Citations

Study Design. Post hoc analysis of prospectively-collected data. Objective. To identify factors predicting the most (and least) satisfaction following surgery for cervical spondylotic myelopathy (CSM). Summary of Background Data. Patient satisfaction affects long-term outcomes after surgery but the preoperative factors that influence postoperative satisfaction have not been well studied in patients with CSM. Methods. We conducted a post hoc analysis of prospectively-collected data from the Quality Outcomes Database (QOD) CSM registry cohort. Baseline and surgical characteristics were compared for patients with CSM reporting the most [North American Spine Society Satisfaction Score (NASS) 1] and least (NASS 4) satisfaction 24 months postoperatively. A multivariable logistic regression model was constructed using backward stepwise elimination to determine significant predictors of most versus least satisfaction. Twenty-four-month patient-reported outcomes (PROs) were compared. Results. Overall, 1141 patients were prospectively enrolled with 948 (83.1%) reaching 24-month follow-up. Of these, 699 met prespecified inclusion criteria: 610 (87.3%) were most satisfied and 89 (12.7%) were least satisfied. Though there were mean improvements in all 24-month PROs for the most satisfied cohort ( P <0.001), there were no significant improvements in 24-month PROs for the least satisfied cohort ( P >0.05). Using multivariable logistic regression modeling, a preoperative symptom of upper extremity weakness (OR=2.5, P =0.003), subjective myelopathy (OR=2.0, P =0.04), absence of numbness complaints (OR=2.2, P =0.003), symptom duration under 12 months (OR=1.6, P =0.047), Caucasian race (OR=2.3, P =0.001), participation in activities outside of the home (OR=2.0, P =0.04), anterior approach (OR=2.3, P <0.001), and higher baseline quality of life (OR=4.0, P =0.01) were predictive of the most satisfaction. Conclusion. Compared with the least satisfied, those most satisfied following surgery for CSM more often had a preoperative symptom of arm weakness, subjective myelopathy, the absence of numbness complaints, symptom duration under 12 months, higher baseline quality of life, and participation in activities outside of the home. Compared with a posterior approach, an anterior approach was associated with the most satisfaction. Taken together, early surgical treatment--before myelopathic symptoms significantly impact one's quality of life--may be considered to optimize patient satisfaction following CSM surgery.

Abstract Unvetted scientific claims about vaccines can spread rapidly and undermine decades of progress in immunization and public trust. A recent non-peer-reviewed analysis, promoted at political hearings, in the documentary “An Inconvenient Study,” and on social media, has been used to suggest that vaccinated children experience higher rates of chronic illness than unvaccinated peers. Despite standard regression models, critical flaws - uncontrolled confounding, exposure misclassification, unequal follow-up, and outcome multiplicity, invalidate causal inference. An independent group of international experts critically appraises this analysis and contrast its claims with the consistent evidence confirming vaccine safety and effectiveness. We also show how poorly designed studies can distort public discourse, amplify misinformation, and fuel vaccine hesitancy. We outline actions to strengthen research integrity, such as transparent data sharing, labeling of non-peer-reviewed content, and evidence-based communication. Safeguarding public health demands that vaccine evidence be methodologically sound, reviewed, and interpreted by qualified experts.

Abstract INTRODUCTION Neurodegenerative diseases often involve overlapping alpha‐synuclein (asyn), amyloid beta, and tau proteinopathies, yet the mechanisms, impact, and directionality of their interactions remain unclear. METHODS We induced brain‐wide neuronal asyn/tau pathologies via viral expression of wild‐type asyn, mutant asyn E46K , mutant tau A152T , or both asyn E46K /tau A152T in adult amyloidosis knock‐in mice and controls, either post‐plaque deposition (6 months old) or pre‐plaque (3 months old). Open‐field behavior was assessed baseline and 3 and 6 months post‐transduction, followed by neuropathology and neuroinflammation analyses. RESULTS Post‐plaque induction in amyloid mice increased asyn/tau total and phosphorylated levels and exacerbated amyloid‐related hyperlocomotion/anxiety. Pre‐plaque induction produced robust phosphorylated pathologies irrespective of amyloid, while causing similar amyloid‐dependent behavioral synergy. Tau pathology drove LGALS3 + inflammatory glial responses in white‐matter fibers. DISCUSSION Amyloid context gates vulnerability, with certain synergies manifesting across stages. White‐matter gliosis is a novel mechanism of tau A152T risk. Together, our data argue for the development of stage‐aware, multitarget interventions and biomarkers.

ABSTRACT Objective To evaluate long‐term failure rates and complications after retropubic and transobturator midurethral sling procedures for primary stress urinary incontinence (SUI). Design Retrospective cohort study. Setting Academic medical centre. Population A previously described cohort of patients ( n = 1881) who underwent midurethral sling procedures (2002–2012) and a covariate‐matched cohort of patients with retropubic ( n = 570) or transobturator ( n = 317) slings. Methods Health record review with follow‐up extended by 9 years (through December 31, 2022). Main Outcome Measures Treatment failure (reoperation for recurrent SUI) and procedure‐associated complications. Results The duration of assessment was extended by 6.9 years for the retropubic group and by 6.4 years for the transobturator group. The median (IQR) follow‐up was 11.1 (5.1–14.5) years (retropubic, 11.4 [5.9–14.6]; transobturator, 9.6 [2.6–13.7]). Higher risk of reoperation was observed with transobturator (8.8%) than retropubic (4.4%) slings (unadjusted hazard ratio [HR], 2.29 [95% CI, 1.49–3.54]; p < 0.001; covariate‐matched analysis HR, 1.91 [95% CI, 1.15–3.17]; p = 0.01). The increased risk of reoperation with a transobturator sling was higher when the procedure was combined with prolapse repair (unadjusted HR, 6.34 [95% CI, 3.09–13.02]; p < 0.001; covariate‐matched analysis HR, 3.96 [95% CI, 1.35–11.58]; p = 0.01). Higher rates of reoperation for urinary retention were observed for the retropubic group than for the transobturator group (covariate‐matched analysis HR, 8.39 [95% CI, 1.11–63.22]; p = 0.04). Conclusion In this long‐term follow‐up study, midurethral slings had a low failure rate. Women with SUI undergoing transobturator sling placement plus prolapse repair had a greater risk of reoperation. However, women with retropubic slings had a greater risk of urinary retention requiring intervention.

Patients with plasma cell leukemia (PCL) are generally excluded from pivotal T-cell redirecting bispecific antibody (BsAb) trials. We evaluated real-world outcomes in a multicenter retrospective study of 122 patients with primary or secondary PCL across 15 academic centers, categorized as 'active' (≥5% circulating plasma cells within 30 days of BsAb initiation) or 'historical'. In a heavily pretreated population, patients received teclistamab (37%), elranatamab (11%), talquetamab as a line of therapy (Tal LOT, 42%), or talquetamab as bridging therapy to CAR-T (Tal Bridge, 11%). Cytokine release syndrome (CRS) was grade 1-2 in 56% and grade 3-4 in 4%, whereas neurotoxicity was grade 1-2 in 16% and grade 3-4 in 5%. Among 110 evaluable patients, the overall response rate (ORR) was 55%, including 61% with Tal LOT, 58% with Tal Bridge, 46% with elranatamab, and 33% with teclistamab. With a median follow-up of 8.3 months, talquetamab demonstrated superior survival. Tal LOT showed a median progression-free survival (mPFS) of 5.5 months and a median overall survival (mOS) of 11.5 months, and both were unreached in the Tal Bridge cohort. In contrast, teclistamab and elranatamab showed a mPFS of 1.2 and 1.6 months and mOS of 8.1 and 3.6 months, respectively (P=0.007, P=0.023). In active PCL, Tal LOT achieved mPFS/mOS of 6.9/12.2 months versus 0.7/1.4 months with teclistamab and 1.0/3.1 months with elranatamab, respectively (P&lt;0.001, P=0.002). Multivariable analysis associated active PCL with worse survival and Tal LOT with improved outcomes. BsAbs were safe in PCL, with talquetamab showing superior outcomes compared with BCMA-directed BsAbs.

Purpose To evaluate return‐to‐sport (RTS) rates and patient‐reported outcome measures (PROMs) following hip arthroscopic labral repair for femoroacetabular impingement in active basketball players with a minimum of 2‐year follow‐up. Methods All patients who were active basketball players and underwent hip arthroscopy with labral repair for femoroacetabular impingement from 2009 to 2022 were identified. Patients were evaluated for postoperative RTS and revision surgery at a minimum 2‐year follow‐up. RTS was defined as resuming basketball participation, at any level. Modified Harris Hip Score (mHHS), Hip Outcome Score‐Activities of Daily Living (HOS‐ADL) and Sport (HOS‐Sport), and surgery satisfaction were also collected. Results Sixty‐seven hips in 54 athletes (29 male, 25 female) with a mean age of 22.2 years (range 13‐39 years) were included. Eighty‐six (86%) were recreational or high school basketball players. There was significant improvement in all PROMs from baseline to a minimum 2‐year follow‐up (all P < .001). After excluding for athletes who did not RTS for nonmedical reasons, 78% of athletes returned to basketball following hip arthroscopy. Including patients who cited nonmedical reasons for not returning, the overall RTS rate was 65%. Athletes who RTS had significantly higher mHHS ( P = .012), HOS‐ADL ( P = .006), and HOS‐Sport ( P = .002), as well as lower visual analog scale pain (2.2 vs 3.4, P = .037) than those who did not RTS. Calculated minimal clinically important difference values were 8.3 for mHHS, 7.2 for HOS‐ADL, and 13.4 for HOS‐Sport. Anchor‐based patient acceptable symptom state calculations yielded thresholds of 83.5 for mHHS, 92.6 for HOS‐ADL, and 79.2 for HOS‐Sport—with 70%, 63%, and 67% of patients achieving these thresholds, respectively. Conclusions Basketball players who undergo hip arthroscopic labral repair for femoroacetabular impingement show significant improvements in PROMs with 78% RTS rate at a minimum 2‐year follow‐up. Although many athletes discontinued basketball for reasons unrelated to the hip, 18% cited hip issues. Basketball players who successfully return to basketball report higher PROMs than nonreturners, and cohort‐specific minimal clinically important difference analysis indicates that most athletes achieve clinically meaningful improvements. Level of Evidence Level IV, therapeutic retrospective case series.

Abstract Rationale Idiopathic Pulmonary Fibrosis (IPF) is characterized by chronic progressive pulmonary fibrosis and high mortality. Genetic markers, summarized into a polygenic risk score (PRS), associate with IPF in well-phenotyped research cohorts. Objectives To evaluate the performance of the PRS using real-world data from routinely captured electronic healthcare records. Methods We conducted an observational study evaluating the association of a PRS for IPF with electronic healthcare record diagnosis of IPF as well as lung transplant-free survival in four independent cohorts; the Mass General Brigham Biobank (MGBB), Mayo Clinic Biobank (MCBB), Mayo Clinic Tapestry Cohort (Tapestry), and U.K. Biobank (UKBB). We used multivariable logistic regression and multivariable Cox proportional hazards models adjusting for age, gender, and principal components of ancestry. The cohorts then underwent fixed and random effects meta-analysis. Measurements and Main Results Of 37,709; 44,195; 43,202; and 447,422 participants from MGBB, MCBB, Tapestry and UKBB respectively, 1,015 (2.7%) 2,879 (6.5%), 1,310 (3.0%), and 2,742 (0.6%) participants had an IPF diagnosis. Meta-analysis demonstrated a high-risk PRS associated with IPF diagnosis, OR 2.88 (95%CI 2.41-3.44) compared to all other individuals. A high-risk PRS also associated with the composite endpoint of mortality or lung transplant among those with an IPF diagnosis, HR 1.23(95%CI 1.11-1.35) compared to all other individuals. Conclusions A PRS can identify those at risk for an IPF diagnosis and mortality in biobank-scale data, which may have implications for clinical decisions. Further work is necessary to evaluate the utility of adding genetics in clinical settings.

Emerging evidence links veno-venous extracorporeal membrane oxygenation (VV-ECMO) to right ventricular (RV) dysfunction, but the relative contribution of ECMO versus underlying disease progression remains unclear. We conducted a multicenter, retrospective, propensity-matched study including 408 intubated acute respiratory distress syndrome (ARDS) patients who were admitted between January 2020 and October 2024 in a quaternary referral hospital network within the United States and underwent at least two transthoracic echocardiograms (TTEs) after intubation. Using 1:2 propensity score matching, we adjusted for baseline comorbidities, baseline hemoglobin, lactate, and worst PaO 2 /FiO 2 ratio (P/F). Longitudinal echocardiographic changes were analyzed with a cumulative link mixed model (CLMM), evaluating RV size and function as ordinal outcomes. Within 408 patients (112 received ECMO support), propensity matching identified 55 ECMO and 110 non-ECMO patients with balanced baseline characteristics. Among 469 serial echocardiograms, RV size and function worsened more frequently in ECMO patients. In longitudinal modeling, ECMO use alone was not associated with RV dilation ( p = 0.23) or dysfunction ( p = 0.43). However, longer ECMO duration was associated with RV dilation (OR: 1.04 per day, p = 0.004) and dysfunction (odds ratio [OR]: 1.04 per day, p < 0.001). Higher ECMO circuit flow had a trend toward progressive RV dilation and dysfunction but did not reach statistical significance. These findings highlight the need for vigilant RV monitoring during ECMO support.