Citations

ABSTRACTBackground and AimsChronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is difficult to distinguish from mimicking disorders, with misdiagnosis resulting in IVIG overutilization. We evaluate a clinical‐electrophysiological model to facilitate CIDP versus mimic neuropathy prediction.MethodsUsing the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) 2021 CIDP guidelines we derived 26 clinical and 144 nerve conduction variables. The model was generated and validated utilizing total CIDP (n = 129) and mimics (n = 309); including (1) IgG4‐nodopathies; (2) POEMS (polyneuropathy–organomegaly–endocrinopathy–monoclonal protein‐skin changes); (3) anti‐myelin‐associated‐glycoprotein; (4) paraneoplastic; (5) Waldenström B‐cell lymphoma; (6) diabetic neuropathies; (7) amyloidosis; (8) Charcot–Marie–Tooth; (9) motor neuropathies/neuronopathies; and (10) idiopathic‐inflammatory‐myopathies.ResultsWe analyzed 9282 clinical and 51 408 electrophysiological data points. Univariate analysis identified 11 of 26 clinical variables with significant odds ratios. A multivariate regression model using four clinical and two electrophysiologic variables achieved 93% area‐under‐curve (95% CI 91–95): progression over 8 weeks (OR 40.66, 95% CI 5.31–311.36), absent autonomic involvement (OR 17.82, 95% CI 2.93–108.24), absent muscle atrophy (OR 16.65, 95% CI 3.27–84.73), proximal weakness (OR 3.63, 95% CI 1.58–8.33), ulnar motor conduction velocity slowing < 35.7 m/s (OR 5.21, 95% CI 2.13–12.76), and ulnar motor conduction block (OR 13.37, 95% CI 2.47–72.40). A web‐based probability calculator (https://news.mayocliniclabs.com/cidp‐calculator/) was developed, with 100% sensitivity and 68% specificity at a 92% probability threshold. Specificity improved to 93% when considering “red flags,” electrophysiologic criteria, and laboratory testing.InterpretationA probability calculator using clinical electrophysiological variables assists CIDP differentiation from mimics, with scores below 92% unlikely to have CIDP. The highest specificity is achieved by considering clinical “red flags,” electrophysiologic demyelination, and laboratory testing.

Abstract The skip phenomenon (SP) is a pattern where blood cultures are intermittently positive before final clearance. We report that one-third of patients with Staphylococcus lugdunensis infective endocarditis experienced the SP. Patients with the SP experienced both a longer duration of bacteremia and hospital stay, with a higher 1-year mortality rate.

Background: Chordoma is a rare bone cancer with limited treatment options. Clinical trials are crucial for developing effective therapies, but their success depends on including diverse patient populations. The objective of this study was to systematically evaluate the reporting of racial, ethnic, and socioeconomic diversity in United States clinical trials exploring treatment for chordoma. Methods: A literature search was conducted through PubMed/Medline, Cochrane, Epistemonikos, and ClinicalTrials.gov databases for published US chordoma trials up until 19 August 2024. The data collected included trial characteristics and racial and ethnic data, as well as socioeconomic indicators when available. Methodological Index for Non-Randomized Studies (MINORS) and Revised Cochrane Risk-of-Bias Tool for Randomized Trials (RoB2) analyses were adopted to assess the methodological quality. The N-1 Chi-squared (χ2) test was implemented to compare the reported racial and ethnic data with the most recent US Census Bureau data. Results: Five trials involving 111 patients (median age: 63 years; 34% female) were included. Four studies (80%) were single-arm non-randomized studies with one study (25%) having a high methodological quality and three (75%) having a moderate quality based on the MINORS analysis. Most patients (91%, n = 82) were White/Caucasian, representing a proportion which was significantly higher than the reported 75% in the US population (p = 0.0005). Black/African American patients (2%, n = 2) were significantly underrepresented compared to the 14% in the US population (p = 0.0015). Regarding ethnicity, Hispanic/Latino patients (7%, n = 6) were significantly underrepresented compared to the 20% in the US population (p = 0.0021). No measures of socioeconomic status were reported. Conclusions: This systematic review highlighted the need for improved racial and ethnic diversity in chordoma trials and the better reporting of socioeconomic data. The underrepresentation of minority groups may obscure potential disparities in disease incidence, treatment access, and clinical outcomes.

Study Design Narrative Review. Objective The management of spinal tumors requires a multi-disciplinary approach including surgery, radiation, and systemic therapy. Surgical approaches typically require posterior segmental instrumentation to maintain long-term spinal stability. Carbon fiber reinforced pedicle screws (CFRP) are increasingly used in the oncologic setting due to reductions in both imaging artifacts and radiotherapy perturbations compared to titanium implants. We performed a review of the literature and highlight advantages and future areas of study for CFRP. Methods We performed a systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and identified 10 articles including 573 patients. Across all studies we reviewed patient demographics, tumor types treated, hardware-related features, complication rates, recurrence, survival, and follow-up. Results Across 10 studies, a total of 1371 screws placed. Surgical and non-surgical complications were reported in 18.3% of patients. Disease progression at the surgical site was detected in 7.3% of patients. There was no significant difference in clinical or hardware complications between CFRP or titanium implants. The most frequent complication attributable to implanted CFRP hardware included screw breakage in 2.4% and loosening in 1.7% of patients, respectively. Conclusion CFRP provide a unique tool in the setting of spinal oncology. With a safety profile comparable to titanium, we review the documented advantages of CFRP posterior implants compared to titanium, while also addressing their current limitations. Additionally, we highlight several areas of future research to identify the optimal patients who will achieve the greatest benefit of CFRP.

BACKGROUND Adamantinomatous craniopharyngiomas (ACPs) are slow-growing, cystic, highly morbid central nervous system tumors located adjacent to vital structures including the pituitary, hypothalamus, and optic chiasm. Tumor recurrence is common. Treatment relies on resection with or without adjuvant radiation and is highly individualized. Targeted chemotherapies have not been routinely used in the treatment of ACPs. OBSERVATIONS The authors present the case of an adult patient with recurrent ACP that was clinically and radiologically stabilized with a combination of bevacizumab and tocilizumab every 3 weeks. LESSONS The combination of tocilizumab and bevacizumab could be an effective therapy for shrinkage of the cystic and solid components of ACP, sparing patients from further neurological damage from the tumor, additional surgery, or radiation. The patient’s positive response to tocilizumab and bevacizumab supports the growing literature that interleukin-6 and vascular endothelial growth factor are important for ACP pathogenesis. The patient’s response supports prior research, suggesting that systemic chemotherapy can be effectively delivered to this rare brain tumor. https://thejns.org/doi/10.3171/CASE24410

Objective The aim of this study was to determine whether pollutants such as fire smoke–related particulate matter <2.5 μm (PM 2.5 ) are associated with incident rheumatoid arthritis (RA) and RA‐associated interstitial lung disease (RA‐ILD). Methods This patient–control study used Veterans Affairs (VA) data from October 1, 2009, to December 31, 2018. We identified patients with incident RA and RA‐ILD using validated algorithms, matching each patient to ≤10 controls on age, sex, and VA enrollment year. We obtained pollutants including fire smoke PM 2.5 , carbon monoxide, nitrogen oxides (NOx), ozone, overall PM 2.5 , PM 10 , and sulfur dioxide (SO 2 ) at least one year before the index date. We fit conditional logistic regression models to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for incident RA and RA‐ILD, adjusted for confounders. Results We identified 9,701 patients with incident RA (mean age 65 years, 86% male), including 531 patients with RA‐ILD (mean age 69 years, 91% male), and 68,852 matched controls. Fire smoke PM 2.5 was not associated with RA (aOR 1.07, 95% CI 0.92–1.23) but was associated with RA‐ILD (aOR 1.98, 95% CI 1.08–3.62, per 1 μg/m 3 ). Increased levels of NOx were associated with RA (aOR 1.16, 95% CI 1.06–1.27, highest vs lowest quartile). The highest quartiles of ozone (aOR 1.19, 95% CI 1.06–1.34) and PM 10 (aOR 1.25, 95% CI 1.10–1.43) were associated with seronegative RA. Carbon monoxide, overall PM 2.5 , and SO 2 were not, or negatively, associated with RA and RA‐ILD. Conclusion Increased fire smoke PM 2.5 was associated with RA‐ILD, whereas NOx, ozone, and PM 10 were associated with RA risk. Thus, air pollution may increase the risk of RA and RA‐ILD. image

Rheumatoid arthritis (RA) is a life‐long autoimmune disease caused by the confluence of genetic and environmental variables that lead to loss of self‐tolerance and persistent joint inflammation. RA occurs at the highest incidence in individuals >65 years old, implicating the aging process in disease susceptibility. Transformative approaches in molecular immunology and in functional genomics have paved the way for pathway paradigms underlying the replacement of immune homeostasis with autodestructive immunity in affected patients, including the process of immune aging. Patients with RA have a signature of premature immune aging, best understood for CD4 + T cells, which function as pathogenic effectors in this HLA class II–associated disease. Premature immune aging is present in healthy HLA–DRB1*04 + individuals, placing accelerated immune aging before joint inflammation. Aging‐related molecular abnormalities directly implicated in turning RA CD4 + T cells into proinflammatory effector cells are linked to malfunction of subcellular organelles, such as mitochondria, lysosomes, lipid droplets, and the endoplasmic reticulum. Resulting changes in T cell behavior include cellular hypermobility, tissue invasiveness, unopposed mammalian target of rapamycin complex (mTORC)1 activation, excessive release of tumor necrosis factor, lysosomal failure, clonal expansion, and immunogenic cell death. Aged and metabolically reprogrammed T cells in patients with RA are accompanied by age‐associated B cells, which specialize in autoantibody production. Clonal hematopoiesis drives myeloid cell aging by producing aged monocytes and hypermetabolic macrophages, which sustain the process of inflammaging. Here, we synthesize insights into the relationship of RA risk and immune aging and discuss mechanisms through which immune aging can cause autoimmunity. image

Abstract Context Literature suggests patients with thyroid cancer have unmet informational needs in many aspects of care. Patients often turn to online resources for their health-related information, and generative artificial intelligence programs such as ChatGPT are an emerging and attractive resource for patients. Objective To assess the quality of ChatGPT's responses to thyroid cancer-related questions. Methods Four endocrinologists and 4 endocrine surgeons, all with expertise in thyroid cancer, evaluated the responses to 20 thyroid cancer-related questions. Responses were scored on a 7-point Likert scale in areas of accuracy, completeness, and overall satisfaction. Comments from the evaluators were aggregated and a qualitative analysis was performed. Results Overall, only 57%, 56%, and 52% of the responses “agreed” or “strongly agreed” that ChatGPT's answers were accurate, complete, and satisfactory, respectively. One hundred ninety-eight free-text comments were included in the qualitative analysis. The majority of comments were critical in nature. Several themes emerged, which included overemphasis of diet and iodine intake and its role in thyroid cancer, and incomplete or inaccurate information on risks of both thyroid surgery and radioactive iodine therapy. Conclusion Our study suggests that ChatGPT is not accurate or reliable enough at this time for unsupervised use as a patient information tool for thyroid cancer.

Abstract There are ~100 genes or copy number variants (CNVs) used in genetic testing for Autism Spectrum Disorder (ASD, or autism). These genes are protein-coding, and the associated phenotypes often extend beyond socio-behavioral traits seen in autism including cognitive/medical complexities, epilepsy, and ADHD. Here, we characterize 27 males with ASD through whole genome sequencing (WGS), delineating X-chromosome microdeletions that implicate the long non-coding RNA (lncRNA) PTCHD1-AS as an ASD-susceptibility gene (OR=2.56, p=0.01). Two Ptchd1-as knockout (KO) murine models, created by removing the evolutionarily conserved exon-3, show ASD-like features in males, increasing repetitive behaviors and impairing typical social behavior and communication without overt cognitive comorbidities or ADHD-like behaviors. Hippocampus-dependent synaptic function, complex learning, and locomotor activity are unaffected in KO mice. Native nuclear-enriched mouse Ptchd1-as showed sustained expression from post-natal day-7 onward in the dorsal striatum, a predominantly GABAergic brain region implicated in ASD. Multi-omics revealed transcriptomic alterations in striatal oligodendrocyte, astrocyte and neurons impacting myelination and plasticity pathways. Disrupting Ptchd1-as led to reductions in conventional Protein Kinase-C, altered Src and GSK3α/β phosphorylation, and an enhancement of synaptic plasticity (long-term potentiation and long-term depression). Together, these findings implicate striatal molecular and circuit level dysregulation via Ptchd1-as in ASD etiology.