Faculty Bibliography

BACKGROUND:While genetic testing in Movement Disorders (MD) has expanded enormously, access to genetic testing and genetic counseling remains asymmetric at the global scale. Guidance on efficient testing strategies for clinicians, governments and stakeholders is crucial. OBJECTIVES/OBJECTIVE:Establish a list of genetic movement disorders considered essential as determined by a group of MD experts. METHODS:All genes associated with MD were searched using the OMIM and MDS Gene database. We collected all additional tests available at 4 different laboratories from the EuroGentest database. The results were compiled in 6 questionnaires. A genetic test was considered essential if molecular testing had a direct impact in the management of the patient, including treatment of the disease or its comorbidities, or genetic counseling of the patient and family members. Two Delphi rounds were conducted asking MD experts which specific tests they considered essential in an adult MD clinic. RESULTS:Fifty-nine disorders were considered essential to genetically identify by the MD experts. This included 25 genes associated with ataxia, 15 with parkinsonism, 14 with dystonia, eight with chorea, five with paroxysmal disorders, four with myoclonus, four with hereditary spastic paraparesis, and one with tremor. Sixteen disorders reached 100% consensus among experts: Huntington's disease, PxMD-PPRT2, Wilson's disease, DYT-SGCE, DYT-THAP1, DYT-TOR1A, DYT/PARK-GCH1, Fragile-X Tremor-ataxia syndrome, PARK-GBA, PARK-LRRK2, PARK-PINK1, PARK-PRKN, PARK-SNCA, Cerebrotendinous Xanthomatosis, Ataxia-Telangiectasia, and Niemann-Pick disease type C. CONCLUSION/CONCLUSIONS:This study provides a list of genetic MD that should be molecularly tested in adult centers with a compatible phenotype according to a group of MD experts.

Therapeutic cancer vaccines can generate measurable antigen-specific immune responses in humans, yet tumor regression is often incomplete, inconsistent, or short-lived. In immunologically cold tumors, this pattern may reflect not an absolute inability to prime immunity, but difficulty advancing induced immunity through the full sequence required for tumor control. Peripheral blood responses may be real and still be biologically inadequate if they contract early, fail to acquire productive trafficking programs sufficient for tissue entry, lose functional competence under chronic antigen stress, or remain constrained by the suppressive tumor microenvironment. The manuscript advances a sequential, feedback-guided adjuvant framework in which peptide vaccination remains the backbone but is preceded and followed by distinct support phases. A Phase 0 immune-readiness step, potentially using IL-7 (e.g., CYT107), is intended to improve the baseline substrate before antigen exposure. Phase 1 priming uses peptide vaccination on a commonly used adjuvant backbone such as Montanide ISA-51 or poly-ICLC (Hiltonol), while radiation and/or STING-based strategies are treated as context-dependent enhancers rather than replacements for priming. IL-15-centered consolidation is then used to support expansion and persistence. A formal trafficking assessment follows so that blood-only success is not overinterpreted. IL-21 is positioned later as a persistence- and quality-support cytokine when response quality declines. The framework also addresses why otherwise rational protocols can fail at the chemokine-trafficking step: CXCR3-dependent tumor entry is not interchangeable with generic inflammation, CCR5 biology is context dependent, and IL-12, although biologically attractive and previously tested as a vaccine adjuvant, is best viewed here as an optional, context-specific amplifier rather than a universal backbone. Although organized as sequential phases, the framework is intended as a bottleneck-guided and iterative design logic in which phases may overlap, repeat, or be entered in partial parallel depending on the dominant biologic constraint. The central hypothesis is that vaccine programs that progress beyond priming into trafficking-competent and functionally sustained states are predicted to correlate more closely with disease control than programs judged mainly by early blood immunogenicity.

Murine studies show that the gut microbiota-the collection of the microbes residing in the large intestine-affects memory performance in the host. However, whether commensal gut bacteria are linked to human episodic memory remains unknown. Here, we investigated whether individual differences in episodic memory performance were associated with differences in the indigenous gut microbiota composition between individuals. We show that greater gut microbiota α diversity was associated with better item recognition and that gut microbiota dissimilarity index (β diversity) between participants was associated with differences in their performance. Finally, our results suggest that Prevotella copri might play a role in the relationship between gut microbiota and human item recognition in healthy individuals. In a sample size larger than previous human studies and examining unmanipulated gut microbiota, we provide evidence that episodic memory in healthy humans is linked to their gut microbiota composition.

BACKGROUND/UNASSIGNED:Lung cancer remains the leading cause of cancer mortality, yet blood-based biomarkers are not routinely used in diagnosis. This study evaluated four commercial blood protein assays, originally validated for other indications, in indeterminate pulmonary nodules (IPN). METHODS/UNASSIGNED:Using a prospective specimen collection, retrospective blinded evaluation design, samples were collected from patients with screening-detected, incidental, or symptomatic IPNs. Cytokeratin 19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125), and human epididymis protein 4 (HE-4) concentrations were quantified on commercial immunoassays. Logistic regression models were developed using internal training (Train), external testing (Test), and combined reestimation (Train + Test) cohorts and externally validated in an outcome-blinded multicenter cohort (Lung Team Project-2, LTP-2). RESULTS/UNASSIGNED:This study included 816 patients: 371 in Train, 166 in Test, and 279 in LTP-2. Malignancy rates were 54%, 44%, and 64%, respectively. In Train + Test, the area under the receiver operating curve (AUC) for lung cancer was 0.60 (95% confidence interval, 0.56-0.65) for CYFRA 21-1, 0.62 (0.58-0.67) for CEA, 0.60 (0.55-0.65) for CA-125, and 0.65 (0.60-0.70) for HE-4. In LTP-2, AUCs were 0.63 (0.56-0.70), 0.64 (0.57-0.70), 0.48 (0.40-0.55), and 0.61 (0.54-0.68), respectively. Combining all four biomarkers yielded an AUC of 0.70 (0.65-0.74) in Train + Test and 0.61 (0.54-0.68) in LTP-2. CONCLUSIONS/UNASSIGNED:In the first biomarker study reporting external validation in LTP-2, CYFRA 21-1, CEA, CA-125, and HE-4 demonstrated diagnostic value in IPNs. IMPACT/UNASSIGNED:By leveraging commercial assays, this study highlights opportunities to enhance lung cancer risk stratification using widely available diagnostics that could be rapidly integrated into clinical workflows.

BACKGROUND/UNASSIGNED:The placement of Spinal Cord Stimulator (SCS) trial or permanent electrodes carries a 31.9-43% morbidity/adverse event (AE) rate. Most AEs are attributed to electrode migration (EM: device-related AE 26.7% older cohort vs. 9.7% newer cohort), spinal epidural hematomas (SEHs: 0.81-2.6%), infection (3.4% older vs. 1.9% recent cohort), SCI (spinal cord injury: percutaneous 0.45% vs. 0.36% paddle electrodes), dural tears (DT/ cerebrospinal fluid leaks (CSF leaks)), foreign body/fibrous reactions, or syrinx formation. METHODS/UNASSIGNED:SCSs are typically applied to address chronic neuropathic pain syndromes. Here, we evaluated 20 articles focusing on patients who developed postoperative myelopathy/radiculopathy, variously attributed to MR-documented AE warranting medical or surgical intervention. RESULTS/UNASSIGNED:Postoperative symptoms/signs of AE typically included the acute development of new/increased weakness, sensory loss, and/or sphincter dysfunction. Requisite STAT MR scans usually confirmed the etiology of AE including electrode migration, SEH, DT, SCI, and/or postoperative scarring/fibrosis. Most patients warranted STAT surgery, while a small subset could be managed conservatively. CONCLUSION/UNASSIGNED:The AE rate for spinal cord stimulators ranges from 31.9 to 43%. While the majority are due to electrode migration, other etiologies include SEH, SCI, DT, and foreign body reactions. Those who become acutely myelopathic usually warrant STAT MR scans with the majority additionally necessitating STAT surgical intervention to limit short/long-term neurological morbidity.

BACKGROUND:Artificial intelligence (AI)-enabled "ambient" documentation may reduce clinician administrative burdens and improve care delivery, but implementation in clinical practice is complex. AIM/OBJECTIVE:To evaluate the implementation of commercially available ambient documentation tools in multi-specialty ambulatory clinical workflows at an academic medical center. SETTING/METHODS:A large urban academic health system in New York City. PARTICIPANTS/METHODS:Ninety-seven ambulatory clinicians across specialties. PROGRAM DESCRIPTION/METHODS:A multidisciplinary team conducted a 6-month proof-of-concept structured evaluation of two commercially available ambient documentation tools through initial vendor evaluations, technical review and integration with the electronic health record (EHR), clinician training and onboarding, implementation and technical support, and structured evaluation based on objective and key results (OKR) metrics. A single-group, pre-post evaluation of the impact of the tools on clinician EHR-based efficiency was conducted on a subset of participating clinicians. PROGRAM EVALUATION/RESULTS:Compared to the 3-month period immediately prior to initiating the ambient trial, clinicians experienced a 0.35-min-per-note and a 2.07-min-per-day reduction in documentation time. "Vendor B" showed higher utilization rates and superior user experience compared to "Vendor A." Implementation challenges included workflow integration, training resource requirements, data interoperability and analytics, and ongoing technical support needs. DISCUSSION/CONCLUSIONS:Ambient documentation shows promise in reducing documentation burden, but its success depends on technical stability and integration, product fit and support for clinicians, and adequate implementation resourcing. A multidisciplinary approach with clear metrics, strong vendor partnership and executive sponsorship, and ongoing technical support enables scalability.

BACKGROUND:Legalization of cannabis across several US states may increase its use by individuals on hemodialysis, particularly among those with chronic pain. Contemporary data on frequency or factors associated with cannabis use by this population are limited. METHODS:We conducted a secondary analysis of the HOPE Consortium Trial to Reduce Pain and Opioid Use in Hemodialysis, a randomized trial that tested whether a cognitive behavioral therapy intervention lowered pain interference in people with chronic pain receiving hemodialysis at 103 US dialysis facilities. We analyzed baseline demographic characteristics, social and medical history, pain intensity, pain interference, and cannabis use. Multivariable logistic regression was used to examine associations of baseline data with cannabis use. Linear regression was used to examine whether cannabis use modified the response to the intervention. RESULTS:Among 643 participants, 102 (16%) reported current cannabis use, 133 (21%) reported former use, and 408 (63%) had never used. Current users were younger than never or past users combined (median age 54 vs. 63 years) and more likely to be disabled (79% vs. 66%), to have received dialysis for >5 years (40% vs. 30%), and to self-report depression (41% vs. 31%), anxiety (28% vs. 20%), or any psychological disorder (51% vs. 38%), and less likely to be married (16% vs. 34%). Current cigarette smoking (odds ratio [OR]=3.22, 95% confidence interval (CI) 1.61-6.46) and alcohol use (OR=2.82, 95% CI 1.37-5.80) were independently associated with cannabis use, as were age, relationship status, neighborhood segregation index, and cocaine/heroin use. Cannabis use did not modify response to the intervention. CONCLUSIONS:Current cannabis use was reported by 16% of HOPE participants and was more common among younger, unmarried individuals who use other substances, but did not alter response to our intervention. More research is needed on the consequences of cannabis use among people receiving hemodialysis.

BACKGROUND:Vancouver B2 and B3 periprosthetic femur fractures (PPFF) have posed significant treatment challenges due to stem instability and lack of adequate femoral bone stock. This study investigated subsidence, survivorship, and outcomes of Vancouver B2 and B3 fractures, based on the order in which revision stem placement and fracture reduction occurred during revision total hip arthroplasty (rTHA). METHODS:This retrospective, cohort study included 46 rTHAs between June 2011 and April 2023. Included patients underwent rTHA for Vancouver B2 or B3 PPFF with minimum one-year radiographic and two-year clinical follow-up. All patients were treated with diaphyseal-engaging tapered fluted titanium stems and stem modularity decisions were based on surgeon preference. Cohorts were separated based on if stem placement (SF, n = 19), or fracture reduction (RF, n = 27) occurred first. Patient demographics, intraoperative information, and clinical and radiographic outcomes were collected. RESULTS:The SF and RF cohort showed no statistically significant differences in rate of subsidence ≥5 mm [26.3%[SF], 22.2%[RF], P = 0.749), rate of subsidence ≥ 10 mm (15.8%[SF], 14.8%[RF], P = 0.928), nor average subsidence (4.1 mm[SF], 4.4 mm[RF], P = 0.861). We found no statistically significant differences in surgery-related clinical outcomes or all-cause revision rates within a two-year follow-up period. The groups demonstrated comparable rates of procedure-related 90-day emergency department visits(P = 0.370) and readmissions(P = 0.712). The SF group underwent four revisions for three PJIs and one acetabular component aseptic loosening. The RF cohort underwent four revisions for one acetabular component aseptic loosening, one dislocation, one PPFF, and one PJI. Rates of all-cause revision were comparable(P = 0.583). There was one case within the RF cohort to explant the trochanteric plate with no revision of arthroplasty components. CONCLUSIONS:The present analysis suggests the order in which intraoperative femoral stem implantation and fracture reduction occurs does not affect short-term clinical and radiographic outcomes. This intraoperative decision should be based upon patient anatomy, fracture patterns, and surgeon discretion.