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AbstractBackgroundIn preclinical studies whole gut transit (WGT) in mice is a gold‐standard “leading‐edge” approach that measures the time between orogastric gavage of carmine red and defecation of the first carmine red pellet. Transit studies in humans are performed during the active day because GI motility and transit are suppressed during the night. Since mice are nocturnal, WGT studies traditionally done during the day occur during their rest phase. How circadian rhythm affects WGT in mice is not known.MethodsWe used an automated approach for high temporal resolution uninterrupted testing of mouse WGT and activity. We housed wild‐type Bl6/C57 mice under the standard 12 h light–dark cycles. At 8 weeks, we performed carmine red orogastric gavage and assessed WGT during Light (rest) conditions. Then, we exposed mice to a reverse 12 h light–dark cycle for 2 weeks and tested them in the Dark (active) under red light conditions. Timelapse videos were analyzed to quantify activity and to timestamp all pellets, and multiple parameters were analyzed.Key ResultWhen complementary light cycle reversal experiments were performed, we found a significant increase in mouse activity when mice were tested during their Dark (active) phase, compared to their Light (rest) phase. In mice tested in the Active phase compared to the Rest phase, we found a significant acceleration in WGT, increased rate and total number of pellets produced, and more pellet clustering. These data show that the mice tested in the Active phase have important differences in activity that correlate with multiple alterations in gastrointestinal transit.Conclusion & InferencesDuring the Active phase mice have faster WGT, produce more pellets, and cluster their output compared to testing in the Rest phase. Like in humans, circadian rhythm is an important consideration for transit studies in mice, and a simple reverse light cycle approach facilitates further studies on the role of circadian rhythm in GI motility.

Abstract Backgound Infections of the left ventricular assist device (LVAD) driveline are a dreaded complication that results in high mortality and morbidity. Method We retrospectively reviewed five consecutive patients with severe continuous‐flow LVAD (HVAD, Heartmate 2, and Heartmate 3) driveline infection. These infections, which developed on an average of 960.4 ± 843.9 days after LVAD placement, were refractory to systemic antibiotics and local wound care. All were treated with extensive surgical debridement, local installation of absorbable antibiotic‐loaded calcium sulfate beads (vancomycin and tobramycin), primary wound closure, and 6 weeks of systemic antibiotics after surgery. Results Four patients had resolution of DLI, and one had a recurrent infection at another part of the driveline 7 months after the complete resolution of the previous site. This patient was successfully treated with debridement and bead placements. Three patients still have their LVADs, while two received orthotopic heart transplants. At the time of the transplant, there was no evidence of gross infection of the LVAD drivelines or pumps. At the average follow‐up time of 425.8 ± 151 days, no patients have an active infection. Conclusion Treatment of LVAD driveline infection with absorbable antibiotic beads with primary wound closure is a viable option and merits further investigation.

Abstract Labral tears most commonly occur anteriorly between the 12‐ and 3‐o'clock positions, with the 12‐o'clock position denoted as superior and the 3‐o'clock position denoted as anterior. When approaching the 3‐o'clock position and beyond, suture anchor placement becomes difficult given the challenging arthroscopic trajectory and an overall thin anterior rim of cortical bone for anchor purchase, resulting in a narrow angle of safe drilling. The purpose of this technical note is to present a safe and reproducible method of suture anchor placement during acetabular labral repair approaching the 3‐ and 4‐o'clock positions, with the 12‐o'clock position representing the superior anatomic location and the 3‐o'clock position representing the anterior anatomic location regardless of hip laterality. We use an inside‐out anchor placement technique to place far medial anchors, which differs from the conventional techniques (e.g., outside‐in technique) in which anchor placement is performed along the external margin of the acetabular labrum. Technique Video video See video under supplementary data.

AbstractINTRODUCTIONIncreasing evidence suggests that amyloid reduction could serve as a plausible surrogate endpoint for clinical and cognitive efficacy. The double‐blind phase 3 DIAN‐TU‐001 trial tested clinical and cognitive declines with increasing doses of solanezumab or gantenerumab.METHODSWe used latent class (LC) analysis on data from the Dominantly Inherited Alzheimer Network Trials Unit 001 trial to test amyloid positron emission tomography (PET) reduction as a potential surrogate biomarker.RESULTSLC analysis categorized participants into three classes: amyloid no change, amyloid reduction, and amyloid growth, based on longitudinal amyloid Pittsburgh compound B PET standardized uptake value ratio data. The amyloid‐no‐change class was at an earlier disease stage for amyloid amounts and dementia. Despite similar baseline characteristics, the amyloid‐reduction class exhibited reductions in the annual decline rates compared to the amyloid‐growth class across multiple biomarker, clinical, and cognitive outcomes.DISCUSSIONLC analysis indicates that amyloid reduction is associated with improved clinical outcomes and supports its use as a surrogate biomarker in clinical trials.Highlights We used latent class (LC) analysis to test amyloid reduction as a surrogate biomarker. Despite similar baseline characteristics, the amyloid‐reduction class exhibited remarkably better outcomes compared to the amyloid‐growth class across multiple measures. LC analysis proves valuable in testing amyloid reduction as a surrogate biomarker in clinical trials lacking significant treatment effects.

AbstractINTRODUCTIONLittle is known regarding quality of life (QoL) in dementia with Lewy bodies (DLB), particularly in advanced stages.METHODSDyads of individuals with moderate–advanced DLB and their primary caregivers were recruited from specialty clinics, advocacy organizations, and research registries. The study collected demographics, disease‐related measures, and measures of patient/caregiver experiences.RESULTSThe Quality of Life in Alzheimer's Disease (QoL‐AD) was completed by the person with DLB and the caregiver (proxy) in 61 dyads; 85 dyads had only a proxy‐completed QoL‐AD. Patient‐ and proxy‐reported scores were moderately correlated (r = 0.57, P < 0.0001). Worse patient‐reported QoL correlated with daytime sleepiness, autonomic symptom burden, and behavioral symptoms. Proxy ratings correlated with dementia severity, daytime sleepiness, behavioral symptoms, dependence in activities of daily living, and caregiver experience measures.DISCUSSIONPatient‐ and proxy‐reported quality of life (QoL) should be assessed separately in advanced DLB. Some symptoms associated with QoL have available therapeutic options. Research is needed regarding strategies to optimally improve QoL in DLB.Highlights Patient and proxy quality of life (QoL) ratings had moderate correlation in advanced dementia with Lewy bodies. Daytime sleepiness affected patient‐ and proxy‐reported QoL. Behavioral symptoms affected patient‐ and proxy‐reported QoL. Autonomic symptom burden affected patient‐reported QoL. Dementia severity, dependence, and caregiver experiences affected proxy ratings.

AbstractIntra-articular lipomas are infrequently reported, with most reported cases occurring in the knee joint. A case of intra-articular lipoma in the small joints of the hand, specifically in the pisotriquetral joint, has been documented for the first time. A 24-year-old male visited the emergency department after a road traffic accident with a painful and swollen wrist. Radiographic examination revealed fractures of the distal radius and triquetrum. A subsequent wrist computed tomography scan identified an intra-articular lipoma within the pisotriquetral joint, further confirmed by ultrasonography. This article underscores the importance of recognizing that, though exceedingly rare, intra-articular lipomas should be considered in the differential diagnosis of soft-tissue tumors affecting the hand and wrist.

The NCCN Guidelines for Kidney Cancer provide multidisciplinary recommendations for diagnostic workup, staging, and treatment of patients with renal cell carcinoma (RCC). These NCCN Guidelines Insights focus on the systemic therapy options for patients with advanced RCC and summarize the new clinical data evaluated by the NCCN panel for the recommended therapies in Version 2.2024 of the NCCN Guidelines for Kidney Cancer.

Background Mental health characteristics such as negative mood, fear avoidance, unhelpful thoughts regarding pain, and low self-efficacy are associated with symptom intensity and capability among patients with hip and knee osteoarthritis (OA). Knowledge gaps remain regarding the conceptual and statistical overlap of these constructs and which of these are most strongly associated with capability in people with OA. Further study of these underlying factors can inform us which mental health assessments to prioritize and how to incorporate them into whole-person, psychologically informed care. Questions/purposes (1) What are the distinct underlying factors that can be identified using statistical grouping of responses to a multidimensional mental health survey administered to patients with OA? (2) What are the associations between these distinct underlying factors and capability in knee OA (measured using the Knee Injury and Osteoarthritis Outcome Score, Joint Replacement [KOOS JR]) and hip OA (measured using Hip Disability and Osteoarthritis Outcome Score, Joint Replacement [HOOS JR]), accounting for sociodemographic and clinical factors? Methods We performed a retrospective cross-sectional analysis of adult patients who were referred to our program with a primary complaint of hip or knee pain secondary to OA between October 2017 and December 2020. Of the 2006 patients in the database, 38% (760) were excluded because they did not have a diagnosis of primary osteoarthritis, and 23% (292 of 1246) were excluded owing to missing data, leaving 954 patients available for analysis. Seventy-three percent (697) were women, with a mean age of 61 ± 10 years; 65% (623) of patients were White, and 52% (498) were insured under a commercial plan or via their employer. We analyzed demographic data, patient-reported outcome measures, and a multidimensional mental health survey (the 10-item Optimal Screening for Prediction of Referral and Outcome-Yellow Flag [OSPRO-YF] assessment tool), which are routinely collected for all patients at their baseline new-patient visit. To answer our first question about identifying underlying mental health factors, we performed an exploratory factor analysis of the OSPRO-YF score estimates. This technique helped identify statistically distinct underlying factors for the entire cohort based on extracting the maximum common variance among the variables of the OSPRO-YF. The exploratory factor analysis established how strongly different mental health characteristics were intercorrelated. A scree plot technique was then applied to reduce these factor groupings (based on Eigenvalues above 1.0) into a set of distinct factors. Predicted factor scores of these latent variables were generated and were subsequently used as explanatory variables in the multivariable analysis that identified variables associated with HOOS JR and KOOS JR scores. Results Two underlying mental health factors were identified using exploratory factor analysis and the scree plot; we labeled them “pain coping” and “mood.” For patients with knee OA, after accounting for confounders, worse mood and worse pain coping were associated with greater levels of incapability (KOOS JR) in separate models but when analyzed in a combined model, pain coping (regression coefficient -4.3 [95% confidence interval -5.4 to -3.2], partial R2 0.076; p < 0.001) had the strongest relationship, and mood was no longer associated. Similarly, for hip OA, pain coping (regression coefficient -5.4 [95% CI -7.8 to -3.1], partial R2 0.10; p < 0.001) had the strongest relationship, and mood was no longer associated. Conclusion This study simplifies the multitude of mental health assessments into two underlying factors: cognition (pain coping) and feelings (mood). When considered together, the association between capability and pain coping was dominant, signaling the importance of a mental health assessment in orthopaedic care to go beyond focusing on unhelpful feelings and mood (assessment of depression and anxiety) alone to include measures of pain coping, such as the Pain Catastrophizing Scale or Tampa Scale for Kinesiophobia, both of which have been used extensively in patients with musculoskeletal conditions. Level of Evidence Level III, prognostic study.