Citations

ABSTRACT Objective To (1) validate GAD65‐ELISA detection and quantification for type 1 diabetes mellitus and autoimmune neurological diagnoses, (2) correlate ELISA results (reference range < 5 IU/mL) with established radioimmunoprecipitation assay (RIA; ≤ 0.02 nmol/L), and (3) define ELISA clinical utility and pitfalls. Methods Serum performance for diabetes (FDA‐cleared, undiluted) was verified, and neurological laboratory‐developed serum and CSF dilution protocols were validated to extend the reportable range beyond > 250 IU/mL. ELISA and RIA values were correlated, including established neurological RIA cut‐offs (serum ≥ 20 nmol/L; CSF any positive). Results ELISA met analytical criteria (precision, accuracy, sensitivity, specificity, reference range) in serum and CSF and was clinically equivalent to RIA for autoimmune diabetes. Neurological ELISA cut‐offs were established at 10,000 IU/mL (serum) and 100 IU/mL (CSF). Precision was better below 10,000 IU/mL (CVs < 20%) than above (CVs 30.8% serum; 26.5% CSF). ELISA–RIA correlation and agreement was stronger below the neurological cut‐off (R 2 = 0.89) than above (R 2 = 0.36). Positive agreement for RIA‐defined neurological disease was 100% in serum and CSF; all serums were > 10,000 IU/mL. Clinical specificity was 97.5% in serum and 100% in CSF, exceeding reported RIA specificity. Screen results > 250 IU/mL spanned a wide range of dilution values; many were below the neurological cut‐off. Most patients with paired serum/CSF positivity showed elevated GAD65 IgG indices. Interpretation GAD65 ELISA and RIA have equivalent sensitivity for autoimmune diabetes and neurological testing, with higher specificity for ELISA. A serum cut‐off of 10,000 IU/mL is informative but requires clinical context, and dilution of screen > 250 IU/mL samples is essential for neurological interpretation.

Objective: This study aimed to examine whether parent–child interaction therapy (PCIT), compared with other therapy modalities, was associated with differences in substance use and psychiatric outcomes in a cohort of children with attention-deficit/hyperactivity disorder (ADHD). Methods: This retrospective cohort study was conducted using medical record data from the Rochester Epidemiology Project (REP). The sample included 643 children aged ≤7 years who were diagnosed with ADHD and received either stimulant or nonstimulant medication, along with psychosocial therapy. Participants were categorized into two groups: those who documented exposure to PCIT versus other therapy modalities such as behavioral management, play therapy, cognitive behavioral therapy, parent management training, occupational therapy, speech therapy, parenting class, applied behavior analysis, and social skills training. Conditional logistic regression models were used to examine differences in baseline characteristics and outcomes between the two treatment groups. Results: Individuals in the PCIT group were more likely to have private insurance (66% vs. 57%; p = 0.016) and to fall into higher socioeconomic status quartiles ( p = 0.024) at baseline. PCIT recipients also had a higher prevalence of emotional and behavioral disturbances at baseline (40% vs. 25%; p < 0.001). The median age of the participants at follow-up was 19.6 years, indicating a median follow-up period of approximately 13 years from the initiation of treatment. At follow-up, the PCIT group demonstrated higher rates of problematic alcohol (24% vs. 17%; HR = 1.50, 95% CI: [1.02, 2.20]; p = 0.038) and cannabis use (25% vs. 18%; HR = 1.48, 95% CI: [1.03, 2.15]; p = 0.037). However, after controlling for covariates in the adjusted model, no statistically significant differences emerged between the groups across any substance use outcome. No significant differences were observed in other psychiatric diagnoses or mental health service utilization. Conclusions: Findings indicate that individuals who documented exposure to PCIT demonstrated elevated rates of alcohol and cannabis use in young adulthood, but had no other differences in psychiatric outcomes. While this aligns with prior literature reporting increased substance use risk in ADHD populations, our study cannot confirm this association relative to non-ADHD controls because such a comparison was not included. These associations likely reflect underlying differences in clinical severity and clinical comorbidities at baseline, rather than a direct effect of PCIT. Further investigation is warranted to determine the treatment effects based on baseline risk factors.

High insertion torque can cause conventional bioactive implant coatings to delaminate, generating debris and compromising osseointegration. We developed and evaluated an injectable, self-assembling peptide nanofiber interface designed to be applied in the osteotomy site to enhance biomechanical stability and accelerate bone formation. A multifunctional, injectable gel was formed from self-assembling peptide amphiphiles designed to be osteoinductive, adhesive, and antimicrobial. In a rabbit model, custom titanium implants were placed with either the nanofiber interface or a standard sand-blasted, large-grit, acid-etched (SLA) surface. Osseointegration was evaluated at 3 and 5 wk using micro–computed tomography (micro-CT) for bone-to-implant contact (BIC) and bone volume/total volume (BV/TV), as well as biomechanical reverse torque testing. At 5 wk, implants with the nanofiber interface demonstrated significantly superior osseointegration. BIC reached 58.7% compared to 50.5% for SLA-treated implants ( P < 0.001). BV/TV was also significantly higher at 51.8% versus 42.6% for the SLA group ( P < 0.001). Crucially, biomechanical stability was markedly improved, with the nanofiber group withstanding a reverse torque of 53.2 N·cm, significantly higher than the 41.8 N·cm for the SLA group ( P < 0.01). This injectable nanofiber interface successfully overcomes the limitations of traditional coatings by enhancing bone–implant integration and providing superior biomechanical stability. Uniquely, it is designed to prevent or repair drilling-induced microdamage, occupy peri-implant microcracks with a structural nanoscaffold, and act as a flowable, conformal osteotomy liner when applied prior to implant insertion. This practical approach represents a promising strategy to improve long-term clinical outcomes, particularly in patients with compromised bone quality or a higher risk of implant failure.

Introduction: Upper limb spasticity can result from a variety of insults to the central nervous system. Disruption of the closely regulated spinal reflex arc, owing to loss of brain inhibition, results in an imbalance between antagonist and agonist muscle groups, leading to a loss of fluid coordination of motion across joints. Management strategies: A detailed, individualized assessment of each patient is mandatory in a multidisciplinary setting. Although there are objective parameters which guide treatment, variation and customization of strategies are needed for each patient, including defining a functional vs. a non-functional hand, and whether mobility or stability is the primary goal for surgery. Challenging areas in spasticity management: Surgical options include bony, tendon and nerve procedures. These aim to reduce tone, release contractures or reanimate paralysed muscles. This article examines four challenging areas in decision making for choosing these options: lengthening vs. hyperselective neurectomy for tone management, stability vs. mobility in wrist spasticity, grasp and release recovery through finger flexion and extension, and dystonia. Evidence-based treatments are discussed where available, along with key unresolved issues and future research directions. Conclusion: Restoring balance in the spastic upper limb, especially when voluntary control is lost, remains one of the most complex challenges in hand surgery. A thorough understanding of biomechanical principles and neurological pathways is necessary for the hand surgeon. Furthermore, working within a multidisciplinary team is essential to utilize a comprehensive array of assessment tools, ensuring accurate diagnosis and individualized patient care.

ABSTRACT Electrocardiography (ECG) is a critical diagnostic tool for identifying cardiac conditions. While standard lead positions are widely used to ensure diagnostic accuracy, alternative lead placements have been developed to address specific clinical scenarios. These alternative configurations can overcome physical or technical challenges, enhance rhythm assessment, improve signal quality, and provide greater specificity for certain conditions, ultimately enabling more personalized diagnostic strategies. This paper examines the clinical significance of alternative ECG lead positions, highlighting their advantages, limitations, and potential applications in various clinical settings.

ABSTRACT Background Minimal‐invasive surgery (MIS) was proven beneficial in Crohn's Disease (CD). Intracorporeal anastomosis (ICA) represents a further improvement as it is associated with decreased complications and shorter hospitalization. Extracorporeal anastomosis (ECA) is preferred to ICA as it allows haptic feedback of the bowel and mesentery, which is historically required for bowel resection in CD to minimize recurrences. We compared ICA and ECA in terms of recurrences and complications. Methods All patients between 2016 and 2022 with Crohn's disease who underwent a MIS ileocecectomy were identified and divided into ICA and ECA groups. Exclusion criteria were open surgery, end ileostomies, follow‐up < 1 month, and ileocecectomy not due to CD. Results 107 patients were included in the ICA group (44.9% male, mean age of 40.2 [±16.6] years), while 270 patients were in the ECA group (46.7% male, mean age of 41.9 [±17.3] years). The rate of endoscopic recurrences with a Rutgeerts score > 2, clinical recurrence, and surgical recurrence were not statistically different between the two cohorts. On the multivariable analysis for endoscopic and clinical recurrences, the ICA/ECA approach was not significant. The ECA group revealed a higher overall complication rate (30.4% versus 15.9%, p = 0.004). The median length of stay was significantly reduced in the ICA group ( p < 0.001). Conclusion ICA seems to be safe in ileocecectomies for CD. The complication rate and length of stay were reduced while not affecting the endoscopic, clinical, and surgical recurrence rates. MIS technology provides enhanced visualization and haptic feedback, which could be used as surrogates for the tactile evaluation intra‐operatively.

OBJECTIVE The aim of this study was to elucidate the long-term morbidity associated with untreated cerebral cavernous malformation (CCM). METHODS From a prospectively maintained database of patients with CCM, we assessed functional outcome as measured using the modified Rankin Scale (mRS) score at baseline and the last untreated follow-up evaluation. Disability was defined as an mRS score ≥ 3. Kaplan-Meier curves were used to assess the time to disability, and Cox proportional hazards models were used to determine risk factors for disability. Furthermore, the predictive performance of a previously published nomogram for morbidity in CCM was assessed. RESULTS The cohort consisted of 332 patients (58.4% female, mean age at diagnosis 44.5 years), with 19.8% having the familial form and 28.0% having a CCM located in the brainstem. Of 48 patients who presented with symptomatic hemorrhage (SH) and who did not undergo surgery or have a prospective SH, 27.1% had an mRS score ≥ 3 at diagnosis. By 1 year and 5 years, this improved to 6.2% and 4.7%, respectively. Over a mean follow-up duration of 6.6 years, 103 of 332 patients (31.0%) had one prospective SH and 48 (14.5%) had multiple prospective SHs. Patients with brainstem-located CCM had an 18.8% 5-year and 35.4% 10-year risk of disability compared with 4.1% and 7.5%, respectively, in patients with a nonbrainstem location (p < 0.0001). Multivariate analysis showed that a brainstem location, history of self-reported psychiatric disorder, and ≥ 2 SHs were predictive of disability at the last follow-up. External validation of a published nomogram demonstrated high specificity but limited sensitivity for predicting disability, with an area under the receiver operating curve of 0.687 for mRS scores ≥ 2 and 0.783 for mRS scores ≥ 3. CONCLUSIONS Most patients improved after a first hemorrhage, with the most improvement occurring in year 1. Disability increased with each SH. Disability was associated with 2 or more SHs, a brainstem location, and a self-reported psychiatric diagnosis. Ten-year disability risk with a nonbrainstem CCM location was < 8%.

OBJECTIVE Magnetic resonance–guided focused ultrasound (MRgFUS) thalamotomy has become a popular tool in the neurosurgical armamentarium for managing tremor in patients with essential tremor (ET) and Parkinson’s disease (PD). METHODS Given the recent exponential growth in the use of this technology, the American Society for Stereotactic and Functional Neurosurgery, which acts as the joint section representing the field of stereotactic and functional neurosurgery on behalf of the Congress of Neurological Surgeons and the American Association of Neurological Surgeons, provides an update on treatment indications and the efficacy and safety of MRgFUS for the treatment of tremor. RESULTS In ET, the efficacy of MRgFUS thalamotomy is supported by several open-label and 1 prospective, double-blind, sham-controlled randomized clinical trial (RCT) that showed a 47% improvement in hand tremor in the short term. Follow-up studies demonstrated that the benefits of MRgFUS for ET are sustained in the long term. Studies investigating the effects of bilateral staged MRgFUS thalamotomy in patients with ET have shown that tremor improvement on the second side was as significant as that observed after the first procedure. The efficacy of MRgFUS thalamotomy for PD tremor is supported by a systematic meta-analysis that consisted predominantly of smaller, nonrandomized studies; 1 RCT; and 1 prospective cohort study. Despite a significant short-term improvement in PD tremor, the long-term effects of this therapy remain unknown. Common early adverse effects of MRgFUS thalamotomy include gait disturbance and paresthesias. These, however, tend to subside over time. Other reported side effects are dysarthria, ataxia, taste disturbance, motor deficits, and speech difficulty. CONCLUSIONS MRgFUS thalamotomy is a safe, effective, and durable intervention for refractory ET in appropriately selected patients. The procedure appears to be safe and effective for PD tremor, although the long-term durability of the technique remains a concern. Early experience with bilateral staged lesions for ET suggests the procedure to be safe and effective.