Citations

Abstract Background: The genotoxin colibactin causes a tumor single-base substitution (SBS) mutational signature, SBS88. It is unknown whether epidemiologic factors’ association with colorectal cancer risk and survival differs by SBS88. Methods: Within the Genetic Epidemiology of Colorectal Cancer Consortium and Colon Cancer Family Registry, we measured SBS88 in 4,308 microsatellite stable/microsatellite instability low tumors. Associations of epidemiologic factors with colorectal cancer risk by SBS88 were assessed using multinomial regression (N = 4,308 cases, 14,192 controls; cohort-only cases N = 1,911), and with colorectal cancer–specific survival using Cox proportional hazards regression (N = 3,465 cases). Results: 392 (9%) tumors were SBS88 positive. Among all cases, the highest quartile of fruit intake was associated with lower risk of SBS88-positive colorectal cancer than SBS88-negative colorectal cancer [odds ratio (OR) = 0.53, 95% confidence interval (CI) 0.37-0.76; OR = 0.75, 95% CI 0.66–0.85, respectively, Pheterogeneity = 0.047]. Among cohort studies, associations of body mass index (BMI), alcohol, and fruit intake with colorectal cancer risk differed by SBS88. BMI ≥30 kg/m2 was associated with worse colorectal cancer–specific survival among those SBS88-positive [hazard ratio (HR) = 3.40, 95% CI 1.47–7.84], but not among those SBS88-negative (HR = 0.97, 95% CI 0.78–1.21, Pheterogeneity = 0.066). Conclusions: Most epidemiologic factors did not differ by SBS88 for colorectal cancer risk or survival. Higher BMI may be associated with worse colorectal cancer–specific survival among those SBS88-positive; however, validation is needed in samples with whole-genome or whole-exome sequencing available. Impact: This study highlights the importance of identification of tumor phenotypes related to colorectal cancer and understanding potential heterogeneity for risk and survival.

BACKGROUND: Clinical trials in heart failure (HF) traditionally use time-to-event analyses focusing on death and hospitalization for HF. These time-to-first event analyses may have more limited abilities to assess the probability of benefiting from a therapy, especially if that benefit manifests as improved functional status rather than reduced risk of death or HF hospitalization. Hierarchical end points including clinical outcomes and patient status measures allow for ranked evaluation of outcomes in 1 metric assessing whether patients randomized to intervention or control are more likely to derive an overall benefit while also allowing more patients to contribute to the primary outcome. METHODS: We review the rationale for using hierarchical end points in HF trials, provide examples of HF trials that used this type of end point, and discuss its use in the HEART-FID trial (Randomized Placebo-Controlled Trial of Ferric Carboxymaltose as Treatment for Heart Failure With Iron Deficiency), the largest HF trial to date implementing a hierarchical end point analysis for the primary outcome. RESULTS: Using a hierarchical end point as the primary outcome allows for the inclusion of different types of outcomes in 1 ranked end point, making it possible to more holistically assess the potential utility of a new therapy on patient well-being and outcomes. CONCLUSIONS: Hierarchical end points assess the potential utility of a new therapy on patient well-being and outcome more holistically than time-to-first event analysis. Trials that would not have been feasible due to decreasing rates of death and hospitalization in the HF population can use hierarchical end points to successfully power studies to identify promising HF therapies. The HEART-FID trial used hierarchical end points to better determine the role of intravenous ferric carboxymaltose in patients with HF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03037931.

Abstract Background Given the elevated prevalence and impact of overweight and the potential risk of non-communicable diseases among women of Somali background in high-income countries and recognising the potential positive impact of physical activity (PA) on these health conditions, it becomes imperative to focus on understanding the PA behaviour of this specific population. The objectives of this paper were twofold: firstly, to provide a comprehensive description of both objectively and subjectively measured PA level and sedentary time in a group of overweight women of Somali background in Norway, and secondly, to assess the effectiveness of a tailored, culturally sensitive, and community-based intervention in enhancing PA levels and reducing sedentary time. Methods 169 overweight women of Somali background in Norway were randomised by borough to either a lifestyle programme or a comparison group. The programme consisted of two sessions per week for 12 weeks, combining classroom discussion with graded group-based PA activity led by coaches, followed by monthly sessions over nine months. PA was measured objectively using the ActivPAL monitor and subjectively using the international PA questionnaire short form (IPAQ). Results The women took on average 6804 (SD = 3286) steps per day and were sedentary for 9.1 hours (SD = 3) per day at baseline. There were no differences between groups on any objectively measured PA variable at any timepoint. There were significant differences on vigorous intensity PA and total PA at the 12-month measurement session between the two groups using the IPAQ. Conclusion Despite observing initially low PA levels and high sedentary time at baseline and thus a considerable potential for intervention, the intervention failed in attaining an increase in objectively measured PA or reduction in sedentary time compared to the control condition. However, self-reported measures indicated success in these aspects. The potential threats to the programme's reliability and validity include contamination, low attendance rates, and high drop-out rates possible due to the COVID-19 pandemic. These challenges underscore the complexity of interventions in this demographic, emphasising the need for further exploration and refinement of study methodologies to effectively enhance PA levels and reduce sedentary time in immigrant women living in high-income countries. Trial registration : clinicaltrials.gov NCT04578067. Keywords: Immigrant Somali women, Lifestyle programme, Overweight, Physical activity, Sedentary time, ActivPAL

Background: Approximately 90% of patients who undergo arthroscopic rotator cuff repair (RCR) are satisfied with their pain levels and function after surgery. However, a subset of patients experience continued symptoms that warrant revision surgery. Preoperative risk factors for RCR failure requiring revision surgery have not been clearly defined. Purpose: To (1) determine the rate of RCR failure requiring revision surgery and (2) identify risk factors for revision surgery, which will help surgeons to determine patients who are at the greatest risk for RCR failure. Study Design: Systematic review and meta-analysis; Level of evidence, 4. Methods: A systematic review and meta-analysis in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were performed. The initial search resulted in 3158 titles, and 533 full-text articles were assessed for eligibility. A total of 10 studies met the following inclusion criteria: (1) human clinical studies, (2) arthroscopic RCR, (3) original clinical research, and (4) evaluation of preoperative risk factors for revision. Results: After a full-text review, a total of 16 risk factors were recorded and analyzed across 10 studies. Corticosteroid injection was the most consistent risk factor for revision surgery, reaching statistical significance in 4 of 4 studies, followed by workers’ compensation status (2/3 studies). Patients with corticosteroid injections had a pooled increased risk of revision surgery by 47% (odds ratio, 1.44 [95% CI, 1.36-1.52]). Patients with workers’ compensation had a pooled increased risk of revision surgery by 133% (odds ratio, 2.33 [95% CI, 2.09-2.60]). Age, smoking status, diabetes, and obesity were found to be risk factors in half of the analyzed studies. Conclusion: Corticosteroid injections, regardless of the frequency of injections, and workers’ compensation status were found to be significant risk factors across the literature based on qualitative analysis and pooled analysis. Surgeons should determine ideal candidates for arthroscopic RCR by accounting for corticosteroid injection history, regardless of the frequency, and insurance status of the patient.

Abstract Background. Patients with migraine often have poor sleep quality between and during migraine attacks. Furthermore, extensive research has identified photophobia as the most common and most bothersome symptom in individuals with migraine, second only to headache. Seeking the comfort of darkness is a common strategy for managing pain during an attack and preventing its recurrence between episodes. Given the well-established effects of daily light exposure on circadian activity rhythms and sleep quality, this study aims to investigate the relationship between photophobia symptoms and sleep quality in a cohort of patients with migraine. Methods. A cross-sectional observational study was conducted using existing data extracted from the American Registry for Migraine Research (ARMR). Participants with a migraine diagnosis who had completed the baseline questionnaires (Photosensitivity Assessment Questionnaire (PAQ), Generalized Anxiety Disorder-7 (GAD-7), Patient Health Questionnaire-2 (PHQ-2)), and selected questions of the ARMR Sleep questionnaire were included. Models were created to describe the relationship of photophobia and photophilia with various sleep facets, including sleep quality (SQ), sleep disturbance (SDis), sleep onset latency (SOL), and sleep-related impairments (SRI). Each model was controlled for age, sex, anxiety, and depression. Results. A total of 852 patients meeting the inclusion criteria were included in the analysis (mean age (SD) = 49.8 (13.9), 86.6% (n = 738) female). Those with photophobia exhibited significantly poorer sleep quality compared to patients without photophobia (p < 0.001). Photophobia scores were associated with SQ (p < 0.001), SDis (p < 0.001), SOL (p = 0.011), and SRI (p = 0.014), after controlling for age, sex, depression, and anxiety, signifying that higher levels of photophobia were associated with worse sleep-related outcomes. Conversely, photophilia scores were associated with better sleep-related outcomes for SQ (p < 0.001), SDis (p < 0.001), and SOL (p = 0.016). Conclusion. Results suggest that photophobia is a risk factor for sleep disorders in those with migraine. These results underscore the necessity for comprehensive and systematic investigations into the intricate interplay between photophobia and sleep to enhance our understanding and develop tailored solutions for individuals with migraine.

Background: Irreparable rotator cuff tears represent approximately 12% of all presenting cuff tears, and multiple surgical techniques have been described for treatment, including allograft/bridge augmentation, debridement, partial repair, subacromial balloon, tendon transfer, and superior capsule reconstruction (SCR). SCR has demonstrated durable improvement in range of motion (ROM) and outcome scores at 2 and 5 years. Indications: Surgical indications for SCR include an irreparable tear of the supraspinatus and/or infraspinatus with a preserved or reparable subscapularis and preserved glenohumeral joint cartilage. Technique Description: Diagnostic arthroscopy is performed to identify and characterize the rotator cuff tear. Thorough debridement of the greater tuberosity is performed. Two all-suture FiberTak anchors are placed in the superior aspect of the glenoid. Two 2.6-mm FiberTak suture anchors are placed in the humeral head at the chondral margin. After measuring, the dermal allograft is cut to size with 15-mm overhang left on the far lateral edge. A 12-mm passport cannula is inserted laterally and the sutures from the glenoid and humeral head anchors are brought out through the cannula maintaining their position and orientation. The sutures are passed through the graft outside the cannula. The graft is introduced into the shoulder via the passport cannula with a back grasper. A cannula-in-cannula technique is used to tie the glenoid anchors first and then the medial row anchors. Two lateral row swivel lock anchors are used to complete a standard double row repair. Margin convergence is performed between the dermal allograft and remaining rotator cuff anterior and posterior. Postoperatively, patients are kept in a sling for 6 weeks, with no shoulder ROM. From weeks 6 to 12, patients discontinue sling and begin passive progression to active ROM. Strengthening is initiated at 12 weeks, and return-to-sport or work is at approximately 6 months. Results: Irreparable rotator cuff tears treated with arthroscopic rotator cuff repair and SCR show durable improvement in patient-reported outcomes at 2 and 5 years. Re-tear rates did not differ between athletes and non-athletes. Discussion/Conclusion: Arthroscopic rotator cuff repair with SCR is a durable and reliable surgical option for patients presenting with preserved glenohumeral joint and irreparable supraspinatus and/or infraspinatus tear. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.

AbstractThis article provides recommendations for implementing QSM for clinical brain research. It is a consensus of the International Society of Magnetic Resonance in Medicine, Electro‐Magnetic Tissue Properties Study Group. While QSM technical development continues to advance rapidly, the current QSM methods have been demonstrated to be repeatable and reproducible for generating quantitative tissue magnetic susceptibility maps in the brain. However, the many QSM approaches available have generated a need in the neuroimaging community for guidelines on implementation. This article outlines considerations and implementation recommendations for QSM data acquisition, processing, analysis, and publication. We recommend that data be acquired using a monopolar 3D multi‐echo gradient echo (GRE) sequence and that phase images be saved and exported in Digital Imaging and Communications in Medicine (DICOM) format and unwrapped using an exact unwrapping approach. Multi‐echo images should be combined before background field removal, and a brain mask created using a brain extraction tool with the incorporation of phase‐quality‐based masking. Background fields within the brain mask should be removed using a technique based on SHARP or PDF, and the optimization approach to dipole inversion should be employed with a sparsity‐based regularization. Susceptibility values should be measured relative to a specified reference, including the common reference region of the whole brain as a region of interest in the analysis. The minimum acquisition and processing details required when reporting QSM results are also provided. These recommendations should facilitate clinical QSM research and promote harmonized data acquisition, analysis, and reporting.

Purpose To systematically review the existing literature on the functional performance of athletes at the time of return‐to‐sport (RTS) clearance after anterior cruciate ligament reconstruction (ACLR). Methods A systematic literature search of the MEDLINE, EMBASE, Scopus, and Web of Science databases was performed. The inclusion criteria were original research reports with study populations of athletes who had undergone ACLR and had undergone objective functional testing immediately after clearance to RTS. Functional testing was stratified by hop tests, strength tests, kinetic assessment, and kinematic assessment, and data were extracted from each study using a standardized template. Results Of the 937 unique studies identified, 46 met the inclusion criteria. The average time between ACLR and functional testing was 7.9 months among the included studies. In 10 of 17 studies, patients were found to have an average quadriceps strength limb symmetry index of less than 90%. However, only 2 of 12 studies found the average hop test limb symmetry index to be less than 90%. Kinematics included reduced knee flexion angle and increased trunk flexion on landing in ACLR patients compared with matched controls. On evaluation of kinetics, ACLR patients showed reduced peak vertical ground reaction force, lower peak knee extension and knee flexion moments, and altered energy absorption contribution compared with matched controls. Conclusions This systematic review suggests that athletes show functional deficits at the time of RTS at an average of 7.9 months after ACLR. Traditional functional tests, such as strength and hop tests, are not able to accurately identify patients who continue to show deficits. The most common biomechanical deficits that persist after RTS clearance include diminished peak knee extension moment, decreased knee flexion angle, increased trunk flexion angle, reduced vertical ground reaction force, and increased hamstring central activation ratio during various functional gait and landing tasks. Level of Evidence Level III, systematic review of Level I to III studies.

Context.— The Nottingham Grading System (NGS) developed by Elston and Ellis is used to grade invasive breast cancer (IBC). Glandular (acinar)/tubule formation is a component of NGS. Objective.— To investigate the ability of pathologists to identify individual structures that should be classified as glandular (acinar)/tubule formation. Design.— A total of 58 hematoxylin-eosin photographic images of IBC with 1 structure circled were classified as tubules (41 cases) or nontubules (17 cases) by Professor Ellis. Images were sent as a PowerPoint (Microsoft) file to breast pathologists, who were provided with the World Health Organization definition of a tubule and asked to determine if a circled structure represented a tubule. Results.— Among 35 pathologists, the κ statistic for assessing agreement in evaluating the 58 images was 0.324 (95% CI, 0.314–0.335). The median concordance rate between a participating pathologist and Professor Ellis was 94.1% for evaluating 17 nontubule cases and 53.7% for 41 tubule cases. A total of 41% of the tubule cases were classified correctly by less than 50% of pathologists. Structures classified as tubules by Professor Ellis but often not recognized as tubules by pathologists included glands with complex architecture, mucinous carcinoma, and the “inverted tubule” pattern of micropapillary carcinoma. A total of 80% of participants reported that they did not have clarity on what represented a tubule. Conclusions.— We identified structures that should be included as tubules but that were not readily identified by pathologists. Greater concordance for identification of tubules might be obtained by providing more detailed images and descriptions of the types of structures included as tubules.