Citations

Objective To compare the efficacy of abatacept to placebo for the treatment of relapsing, nonsevere granulomatosis with polyangiitis (GPA). Methods In this multicenter trial, eligible patients with relapsing, nonsevere GPA were randomized to receive abatacept 125 mg subcutaneously once a week or placebo, both together with prednisone 30 mg/day (or equivalent), tapered and discontinued at week 12. Patients already taking methotrexate, azathioprine, mycophenolate, or leflunomide continued this medication at a stable dose. Patients achieving remission remained on their randomized assignment until relapse, early termination, or the common close date 12 months after enrollment of the last patient. Those who had a nonsevere relapse, had nonsevere worsening, or were not in remission by month 6 had the option to receive open‐label abatacept. The primary end point was the rate of treatment failure, defined as relapse, disease worsening, or failure to achieve a Birmingham Vasculitis Activity Score for Wegener's Granulomatosis (BVAS/WG) of 0 or 1 by six months. Results Sixty‐five patients were randomized; 34 received abatacept and 31 received placebo. No statistical difference in the treatment failure rate was found between those who received abatacept and those who received placebo ( P = 0.853). Treatment with abatacept did not demonstrate any statistical difference from placebo in key secondary end points, including time to full remission (BVAS/WG = 0), duration of glucocorticoid‐free remission, relapse severity, prevention of damage, and patient‐reported quality‐of‐life outcomes. There was no difference in the frequency or severity of adverse events between treatment arms, including infection. Conclusion In patients with relapsing, nonsevere GPA, abatacept did not reduce the risk of relapse, severe worsening, or failure to achieve remission.

ObjectivesAchalasia is an esophageal motility disorder that impairs quality of life and is often missed (20–50%) on endoscopy. A newly developed computer‐aided detection (CAD) software has shown high accuracy for achalasia diagnosis in preclinical settings. However, its benefit in a clinical setting remains unclear.MethodsBetween February and August 2023, 83 endoscopists from 27 centers assessed 50 randomized endoscopic videos (25 achalasia, 25 nonachalasia) without and with CAD. Endoscopists assessed videos without CAD, then with CAD after 2 months. The primary end‐point was improvement in sensitivity for nonexperienced endoscopists (no endoscopic experience of achalasia). Sensitivity, specificity, and accuracy with and without CAD were compared using the McNemar test.ResultsSensitivity for diagnosing achalasia increased significantly with CAD, rising from 74.2% (95% confidence interval [CI] 72.2–76.0%) to 91.2% (95% CI 89.9–92.4%) for all readers, showing a difference of 17.1% (95% CI 15.1–19.0%). Specifically, sensitivity improved from 66.9% (95% CI 63.6–70.0%) to 91.9% (95% CI 89.9–93.6%) among nonexperienced endoscopists, resulting in a difference of 25.0% (95% CI 21.7–28.4%), and from 79.5% (95% CI 77.1–81.8%) to 90.8% (95% CI 89.0–92.3%) among experienced endoscopists (endoscopic experience of at least one achalasia case), with a difference of 11.3% (95% CI 8.9–13.6%). Accuracy and specificity improved significantly with CAD assistance, regardless of reader's experience.ConclusionCAD improves achalasia detection by 17%, confirming preclinical results. The benefit was higher for nonexperienced endoscopists. CAD assistance may lead to prompt and effective treatment, minimizing the risk of false‐negative diagnosis in clinical practice.Trial registrationThis study was registered in the University Hospital Medical Information Network Clinical Trial Registry (https://www.umin.ac.jp/ctr/) number: UMIN000053047.

Case: We present a 55-year-old woman with a very short transfemoral amputation who underwent osseointegration. We compared gait analyses before and following osseointegration, demonstrating improvements in kinematics. At follow-up, the patient wore the prosthetic for 16 hours and averaged 10,000 steps daily. She achieved her goal of walking the beach with her prosthetic limb and often traveled without an assistive device. Conclusion: This case study of a patient with a very short transfemoral amputation demonstrated continued improvements in gait and significantly increased prosthetic use over time.

Purpose Part-two of this consensus aimed to provide recommendations for the prevention of meniscus injuries, non-operative treatment of acute tears and degenerative lesions, return to sports, and patient-reported outcome measures. Methods This consensus followed the European Society of Knee Surgery, Sports Traumatology and Arthroscopy (ESSKA) formal consensus methodology. For this combined ESSKA- American Orthopedic Society for Sports Medicine (AOSSM) - American Academy of Sports Physical Therapy (AASPT) initiative, 67 experts from 14 countries, including orthopedic surgeons and physiotherapists, were involved. The 26 Steering Group members established guiding questions, screened the existing evidence, and proposed statements, and provided Grades of recommendations. The 41 Rating Group members assessed the statements according to a Likert scale (1-9). Final documents were assessed by an international peer review group for geographical adaptability. Results Low to moderate scientific level of evidence was available, so that grades of recommendations were low (three Grade A ratings, four Grade B, three Grade C and 13 Grade D), underlining the relevance of this consensus. One strong and 17 relative agreements with overall median of 8 (8-9) and a mean of 7.92 +/- 0.37 were achieved for 23 statements on 18 questions. Prevention of meniscus injuries is possible with general knee injury reduction programs and through avoidance of certain activities. Non-Operative treatment including physical therapy is the first line approach for degenerative meniscus lesions and may be an option for some acute tears. Return to sports after meniscus tear surgery should be both criterion-based and time-based. Patient reported outcomes in combination with performance-based measures are recommended to evaluate the rehabilitation process. Conclusion This international EU-US consensus established recommendations for prevention strategies, describes rehabilitation of non-operated patients and of patients after partial meniscectomy, meniscus repair and meniscus reconstruction, and establishes return to sport criteria. These updated and structured recommendations may be applied by surgeons and physiotherapists. Level of Evidence I, Formal Consensus.

Microdosimetry plays a critical role in particle therapy by quantifying energy deposition within microscopic domains to assess biological effects. This study evaluates the influence of different microdosimetric functions (MFs) and domain geometries (DGs) on relative biological effectiveness (RBE) predictions in carbon ion radiotherapy. Specifically, we compare the analytical microdosimetric function (AMF), calculated for spherical domains and implemented in PHITS, with the Kiefer–Chatterjee (KC) track structure model, which is conventionally applied to cylindrical geometries. To enable a direct comparison, we also introduce a novel implementation of the KC model for spherical domains. Using both models, specific energy distributions were calculated across a range of domain sizes and geometries. These distributions were input into the modified microdosimetric kinetic model (mMKM) to calculate RBE for the HSG cell line and compared against published in vitro data. The results show that both microdosimetric function and domain geometry significantly affect microdosimetric spectra and the resulting RBE, with deviations exceeding 10% when fixed mMKM parameters are used. Parameter optimization within the mMKM enables alignment across models. Our findings emphasize that microdosimetric function and domain geometry selection must be explicitly accounted for in microdosimetry-based RBE modeling, and that model parameters must be tuned accordingly to ensure consistent and biologically accurate predictions.

Abstract INTRODUCTION Temporal cortical microstructural changes precede cortical atrophy during memory decline. We used neurite orientation dispersion and density imaging (NODDI) to assess such early microstructural change. METHODS Cognitively unimpaired (CU, n = 725) and mildly cognitively impaired (MCI, n = 111) participants from the Mayo Clinic Study of Aging underwent 3T magnetic resonance imaging (MRI), including NODDI and neuropsychological evaluation for calculation of memory z scores. Linear mixed effects modelling assessed the relationship between temporal cortical Neurite Density Index (NDI), Orientation Dispersion Index (ODI), and both baseline and mean annual change in memory z scores. RESULTS NDI was significantly associated with both baseline memory z scores and mean annual change of memory z scores, in the hippocampi and amygdalae. Similar significant associations with ODI were seen in hippocampi, parahippocampal, and fusiform gyri. DISCUSSION Temporal cortical NDI and ODI are early imaging biomarkers of cortical microstructural integrity that may predict memory decline in CU and MCI individuals. Highlights We imaged 836 participants in the Mayo Clinic Study of Aging, who were either cognitively unimpaired (CU) or suffered from mild cognitive impairment (MCI). Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion magnetic resonance imaging (MRI) technique We found significant associations between new NODDI imaging biomarkers of microstructural integrity and memory function in CU and MCI individuals These relationships were both cross‐sectional in nature and associated with future memory decline Future application of NODDI imaging biomarkers in the setting of anti‐amyloid monoclonal antibody therapy may provide greater insight into memory decline than current cortical atrophy measures.

SummaryThe goal of this study was to ascertain the effect of patient body size on clinic‐ or patient‐delayed health care during the COVID‐19 pandemic and factors predicting delay. Primary survey data were collected in August 2021 from 3593 individuals living within the communities near Mayo Clinic facilities in Minnesota, Wisconsin, Arizona, and Florida. More people who identified with the higher‐weight BMI categories reported having their care appointments cancelled (62.3%) compared to those who identified with normative weight (38.0%) or underweight (47.7%; p < .001) and reported more frequently delaying their own care (67.9%) relative to those who identified with normative weight (47.0%) or underweight (62.3%; p < .001). Higher‐weight people were more likely than others to report delay was due to not knowing where to get care (UW: 5.6%, NW: 3.5%, HW: 7.0%, pchi‐square < .001), worrying about weight‐based judgement (UW: 2.1%, NW: 2.1%, HW: 4.5%, pchi‐square < .001), and fearing discrimination (UW: 2.9%, NW: 2.4%, HW: 5.5%, pchi‐square < .001). There was no difference across groups in delay due to fear of COVID‐19 exposure. Weight gain was associated with care delay in higher‐weight and normative weight groups. Having experienced more patient‐centred care pre‐COVID was associated with less care delay in the normative weight group, but more care delay in other groups. Higher‐weight people were more likely to have their care delayed by health care providers and to delay care themselves. Patient weight gain and concerns about discrimination and judgement about weight gain may have driven the delay of needed care during COVID‐19.

ABSTRACTBackgroundLate gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) imaging is a well‐established indicator of myocardial fibrosis in hypertrophic cardiomyopathy (HCM). However, its association with electrocardiographic (ECG) abnormalities and the risk of atrial fibrillation (AF) remains uncertain.ObjectivesTo investigate the association between the presence and burden of LGE with ECG characteristics, including precordial voltage, depolarization and repolarization abnormalities, and the incidence of AF in adults with HCM.MethodsWe conducted a retrospective cohort study of 144 adults with HCM with CMR and 12‐lead ECG within 30 days of each other. LGE was quantified as a percentage of LV mass and categorized as absent, < 5%, or ≥ 5%. ECG parameters, including QRS voltage, repolarization abnormalities, and LVH criteria, were analyzed. Incident AF was assessed during a median follow‐up of 6.6 years.ResultsLGE was present in 96 (67%) patients, with 21 (22%) having ≥ 5% LGE. There were no significant differences in precordial voltage between patients with and without LGE across Sokolow‐Lyon, Cornell, and Romhilt‐Estes criteria. However, T‐wave inversion was more common in leads I (41% vs. 19%, p = 0.009), aVL (50% vs. 31%, p = 0.033), and V4 (41% vs. 23%, p = 0.035) in patients with LGE. Patients with ≥ 5% LGE had a significantly lower median LVEF (64% vs. 74%, p = 0.003). Additionally, LGE presence was not associated with an increased risk of incident AF (HR 1.8, 95% CI 0.6–5.3, p = 0.308).ConclusionIn contrast to pediatric HCM, LGE is associated with specific ECG repolarization abnormalities, particularly T‐wave inversion in lateral leads, but does not significantly affect precordial voltage in adults.

Abstract Purpose Lattice radiation therapy (LRT) is a form of spatially fractionated radiation therapy that allows increased total dose delivery aiming for improved treatment response without an increase in toxicities, commonly utilized for palliation of bulky tumors. The LRT treatment planning process is complex, while eligible patients often have an urgent need for expedited treatment start. In this study, we aimed to develop a simulation‐free workflow for volumetric modulated arc therapy (VMAT)‐based LRT planning via deep learning‐predicted synthetic CT (sCT) to expedite treatment initiation. Methods Two deep learning models were initially trained using 3D U‐Net architecture to generate sCT from diagnostic CTs (dCT) of the thoracic and abdomen regions using a training dataset of 50 patients. The models were then tested on an independent dataset of 15 patients using image similarity analysis assessing mean absolute error (MAE) and structural similarity index measure (SSIM) as metrics. VMAT‐based LRT plans were generated based on sCT and recalculated on the planning CT (pCT) for dosimetric accuracy comparison. Differences in dose volume histogram (DVH) metrics between pCT and sCT plans were assessed using the Wilcoxon signed‐rank test. Results The final sCT prediction model demonstrated high image similarity to pCT, with a MAE and SSIM of 38.93 ± 14.79 Hounsfield Units (HU) and 0.92 ± 0.05 for the thoracic region, and 73.60 ± 22.90 HU and 0.90 ± 0.03 for the abdominal region, respectively. There were no statistically significant differences between sCT and pCT plans in terms of organ‐at‐risk and target volume DVH parameters, including maximum dose (Dmax), mean dose (Dmean), dose delivered to 90% (D90%) and 50% (D50%) of target volume, except for minimum dose (Dmin) and (D10%). Conclusion With demonstrated high image similarity and adequate dose agreement between sCT and pCT, our study is a proof‐of‐concept for using deep learning predicted sCT for a simulation‐free treatment planning workflow for VMAT‐based LRT.