Citations

Video Analyses of Sudden Unexplained Deaths in Toddlers Gould L, Reid CA, Rodriguez AJ, Devinsky O; for SUDC Video Working Group. Neurology . 2024;102(3):e208038. doi: 10.1212/WNL.0000000000208038 . PMID: 38175965 Background and objectives: More than 2,900 US children aged younger than 4 years die from unknown causes each year, accounting for more than 219,000 life years lost annually. They are mostly sleep-related and unwitnessed with unremarkable autopsies, limiting our understanding of death mechanisms. We sought to understand potential mechanisms of death by evaluating videos of sudden deaths in toddlers. Methods: In our registry of 301 sudden unexplained child deaths, a series of 7 consecutively enrolled cases with home video recordings of the child’s last sleep period were independently assessed by 8 physicians for video quality, movement, and sound. Results: Four boys and 3 girls (13-27 months at death) with terminal videos shared similar demographic features to the 293 other registry cases without video recordings. Five video recordings were continuous and 2 were triggered by sound or motion; 2 lacked audio. All continuous recordings included a terminal convulsive event lasting 8-50 seconds; 4 children survived for >2.5 minutes postconvulsion. Among discontinuous videos, time lapses limited review; 1 suggested a convulsive event. Six were prone with face down, and 1 had autopsy evidence of airway obstruction. Primary cardiac arrhythmias were not supported; all 7 children had normal cardiac pathology and whole-exome sequencing identified no known cardiac disease variants. Discussion: Audio-visual recordings in 7 toddlers with unexplained sudden deaths strongly implicate that deaths were related to convulsive seizures, suggesting that many unexplained sleep-related deaths may result from seizures. Exome Analysis Focusing on Epilepsy-Related Genes in Children and Adults With Sudden Unexplained Death Buerki SE, Haas C, Neubauer J. Seizure . 2023;113:66-75. doi: 10.1016/j.seizure.2023.11.002 . PMID: 37995443 Purpose: Genetic studies in sudden infant death syndrome (SIDS) and sudden unexplained death (SUD) cohorts have indicated that cardiovascular diseases might have contributed to sudden unexpected death in 20% to 35% of autopsy-negative cases. Sudden unexpected death can also occur in people with epilepsy, termed as sudden unexpected death in epilepsy (SUDEP). The pathophysiological mechanisms of SUDEP are not well understood, but are likely multifactorial, including seizure-induced hypoventilation and arrhythmias as well as genetic risk factors. The sudden death of some of the SIDS/SUD victims might also be explained by genetic epilepsy, therefore this study aimed to expand the post-mortem genetic analysis of SIDS/SUD cases to epilepsy-related genes. Methods: Existing whole-exome sequencing data from our 155 SIDS and 45 SUD cases were analyzed, with a focus on 365 epilepsy-related genes. Nine of the SUD victims had a known medical history of epilepsy, seizures or other underlying neurological conditions and were therefore classified as SUDEP cases. Results: In our SIDS and SUD cohorts, we found epilepsy-related pathogenic/likely pathogenic variants in the genes OPA1, RAI1, SCN3A, SCN5A and TSC2. Conclusion: Post-mortem analysis of epilepsy-related genes identified potentially disease-causing variants that might have contributed to the sudden death events in our SIDS/SUD cases. However, the interpretation of identified variants remains challenging and often changes over time as more data is gathered. Overall, this study contributes insight in potentially pathophysiological epilepsy-related mechanisms in SIDS, SUD and SUDEP victims and underlines the importance of sensible counselling on the risk and preventive measures in genetic epilepsy.

Background: OpenAI’s ChatGPT (San Francisco, CA, USA) and Google’s Gemini (Mountain View, CA, USA) are two large language models that show promise in improving and expediting medical decision making in hand surgery. Evaluating the applications of these models within the field of hand surgery is warranted. This study aims to evaluate ChatGPT-4 and Gemini in classifying hand injuries and recommending treatment. Methods: Gemini and ChatGPT were given 68 fictionalized clinical vignettes of hand injuries twice. The models were asked to use a specific classification system and recommend surgical or nonsurgical treatment. Classifications were scored based on correctness. Results were analyzed using descriptive statistics, a paired two-tailed t-test, and sensitivity testing. Results: Gemini, correctly classifying 70.6% hand injuries, demonstrated superior classification ability over ChatGPT (mean score 1.46 vs. 0.87, p-value < 0.001). For management, ChatGPT demonstrated higher sensitivity in recommending surgical intervention compared to Gemini (98.0% vs. 88.8%), but lower specificity (68.4% vs. 94.7%). When compared to ChatGPT, Gemini demonstrated greater response replicability. Conclusions: Large language models like ChatGPT and Gemini show promise in assisting medical decision making, particularly in hand surgery, with Gemini generally outperforming ChatGPT. These findings emphasize the importance of considering the strengths and limitations of different models when integrating them into clinical practice.

Abstract Background Despite advances in medical therapy, many children and adults with ileal Crohn’s disease (CD) progress to fibrostenosis requiring surgery. We aimed to identify MRI and circulating biomarkers associated with the need for surgical management. Methods This prospective, multicenter study included pediatric and adult CD cases undergoing ileal resection and CD controls receiving medical therapy. Noncontrast research MRI examinations measured bowel wall 3-dimensional magnetization transfer ratio normalized to skeletal muscle (normalized 3D MTR), modified Look-Locker inversion recovery (MOLLI) T1 relaxation, intravoxel incoherent motion (IVIM) diffusion-weighted imaging metrics, and the simplified magnetic resonance index of activity (sMaRIA). Circulating biomarkers were measured on the same day as the research MRI and included CD64, extracellular matrix protein 1 (ECM1), and granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies (Ab). Associations between MRI and circulating biomarkers and need for ileal resection were tested using univariate and multivariable LASSO regression. Results Our study sample included 50 patients with CD undergoing ileal resection and 83 patients with CD receiving medical therapy; mean participant age was 23.9 ± 13.1 years. Disease duration and treatment exposures did not vary between the groups. Univariate biomarker associations with ileal resection included log GM-CSF Ab (odds ratio [OR], 2.87; P = .0009), normalized 3D MTR (OR, 1.05; P = .002), log MOLLI T1 (OR, 0.01; P = .02), log IVIM perfusion fraction (f; OR, 0.38; P = .04), and IVIM apparent diffusion coefficient (ADC; OR, 0.3; P = .001). The multivariable model for surgery based upon corrected Akaike information criterion included age (OR, 1.03; P = .29), BMI (OR, 0.91; P = .09), log GM-CSF Ab (OR, 3.37; P = .01), normalized 3D MTR (OR, 1.07; P = .007), sMaRIA (OR, 1.14; P = .61), luminal narrowing (OR, 10.19; P = .003), log C-reactive protein (normalized; OR, 2.75; P = .10), and hematocrit (OR, 0.90; P = .13). Conclusion After accounting for clinical and MRI measures of severity, normalized 3D MTR and GM-CSF Ab are associated with the need for surgery in ileal CD.

Abstract Objectives To perform a systematic review of published academic literature related to lost, mislabeled, and mishandled surgical and clinical pathology specimens during the preanalytical stage. Methods The authors used Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines to search PubMed, MEDLINE, Web of Science, and Scopus for relevant articles published from January 1, 1990, to May 1, 2023. Results The authors screened 1313 articles and identified 44 peer-reviewed, English-language articles published between 1990 and 2021 for inclusion in the final systematic review. Most articles (n = 36) reported results from US-based facilities. Articles primarily focused on general clinical and general surgical pathology. Analysis of the articles revealed that articles reported a range of methodological approaches, including incident reports, implementation analyses, case studies, and commentary recommendations. Most articles focused on mislabeling errors (61.3%) and missing or lost specimens (18.2%), while several articles combined specimen errors (20.5%). Several implementation studies (22.7%) reported using multiple interventions to mitigate errors. Implementation efforts reported between 70% and 100% reduction in pathology errors. Conclusions The review highlights the limited research on the topic, with an average of 2 articles per year discussing lost, mislabeled, or mishandled specimens. Intervention studies addressed The Joint Commission’s patient safety goals for laboratory practice. More research is needed about error incidents and reporting in non-Western countries to gain a more global perspective on the topic.

Purpose: To investigate the molecular characteristics of and potential for precision medicine in KRAS wildtype pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We investigated 27 patients with KRASWT PDAC at our institution. Clinical data were obtained via chart review. Tumor specimens for each subject were interrogated for somatic single nucleotide variants, insertion and deletions, and copy number variants by DNA sequencing. Gene fusions were detected from RNA-seq. A patient-derived organoid (PDO) was developed from a patient with a MET translocation and expanded ex vivo to predict therapeutic sensitivity prior to enrollment in a phase 2 clinical trial. Results: Transcriptomic analysis showed our cohort may be stratified by the relative gene expression of the KRAS signaling cascade. The PDO derived from our patient harboring a TFG-MET rearrangement was found to have in vitro sensitivity to the multi-tyrosine kinase inhibitor crizotinib. The patient was enrolled in the phase 2 SPARTA clinical trial and received monotherapy with vebrelitinib, a c-MET inhibitor, and achieved a partial and durable response. Conclusions: KRASWT PDAC is molecularly distinct from KRASMUT and enriched with potentially actionable genetic variants. In our study, transcriptomic profiling revealed that the KRAS signaling cascade may play a key role in KRASWT PDAC. Our report of a KRASWT PDAC patient with TFG-MET rearrangement who responded to a cMET inhibitor further supports the pursuit of precision oncology in this sub-population. Identification of targetable mutations, perhaps through approaches like RNA-seq, can help enable precision-driven approaches to select optimal treatment based on tumor characteristics.

The adductor magnus ischiocondylar origin (AM‐IO) tendon has often been described as a third proximal hamstring tendon due to its common origin on the ischial tuberosity as well as similar function. Prior studies have described the magnetic resonance imaging characteristics of the AM‐IO; however, its appearance on ultrasound has not been well‐detailed. The purpose of our study is to describe the sonographic appearance of the AM‐IO and provide a structured scanning protocol for complete evaluation of the tendon.

OBJECTIVE The role of interbodies in lumbar arthrodesis has been insufficiently supported by evidence, impacting clinical decision-making and occasionally insurance coverage. This study aimed to compare clinical and radiological outcomes between lumbar arthrodesis with a synthetic interbody spacer (cage) versus structural bone graft alone (autograft or allograft) in patients with degenerative spine disease. METHODS A systematic review of the literature was performed to identify studies directly comparing outcomes of lumbar interbody arthrodesis with and without interbody cage use. The outcomes of individual studies were synthesized in meta-analyses using random-effects models. RESULTS Twenty studies with 1508 patients (769 with an interbody cage and 739 without an interbody cage) were included. Interbody cage placement was associated with a significantly greater increase in disc height after surgery (4.0 mm vs 3.4 mm, p < 0.01). There was a significantly greater reduction of back pain (visual analog scale [VAS] score) in cases in which an interbody cage was used (5.4 vs 4.7, p = 0.03). Fusion rates were 5.5% higher in the cage group (96.3% vs 90.8%) and reached statistical significance (p = 0.03). No statistically significant differences were identified between the two groups regarding all-cause reoperation rates, complication rates, or improvement in Oswestry Disability Index score or leg pain (VAS score). CONCLUSIONS These results suggest that implantation of an interbody cage is associated with higher rates of fusion, more effective maintenance of disc height, and greater improvement of back pain. This study underlines the clinical value of interbody cages in lumbar arthrodesis for patients with degenerative spine disease.