Search

David C Klonoff,1 Brian L Levy,2 Michael J Jaasma,3 Manish Bharara,3 Deborah R Edgar,4 Christian Nasr,5 David L Caraway,3 Erika A Petersen,6 David G Armstrong7 1Diabetes Research Institute, Mills-Peninsula Medical Center, San Mateo, CA, USA; 2New York University Grossman School of Medicine, New York, NY, USA; 3Nevro Corp, Redwood City, CA, USA; 4Commexus Ltd, Dunblane, Scotland, UK; 5Division of Endocrinology, Department of Internal Medicine, The University of Arizona College of Medicine - Phoenix, Phoenix, AZ, USA; 6Department of Neurosurgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA; 7Department of Surgery, Keck School of Medicine of University of Southern California, Los Angeles, CA, USACorrespondence: David C Klonoff, Diabetes Research Institute, Mills-Peninsula Medical Center, 100 South San Mateo Drive, Room 1165, San Mateo, CA, 94401, USA, Tel +1650-218-1142, Email dklonoff@diabetestechnology.orgPurpose: The recent SENZA-PDN study showed that high-frequency (10kHz) spinal cord stimulation (SCS) provided significant, durable pain relief for individuals with painful diabetic neuropathy (PDN), along with secondary benefits, including improved sleep quality and HRQoL. Given that metabolic factors and chronic neuropathic pain are related, we evaluated potential secondary effects of 10kHz SCS on hemoglobin A1c (HbA1c) and weight in SENZA-PDN participants with type 2 diabetes (T2D).Patients and Methods: This analysis included 144 participants with T2D and lower limb pain due to PDN who received 10kHz SCS during the SENZA-PDN study. Changes in HbA1c, weight, pain intensity, and sleep were evaluated over 24 months, with participants stratified according to preimplantation HbA1c (> 7% and > 8%) and body mass index (BMI; ≥ 30 and ≥ 35 kg/m2).Results: At 24 months, participants with preimplantation HbA1c > 7% and > 8% achieved clinically meaningful and statistically significant mean reductions in HbA1c of 0.5% (P = 0.031) and 1.1% (P = 0.004), respectively. Additionally, we observed a significant mean weight loss of 3.1 kg (P = 0.003) across all study participants. In subgroups with BMI ≥ 30 and ≥ 35 kg/m2, weight reductions at 24 months were 4.1 kg (P = 0.001) and 5.4 kg (P = 0.005), respectively. These reductions were accompanied by a mean pain reduction of 79.8% and a mean decrease in pain interference with sleep of 65.2% at 24 months across all cohorts.Conclusion: This is the first study of SCS to demonstrate long-term, significant, and clinically meaningful reductions in HbA1c and weight in study participants with PDN and T2D, particularly among those with elevated preimplantation HbA1c and BMI. Although the mechanism for these improvements has yet to be established, the results suggest possible direct and indirect metabolic benefits with 10kHz SCS in addition to durable pain relief.Trial Registration: ClincalTrials.gov Identifier, NCT03228420.Keywords: diabetic peripheral neuropathy, painful diabetic neuropathy, spinal cord stimulation, neuromodulation, neuropathic pain

Background: Limited treatment options exist for inoperable thyroid cancers. We evaluated whether neoadjuvant use of systemic tyrosine kinase inhibitors facilitates surgery of differentiated thyroid cancers in this challenging context., Methods: A single-institution experience of 42 patients receiving tyrosine kinase inhibitors for papillary, follicular and anaplastic thyroid carcinomas between 2018 and 2023 was reviewed to identify differentiated thyroid cancers treated with neoadjuvant tyrosine kinase inhibitors (dabrafenib/trametinib, lenvatinib/pembrolizumab, or lenvatinib alone) via multidisciplinary protocols., Results: Nine patients with differentiated thyroid cancers (age 49 years, range 19-80, 5 women, 4 men) received neoadjuvant tyrosine kinase inhibitors with intent to improve resectability of primary or recurrent/residual tumors. All had locoregionally advanced disease deemed either unresectable or resectable with unacceptable morbidities. Six exhibited distant metastases (6 lungs, 6 vertebral/axial bones, 1 sternum). Tumors had BRAF V600E (6 papillary thyroid carcinoma) or RAS/TERT (2 follicular thyroid carcinoma) mutations or NCOA4-RET fusion. Most received neoadjuvant tyrosine kinase inhibitors for <6 months with visible results within weeks, radiologically and by examination. All patients completing surgery achieved R0 resection without major surgical complications or aerodigestive structure resection. Neoadjuvant tyrosine kinase inhibitors were generally well-tolerated (4 minor, 1 major toxicity that halted therapy but not surgery). Unique patients with distant metastases continued to receive adjuvant tyrosine kinase inhibitors. At median postoperative follow-up of 2 years, all patients are alive without new locoregional recurrence., Conclusion: Neoadjuvant use of tyrosine kinase inhibitors seems extremely effective in downstaging surgically unresectable differentiated thyroid cancers to achieve R0 resection while avoiding unnecessary surgical morbidities. A multidisciplinary approach with early genomic profiling to guide personalized neoadjuvant use of tyrosine kinase inhibitors is essential. Prospective studies are urgently needed to define the potential role of neoadjuvant tyrosine kinase inhibitors in advanced thyroid cancer management., Competing Interests: Conflicts of Interest/Disclosure Dr Niu serves in consulting/advisory roles for AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Johnson & Johnson, Mirati Therapeutics, Takeda, Sanofi, Pfizer, and G1 Therapeutics. None of the authors have financial conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Volumetric modulated arc therapy (VMAT) is a relatively new treatment technique in the middle-east and north African region. More so, is its application for cranio-spinal irradiation (CSI). We report the experience of this implementation in Tunisia, by comparing dosimetric outcomes between VMAT and Three-Dimensional Conformal Radiotherapy (3DCRT) and evaluating their efficiency in terms of treatment delivery time., Methods: We conducted an in-silico dosimetric study, on 29 patients treated with CSI. Patients treated with 3DCRT were replanned in VMAT and vice-versa. Doses to target volumes (TV) and organs at risk (OAR) were collected from the Treatment Planning System (TPS). Recorded treatment time was extracted from the TPS and beam-on-times were calculated., Results: VMAT provided higher TV coverage for CSI PTV (V95 % = 97.4 % vs 93.4 %, p < 0.001) and for boost PTV (96.3 % vs 93.4 %, p = 0.005). VMAT demonstrated better conformity (0.97 vs 0.93) and homogeneity (0.1 vs 0.26) indexes (p < 0.001). Both techniques met constraints for OAR, but neither achieved recommended limits for the skin, lens, or pituitary gland. VMAT showed lower maximum doses for the majority of OAR and achieved lower mean doses to the cochlea, parotids, heart, oesophagus, pancreas and bladder. However, it resulted in higher low doses to non-target tissue (V5Gy = 45.6 % vs 27.5 %, p < 0.001). Recorded treatment time was longer with VMAT compared to 3DCRT (1387 vs 683 s; p < 0.001), as well as the beam-on-time (453 and 162 s, p < 0.001)., Conclusion: VMAT offered improved TV coverage, conformity, and homogeneity. It protected some OAR better. This came at the expense of higher low-dose exposure to non-target tissue. Treatment times were longer with VMAT., Implications for Practice: Our study suggests the feasibility of implementing VMAT for CSI in low-middle-income countries. Follow-up is required to study the clinical translation of the dosimetric outcomes of VMAT., Competing Interests: Conflict of interest statement None., (Copyright © 2024 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.)

Background: Medulloblastoma is the most common malignant brain tumor in children. This entity in adulthood is rare. The aim of our study is to evaluate therapeutic results and prognostic factors of adult medulloblastoma treated at our institute with post-operative radiotherapy., Methods: We retrospectively reviewed a cohort of 55 patients with medulloblastoma who underwent radiation in the department of radiation oncology of institute Salah Azaiz (Tunis) over a 18-year period (1994-2012)., Results: The surgery was total or subtotal resection in 73% of cases. Forty-eight patients received radiotherapy to the entire craniospinal axis as part of the curative treatment. The median interval from surgery to the initiation of radiotherapy was 83 days. Etoposide-cisplatin chemotherapy was only performed in metastatic patients ( n  = 4). The 5-years and 10-years overall survival rates were respectively 53 and 34%. The dose of radiotherapy to the craniospinal axis was a prognostic factor. The 5-years and 10-years event-free-survival rates were 64 and 41%. Reduction in the dose of radiotherapy to the craniospinal axis and fourth ventricular floor involvement were correlated with a worse event-free survival., Conclusion: Our results, compared to those of the literature, conclude that the reduction in the dose of radiotherapy to the craniospinal axis (<34 Gy) in the standard risk group of adult medulloblastoma could not be done without chemotherapy. In the high-risk group of adult medulloblastoma, radiotherapy to the cerebrospinal axis at the dose of 36 Gy with chemotherapy, is required for disease control.

Background: Burnout among medical students has always been a major concern., Objective: To evaluate changes in the prevalence rates of burnout among Lebanese pre-final and final year medical students while taking into consideration the impact of coronavirus 2019 (COVID-19) on both the academical and clinical experiences., Methods: This is a multi-centered, survey-based, cross-sectional study conducted in October 2021. The Copenhagen Burnout Inventory questionnaire was used on 120 medical students from three different medical schools in Lebanon., Results: The overall burnout prevalence was 40.01%. When further dividing it into domains, 39.36% of students had personal burnout, 41.52% had work-related burnout, and 39.16% had pandemic-related burnout. Theoretical learning and clinical training were reported to be affected in respectively 66.70% and 71.70%. However, only 10.00% of the students have regretted choosing medicine and 67.50% felt comfortable to get to the next academic level., Conclusion: High levels of burnout were reported among pre-final and final year medical students with a subsequent negative impact on their academic life and clinical training. Medical schools should start adopting a conscious view of how to guide medical students in finding adequate coping mechanisms during these times of crisis.

Objectives: Tall cell variant (TCV) papillary thyroid cancer (PTC) is a subtype of PTC associated with aggressive tumor behavior, advanced stage, and higher rates of recurrence and mortality. The present study aimed to test an established dynamic risk stratification tool in the TCV population, with the goal of better predicting the postoperative course of these patients., Study Design: Retrospective chart review., Methods: A total of 94 patients with TCV who underwent total thyroidectomy with radioactive iodine ablation were retrospectively reviewed from 1998 through 2020. Biochemical, structural, and overall response to treatment was determined for each patient, based on postoperative thyroglobulin levels and imaging findings. Primary outcomes were locoregional and distant recurrence, presence of disease at final follow-up, need for additional intervention, and disease-specific mortality., Results: Patients with TCV who were stratified as having an excellent overall response to treatment had lower rates of locoregional recurrence than indeterminate, biochemical incomplete, and structural incomplete responses (2.0%, 33.3%, 55.0%, and 85.7% at 5 years respectively, p < 0.001). The same was true for distant recurrence as well (2.0%, 9.0%, 35.1%, and 42.9%, p < 0.001). An excellent response was also associated with lower rates of presence of disease at final follow-up, need for additional intervention, and disease-specific mortality., Conclusions: Although TCV is an aggressive subtype associated with worse clinical outcomes than classical PTC, patients with an excellent overall response to treatment have significantly improved outcomes when compared to indeterminate, biochemical incomplete, and structural incomplete responses., Level of Evidence: 3 Laryngoscope, 133:2430-2438, 2023., (© 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: Survival outcomes for anaplastic thyroid cancer (ATC), the most aggressive subtype of thyroid cancers, have remained poor. However, targeted therapies and immunotherapies present new opportunities for treatment of this disease. Evaluations of survival outcomes over time with new multimodal therapies are needed for optimizing treatment plans., Objective: To evaluate the association of treatment strategies and tumor characteristics with overall survival (OS) among patients with ATC., Design, Setting, and Participants: This retrospective case series study evaluated the survival outcomes stratified by treatment strategies and tumor characteristics among patients with ATC treated at a tertiary level academic institution from January 1, 2000, to December 31, 2021. Demographic, tumor, treatment, and outcome characteristics were analyzed. Kaplan-Meier method and log rank test modeled OS by treatment type and tumor characteristics. Data were analyzed in May 2022., Main Outcomes and Measures: Overall survival (OS)., Results: The study cohort comprised 97 patients with biopsy-proven ATC (median [range] age at diagnosis, 70 [38-93] years; 60 (62%) female and 85 [88%] White individuals; 59 [61%] never smokers). At ATC diagnosis, 18 (19%) patients had stage IVA, 19 (20%) had stage IVB, and 53 (55%) had stage IVC disease. BRAF status was assessed in 38 patients; 18 (47%) had BRAF-V600E variations and 20 (53%), BRAF wild type. Treatment during clinical course included surgery for 44 (45%) patients; chemotherapy, 41 (43%); definitive or adjuvant radiation therapy, 34 (RT; 35%); and targeted therapy, 28 (29%). Median OS for the total cohort was 6.5 (95% CI, 4.3-10.0) months. Inferior OS was found in patients who did not receive surgery (hazard ratio [HR], 2.12; 95% CI, 1.35-3.34; reference, received surgery), chemotherapy (HR, 3.28; 95% CI, 1.99-5.39; reference, received chemotherapy), and definitive or adjuvant RT (HR, 2.47; 95% CI, 1.52-4.02; reference, received definitive/adjuvant RT). On multivariable analysis, age at diagnosis (HR, 1.03; 95% CI, 1.01-1.06), tumor stage IVC (HR, 2.65; 95% CI, 1.35-5.18), and absence of definitive or adjuvant RT (HR, 1.90; 95% CI, 1.01-3.59) were associated with worse OS., Conclusions and Relevance: This retrospective single-institution study found that lower tumor stage, younger age, and the ability to receive definitive or adjuvant RT were associated with improved OS in patients with ATC.