Tractography-based navigated TMS language mapping protocol

IntroductionThis study explores the feasibility of implementing a tractography-based navigated transcranial magnetic stimulation (nTMS) language mapping protocol targeting cortical terminations of the arcuate fasciculus (AF). We compared the results and distribution of errors from the new protocol to an established perisylvian nTMS protocol that stimulated without any specific targeting over the entire perisylvian cortex.MethodsSixty right-handed patients with language-eloquent brain tumors were examined in this study with one half of the cohort receiving the tractographybased protocol and the other half receiving the perisylvian protocol. Probabilistic tractography using MRtrix3 was performed for patients in the tractography-based group to identify the AF’s cortical endpoints. nTMS mappings were performed and resulting language errors were classified into five psycholinguistic groups.ResultsTractography and nTMS were successfully performed in all patients. The tractogram-based group showed a significantly higher median overall ER than the perisylvian group (3.8% vs. 2.9% p <.05). The median ER without hesitation errors in the tractogram-based group was also significantly higher than the perisylvian group (2.0% vs. 1.4%, p <.05). The ERs by error type showed no significant differences between protocols except in the no response ER, with a higher median ER in the tractogram-based group (0.4% vs. 0%, p <.05). Analysis of ERs based on the Corina cortical parcellation system showed especially high nTMS ERs over the posterior middle temporal gyrus (pMTG) in the perisylvian protocol and high ERs over the middle and ventral postcentral gyrus (vPoG), the opercular inferior frontal gyrus (opIFG) and the ventral precentral gyrus (vPrG) in the tractography-based protocol.DiscussionBy considering the white matter anatomy and performing nTMS on the cortical endpoints of the AF, the efficacy of nTMS in disrupting patients’ object naming abilities was increased. The newly introduced method showed proof of concept and resulted in AF-specific ERs and noninvasive cortical language maps, which could be applied to additional fiber bundles related to the language network in future nTMS studies

Real-world efficacy and safety of Ledipasvir plus Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir +/- Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience

Background/Aims: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population.Material and Methods: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)+/- ribavirin (RBV) ombitasvir/paritaprevir/ritonavir +/- dasabuvir (PrOD)+/- RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed.Results: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90 +/- 54.60 U/L to 17.00 +/- 14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51 +/- 4.54 to 7.32 +/- 3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0 +/- 16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%).Conclusion: LDV/SOF or PrOD +/- RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.Turkish Association for the Study of The Liver (TASL

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

γ-Ray induced graft copolymerization of methyl methacrylate onto poly(ß-hydroxynonanoate)

Copolymers of poly(3-hydroxy-nonanoate), PHN, with methyl methacrylate, MMA, were prepared using 60Co-gamma irradiator. The bulk solutions of PHN in MMA were prepared at different PHN feed concentration and they were irradiated to 8.5 kGy at room temperature. Polymer fractions obtained by solvent-nonsolvent fractional precipitation were carefully characterized using gel permeation chromatography (GPC), nuclear magnetic resonance spectroscopy (NMR), and thermal gravimetric analysis (TGA) techniques. High copolymerization yield was observed and the copolymer compositions obtained from the TGA measurements were consistent with the NMR results. PHN contents of the copolymer samples changed from 5 to 35 wt.-%. The strain at break and tensile strength values of copolymers were between the values of their respective homopolymers. It was observed that pure copolymer samples showed up to 13% strain at break

Hydroxylation of pendant vinyl groups of poly(3-hydroxy undec-10-enoate) in high yield

Poly(3-hydroxy undec-10-enoate) (PHU) was synthesized by feeding Pseudomonas oleovarans with 10-undecenoic acid and nearly 100% hydroxylation of double bonds of PHU was achieved by hydroboration-oxidation reaction using 9-borobicyclononane. The disappearance of vinyl signals of PHU in proton and 13C NMR spectra was observed. Acetylation of hydroxylated PHU was conducted for molecular weight measurements. Molecular weight and polydispersity of hydroxylated PHU were found to be 10,000 and 1.23, respectively, while that of the originals was 32,000 and 2.42. Decomposition temperatures of original and hydroxylated PHU were 280 and 200°C, respectively. © 2005 Wiley Periodicals, Inc