Citations

ABSTRACT Background and Aims Alpha‐gal syndrome (AGS) is an IgE‐mediated hypersensitivity to galactose‐α‐1,3‐galactose, triggered by tick bites. It typically presents with delayed onset allergic or gastrointestinal symptoms after red meat consumption. This study aims to evaluate the prevalence of clinical symptoms and outcomes in AGS patients. Methods A systematic search of PubMed, Embase, and Cochrane Central was conducted to identify studies with at least five AGS patients that utilized alpha‐gal IgE for diagnosis and reported symptomatology. A random‐effects model calculated pooled prevalence and 95% confidence intervals (CIs) for clinical characteristics of AGS. Results Of the 739 studies screened, 15 met the inclusion criteria, comprising 1162 AGS patients (57% female). Urticaria was identified as the most prevalent symptom (63.8%, CI: 34.5–88.3, I 2 = 98.8%). At least one gastrointestinal symptom was reported in 69.2% of patients (CI: 49.3–85.9, I 2 = 97.5%), including abdominal pain (58.3%, CI: 36.0–78.9, I 2 = 96.0%), diarrhea (41.7%, CI: 22.3–62.5, I 2 = 93.4%), nausea (39.1%, CI: 29.2–49.6, I 2 = 79.1%), and vomiting (31.1%, CI: 21.9–41.2, I 2 = 70.4%). Tick bite history was recalled by 78.7% (CI: 46.4–98.1; I 2 = 99.1%), and 91.8% (CI: 84.6–96.8; I 2 = 70.3%) had symptom onset ≥ 1 h post red meat intake. Symptomatic improvement was observed in 86.5% (CI: 73.9–95.4, I 2 = 80.9%) of patients, with complete resolution in 42.7% (CI: 26.4–59.8, I 2 = 73.8%). Conclusion AGS typically presents with delayed onset allergic and GI symptoms after red meat intake, often with tick bite history. Majority of patients report symptomatic improvement on follow‐up.

ABSTRACT Amidst the opioid crisis, understanding the genetic basis of opioid use disorder (OUD) is crucial for identifying biological mechanisms and intervention points. However, genome‐wide association studies (GWASs) have been hampered by inadequate sample sizes and often the use of control populations not assessed for prior opioid exposure. Because opioid exposure is a prerequisite for the development of OUD, consideration of exposure history in controls is important. Electronic health record data (EHR) paired with genomic information allow a broader sampling of patients with OUD and exposed controls. We leveraged data across two healthcare systems to evaluate the impact of using controls not screened for opioid exposure (‘generic’) versus minimally opioid‐exposed control (‘exposed’). First, at the phenotypic level, we conducted phenome‐wide association studies (PheWAS) to compare the medical comorbidity profiles of OUD cases when using generic versus exposed controls. While PheWAS results for OUD‐related comorbidities were more pronounced when using the generic group, 83% of the disease associations were overlapping and of similar effect sizes. Second, at the genetic level, we conducted GWAS (cases vs. generic; cases vs. exposed) and assessed differences in genetic correlations and degrees of phenotypic misclassification. Genetic results were concordant across control groups based on heritability (generic: 0.16 ± 0.07 vs. 0.10 ± 0.07), associations with the coding OPRM1 variant rs1799971 ( p generic = 8.83E‐03 vs. p exposed = 1.83E‐02) and genetic correlations with prior OUD GWAS ( r g‐generic = 0.83 ± 0.26 vs. r g‐exposed = 0.78 ± 0.27). Although GWASs were limited by sample size ( N generic = 6269, N exposed = 6365), compared to an independent OUD GWAS ( N = 425 944), the dilution value for the two GWAS was not different from 1, suggesting no major impact of phenotypic misclassification. This study represents the first effort to enhance OUD genetic research through optimization of control definitions using EHR data. Generic controls ascertained within the US health systems, where exposure to prescription opioids is high, offer a practical alternative for genetic studies of OUD.

Abstract Isolated/idiopathic rapid eye movement sleep behavior disorder (iRBD) is a usually prodromal manifestation of neurodegenerative disorders with α-synuclein pathology: Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Clinical trials in the iRBD population face substantial barriers: limited access to well-characterized cohorts, inconsistent assessment protocols across centers, and the absence of validated biomarkers of disease burden. The North American Prodromal Synucleinopathy (NAPS) Consortium was established to address these challenges and facilitate clinical trials for neuroprotective therapies targeting synucleinopathy at the earliest known stages. In this multi-site, longitudinal, observational study, nine academic centers across North America will enroll and follow over 500 individuals with iRBD from existing sleep centers. Sixty control participants, matched for age, sex, and race will also be recruited. A harmonized protocol—including a standardized clinical battery assessing motor, cognitive, autonomic, psychiatric, sensory, and sleep function; structured diagnostic adjudication; biospecimen collection; and centralized analysis of both polysomnography and neuroimaging data—is outlined herein and reflects NAPS Stage 2. Each participants completes these assessments annually, and are replaced in the event of phenoconversion. By unifying assessments and expanding geographic reach, NAPS lays the groundwork for efficient, well-powered clinical trials designed to delay or prevent progression of iRBD to overt PD, DLB, or MSA—ultimately enabling earlier, more effective therapeutic intervention for neurodegenerative disease. Registered at clinicaltrials.gov (NCT05826457).

Background: Ocular graft-versus-host disease (oGVHD) is a frequent complication after hematopoietic stem cell transplant, with dry eye being the most common presentation. Patient experience with dry eye from oGVHD may negatively affect quality of life. The purpose of this study was to evaluate patients’ perspectives on the symptoms, treatments, and care burdens associated with dry eye from oGVHD. Materials and methods: An electronic questionnaire was sent to patients with dry eye asking about their diagnoses, symptoms, treatments, and experiences associated with dry eye. Results: Of the 639 patients who responded to the questionnaire, 79 reported having dry eye from oGVHD and were included in the analysis. The mean (SD) age of these patients was 55 (10) years (range, 22–73 years; n = 75). Of the patients who reported their sex (n = 78), 32 were male, and 46 were female. The most common ocular symptom was a sandy or gritty feeling (n = 68, 86%). Patients reported a mean (SD) of nine (2) symptoms, despite using four (2) treatments. The most common initial treatment was artificial tears (n = 71, 90%). Most patients (68/75, 91%) reported receiving oGVHD care from an eye care professional (e.g., ophthalmologist or optometrist), whereas a few (4/75, 5%) received oGVHD care from a hematologist. Conclusions: Dry eye symptoms and treatments, along with the associated time and financial costs required, are a burden to patients with oGVHD. These patients should be evaluated by a knowledgeable eye care professional to best treat and manage their disease.

Abstract Secondary central nervous system (CNS) large B-cell lymphoma (SCNSL) occurs in the de novo setting, as a CNS-isolated relapse, or synchronous (concomitant CNS and systemic) relapse. SCNSL is a devastating event without therapeutic consensus. Thus, we aimed to evaluate treatment outcomes in an international cohort. Progression-free survival (PFS), overall survival (OS), and cumulative incidence of relapse (CIR, estimated using competing-risk models) were reported. Prognostic factors were identified in a 6-month landmark multivariate analysis. Outcomes after thiotepa autologous stem cell transplant (ASCT) and chimeric antigen receptor (CAR) T-cell therapy (CAR-T) delivered at relapse were compared after propensity score matching (PSM). A total of 1139 patients were included in the analysis (de novo: 537; relapsed SCNSL: 602). Two-year PFS estimates were 40.4%, 43.9%, and 16.2% for de novo SCNSL, CNS-isolated relapse, and synchronous relapse, respectively. Patients with CNS-isolated relapse demonstrated low rates of systemic recurrence (24-month CIR, 6%). Thiotepa-ASCT correlated with longer survival in de novo SCNSL (PFS: hazard ratio [HR], 0.57; P = .005; and OS: HR, 0.62; P = .023) and CNS-isolated relapses (PFS: HR, 0.55; P = .002; and OS: HR, 0.39; P< .0001). ASCT (thiotepa or no thiotepa) also associated with improved survival in synchronous relapses (PFS: HR, 0.57; P = .023; and OS: HR, 0.48; P = .019). Higher survival with thiotepa-ASCT than CAR-T was observed after PSM (PFS: HR, 0.45; P = .005 and OS: HR, 0.41; P = .014). These data support thiotepa-ASCT in eligible patients, particularly de novo disease and CNS-isolated relapses. CNS-isolated relapse was infrequently associated with systemic recurrence, supporting treatment regimens adopted from primary CNS lymphoma.

Abstract Background Motor disturbances are common in neurodegenerative disorders. Digital health technologies can be a tool for remote, accessible, and low‐burden motor assessments. The ALLFTD Mobile App includes a finger‐tapping test (mApp‐FTT) to assess dexterity. We evaluated the reliability and construct validity of smartphone‐based measures of finger tapping in an in‐person sample. Methods Participants ( n = 33; mean age=68.2 [SD=8.6]) completed the mobile finger‐tapping test (mApp‐FTT) on iOS and Android devices (two counterbalanced 20‐second trials per hand) and the mechanical finger‐tapping test (FTT). The sample included cognitively unimpaired participants (22.2%) and those diagnosed with frontotemporal dementia‐spectrum disorders (41.7%), Alzheimer's dementia (22.2%), and progressive supranuclear palsy or corticobasal syndrome (13.9%). A motor domain was calculated based on neurological exam and added to the Clinical Dementia Rating® plus National Alzheimer's Coordinating Center–Frontotemporal Lobar Degeneration (CDR®+NACC‐FTLD). Pearson's correlations assessed associations between mApp‐FTT performance and FTT performance, clinical severity (CDR®+NACC‐FTLD Box Score), motor rating scales (Progressive Supranuclear Palsy Rating Scale [PSPRS] and Unified Parkinson's Disease Rating Scale [UPDRS]), and cognitive function. Due to small sample size, PSPRS subdomains were dichotomized, and t‐tests were performed to evaluate group differences based on symptom presence. Results Total mApp‐FTT taps on iOS and Android were strongly correlated ( r = 0.86, 95% CI [0.76, 0.92], p < .001). mApp‐FTT was associated with manual FTT on iOS ( r = 0.70, 95% CI [0.52, 0.82], p < .001) and Android ( r = 0.62, 95% CI [0.41, 0.77], p < .001). Among iOS users, total PSPRS score was negatively correlated with mApp‐FTT ( r = ‐0.60, 95% CI [‐0.75, ‐0.39], p < .001). Worse mApp‐FTT performance was observed in participants with higher limb rigidity (mean difference=15.46, 95% CI [3.40, 27.52], p < .001), limb dystonia (mean difference=19.22, 95% CI [5.67, 32.77], p < .001), and finger tapping (mean difference=12.74, 95% CI [3.42, 22.06], p < .001). Total UPDRS score correlated with lower mApp‐FTT ( r = ‐0.48, 95% CI [‐0.66, ‐0.28], p < .001), as did disease severity (CDR®+NACC‐FTLD Box Score; r=‐0.46, 95% CI [‐0.66, ‐0.22], p < .001). Conclusion Smartphone‐based finger‐tapping assessments effectively detect motor and cognitive impairment, with stronger associations for motor function. Findings in iOS users highlight the need to assess operating system‐related biases and validate in Android. Remote smartphone assessments offer a scalable tool for tracking disease progression, warranting larger longitudinal studies.

ABSTRACT Plerixafor (PLX) is FDA approved for use in autologous peripheral blood stem cell donors but not in allogeneic donors. This study was completed by members of the ASFA HPC Donor Subcommittee to examine the incidence and characteristics of poor mobilizers (PM) among matched related donors (MRD), as well as factors associated with PLX use in MRD. Risks of poor mobilization in MRD were older age, especially donors older than 60 years, lower baseline platelet counts, and heavier recipients. PLX use in PM was low but safe, tripling the success rate for collection. This study adds evidence to the body of literature to support use of PLX in allogeneic donors who are PM.

Hemodynamic progression of valvular aortic stenosis was studied in 54 patients who had serial cardiac catheterizations. There were 47 men and 7 women with a mean age of 61.2 years. The time interval between studies was 4.4 years (range, 0.4‐12.2). Associated coronary artery disease was present in 37 patients (69%). The initial mean aortic valve area (Hakki's formula) was 1.26 cm 2 (range, 0.66‐2.85), and the aortic valve area at last follow‐up was 0.77 cm 2 (range, 0.29‐1.95), with mean reduction of 0.49 cm 2 . The mean peak systolic gradient increased from 23.3 ± 15.1 mm Hg at initial study to 52.6 ± 27.5 mm Hg at last study, a mean increase of 29.3 ± 23.6 mm Hg. Patients with no or mild left ventricular impairment and no or mild coronary artery disease are more likely to have progression than patients with more severe left ventricular impairment or coronary artery disease (P < 0.05). Aortic valve replacement for progressive aortic stenosis was required at a later date after coronary artery bypass grafting in a small group of nine patients. In this small group, there was a high intraoperative mortality of 33%.