 12-15 mm Hg. This is particularly important given graft transportation in aircraft, due to the inevitable pressure changes. Case: We describe a case of a donor lung preservation system which maintained proper airway pressure during sudden cabin pressure loss requiring emergent landing. Discussion: The donor lungs were implanted without complication. Post-transplant course was notable for primary graft dysfunction (PGD) grade 1 at 24 hours, grade 2 at 48 hours, and grade 1 at 72 hours. At 3 months post-transplant, the patient has had no respiratory complications and has been noted to be doing well.

Background Traumatic hemorrhage is a prevalent cause of death nationally, with >50% of civilian deaths estimated to be preventable with more timely intervention. This study investigated the efficacy of training large and diverse audiences in bleeding control methods including tourniquets in community health fair settings. Methods A booth was utilized for bleeding control training at community health fairs via direct demonstrations of pressure, wound packing, and commercial and improvised tourniquet application followed by hands-on practice. Participants self-rated their perceived abilities while instructors rated the participant competency. Results 117 community members participated during two fairs, though not every person completed every portion of the training. Average age was 33 (range 6-82) and the majority were female (65.0%). There was no difference in self-perceived skill compared to trainer grading of participant’s ability to identify life-threatening bleeding (112 (97.4%) vs 106 (97.2%); P = 1), apply pressure (113 (98.3%) vs 106 (97.2%); P = .68), and pack a wound (102 (88.7%) vs 92 (84.4%); P = .43). No difference in difficulty was noted in placing commercial vs improvised tourniquets (16 (43%) vs 14 (45%); P = .87). However, participants were overconfident in their ability to place tourniquets compared to trainer grading, respectively (112 (98.2%) vs 100 (91.7%; P = .03)). Discussion Community fair classes provide opportunities to train large and diverse audiences in bleeding control techniques. However, participants overestimated their ability to appropriately apply tourniquets. Further investigation is needed into best educational approaches to optimize the impact of bleeding control kits that have been distributed in multiple states.

Little is known about how health-related quality of life (HRQoL) in breast cancer cases differed from that of controls during and after the COVID-19 pandemic. This study used data from an ongoing, nationwide HRQoL survey of 4279 newly diagnosed breast cancer cases and 2911 controls to investigate how breast cancer patients fared during different phases of the pandemic compared to controls. Responders during 2020–2022 were categorized into three COVID-19-related phases: the social restrictions phase, the high infection rate phase, and the post-pandemic phase. Across phases, breast cancer cases had significantly worse scores in most HRQoL domains compared to controls. Apart from slightly more insomnia in the high infection rate phase for both cases and controls, and better social functioning for young cases in the post-COVID-19 phase, the case-control differences in HRQoL remained consistent across phases. When the phases were assessed as one period, young women and those living with children <18 years of age fared the worst among breast cancer cases, while single women fared the worst among controls. In contrast, controls living with children <18 years of age exhibited better HRQoL than controls without children. In summary, women with breast cancer did not appear to fare differently than controls in terms of HRQoL across COVID-19 phases. However, breast cancer cases with young children fared worse in their HRQoL than other breast cancer cases.

ImportanceYoung women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers.ObjectiveTo investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers.Design, Setting, and ParticipantsInternational, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023.ExposurePregnancy after breast cancer.Main Outcomes and MeasuresPrimary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer–specific survival, overall survival, pregnancy, and fetal and obstetric outcomes.ResultsOf 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer–specific survival and overall survival.Conclusions and RelevanceIn this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival.Trial RegistrationClinicalTrials.gov Identifier: NCT03673306

SummaryBackgroundThe optimal ulcerative colitis biopsy protocol is unclear.AimTo evaluate the number of biopsies required to accurately assess microscopic disease activity in ulcerative colitisMethodsBiopsies from patients with ≥4 rectosigmoid samples, and clinical and endoscopic data, were retrospectively obtained from a prospective biobank. Histology and endoscopic videos were read blindly. A 4‐biopsy Robarts Histopathology Index (RHI) reference score, consisting of the worst item‐level ratings from four biopsies, was compared to 1‐, 2‐ and 3‐biopsy estimates. Agreement was determined using bivariate errors‐in‐variable regression analysis (acceptance interval: ±8.25). Endoscopic activity and disease location subgroup analyses were also performed.ResultsForty‐six patients had ≥4 rectosigmoid biopsies available (N = 287). The 2‐biopsy (tolerance interval: −7.66, 4.79) and 3‐biopsy (tolerance interval: −4.86, 3.46) RHI scores demonstrated acceptable agreement with 4‐biopsy scores. One‐biopsy scores demonstrated unacceptable agreement (tolerance interval: −13.99, 7.78). Mean RHI scores using the 2‐, 3‐ and 4‐biopsy approaches were similar (6.1 ± 9.6 P = 0.36; 6.8 ± 10.5, P = 0.7; 7.5 ± 11.2), whereas the 1‐biopsy estimate was lower (4.4 ± 8.1, P = 0.06). Histological remission rates were identical for the 2‐, 3‐ and 4‐biopsy methods (65.2%, P = 1.0). Subgroup analysis demonstrated that three biopsies were required in patients with endoscopically active disease. Sampling additional colonic locations yielded lower histological remission rates compared to rectosigmoid sampling alone (33.3% vs 61.9%, P = 0.1).ConclusionsA minimum of two — conservatively, three — biopsies are required to reliably assess disease activity in a single colonic segment using the RHI. Further studies are needed of endoscopically active patients and sampling locations. These results have implications for biopsy strategies in clinical trials and practice.

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1 *04 subtypes best accounted for the association, strongest with HLA-DRB1 *04:04 and HLA-DRB1 *04:07, and intermediary with HLA-DRB1 *04:01 and HLA-DRB1 *04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1 *04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1 *04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.

Abstract: Athletes of all ages may be affected by medical and mental health issues. Sports medicine physicians should be familiar with common conditions that may affect the well-being of athletes, such as attention-deficit/hyperactivity disorder (ADHD). ADHD behaviors have the potential to affect a person's ability to concentrate. It is likely that social and cognitive therapies combined with pharmacotherapy will be the most effective way to treat ADHD in athletes. Medications used for ADHD, especially stimulant types, are known to improve alertness, reaction time, anaerobic performance, and endurance, which would potentially improve athletic performance. Furthermore, stimulant medications may enable student athletes with ADHD to focus on academic studies for longer periods of time, beyond usual levels of fatigue, important for those who may be exhausted after practices and games. The purported performance enhancement effects and potential adverse effects of stimulant medications have prompted many sports governing bodies to ban prescription stimulants or establish strict rules for their use. Athletes taking physician-prescribed stimulants to treat ADHD need to provide the appropriate documentation for approval before competition or risk punitive measures. Physicians should strive to provide a high quality of care to athletes with ADHD through early diagnosis, appropriate and careful multidisciplinary treatment, and complete and timely documentation to facilitate continued sports participation.

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.