Citations

Purpose: To report the anatomic and visual outcomes of eyes developing delayed rhegmatogenous retinal detachment (RRD) after macular surgery. Methods: This was a retrospective, multicentric study including eyes undergoing RRD repair at least 3 months after macular surgery for either full-thickness macular hole (FTMH) or epiretinal membrane (ERM). Anatomic and functional assessment, i.e., pre- and postoperative best-corrected visual acuity (BCVA), indications and details of macular and RRD surgery, time interval from macular surgery to RRD, intraocular tamponade, location, extent of RRD, and nature of retinal break, was performed. Results: Sixteen out of 2,906 eyes (0.55%) undergoing macular surgery developed RRD after 8.4 ± 5.8 months (mean ± SD). Intraoperative peripheral retina evaluation showed missed/de novo break (11 eyes; 68.75%), no identifiable break i.e., probable microbreak (two eyes; 12.5%), giant retinal tear (two eyes; 12.5%), and retinoschisis related break (one eye; 6.25%). Anatomical success, i.e., attached retina after one surgery, was seen in 14 eyes (87.5%). BCVA worsened from 0.6 ± 0.3 logMAR (Snellen equivalent 20/80) at baseline to 0.9 ± 0.8 logMAR (20/160) through the last visit (P < 0.001). Conclusion: RRD after macular surgery occurs predominantly via missed/de novo retinal breaks. A significant percentage (50%) of eyes showed worse visual acuity compared with baseline despite successful retinal reattachment.

Migraine is one of the most prevalent and disabling neurological diseases, significantly affecting quality of life and productivity, as well as contributing to substantial societal costs. Recent innovations, including calcitonin gene-related peptide (CGRP) pathway inhibitors and onabotulinumtoxinA, have transformed migraine prevention by offering high efficacy and excellent tolerability, thus improving adherence. Clinical trials and real-world studies show that significant reductions in migraine frequency and, in some cases, complete migraine freedom is achievable. In this Position Statement, we advocate for raising the standards of migraine prevention by setting ambitious treatment goals aimed at optimal outcomes, such as migraine freedom or very low number of days with migraine or moderate/severe headache. We emphasize the importance of addressing residual migraine burden, highlighting that achieving a ≥50% reduction in monthly migraine days, although often considered a successful response, may not fully restore quality of life. Relying solely on percentage-based improvements can obscure the persisting impact of residual burden. This Position Statement does not want to change the standards for clinical trials but aims primarily at real-world clinical practice and proposes a shift from percentage-based measures of success to absolute goals while on treatment. We outline a framework that categorizes outcomes into four tiers: migraine freedom (no days with migraine or moderate-to-severe headache), optimal control (less than four days with migraine or moderate-to-severe headache), modest control (four to six days with migraine or moderate-to-severe headache) and insufficient control (more than days with migraine or moderate-to-severe headache). Focusing on residual burden while on treatment aims to further improve patient quality of life and drive innovation in preventive therapies and non-pharmacological approaches. By advocating for higher standards, this Position Statement, is not aimed primarily to drive reimbursement policies for migraine preventive treatments, but seeks to inspire clinicians, researchers and policymakers to prioritize ambitious goals in migraine prevention, ultimately enhancing patient outcomes and reducing the broader societal and economic impact of this debilitating condition.

Abstract INTRODUCTION Early‐onset and late‐onset Alzheimer's disease (EOAD and LOAD, respectively) have distinct clinical manifestations, with prior work based on small samples suggesting unique patterns of neurodegeneration. The current study performed a head‐to‐head comparison of cortical atrophy in EOAD and LOAD, using two large and well‐characterized cohorts (LEADS and ADNI). METHODS We analyzed brain structural magnetic resonance imaging (MRI) data acquired from 377 sporadic EOAD patients and 317 sporadicLOAD patients who were amyloid positive and had mild cognitive impairment (MCI) or mild dementia (i.e., early‐stage AD), along with cognitively unimpaired participants. RESULTS After controlling for the level of cognitive impairment, we found a double dissociation between AD clinical phenotype and localization/magnitude of atrophy, characterized by predominant neocortical involvement in EOAD and more focal anterior medial temporal involvement in LOAD. DISCUSSION Our findings point to the clinical utility of MRI‐based biomarkers of atrophy in differentiating between EOAD and LOAD, which may be useful for diagnosis, prognostication, and treatment. Highlights Early‐onset Alzheimer's disease (EOAD) and late‐onset AD (LOAD) patients showed distinct and overlapping cortical atrophy patterns. EOAD patients showed prominent atrophy in widespread neocortical regions. LOAD patients showed prominent atrophy in the anterior medial temporal lobe. Regional atrophy was correlated with the severity of global cognitive impairment. Results were comparable when the sample was stratified for mild cognitive impairment (MCI) and dementia.

Background: Anterior cruciate ligament reconstruction (ACLR) is one of the most common orthopaedic procedures and one of the most well studied. Despite extensive research dedicated to ACLR, there is limited understanding of how chronic inflammatory systemic diseases (CIDs) such as rheumatoid arthritis and systemic lupus erythematosus affect outcomes. Purpose: To compare the outcomes of ACLR in cohorts of patients with and without CID. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective query of a regional data set was conducted for all patients who underwent ACLR from 1990 to 2021 for traumatic ACL rupture. All patients with CID were identified and propensity matched to non-CID controls. Baseline characteristics and clinical outcomes were identified through retrospective chart review, and patients were contacted for subjective outcomes. Results: A total of 30 patients with ACLR and a diagnosis of CID were identified. These patients were propensity matched to 120 non-CID controls. Baseline demographic and surgical characteristics demonstrated no statistical differences. Follow-up duration was similar between the CID and non-CID groups (mean, 14.6 vs 14.2 years; P = .868). The CID cohort had a higher arthrofibrosis rate (16.7% vs 4.3%; P = .031), higher osteoarthritis rate (33.3% vs 16.7%; P = .041), higher total knee arthroplasty (TKA) rate (16.7% vs 3.3%; P = .016), and earlier time to TKA (14.7 vs 23.5 years; P = .032). Knee range of motion, infection rate, retear rate, time to retear, and time to osteoarthritis were not statistically different between the cohorts. The CID cohort had higher visual analog scale pain scores (mean, 2.00 vs 1.20; P = .043) but slightly higher satisfaction (mean, 3.92 vs 3.39; P = .043). There were no differences in preinjury Tegner, postoperative Tegner, change in Tegner, or IKDC score. In a univariate Cox regression model, the CID cohort had a retear hazard ratio of 1.43 (95% CI, 0.46-4.51; P = .537). Kaplan-Meier survival revealed no significant differences in retear-free survival between the CID and non-CID cohorts at 25 years (85.7% vs 87.3%; P = .53). The CID cohort had a TKA hazard ratio of 3.94 (95% CI, 1.05-14.8; P = .042). Kaplan-Meier survival demonstrated significantly decreased TKA-free survival at 25 years in the CID cohort (64.9% vs 91.2%; P = .029). Conclusion: CID increases the incidence of arthrofibrosis, osteoarthritis, and TKA in those undergoing ACLR. Patients with CID also undergo TKA significantly sooner than non-CID counterparts. Notably, the majority of patient-reported outcome measures are no worse in patients who have a CID diagnosis. Thus, ACLR constructs themselves may not necessarily fare worse in patients with CID. Nonetheless, these patients need to be cautiously counseled on the clinical outlook after their ACLR.

Importance There is a lack of long-term efficacy and safety data on hereditary transthyretin amyloidosis with polyneuropathy (hATTR-PN) and on RNA interference (RNAi) therapeutics in general. This study presents the longest-term data to date on patisiran for hATTR-PN. Objective To present the long-term efficacy and safety of patisiran in adults with hATTR-PN. Design, Setting, and Participants This global open-label extension (OLE) of the APOLLO randomized clinical trial and phase 2 OLE study enrolled patients from 43 hospitals or clinical centers across 19 countries between July 2015 and August 2017, with follow-up until November 2022. Of 212 eligible patients with hATTR who completed the phase 3 APOLLO or phase 2 OLE parent studies, 211 enrolled in and 138 completed the global OLE. Intervention Patisiran, 0.3 mg/kg, intravenously once every 3 weeks for up to 5 years. Main Outcomes and Measures Outcomes evaluated at year 5 of the global OLE included disability (polyneuropathy disability [PND] score); polyneuropathy severity (Neuropathy Impairment Score [NIS]), nutritional status (modified body mass index [mBMI]), quality of life (Norfolk Quality of Life–Diabetic Neuropathy [Norfolk QOL-DN]), and Rasch-Built Overall Disability Scale (R-ODS), with no statistical hierarchy. Safety, survival probability, and mortality were also assessed. Results At the global OLE baseline, the mean (SD) age was 61.3 (12.3) years, and 156 patients (73.9%) were male. In 138 patients completing the study, PND scores remained stable or improved in 89 patients (65.0%), NISs showed a mean (SD) change of 10.9 (14.7), and mean (SD) mBMI (calculated as weight in kilograms divided by height in meters squared times serum albumin in grams per liter) increased by 46.4 (120.7) over 5 years from baseline. Norfolk QOL-DN and R-ODS scores showed mean (SD) changes of 4.1 (16.7) and –3.7 (6.2), respectively. Adverse events (AEs) leading to study withdrawal occurred in 47 patients (22.3%). Infusion-related reactions were the most common treatment-related AE (n = 34 [16.1%]). Overall, 41 patients (19.4%) died during the study. Patisiran treatment in the parent study and low familial amyloid polyneuropathy score at parent study baseline were associated with significantly improved survival. Conclusions and Relevance In the longest study of an RNAi therapeutic for any disease, patisiran treatment resulted in modest changes for patients with hATTR-PN with an acceptable safety profile. These results highlight the importance of initiating early treatment for hATTR and the potential of RNAi therapeutics in medicine. Trial Registration ClinicalTrials.gov Identifier: NCT02510261

Introduction. Non-cystic fibrosis bronchiectasis is a complex medical condition with multiple etiologies, characterized by chronic productive cough and radiologic evidence of airway lumen dilation and wall thickening. Associated exacerbations and declining lung function contribute to increasing disability and mortality. There are no data about the prevalence of non-cystic fibrosis bronchiectasis etiologies in the Colombian population.Objective. To investigate non-cystic fibrosis bronchiectasis etiology and clinical characteristics in adults evaluated in the southwest of Colombia.Materials and methods. We conducted a cross-sectional, non-interventional study. Subjects diagnosed with non-cystic fibrosis bronchiectasis were referred to by theirhealthcare providers and then enrolled between October 2018 and April 2021. Medical records and radiological studies were evaluated. Participants underwent laboratory tests, including complete blood count, serum immunoglobulin levels, and, in some cases, additional tests.Results. We included 161 subjects. The average age was 50 years old, and 59% were females. Bronchiectasis etiology was identified in 84.6% of the cases. Postinfectious(34.6%) and immune disorders (25.3%), represented by autoimmunity (13.6%) and immunodeficiency (11.7%), were the leading causes. Gender differences were noted in autoimmune (females: 18.8% versus males: 6.1%, p = 0.021) and immunodeficiency-related bronchiectasis (males: 21.2% versus females 5.2%, p = 0.002). Immunodeficiencies-associated bronchiectases were more frequent in subjects under 50 years of age, while chronic obstructive pulmonary disease-associated bronchiectases were common in subjects over 50 years of age.Discussion. The etiologies of non-cystic fibrosis bronchiectasis in Colombia are diverse, exhibiting notable differences from other global regions. Serum immunoglobulin levels and clinical immunologist consultation should be prioritized in diagnosing patients with unclear bronchiectasis etiology, particularly those with recurrent sinopulmonary infections.

AbstractBackgroundAs new anti‐amyloid immunotherapies emerge for Alzheimer’s disease (AD), it is clear that early diagnosis of AD pathology is crucial for treatment success. This can be challenging in atypical presentations of AD and, together with our reliance on CSF or PET scans, can, at times, lead to delayed diagnosis. Here, we further explore the possible role of plasma tau phosphorylated at threonine 217 (P‐tau217) for the detection of primary AD or AD co‐pathology when frontotemporal dementia spectrum disorders are the main clinical presentation.MethodParticipants were recruited through ALLFTD, a North American multisite research consortium for the longitudinal assessment of frontotemporal lobar degeneration. After excluding cases with known FTD‐causing mutations, 573 participants with sporadic disease, mild cognitive/behavioral impairment, or healthy familial controls evaluated between 2014 and 2023 were included in this analysis (45.8% female, median age 66 years). 39 of those cases underwent neuropathological evaluation. Plasma P‐tau217 was measured with the Eli Lilly electrochemiluminescence‐based assay. P‐tau217 concentrations were compared by phenotype, disease severity, genotype, and, when available, neuropathological diagnosis with non‐parametric tests. Its diagnostic performance was tested with ROC curves. Associations between plasma P‐tau217 concentrations and clinical scales of global cognition, memory, executive function, motor function, and social cognition with linear regressions and non‐parametric tests.ResultPlasma P‐tau217 concentrations were higher in logopenic variant primary progressive aphasia (lvPPA) and amnestic dementia (AmDem), compared to participants with normal cognition or other FTD phenotypes. P‐tau217 concentrations were higher in APOE e4 carriers, compared to non‐carriers, regardless of phenotype, but were not affected by disease severity. P‐tau217 concentrations showed associations with clinical measures of global cognition, memory, and executive function, but had no associations with measures of motor function or social cognition. Plasma P‐tau217 concentrations were elevated in high and intermediate ADNC scoring, or more advanced Braak stages, even when AD was not the primary pathology.ConclusionEven when FTD is suspected, high plasma p‐tau 217 concentrations are strongly associated with underlying AD as primary pathology or contributing co‐pathology. Plasma P‐tau217 could be a tool to support the development of disease‐modifying therapies for atypical Alzheimer’s disease presentations or for FTD cases with Alzheimer’s disease co‐pathology.

ABSTRACTPurposeDouble‐level osteotomies (DLOs) have shown promising results for knee joint preservation, however, most ultimately progress in terms of degenerative disease resulting in conversion to total knee arthroplasty (TKA). Therefore, the purpose of this study was to examine the time to TKA conversion, long‐term clinical outcomes and revision rates of patients who have undergone TKA after prior ipsilateral DLO.MethodsPatients who underwent simultaneous or staged DLO and subsequently underwent conversion to TKA at a single academic institution from 1997 to 2022 were evaluated. The type of osteotomy performed (opening‐ vs. closing‐wedge), osteotomy hardware fixation, when and if osteotomy hardware was removed, implanted TKA components and revision rates were recorded. Postoperative outcomes, including Forgotten Joint Score‐12 (FJS‐12), Tegner Activity Scale score and subjective knee preference were also obtained.ResultsA total of 22 patients (24 knees) underwent TKA following DLO and were followed for an average of 26.1 ± 7.7 years. The average time from DLO to TKA conversion was 14.1 ± 6.5 years, with 70.8% of knees converting to TKA more than 10 years after DLO. The mean follow‐up after conversion to TKA was 12.0 ± 7.7 years. Only 12.5% of patients received a varus‐valgus or hinged‐constrained TKA. At the final follow‐up, the mean FJS‐12 was 75.8 ± 23.1, while the mean Tegner Activity Scale score was 2.5 ± 1.1. Seventy‐seven percent of patients had no subjective knee preference or preferred their DLO‐TKA knee. Only two knees (7.4%) underwent subsequent revision after index arthroplasty at a mean of 9.3 years postoperatively.ConclusionsA majority of DLOs (70.8%) converted to TKA after more than a decade. Subsequent TKA function was favorable as most patients had either no subjective knee preference or preferred their DLO‐TKA knee. This study demonstrates both long‐term joint preservation and uncompromised TKA function after prior DLO.Level of EvidenceLevel IV.

Background: Medial patellofemoral ligament reconstruction (MPFLR) is an excellent surgical option for patients with recurrent patellar instability. This technique has demonstrated significant improvements in patient-reported outcomes, high rates of return to sport, and low rates of failure. However, there is debate regarding the use of isolated MPFLR in the setting of concomitant pathoanatomic features such as patella alta, trochlear dysplasia, or a lateralized tibial tubercle. Purpose: To estimate the overall relative effect sizes as well as strength of evidence supporting described risk factors for recurrent instability after isolated MPFLR. Study Design: Systematic review and meta-analysis. Methods: A systematic review was performed in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The PubMed, Embase, Cochrane, and Ovid/MEDLINE databases were queried. Clinical studies for outcomes of isolated MPFLR reporting recurrent instability and associated risk factors were included. Data for each risk factor analyzed by at least 2 studies were extracted, and the heterogeneity of studies was determined by I 2 value. For variables evaluated in studies determined to have fair homogeneity, defined as I 2 <25%, DerSimonian-Laird random-effects models were generated and effect sizes were represented as mean differences or odds ratios. Results: Nine studies examining risk for recurrent instability after isolated MPFLR were identified, with 5 overlapping risk factors with low heterogeneity between studies: age, sex, tibial tubercle to trochlear groove (TT-TG) distance, Caton-Deschamps Index (CDI), and trochlear dysplasia. There was strong evidence to support the risk of recurrent instability associated with CDI >1.3 (OR, 2.72; P = .02) and dysplasia with a trochlear bump (DeJour type B or D; OR, 3.28; P <.001). Age, sex, and TT-TG distance did not cause an increased risk of recurrent instability with currently available aggregate data. Conclusion: There are signs of increased risk of failure of isolated MPFLR in the setting of DeJour type B and D trochlear dysplasia and patella alta (CDI, >1.3). Currently available data suggest that age, sex, and TT-TG distance do not cause a higher risk of recurrence for patients undergoing isolated MPFLR.

Background: Mismatch between osteochondral allograft (OCA) donor and recipient sex has been shown to negatively affect outcomes. This study accounts for additional donor variables and clinically relevant outcomes. Purpose: To evaluate whether donor sex, age, donor-recipient sex mismatch, and duration of graft storage affect clinical outcomes and failure rates after knee OCA transplantation. Study Design: Cohort study; Level of evidence, 3. Methods: Patients undergoing knee OCA transplantation between 2003 and 2018 were prospectively followed. Inclusion criteria consisted of primary OCA transplantation and minimum 2-year follow-up. Patient descriptive data and allograft donor sex, age, and graft storage time before implantation were collected. Patients were evaluated for reoperation, failure, and achievement of clinically significant outcomes for International Knee Documentation Committee scores. Reoperation was defined as subsequent surgical intervention of the transplanted allograft, including second-look arthroscopy for graft evaluation, debridement, and loose body removal. Failure was defined as revision of the primary OCA transplantation or conversion to arthroplasty. A Kaplan-Meier curve determined cumulative survivability of OCA transplantations, and log-rank testing was used to compare survivorship between groups. Stepwise regression analysis was utilized to evaluate associations between donor variables and achievement of clinically significant outcomes, reoperation, and failure. Results: A total of 372 patients undergoing OCA transplantation were included and followed for a mean 5.4 years (SD, 2.7; range, 2.0-16.3). Isolated OCA transplantation was performed in 45% of cases (169/372). A mismatch in donor and recipient sex was present for more female patients (90%) than male patients (10%; P < .001). Those who had a sex-mismatched graft more frequently underwent concomitant tibial tubercle osteotomy ( P = .034). When controlling for patient sex, no other differences were seen between groups matched and mismatched by sex. Univariable and multivariable analysis found no significant difference in survival free from reoperation or failure on the basis of donor-recipient sex mismatch, donor age, or graft storage time before implantation. Conclusion: In contrast to previous historical data, no donor variables were associated with inferior clinical outcomes in patients who underwent OCA transplantation. These data can help inform graft selection, expedient recipient selection, and outcome optimization after OCA transplantation.