Attenuating midline thalamus bursting to mitigate absence epilepsy.

Advancing the mechanistic understanding of absence epilepsy is crucial for developing new therapeutics, especially for patients unresponsive to current treatments. Utilizing a recently developed mouse model of absence epilepsy carrying the BK gain-of-function channelopathy D434G, here we report that attenuating the burst firing of midline thalamus (MLT) neurons effectively prevents absence seizures. We found that enhanced BK channel activity in the BK-D434G MLT neurons promotes synchronized bursting during the ictal phase of absence seizures. Modulating MLT neurons through pharmacological reagents, optogenetic stimulation, or deep brain stimulation effectively attenuates burst firing, leading to reduced absence seizure frequency and increased vigilance. Additionally, enhancing vigilance by amphetamine, a stimulant medication, or physical perturbation also effectively suppresses MLT bursting and prevents absence seizures. These findings suggest that the MLT is a promising target for clinical interventions. Our diverse approaches offer valuable insights for developing next generation therapeutics to treat absence epilepsy.

Descriptive Analysis of Amputation-Free Survival After First Time Infra-Inguinal Bypass Occlusion.

INTRODUCTION: Occlusion after infra-inguinal bypass surgery for peripheral artery disease is a major complication with potentially devastating consequences. In this descriptive analysis, we sought to describe the natural history and explore factors associated with long-term major amputation-free survival following occlusion of a first-time infra-inguinal bypass. METHODS: Using a prospective database from a tertiary care vascular center, we conducted a retrospective cohort study of all patients with peripheral artery disease who underwent a first-time infra-inguinal bypass and subsequently suffered a graft occlusion (1997-2021). The primary outcome was longitudinal rate of major amputation-free survival after bypass occlusion. Cox proportional hazard models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) to explore predictors of outcomes. RESULTS: Of the 1318 first-time infra-inguinal bypass surgeries performed over the study period, 255 bypasses occluded and were included in our analysis. Mean age was 66.7 (12.6) years, 40.4% were female, and indication for index bypass was chronic limb threatening ischemia (CLTI) in 89.8% (n = 229). 48.2% (n = 123) of index bypass conduits used great saphenous vein, 29.0% (n = 74) prosthetic graft, and 22.8% (n = 58) an alternative conduit. Median (interquartile range) time to bypass occlusion was 6.8 (2.3-19.0) months, and patients were followed for median of 4.3 (1.7-8.1) years after bypass occlusion. Following occlusion, 38.04% underwent no revascularization, 32.94% graft salvage procedure, 25.1% new bypass, and 3.92% native artery recanalization. Major amputation-free survival following occlusion was 56.9% (50.6%-62.8%) at 1 y, 37.1% (31%-43.3%) at 5 y, and 17.2% (11.9%-23.2%) at 10 y. In multivariable analysis, factors associated with lower amputation-free survival were older age, female sex, advanced cardiorenal comorbidities, CLTI at index procedure, CLTI at time of occlusion, and distal index bypass outflow. Initial treatment after occlusion with both a new surgical bypass (HR 0.44, CI: 0.29-0.67) or a graft salvage procedure (HR 0.56, CI: 0.38-0.82) showed improved amputation-free survival. One-year rate of major amputation or death were 59.8% (50.0%-69.6%) for those who underwent no revascularization, 37.9% (28.7%-49.0%) for graft salvage, and 26.7% (17.6%-39.5%) for new bypass. CONCLUSIONS: Long-term major amputation-free survival is low after occlusion of a first-time infra-inguinal bypass. While several nonmodifiable risk factors were associated with lower amputation-free survival, treatment after graft occlusion with either a new bypass or a graft salvage procedure may improve longitudinal outcomes.

Real-World Vein Mapping Practice Patterns Before Endovascular Treatment of Limb Ischemia.

INTRODUCTION: The Best Endovascular versus Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) trial results suggest that in patients with chronic limb-threatening ischemia (CLTI) and adequate single-segment great saphenous vein (SSGSV) by preoperative duplex ultrasonography, a surgical-first treatment strategy is superior to an endovascular-first strategy. However, the utilization of vein mapping prior to endovascular-first revascularization for CLTI in actual clinical practice is not known. METHODS: Data from a multicenter clinical data warehouse (2008-2019) were linked to Medicare claims data for patients undergoing endovascular-first treatment of infra-inguinal CLTI. Only patients who would have otherwise been eligible for enrollment in BEST-CLI were included. Adequate SSGSV was defined as healthy vein >3.0 mm in diameter from the groin through the knee. Logistic regression was used to estimate associations between preprocedure characteristics and vein mapping. Survival methods were used to estimate the risk of major adverse limb events and death. RESULTS: A total of 142 candidates for either surgical or endovascular treatment underwent endovascular-first management of CLTI. Ultrasound assessment for SSGSV was not performed in 76% of patients prior to endovascular-first revascularization. Of those who underwent preprocedure vein mapping, 44% had adequate SSGSV for bypass. Within one year postprocedure, 12.0% (95% confidence interval 7.4-18.0%) of patients underwent open surgical bypass and 54.7% (95% confidence interval 45.3-62.4%) experienced a major adverse limb event or death. CONCLUSIONS: In a real-world cohort of BEST-CLI-eligible patients undergoing endovascular-first intervention for infra-inguinal CLTI, three-quarters of patients had no preprocedure ultrasound assessment of great saphenous vein conduit. Practice patterns for vein conduit assessment in the real-world warrant reconsideration in the context of BEST-CLI trial results.

Evaluating the Effectiveness of Systemic Heparin During Arteriovenous Fistula Creation by Emulating a Target Trial.

Most of the 800,000 people living with end-stage kidney disease in the United States rely on a functioning vascular access to provide life-sustaining hemodialysis, yet one-third of arteriovenous fistulas experience early failures. Determining the safety and effectiveness of systemic heparin during fistula creation could improve the quality and quantity of life for these vulnerable patients. In this paper, a pragmatic randomized trial was emulated to assess the effect of systemic heparin administration (vs. none) during radiocephalic arteriovenous fistula creation on early bleeding and thrombosis using data from two international multicenter randomized trials performed between 2014 and 2019. Marginal risks were estimated using inverse probability weighted parametric survival analysis and confidence intervals were generated with bootstrapping. A total of 914 patients were enrolled and 61% received systemic heparin; median (IQR) age was 58 (49, 67) years and 45% were on hemodialysis at enrollment. No difference in the risk of bleeding events was observed, with a risk difference (95% CI) at 14 days of -0.1% (-1.6, 1.4). The risk of access thrombosis was lower in the heparin group, with a risk of 3.7% (2.6, 4.8) after heparin and 5.3% (3.4, 7.4) without heparin at 14 days (risk ratio 0.72, 95% CI 0.50, 0.98).

Human brain tissue identification using coherent anti-Stokes Raman scattering spectroscopy and diffuse reflectance spectroscopy for deep brain stimulation surgery.

Significance: We assess the feasibility of using diffuse reflectance spectroscopy (DRS) and coherent anti-Stokes Raman scattering spectroscopy (CARS) as optical tools for human brain tissue identification during deep brain stimulation (DBS) lead insertion, thereby providing a promising avenue for additional real-time neurosurgical guidance. Aim: We developed a system that can acquire CARS and DRS spectra during the DBS surgery procedure to identify the tissue composition along the lead trajectory. Approach: DRS and CARS spectra were acquired using a custom-built optical probe integrated in a commercial DBS lead. The lead was inserted to target three specific regions in each of the brain hemispheres of a human cadaver. Spectra were acquired during the lead insertion at constant position increments. Spectra were analyzed to classify each spectrum as being from white matter (WM) or gray matter (GM). The results were compared with tissue classification performed on histological brain sections. Results: DRS and CARS spectra obtained using the optical probe can identify WM and GM during DBS lead insertion. The tissue composition along the trajectory toward a specific target is unique and can be differentiated by the optical probe. Moreover, the results obtained with principal component analysis suggest that DRS might be able to detect the presence of blood due to the strong optical absorption of hemoglobin. Conclusions: It is possible to use optical measurements from the DBS lead during surgery to identify WM and GM and possibly the presence of blood in human brain tissue. The proposed optical tool could inform the surgeon during the lead placement if the lead has reached the target as planned. Our tool could eventually replace microelectrode recordings, which would streamline the process and reduce surgery time. Further developments are required to fully integrate these tools into standard clinical procedures.

Comparative Effectiveness of Intravascular Ultrasound Versus Angiography in Abdominal and Thoracic Endovascular Aortic Repair: Systematic Review and Meta-Analysis.

The effectiveness of intravascular ultrasound (IVUS) with angiography compared with angiography guidance alone in treating aortic conditions, such as dissections, aneurysms, and blunt traumatic injuries, remains unclear. This systematic review and meta-analysis evaluates the current literature for IVUS use during thoracic endovascular aortic repair (TEVAR) and abdominal endovascular aortic repair (EVAR). A comprehensive search of MEDLINE, EMBASE, and Cochrane CENTRAL databases was conducted in March 2024 adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies comparing outcomes of TEVAR/EVAR with and without IVUS were identified. The outcomes of interest included contrast volume, fluoroscopy and procedural time, perioperative endoleak, and reinterventions and all-cause mortality during follow-up. Data with 95% confidence intervals (CIs) were extracted. Pooled analysis was performed using a random-effect model. Subgroup analysis was performed stratified by the condition being treated. Risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies. A total of 4,219 patients (n = 2,655 IVUS and n = 1,564 non-IVUS) from 9 observational studies were included. The IVUS group exhibited a reduction in contrast agent volume (weighted mean difference -34.65 mL, 95% CI -54.73 to -14.57) and fluoroscopy time (weighted mean difference -6.13 minutes, 95% CI -11.10 to -1.15), with no difference in procedural time. The perioperative type I and III endoleak occurrences were similar (risk ratio 2.36, 95% CI 0.55 to 10.11; risk ratio 0.72, 95% CI 0.09 to 5.77, respectively). Reintervention and mortality during follow-up were comparable (hazard ratio 0.80, 95% CI 0.33 to 1.97; hazard ratio 0.75, 95% CI 0.47 to 1.18, respectively). All the included studies had small risks of bias. In conclusion, this meta-analysis provides evidence that IVUS enables the safe deployment of TEVAR/EVAR with reduced contrast agent and radiation exposure.

Wide en-bloc thymectomy and venous axis reconstruction in Masaoka stage IIIB thymoma: a case report and literature review.

Thymomas are rare tumors originating from thymic tissue and rarely metastasize. They can be diagnosed either incidentally or symptomatically when compressing or invading nearby structure. A 36-year-old man presented with significant high-grade fever, chest pain that worsens upon lying down, and dyspnea. A chest X-Ray and computed tomography followed by biopsy confirmed the diagnosis of thymoma. The management included chemotherapy cycles, followed by surgery. Pericardiectomy was performed with en-bloc thymectomy and partial resection of the infiltrating lung. Venous drainage was restored by 8/16 mm inverted bifurcated brachiocephalic-superior vena cava Dacron bypass. The pericardium was reconstructed by a synthetic Dacron patch, and the right diaphragm metastasis was resected. Neoadjuvant chemotherapy was initiated. After 3 months of follow-up, no recurrence was evidenced by computed tomography.

The Effect of Chitosan Gel 15% in the Surgical Treatment of Stage III Periodontitis: A Case Report of Two Cases.

Periodontal diseases are widely spread, particularly in adults. Chitosan has non-toxicity and biocompatibility properties, as it has been studied in many studies in various surgical applications. This case report includes two female patients (aged 23 and 48) who were treated by the application of Chitosan gel 15% during open flap debridement in an aggregate of 26 periodontal pockets. Several clinical measurements were evaluated (probing depth, gingival recession, and bleeding on probing) for the treated periodontal pockets, between two periods, the first in baseline and then after six months. The results showed a reduction in probing depth of (3.30±0.27) after six months. The bleeding on probing also decreased from 84.61% to 0%. This case report concluded that the application of Chitosan gel 15% reduced pocket depth and bleeding on probing when applied in open flap debridement.

Predicting Outcomes Following Lower Extremity Endovascular Revascularization Using Machine Learning.

BACKGROUND: Lower extremity endovascular revascularization for peripheral artery disease carries nonnegligible perioperative risks; however, outcome prediction tools remain limited. Using machine learning, we developed automated algorithms that predict 30-day outcomes following lower extremity endovascular revascularization. METHODS AND RESULTS: The National Surgical Quality Improvement Program targeted vascular database was used to identify patients who underwent lower extremity endovascular revascularization (angioplasty, stent, or atherectomy) for peripheral artery disease between 2011 and 2021. Input features included 38 preoperative demographic/clinical variables. The primary outcome was 30-day postprocedural major adverse limb event (composite of major reintervention, untreated loss of patency, or major amputation) or death. Data were split into training (70%) and test (30%) sets. Using 10-fold cross-validation, 6 machine learning models were trained using preoperative features. The primary model evaluation metric was area under the receiver operating characteristic curve. Overall, 21 886 patients were included, and 30-day major adverse limb event/death occurred in 1964 (9.0%) individuals. The best performing model for predicting 30-day major adverse limb event/death was extreme gradient boosting, achieving an area under the receiver operating characteristic curve of 0.93 (95% CI, 0.92-0.94). In comparison, logistic regression had an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.70-0.74). The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.09. The top 3 predictive features in our algorithm were (1) chronic limb-threatening ischemia, (2) tibial intervention, and (3) congestive heart failure. CONCLUSIONS: Our machine learning models accurately predict 30-day outcomes following lower extremity endovascular revascularization using preoperative data with good discrimination and calibration. Prospective validation is warranted to assess for generalizability and external validity.

The epidemiology of neck and low back pain in Iran: a national and sub-national analysis from 1990 to 2019.

Background: Neck pain (NP) is a condition influenced by multiple factors. It places a significant burden on individuals suffering from NP and on social and economic systems. On a global scale, low back pain (LBP) stands out as a significant contributor to years lost to disability, and this burden is on the rise due to population growth and aging. Methods: The Global Burden of Disease database was used to collect data on the prevalence, incidence, and years lived with disability (YLD) of NP and LBP between 1990 and 2019. Various factors, including age group, gender, Iran, and its 31 provinces, were used to classify the data. Results: Iran accounted for 0.86 million incident cases of NP in 2019, with age-standardized incident rate per 100 000 population of 934.1. Tehran has the maximum age-standardized prevalence, incidence, and YLD. Iran accounted for the age-standardized incidence rate for LBP per 100 000 population of 3492.9, and it reduced to -8.35% from 1990. Mazandaran exhibits the highest levels of prevalence, incidence, and YLD for LBP in 2019. In Iran, the point prevalence of NP in 2019 was higher in females and increased with age up to 50-54 years for females and 70-74 years for males. However, there is only a slight difference between females and males in Iran regarding LBP prevalence. Conclusions: In this study, the authors report the prevalence, incidence, YLD, and age-standardized rates for NP and LBP in the world's general population and Iran's population based on its sub-nations in 1990 and 2019.

Post-publication research integrity concerns in randomized clinical trials: A scoping review of the literature.

BACKGROUND: Post-publication handling of integrity concerns in randomized clinical trials (RCTs) is a contentious matter. OBJECTIVES: We undertook a scoping systematic review to map the literature regarding post-publication integrity issues in RCTs. SEARCH STRATEGY AND SELECTION CRITERIA: Following prospective registration (https://osf.io/pgxd8) we initially searched PubMed and Scopus but subsequently extended it to include the Cochrane Library, and Google Scholar databases without language, article type or publication time restriction until November 2022. Reviewers independently selected published articles covering any aspect of post-publication research integrity concerns in RCTs. DATA COLLECTION AND ANALYSIS: The study findings grouped within domains relating to issues concerning post-publication integrity were extracted in duplicate, verified by a third reviewer, and then tabulated. MAIN RESULTS: The initial search captured 3159 citations, of which 89 studies were included in the review. Cross-sectional studies constituted the majority of included studies (n = 34, 38.2%), followed by systematic reviews (n = 10, 11.2%), methodology reviews/studies (n = 9, 10.1%) and other types of descriptive studies (n = 8, 9.0%). A total of 21 articles (23.6%) covered the domain on general issues, 25 (28.1%) in the journal's instructions and policies domain, eight (9.0%) in the editorial and peer review domain, one (1.1%) in the correspondence and complaints (post-publication peer review) domain, 12 (13.5%) in the investigation for concerns domain, six (6.7%) in the post-investigation decisions and sanctions domain, none in the critical appraisal guidance domain, five (5.6%) in the integrity assessment in systematic reviews domain, and 26 (29.2%) in the recommendations for future research domain. A total of 12 of the selected articles (13.5%) covered two (n = 9) or three (n = 3) different domains. CONCLUSIONS: Various research integrity domains and issues covering post-publication aspects of RCT integrity were captured and gaps were identified, mostly related with the necessary implications for all stakeholders to improve research transparency. There is an urgent need for a multistakeholder consensus towards creating specific statements for addressing post-publication integrity concerns in RCTs.

Grey water footprint for evaluating Zefta wastewater treatment plant: a case study.

The numbers of wastewater treatment plants (WWTP) in Egypt are increasing, yet the general level of pollution associated with wastewater discharge after treatment has not been evaluated. Grey water footprint (GWF) was used to assess the effluent discharges from Zefta WWTP. GWF, before and after treatment, was calculated and followed up to determine its impact on the receiving freshwater body. 150 samples were collected and analysed for BOD5 to determine the optimum operating conditions. Averages values were DO = 2.2, SV30 = 500, SVI = 167, SA = 9.3 d, MLVSS = 2392 mg/L, f/m = 0.16, MLSS in RAS = 7922 mg/L, WAS = 140 m3/d and the HRT = 12 h. The removal efficiency of COD and TSS in the primary settling tank reached 39% and 69%, respectively. Average calculations of removal efficiency percentile reached 90-93%. Average freshwater quantities required to reduce pollutants in the receiving body stream were seasonally determined for Zefta WWTP as 5.3 × 107 m3/year. The average influent BOD5 was 376 mg/L, it was reduced to 47 mg/L in the effluent, wherever the Cmin is 6 mg/L and Cnat is 10 mg/L. Statistical analysis has shown a significant direct relation between ΔWFG,mef and WFG,ref reached 0.952 and a significant inverse relation with Cef -0.982. WFG,T has shown a significant direct relation with Cr 0.974. WFG,T- ref has shown a significant direct relation with Cr as 0.971 and WFG,T as 0.803. It can be concluded that ΔWF is effective in evaluating the efficiency of wastewater treatment and its effect on the quality of receiving water bodies.

NSABP FB-10: a phase Ib/II trial evaluating ado-trastuzumab emtansine (T-DM1) with neratinib in women with metastatic HER2-positive breast cancer.

BACKGROUND: We previously reported our phase Ib trial, testing the safety, tolerability, and efficacy of T-DM1 + neratinib in HER2-positive metastatic breast cancer patients. Patients with ERBB2 amplification in ctDNA had deeper and more durable responses. This study extends these observations with in-depth analysis of molecular markers and mechanisms of resistance in additional patients. METHODS: Forty-nine HER2-positive patients (determined locally) who progressed on-treatment with trastuzumab + pertuzumab were enrolled in this phase Ib/II study. Mutations and HER2 amplifications were assessed in ctDNA before (C1D1) and on-treatment (C2D1) with the Guardant360 assay. Archived tissue (TP0) and study entry biopsies (TP1) were assayed for whole transcriptome, HER2 copy number, and mutations, with Ampli-Seq, and centrally for HER2 with CLIA assays. Patient responses were assessed with RECIST v1.1, and Molecular Response with the Guardant360 Response algorithm. RESULTS: The ORR in phase II was 7/22 (32%), which included all patients who had at least one dose of study therapy. In phase I, the ORR was 12/19 (63%), which included only patients who were considered evaluable, having received their first scan at 6 weeks. Central confirmation of HER2-positivity was found in 83% (30/36) of the TP0 samples. HER2-amplified ctDNA was found at C1D1 in 48% (20/42) of samples. Patients with ctHER2-amp versus non-amplified HER2 ctDNA determined in C1D1 ctDNA had a longer median progression-free survival (PFS): 480 days versus 60 days (P = 0.015). Molecular Response scores were significantly associated with both PFS (HR 0.28, 0.09-0.90, P = 0.033) and best response (P = 0.037). All five of the patients with ctHER2-amp at C1D1 who had undetectable ctDNA after study therapy had an objective response. Patients whose ctHER2-amp decreased on-treatment had better outcomes than patients whose ctHER2-amp remained unchanged. HER2 RNA levels show a correlation to HER2 CLIA IHC status and were significantly higher in patients with clinically documented responses compared to patients with progressive disease (P = 0.03). CONCLUSIONS: The following biomarkers were associated with better outcomes for patients treated with T-DM1 + neratinib: (1) ctHER2-amp (C1D1) or in TP1; (2) Molecular Response scores; (3) loss of detectable ctDNA; (4) RNA levels of HER2; and (5) on-treatment loss of detectable ctHER2-amp. HER2 transcriptional and IHC/FISH status identify HER2-low cases (IHC 1+ or IHC 2+ and FISH negative) in these heavily anti-HER2 treated patients. Due to the small number of patients and samples in this study, the associations we have shown are for hypothesis generation only and remain to be validated in future studies. Clinical Trials registration NCT02236000.

Predicting the need for subclavian artery revascularization in thoracic endovascular aortic repair: A systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis aims to investigate the effectiveness of left subclavian artery revascularization compared with non-revascularization in thoracic endovascular aortic repair, and to summarize the current evidence on its indications. METHODS: A computerized search was conducted across multiple databases, including MEDLINE, SCOPUS, Cochrane Library, and Web of Science, for studies published up to November 2023. Study selection, data abstraction, and quality assessment (using the Newcastle-Ottawa Scale) were independently conducted by two reviewers, with a third author resolving discrepancies. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models and publication bias was assessed using funnel plots. RESULTS: In the 76 included studies, left subclavian artery revascularization was associated with reduced risks of stroke (OR, 0.67; 95% CI, 0.45-0.98; n = 15,331), spinal cord ischemia (OR, 0.75; 95% CI, 0.56-0.99; n = 11,995), and arm ischemia (OR, 0.09; 95% CI, 0.01-0.59; n = 8438). No significant reduction in paraplegia (OR, 0.56; 95% CI, 0.21-1.47; n = 1802) or mortality (OR, 0.77; 95% CI, 0.53-1.12; n = 11,831) was observed. Moreover, the risk of endoleak was comparable in both groups (OR, 1.25; 95% CI, 0.55-2.84; P = .60; n = 793), whereas the risk of reintervention was significantly higher in the revascularization group (OR, 1.98; 95% CI, 1.03-3.83; P = .04; n = 272). Both groups had similar risks of major (OR, 0.45; 95% CI, 0.19-1.09; P = .08; n = 1113), minor (OR, 0.21; 95% CI, 0.01-3.45; P = .27; n = 183), renal (OR, 0.61; 95% CI, 0.12-3.06; P = .55; n = 310), and pulmonary (OR, 0.59; 95% CI, 0.16-2.15; P = .42; n = 8083) complications. The most frequent indications for left subclavian artery revascularization were primary prevention of spinal cord ischemia, augmentation of the landing zone, and primary stroke prevention. CONCLUSIONS: Left subclavian artery revascularization in thoracic endovascular aortic repair was associated with reduced neurological complications but was not found to impact mortality. The study highlights important indications for revascularization as well as significant predictors of complications, providing a basis for clinical decision-making and future research.

Thyroidectomy Effects on the Body Mass Index and Thyroid-Stimulating Hormone: A Systematic Review and Meta-Analysis.

Thyroidectomy is common and is performed for malignancy, goiters with pressure symptoms, and certain types of Grave's disease. Weight and body mass index (BMI) following thyroidectomy were discussed controversially. This meta-analysis aimed to assess weight and BMI following thyroidectomy. A systematic literature search was conducted in PubMed, Medline, and Google Scholar with interest in articles that assessed body weight and BMI following total or subtotal thyroidectomy. The search engine was limited to the period from inception up to January 2024. Keywords "total thyroidectomy", "subtotal thyroidectomy", "Graves' disease", "multinodular goiter", "differentiated thyroid carcinoma", and "toxic nodules" were used. Out of the 634 articles retrieved, 89 full texts were screened, and only six studies (five retrospective and one prospective cohort) fulfilled the inclusion and exclusion criteria. No differences were evident regarding weight and BMI before and after thyroidectomy (odds ratio: -0.63, 95%CI: -1.50 to -0.24, P-value for the overall effect: 0.15; and odds ratio: -0.12, 95% CI: -0.41 to -0.16, P-value for the overall effect: 0.40 respectively). No heterogeneity was observed (I2 for heterogeneity: 0.0%). No association between thyroidectomy (when performed for differentiated thyroid carcinoma and hyperthyroidism), weight, and BMI was found. Further studies assessing thyroid-stimulating hormone (TSH) levels, radioactive iodine therapy, and thyroxine dose are needed.

Predicting outcomes following lower extremity open revascularization using machine learning.

Lower extremity open revascularization is a treatment option for peripheral artery disease that carries significant peri-operative risks; however, outcome prediction tools remain limited. Using machine learning (ML), we developed automated algorithms that predict 30-day outcomes following lower extremity open revascularization. The National Surgical Quality Improvement Program targeted vascular database was used to identify patients who underwent lower extremity open revascularization for chronic atherosclerotic disease between 2011 and 2021. Input features included 37 pre-operative demographic/clinical variables. The primary outcome was 30-day major adverse limb event (MALE; composite of untreated loss of patency, major reintervention, or major amputation) or death. Our data were split into training (70%) and test (30%) sets. Using tenfold cross-validation, we trained 6 ML models. Overall, 24,309 patients were included. The primary outcome of 30-day MALE or death occurred in 2349 (9.3%) patients. Our best performing prediction model was XGBoost, achieving an area under the receiver operating characteristic curve (95% CI) of 0.93 (0.92-0.94). The calibration plot showed good agreement between predicted and observed event probabilities with a Brier score of 0.08. Our ML algorithm has potential for important utility in guiding risk mitigation strategies for patients being considered for lower extremity open revascularization to improve outcomes.

Socioeconomic Disparities in Anal Cancer: Effect on Treatment Delay and Survival.

BACKGROUND: Socioeconomic inequities have implications for access to health care and may be associated with disparities in treatment and survival. OBJECTIVE: To investigate the impact of socioeconomic inequities on time to treatment and survival of anal squamous-cell carcinoma. DESIGN: This is a retrospective study using a nationwide data set. SETTINGS: The patients were selected from the National Cancer Database and enrolled from 2004 to 2016. PATIENTS: We identified patients with stage I to III squamous-cell carcinoma of the anus who were treated with chemoradiation therapy. MAIN OUTCOMES MEASURES: Socioeconomic factors, including race, insurance status, median household income, and percentage of the population with no high school degrees, were included. The association of these factors with treatment delay and overall survival was investigated. RESULTS: A total of 24,143 patients who underwent treatment for grade I to III squamous-cell carcinoma of the anus were identified. The median age was 60 years, and 70% of patients were women. The median time to initiation of treatment was 33 days. Patients from zip codes with lower median income, patients with a higher percentage of no high school degree, and patients with other government insurance followed by Medicaid insurance had treatment initiated after 60 days from diagnosis. Kaplan-Meier survival analysis showed that the late-treatment group had worse overall survival compared to the early treatment group (98 vs 125 months; p < 0.001). LIMITATIONS: No detailed information is available about the chemoradiotherapy regimen, completion of treatment, recurrence, disease-free survival, and individual-level socioeconomic condition and risk factors. CONCLUSION: Patients from communities with lower median income, level of education, and enrolled in public insurance had longer time to treatment. Lower socioeconomic status was also associated with poorer overall survival. These results warrant further analysis and measures to improve access to care to address this disparity. See Video Abstract . DESIGUALDADES SOCIOECONMICAS EN CASOS DE CNCER ANAL EFECTOS EN EL RETRASO DEL TRATAMIENTO Y LA SOBREVIDA: ANTECEDENTES:Las desigualdades socio-económicas tienen implicaciones en el acceso a la atención médica y pueden estar asociadas con disparidades en el tratamiento y la sobrevida.OBJETIVO:Indagar el impacto de las desigualdades socio-económicas sobre el tiempo de retraso en el tratamiento y la sobrevida en casos de carcinoma a células escamosas del ano (CCEA).DISEÑO:Estudio retrospectivo utilizando un conjunto de datos a nivel nacional.AJUSTES:Todos aquellos pacientes inscritos entre 2004 a 2016 y que fueron seleccionados de la Base Nacional de Datos sobre el Cáncer.PACIENTES:Identificamos pacientes con CCEA en estadíos I-III y que fueron tratados con radio-quimioterápia.PRINCIPALES MEDIDAS DE RESULTADOS:Se incluyeron factores socio-económicos tales como la raza, el tipo de seguro de salud, el ingreso familiar medio y el porcentaje de personas sin bachillerato de secundaria (SBS). Se investigó la asociación entre estos factores con el retraso en iniciar el tratamiento y la sobrevida global.RESULTADOS:Se identificaron un total de 24.143 pacientes que recibieron tratamiento para CCEA estadíos I-III. La mediana de edad fue de 60 años donde 70% eran de sexo femenino. La mediana del tiempo transcurrido desde el diagnóstico hasta el inicio del tratamiento fue de 33 días. Los pacientes residentes en zonas de código postal con ingresos medios más bajos, con un mayor porcentaje de individuos SBS y los pacientes con otro tipo de seguro gubernamental de salud, seguidos del seguro tipo Medicaid iniciaron el tratamiento solamente después de 60 días al diagnóstico inicial de CCEA. El análisis de Kaplan-Meier de la sobrevida mostró que el grupo de tratamiento tardío tuvo una peor supervivencia general comparada con el grupo de tratamiento precoz o temprano (98 frente a 125 meses; p <0,001).LIMITACIONES:No se dispone de información detallada sobre el tipo de radio-quimioterapia utilizada, ni sobre la finalización del tratamiento o la recurrencia, tampoco acerca de la sobrevida libre de enfermedad ni sobre las condiciones socio-económicas o aquellos factores de riesgo a nivel individual.CONCLUSIÓN:Los pacientes de comunidades con ingresos medios más bajos, con un nivel de educación limitado e inscritos en un seguro público tardaron mucho más tiempo en recibir el tratamiento prescrito. El nivel socio-económico más bajo también se asoció con una sobrevida global más baja. Los presentes resultados justifican mayor análisis y medidas mas importantes para mejorar el acceso a la atención en salud y poder afrontar esta disparidad. (Traducción-Dr. Xavier Delgadillo ).

Real life retrospective study of cannabidiol therapy in alternating hemiplegia of childhood.

BACKGROUND: Many alternating hemiplegia of childhood (AHC) patients have received Cannabidiol (CBD) but, to our knowledge, there are no published data available. GOALS: Test the hypothesis that CBD has favorable effects on AHC spells. METHODS: Retrospective review of available data of AHC patients who received CBD. Primary analysis: Clinical Global Impression Scale of Improvement (CGI-I) score for response of AHC spells to CBD with calculation of 95% confidence interval (CI) for rejection of the null hypothesis. Secondary analyses, performed to achieve an understanding of the effect of CBD as compared to flunarizine, were CGI-I scores of 1) epileptic seizures to CBD, 2) AHC spells to flunarizine, 3) epileptic seizures to flunarizine. Also, Mann-Whitney test was done for comparison of CGI-I scores of CBD and flunarizine to both AHC spells and seizures. RESULTS: We studied 16 AHC patients seen at Duke University and University of Lyon. CI of CGI-I scores for AHC spells in response to CBD and to flunarizine, each separately, indicated a positive response to each of these two medications: neither overlapped with the null hypothesis score, 4, indicating significant positive responses with p < 0.05 for both. These two scores also did not differ (p = 0.84) suggesting similar efficacy of both: CBD score was 2 ± 1.1 with a 95% CI of 1.5-2.6 and flunarizine score was 2.3 ± 1.3 with a 95% CI of 1.7-3.1. In patients who had seizures, CI calculations indicated a positive effect of CBD on seizure CGI scores but not of flunarizine on seizure scores. CBD was well tolerated with no patients discontinuing it due to side effects and with some reporting positive behavioral changes. CONCLUSION: Our study indicates a real-life positive effect of CBD on AHC type spells.