Citations

Sex differences in Alzheimer's disease (AD) phenotypes are well documented. Wang et al. examined sex-specific tau propagation across Braak neurofibrillary tangle stages in an Alzheimer's Disease Neuroimaging Initiative cohort, while considering cognitive and amyloid status, using longitudinal tau-PET imaging. They found that females exhibit faster tau spread and accelerated clinical decline in advanced stages. While the study offers valuable insights, factors such as neuroimaging-pathology discordance, coexisting conditions, and limited cohort diversity warrant caution before making broad generalizations. Nonetheless, these findings highlight sex-dependent AD trajectories and reinforce the need for precision medicine and timely, individualized interventions to improve outcomes and address biological variability in disease progression.

Abstract Within the field of regenerative medicine for musculoskeletal regenerative medicine, orthobiologics and cellular therapies are evolving at a rapid pace. Exuberant ideas for new treatments often outpace their scientific evidence, which may create confusion for both patients and providers on what treatments are evidence based. Orthobiologics and cellular therapies are a subset of regenerative therapies focused on treatment of musculoskeletal disease. For the field of orthobiologics to progress, it is essential that musculoskeletal providers understand the necessary components for translating novel therapies from discovery into practice. In this article, we provide an overview of both the lexicon and regulatory processes related to translation of orthobiologics and cellular therapies along with a comparison of how to translate orthobiologics and related novel cellular therapies in hopes to dispel misinformation while promoting responsible advancements and ethical practices in medicine.

ABSTRACT The epidemiology of myelodysplastic syndromes/neoplasms (MDS) is challenging to define due to inconsistent reporting, complex diagnostic procedures, and evolving diagnostic criteria. Using the National MDS Natural History Study—a prospective cohort with centrally adjudicated histopathology and genetic variant review—we characterized the landscape of MDS across the United States and identified differences across demographics. Among 2115 participants, 64% (1346) had an MDS spectrum condition, including MDS (24%), MDS/myeloproliferative neoplasm (5%) and precursor conditions—clonal cytopenia of undetermined significance (22%) and idiopathic cytopenia/dysplasia of undetermined significance (13%). The median age was 74 years, and participants were predominantly male (66%), White (91%), and Non‐Hispanic (92%). Myeloid‐associated variants were detected in 68% of participants, most commonly in TET2, DNMT3A, ASXL1, SF3B1, and SRSF2 . Black, compared to White, participants were younger at diagnosis (69 vs. 74 years, p = 0.01), had equal or increased prevalence of higher‐risk MDS, lower hemoglobin, and higher peripheral blood blasts, yet were less likely to receive MDS‐directed therapy (14% vs. 42%, p = 0.008). Black and Hispanic participants had fewer detectable gene mutations than White participants. Females had lower variant allele frequencies and fewer RNA splicing gene mutations than males. After multivariable adjustment, TP53 mutations, MDS diagnosis, and higher‐risk disease were associated with worse progression‐free and overall survival; age was also associated with overall survival. Black race trended toward improved progression‐free survival. These findings highlight the need for enhanced understanding of MDS pathogenesis across patient groups and refined prognostic tools to improve personalized management of MDS spectrum conditions. Trial Registration: ClinicalTrials.gov identifier: NCT02775383

ABSTRACT Background Hidradenitis suppurativa (HS) is a chronic inflammatory disease associated with substantial impairment in quality of life and psychological well‐being. The impact of cumulative treatment exposure and its relationship with multidimensional disease burden in HS has not been sufficiently discussed. The aim of this study is to investigate the associations between cumulative treatment burden, quality of life impairment, psychological symptom burden, disease activity, and patient‐perceived severity in patients with HS. Methods This multicenter cross‐sectional study included previously treated adult HS patients. Participants completed validated Turkish versions of the Dermatology Life Quality Index (DLQI), Symptom Checklist‐90‐Revised (SCL‐90‐R), and the Hidradenitis Suppurativa Self‐Assessment Tool (HSSA). A Treatment Burden Index (TBI) was developed to quantify cumulative therapeutic exposure based on guideline‐weighted treatment modalities. Results Ninety‐three patients were included (mean age 34.5 ± 11.0 years; 57% male). Higher TBI was moderately correlated with greater QoL impairment (Spearman ρ = 0.401, p < 0.001) and flare frequency. TBI was weakly correlated with psychological symptom burden. DLQI scores were positively associated with flare frequency and SCL‐90‐R scores, whereas the SCL‐90‐R scores were not associated with flare frequency or patient‐perceived disease severity. Conclusions HS burden is multidimensional, with partially independent domains of disease activity, treatment burden, quality of life impairment, and psychological distress. Cumulative treatment exposure is closely linked to QoL impairment and disease activity but only weakly associated with psychological symptom burden. Identification of distinct burden phenotypes may facilitate more personalized and patient‐centered management strategies in HS. image

Background: Anti-cyclic citrullinated peptide antibodies (ACPAs) are associated with more aggressive rheumatoid arthritis disease. We aimed to determine the effect of ACPA serostatus on survival free from revision, all-cause reoperation, and recurrence of coronal plane deformity in patients with rheumatoid arthritis (RA) undergoing silicone metacarpophalangeal (MCP) arthroplasty. Methods: We retrospectively identified silicone MCP arthroplasties performed in patients with RA with known ACPA serostatus from 2000 to 2022. Kaplan-Meier estimates were used to report survival free from revision, all-cause reoperation, and recurrence of coronal plane deviation >10° on postoperative radiographs. We analyzed ACPA serostatus as a risk factor for these endpoints using cluster-robust Cox proportional hazard models, adjusting for patient sex. Results: We included 133 joints in 39 ACPA seropositive patients (9.0 years mean follow-up) and 63 joints in 21 ACPA seronegative patients (5.7 years mean follow-up). Survival free from revision, all-cause reoperation, and recurrent coronal deformity was higher in seropositive patients than in seronegative patients. Anti-cyclic citrullinated peptide antibody seropositivity was significantly associated with lower risk for revision (hazard ratio [HR] = 0.16), all-cause reoperation (HR = 0.20), and recurrent coronal plane deviation >10° (HR = 0.28). Seropositive patients had longer average time to recurrent coronal deviation >10° (3.5 years vs 1.3 years) and less coronal deviation at final radiographic follow-up (15.9° vs 21.5°). Conclusions: Anti-cyclic citrullinated peptide antibody seropositivity is associated with improved silicone MCP implant survivorship and lower risk of recurrent coronal plane deformity in patients with rheumatoid arthritis. More work is needed to better understand the biologic basis of these findings.

Spontaneous pneumothorax (SP) is defined by the presence of air in the pleural space arising from neither trauma nor iatrogenic causes. It can develop secondary to various etiologies. The familial clustering observed in some patients with SP supports the view that genetic factors play a role in the pathogenesis of SP. Several recognizable pneumothorax-associated genetic syndromes exist, including Birt-Hogg-Dubé syndrome (BHD), tuberous sclerosis complex-associated lymphangioleiomyomatosis (TSC-LAM), Marfan syndrome (MFS), cystic fibrosis (CF), alpha-1 antitrypsin deficiency (AATD), vascular Ehlers-Danlos syndrome (vEDS), Loeys-Dietz syndrome (LDS), and a few others. Recognition of these syndromes underlying SP facilitates optimal management and counseling regarding prognosis and potential comorbidities. In this review, we systematically summarize several genetic syndromes associated with pneumothorax, in which SP may manifest either as an initial presenting symptom or as a potential complication that adversely affects the prognosis.

Abstract Background Photon‐counting‐detector (PCD) CT systems offer ultra‐high spatial resolution, yet the visual spatial resolution on clinical images often constrained by large pixel size, yielding resolutions below system capabilities. While reducing pixel size and using sharp kernels enhance visual spatial resolution, it increases noise, compromising image quality. Purpose To investigate the combined effects of pixel size and reconstruction kernels on visual spatial resolution using phantom and clinical images and to develop a dedicated high‐resolution deep convolutional neural network (HR‐CNN) to better utilize the intrinsic high spatial resolution of PCD‐CT in clinical imaging. Methods The relationship between spatial resolution, reconstruction kernel, and pixel size was investigated to identify strategies for utilizing the full spatial resolution potential of PCD‐CT. To overcome the increased noise associated with high‐resolution settings, a dedicated HR‐CNN was developed to push the limit of spatial resolution in routine PCD‐CT exams. The HR‐CNN was trained using patient exams acquired with ultra‐high‐resolution (UHR) mode and reconstructed with a 150‐mm field of view (FOV), matrix size of 1024×1024 (0.15‐mm pixel size) and sharpest quantitative kernel (Qr89). The impact of FOV, kernel, and denoising on spatial resolution was studied using bar‐pattern phantoms and a pilot clinical evaluation including 5 patients with interstitial lung diseases. Two thoracic radiologists evaluated 4 different FOV/reconstruction conditions: (1) FOV‐410/Qr56‐Iterative reconstruction (IR), (2) FOV‐410/Qr89‐IR, (3) FOV‐150/Qr89‐IR, and (4) FOV‐150/Qr89‐HR‐CNN in terms of overall image quality, noise, visual spatial resolution, and overall preference. Results With a FOV of 410 mm, the Qr89 sharp kernel displayed bar‐patterns up to 14 lp/cm, not much higher than the routine lung kernel Qr56. When the FOV was reduced to 150 mm, Qr89‐IR allowed for the visualization of line pair patterns ranging from 18 to 20 lp/cm, with 20 lp/cm being moderately discernible. The application of Qr89‐HR‐CNN yielded further improvement, enabling the display of line pair patterns as high as 20–22 lp/cm. In patient cases, both radiologists consistently ranked the FOV‐150 images processed with HR‐CNN as superior across metrics including overall image quality, noise reduction, visual spatial resolution, and overall preference. The HR‐CNN reduced the noise in patients’ images by 93.0 ± 0.6% and 44.9 ± 5.3% in comparison with the original FBP and IR images, respectively. Conclusions The spatial resolution of PCD‐CT is not maximized in routine practice due to the large FOV and high noise levels at sharp kernels. The proposed HR‐CNN denoising method, along with small pixel size, may allow the high spatial resolution toward the system limit to be implemented in practice, which is beneficial in the diagnosis of many diseases, including interstitial lung disease.

Background: The medial femoral trochlea flap is used for treating recalcitrant scaphoid proximal pole nonunions. Although this requires resecting a substantial portion of the scapholunate interosseous ligament, the intercarpal angular relationships are preserved. Studies have demonstrated that lunate alignment is preserved despite loss of the scapholunate ligament because the scaphoid is reconstructed with an osteochondral flap that is larger than the resected nonunited proximal scaphoid. The technique of purposeful expansion of the scaphoid height has been termed scaphoid overstuffing . The purpose of this study is to characterize the effect of scaphoid overstuffing on force transmission across the scaphoid and lunate facets of the radius. Methods: Eleven fresh frozen cadaveric upper extremities without ligament instability were selected. The radiocarpal joint was exposed via a dorsal approach, and electronic pressure sensors were introduced. Three different states of the wrist were evaluated: native, scapholunate dissociation (SLD), and overstuffed (OS). Pressures were measured in 4 positions: 30° flexion, full wrist extension, 30° extension, and clenched fist. Pressures were measured in kPa and contact areas in mm 2 . Results: In all functional positions, the OS state had higher peak pressures across the scaphoid facet. This included 30° wrist flexion (OS 383 ± 221 kPa, P = .033), full wrist extension (OS 1068 ± 767 kPa, P = .022), 30° wrist extension (OS 880 ± 518 kPa, P < .001), and clenched fist (OS 1040 ± 736 kPa, P = .02). Conclusions: In functional wrist positions, overstuffing the scaphoid increases scaphoid facet peak contact pressures. Further study is needed to examine the long-term clinical consequences of these changes and the potential for accelerated cartilage degeneration.

Abstract Aims This systematic review evaluated the impact of metabolic and bariatric surgery (MBS) on weight loss, glycaemic control, insulin requirements and postoperative complications. Methods A PRISMA‐compliant, PROSPERO‐registered systematic review and meta‐analysis (CRD42025123500) was conducted. Medline, PubMed, Embase, Scopus and CENTRAL were searched. Primary outcomes were changes in body weight, BMI, HbA1c and insulin requirements following MBS. Risk of bias was assessed using ROBINS‐I and RoB‐2, and certainty of evidence using GRADE. Results Twenty‐two studies, including 1324 adults with type 1 diabetes mellitus (mean age 42.2 ± 11.6 years; mean follow‐up 31.6 ± 18.2 months), were analysed. Of 753 participants with reported sex, 74.6% were women ( n = 562). A total of 1304 procedures were performed, most commonly Roux‐en‐Y gastric bypass (44.5%; n = 580) and sleeve gastrectomy (39.2%; n = 512), followed by adjustable gastric banding (13.0%; n = 170). Meta‐analysis demonstrated significant reductions in body weight (mean difference 29.55 kg; 95% CI 25.72 to 33.39; I 2 = 20%) and BMI (11.35 kg/m 2 ; 95% CI 10.36 to 12.34; I 2 = 32%). HbA1c decreased by 4 mmol/mol (95% CI 2.05 to 6.78; I 2 = 19%), and insulin requirements declined by 43%–48% (0.20 U/kg; 95% CI 0.13 to 0.26; I 2 = 58%). Postoperative complications included diabetic ketoacidosis (15/182, 8%) and severe hypoglycaemia (21/516, 4%); any complication occurred in 21/495 (4%). Evidence quality was low. Conclusion MBS achieves weight loss and reduces insulin requirements in adults with type 1 diabetes mellitus and obesity, but glycaemic improvements are minimal. Given the observational evidence base and inconsistent safety reporting, true metabolic risk remains uncertain. High‐quality prospective studies with standardised outcome definitions are needed.