tbuckley/cabot-search huggingface dataset:
Effect of therapeutic suggestions during general anaesthesia on postoperative pain and opioid use: multicentre randomised controlled trial
Authors: Hartmuth Nowak, Nina Zech, Sven Asmussen, Tim Rahmel, Michael Tryba, Guenther Oprea, Lisa Grause, Karin Schork, Manuela Moeller, Johannes Loeser, Katharina Gyarmati, Corinna Mittler, Thomas Saller, Alexandra Zagler, Katrin Lutz, Michael Adamzik, Ernil Hansen
Journal: BMJ (2020)

To investigate the effect of therapeutic suggestions played to patients through earphones during surgery on postoperative pain and opioid use.Blinded randomised controlled study.Five tertiary care hospitals in Germany.385 of 400 patients consecutively recruited from January to December 2018 who were to undergo surgery for 1-3 hours under general anaesthesia. In the per protocol analysis 191 patients were included in the intervention group and 194 patients in the control group.The intervention comprised an audiotape of background music and positive suggestions based on hypnotherapeutic principles, which was played repeatedly for 20 minutes followed by 10 minutes of silence to patients through earphones during general anaesthesia. Patients in the control group were assigned to a blank tape.The main outcome was dose of opioid administered by patient controlled analgesia or nurse controlled analgesia within the first postoperative 24 hours, based on regular evaluation of pain intensity on a numerical rating scale (range 0-10, with higher scores representing more severe pain).Compared with the control group, the intervention group required a significantly (P=0.002) lower opioid dose within 24 hours after surgery, with a median of 4.0 mg (interquartile range 0-8) morphine equivalents versus 5.3 (2-12), and an effect size (Cohen's d) of 0.36 (95% confidence interval 0.16 to 0.56). The number of patients who needed opioids postoperatively was significantly (P=0.001) reduced in the intervention group: 121 of 191 (63%, 95% confidence interval 45% to 70%) patients in the intervention group versus 155 of 194 (80%, 74% to 85%) in the control group. The number needed to treat to avoid postoperative opioids was 6. Pain scores were consistently and significantly lower in the intervention group within 24 hours after surgery, with an average reduction of 25%. No adverse events were reported.Therapeutic suggestions played through earphones during general anaesthesia could provide a safe, feasible, inexpensive, and non-drug technique to reduce postoperative pain and opioid use, with the potential for more general use. Based on the finding of intraoperative perception by a considerable number of patients, surgeons and anaesthetists should be careful about background noise and conversations during surgery.German Clinical Trial Register DRKS00013800.
Updates in the Management of CLL/SLL: Sequencing Therapy and the Role of Minimal Residual Disease Testing
Authors: William G. Wierda
Journal: Journal of the National Comprehensive Cancer Network (2020)

Progress in the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma has led to a renewed focus on minimal residual disease as a treatment endpoint, particularly in assessing survival outcomes with combination therapies. B-cell receptor signaling pathway inhibitor monotherapy is associated with low rates of undetectable minimal residual disease, and continued treatment is still required; however, BCL-2 inhibitor therapy with venetoclax is associated with high rates of undetectable minimal residual disease, as are new combinations with BCL-2 inhibitors. Early research indicates that BCL-2 inhibitors may be an effective treatment option for disease that is refractory to Bruton’s tyrosine kinase (BTK) inhibitor therapy.
LINC-15. OUTCOME OF CHINESE CHILDREN WITH MEDULLOBLASTOMA: A MULTI-CENTER EXPERIENCE WITH RISK-ADAPTED THERAPY
Authors: Xiaofei Sun, Anthony Pak-Yin Liu, Qunying Yang, Jian Wang, Shaoxiong Wu, Zijun Zhen, Jingsheng Wang, Haixia Guo, Lian Jiang, Xiaoli Ma, Wenjun Weng, Lihua Yang, Libin Huang, Juan Li, Godfrey Chi-Fung Chan
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND Medulloblastoma is the commonest brain tumor in young children but literature on Chinese is scarce. We hereby present the outcome of children with medulloblastoma managed according to a risk- and age-stratified guideline from ten institutions across China. METHODS Patients &amp;lt;18 years of age diagnosed with medulloblastoma between January 2016 and April 2019 were reviewed. Patients ≥3 years, stratified into average-risk (≤1.5cm2 residual tumor, non-metastatic, non-anaplastic histology) and high-risk (others) groups, were treated with risk-adapted craniospinal irradiation (average-risk: 23.4Gy, high-risk: 36Gy), tumor boost, and chemotherapy (lomustine/cisplatin/vincristine). Patients &amp;lt;3 years (considered high-risk, other than patients with localized and desmoplastic/nodular histology) received chemotherapy (cyclophosphamide/vincristine, high-dose methotrexate, carboplatin/etoposide) with/without delayed irradiation. RESULTS 112 patients were included with a median age at diagnosis of 6.5 years (range: 0.5–16.7). 16 patients (14.3%) had residual tumor &amp;gt;1.5cm2 and 36 (32%) had metastasis. Available data on histological subtype (n=87) were classic in 56 (64%), desmoplastic/nodular or extensive nodularity in 23 (26%), and large cell/anaplastic in 8 (9%). Molecular subgrouping (n=55) assigned tumors as WNT-activated (n=8, 15%), SHH-activated (n=17, 31%), Group 3 (n=12, 22%) and Group 4 (n=18, 33%). Respective 2-year EFS/OS for patients ≥3 and &amp;lt;3 years were 86.0±4.0%/96.4±2.1% and 57.8±12.6%/81.4±9.8% (EFS/OS p&amp;lt;0.001/p=0.009). Significant difference in outcome was also observed between patients with average-risk and high-risk disease (EFS/OS p=0.006/p=0.018). CONCLUSION We demonstrated feasibility in protocolizing the inter-disciplinary treatment for medulloblastoma in China. This will serve as a prototype for the standardization of pediatric neuro-oncology care in the country.
Abstract 13697: Calcific Aortic Valve Stenosis is Associated with an Alteration in HMGB1 Secretion by Endothelial Cells, Myofibroblasts and Macrophages
Authors: Margaret Passmore, Maria Nataatmadja, Satsuki Fukushima, Bronwyn Pearse, John F Fraser
Journal: Circulation (2012)

Calcific aortic valve stenosis (CAVS) is an important clinical problem. Studies suggest the progression of CAVS is actively regulated with endothelial injury leading to a sustained and chronic infl...
Greater Somatosensory Afference With Acupuncture Increases Primary Somatosensory Connectivity and Alleviates Fibromyalgia Pain via Insular γ‐Aminobutyric Acid: A Randomized Neuroimaging Trial
Authors: Ishtiaq Mawla, Eric Ichesco, Helge J. Zöllner, Richard A. E. Edden, Thomas Chenevert, Henry Buchtel, Meagan D. Bretz, Heather Sloan, Chelsea M. Kaplan, Steven E. Harte, George A. Mashour, Daniel J. Clauw, Vitaly Napadow, Richard E. Harris
Journal: Arthritis & Rheumatology (2020)

Objective Acupuncture is a complex multicomponent treatment that has shown promise in the treatment of fibromyalgia (FM). However, clinical trials have shown mixed results, possibly due to heterogeneous methodology and lack of understanding of the underlying mechanism of action. The present study was undertaken to understand the specific contribution of somatosensory afference to improvements in clinical pain, and the specific brain circuits involved. Methods Seventy‐six patients with FM were randomized to receive either electroacupuncture (EA), with somatosensory afference, or mock laser acupuncture (ML), with no somatosensory afference, twice a week over 8 treatments. Patients with FM in each treatment group were assessed for pain severity levels, measured using Brief Pain Inventory (BPI) scores, and for levels of functional brain network connectivity, assessed using resting state functional magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy in the right anterior insula, before and after treatment. Results Fibromyalgia patients who received EA therapy experienced a greater reduction in pain severity, as measured by the BPI, compared to patients who received ML therapy (mean difference in BPI from pre‐ to posttreatment was −1.14 in the EA group versus −0.46 in the ML group; P for group × time interaction = 0.036). Participants receiving EA treatment, as compared to ML treatment, also exhibited resting functional connectivity between the primary somatosensory cortical representation of the leg (S1 leg ; i.e. primary somatosensory subregion activated by EA) and the anterior insula. Increased S1 leg –anterior insula connectivity was associated with both reduced levels of pain severity as measured by the BPI ( r = −0.44, P = 0.01) and increased levels of γ‐aminobutyric acid (GABA+) in the anterior insula ( r = 0.48, P = 0.046) following EA therapy. Moreover, increased levels of GABA+ in the anterior insula were associated with reduced levels of pain severity as measured by the BPI ( r = −0.59, P = 0.01). Finally, post–EA treatment changes in levels of GABA+ in the anterior insula mediated the relationship between changes in S1 leg –anterior insula connectivity and pain severity on the BPI (bootstrap confidence interval −0.533, −0.037). Conclusion The somatosensory component of acupuncture modulates primary somatosensory functional connectivity associated with insular neurochemistry to reduce pain severity in FM.
All-Cause Excess Mortality and COVID-19–Related Mortality Among US Adults Aged 25-44 Years, March-July 2020
Authors: Jeremy Samuel Faust, Harlan M. Krumholz, Chengan Du, Katherine Dickerson Mayes, Zhenqiu Lin, Cleavon Gilman, Rochelle P. Walensky
Journal: JAMA (2020)

This study compares all-cause excess mortality and COVID-19–related mortality during the early pandemic period (March-July 2020) with unintentional drug overdoses, the usual leading cause of death in young adults, during the same period in 2018 among adults aged 25 to 44 years.
Robust barcoding and identification of Mycobacterium tuberculosis lineages for epidemiological and clinical studies
Authors: Gary Napier, Susana Campino, Yared Merid, Markos Abebe, Yimtubezinash Woldeamanuel, Abraham Aseffa, Martin L. Hibberd, Jody Phelan, Taane G. Clark
Journal: Genome Medicine (2020)

Abstract Background Tuberculosis, caused by bacteria in the Mycobacterium tuberculosis complex (MTBC), is a major global public health burden. Strain-specific genomic diversity in the known lineages of MTBC is an important factor in pathogenesis that may affect virulence, transmissibility, host response and emergence of drug resistance. Fast and accurate tracking of MTBC strains is therefore crucial for infection control, and our previous work developed a 62-single nucleotide polymorphism (SNP) barcode to inform on the phylogenetic identity of 7 human lineages and 64 sub-lineages. Methods To update this barcode, we analysed whole genome sequencing data from 35,298 MTBC isolates (~ 1 million SNPs) covering 9 main lineages and 3 similar animal-related species ( M. tuberculosis var. bovis , M. tuberculosis var. caprae and M. tuberculosis var. orygis ). The data was partitioned into training ( N = 17,903, 50.7%) and test ( N = 17,395, 49.3%) sets and were analysed using an integrated phylogenetic tree and population differentiation ( F ST ) statistical approach. Results By constructing a phylogenetic tree on the training MTBC isolates, we characterised 90 lineages or sub-lineages or species, of which 30 are new, and identified 421 robust barcoding mutations, of which a minimal set of 90 was selected that included 20 markers from the 62-SNP barcode. The barcoding SNPs (90 and 421) discriminated perfectly the 86 MTBC isolate (sub-)lineages in the test set and could accurately reconstruct the clades across the combined 35k samples. Conclusions The validated 90 SNPs can be used for the rapid diagnosis and tracking of MTBC strains to assist public health surveillance and control. To facilitate this, the SNP markers have now been incorporated into the TB-Profiler informatics platform ( https://github.com/jodyphelan/TBProfiler ).
Abstract 13871: Evolocumab and Cardiovascular Outcomes in Patients With Recent Myocardial Infarction: Analysis From FOURIER
Authors: Baris Gencer, François Mach, Sabina A Murphy, Gaetano M De Ferrari, Kurt Huber, Basil S Lewis, Jorge Ferreira, Christopher E Kurtz, Huei Wang, Narimon Honarpour, Anthony C Keech, Peter S Sever, Terje R Pedersen, Marc S Sabatine, Robert P Giugliano
Journal: Circulation (2019)

Background: The 2018 Cholesterol Guideline identified pts with recent MI (within 12 months) as very-high risk and for whom it is reasonable to add a PCSK9 inhibitor antibody to maximal statin if LD...
Abstract 14109: Clinic Non-Attendance is Associated With Increased Emergency Department Visits in Adults With Congenital Heart Disease
Authors: Katherine Awh, Morgan A Venuti, Lacey P Gleason, Rachel Rogers, Srinivas Denduluri, Yuli Y Kim
Journal: Circulation (2018)

Introduction: Clinic non-attendance is associated with adverse clinical outcomes in adults with congenital heart disease (ACHD). It is not known whether non-attendance is associated with urgent vis...
RADT-36. PROSPECTIVELY ASSESSED TUMOR CONTROL AND TOXICITY OF BENIGN INTRACRANIAL PATHOLOGIES TREATED WITH AUTOMATED VMAT RADIOSURGERY – INITIAL 2 YEAR EXPERIENCE WITH FIRST 100 PATIENTS
Authors: Evan Thomas, Clarence Mullins, Markus Bredel, Michael Dobelbower, Christopher Willey, Sharon Spencer, Barton Guthrie, Kristen Riley, James Markert, John Fiveash, Drexell Boggs
Journal: Neuro-Oncology (2020)

Abstract BACKGROUND HyperArc is a treatment planning technology that automates treatment planning and delivery of single-isocenter VMAT radiosurgery (SRS). The technique generates high quality, rapidly deliverable plans. It is unknown whether HyperArc is effective for commonly-encountered, benign, intracranial conditions managed with SRS. Under IRB-approved prospective registry, we collected data on treatment planning/delivery, and clinical outcomes of non-malignant conditions managed with single-fraction or fractionated SRS since deployment in October 2017. METHODS Patients received either single-fraction or fractionated SRS with HyperArc™ (Varian Medical Systems) between October 2017 &amp; October 2019. Patients with &amp;lt; 3 months follow-up were censored. All patients treated received prescription dose to ≥ 99% of gross tumor volume without PTV expansion. All treatments were delivered on Varian Edge linac with 10MV flattening-filter free beam at 2400 MU/min with high-definition (2.5mm) multi-leaf collimator. Standard pathology-specific outcomes and toxicities were assessed. Significant CNS toxicity was defined as Grade 3 or higher event by CTCAE. RESULTS Total of 100 targets (min=0.13cc, max=58.9cc) were treated. 55 received single-fraction SRS (12-22Gy), two received 2-fraction fSRS boost (12Gy) following fractionated treatment, and 43 received 5-fraction fSRS (25-30Gy). The most common pathology was meningioma (n=55), followed by AVM (n=18), non-secretory pituitary adenoma (n=12), acoustic schwannoma (n=9), secretory pituitary adenoma (n=3), glomus tumor (n=2), pineocytoma (n=1), and paraganglioma (n=1). Follow-up ranged from 1.2 to 19.5 months (median 7.2). There were three local failures, all in atypical meningiomas. One patient in the cohort experienced ≥Gr3 toxicity. Each radiosurgery session used median of 3 arcs, with median treatment and beam-on time of 12.03 and 2.3 minutes. Plan quality was excellent; median RTOG conformity was 1.15, and median Paddick GI was 3.52. CONCLUSION Although HyperArc was developed for automated multiple-metastasis radiosurgery, we found it effective and efficient for benign intracranial indications too. Early clinical outcomes appear congruent with historical controls.
The Elusive Scourge of Sudden Cardiac Death: Is Rational Decision Making Possible? Should There Be Standards of Risks and Predictions in Medicine?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Javed Butler, Angel Leon
Journal: Journal of the American College of Cardiology (2007)
CBIO-25. INTEGRATED MOLECULAR AND BH3 PROFILING OF THE INTRINSIC APOPTOTIC MACHINERY IDENTIFIES THERAPEUTIC VULNERABILITIES IN GLIOBLASTOMA
Authors: Elizabeth Fernandez, Wilson Mai, Nicholas Bayley, Christopher Tse, Linda Liau, Timothy Cloughesy, Anthony Letai, David Nathanson
Journal: Neuro-Oncology (2020)

Abstract Resistance to apoptosis is a hallmark of cancer. However, the underlying molecular mechanisms of intrinsic-apoptotic resistance in glioblastoma (GBM) are largely unknown. Here we performed integrated molecular and functional characterization (via BH3 profiling) of the intrinsic apoptotic machinery in 50 GBM patient specimens. We found that, despite significant genetic heterogeneity of our GBM samples, all GBMs have a cross compensatory reliance on BCLXL and MCL1 for basal survival. Treatment with standard of care (e.g., temozolomide or radiation) caused minimal apoptosis, yet ablated the MCL-1 block in a p53-dependent manner, thus creating an exclusive dependence on BCLXL for survival in p53 wild-type GBM tumors (65% of GBM tumors). Consequently, BCLXL inhibition caused synergistic cell death with IR/TMZ in GBM tumors with intact p53 signaling. Importantly, the degree of synergistic cell kill was best predicted by combining molecular features with BH3 profiling, providing an integrated predictive signature of response to this novel therapeutic approach. Collectively, these studies identify mechanisms of intrinsic apoptosis resistance in both basal and treatment states of GBM and demonstrate how functional and molecular data can be complementary to robustly predict therapy-induced cell death.
Immune-mediated ototoxicity associated with immune checkpoint inhibitors in patients with melanoma
Authors: Samuel Rosner, Yuri Agrawal, Daniel Q Sun, Nafi Aygun, Megan D Schollenberger, Evan Lipson, Jarushka Naidoo
Journal: Journal for ImmunoTherapy of Cancer (2020)

Immune checkpoint inhibitors (ICIs) are associated with a range of organ-specific toxicities known as immune-related adverse events (irAEs). Immune-mediated ototoxicity from ICIs is poorly described. Herein, we describe the clinical presentation, diagnostic evaluation and management of six ICI-treated patients who developed immune-mediated ototoxicity, identified by a multidisciplinary immune-related toxicity team. This is the largest case series to date and identifies bilateral high-frequency hearing loss and tinnitus as the most common reported symptoms and can be associated with abnormal speech reception thresholds and word recognition ability on audiogram in select patients. We propose multidisciplinary evaluation of patients with suspected otologic irAEs including referral to otolaryngology, audiometry evaluation±magnetic resonance imaging for evaluation of suspected immune-mediated ototoxicity.
NIMG-60. ATYPICAL POSTERIOR REVERSIBLE LEUKOENCEPHALOPATHY SYNDROME MIMICKING TUMOR IN 1ST TRIMESTER PREGNANCY-’DON’T BELIEVE EVERYTHING YOU SEE’
Authors: Humsini Vishwanath, Akhil Shivaprasad, Ivo Tremont-Lukats, Suzanne Powell
Journal: Neuro-Oncology (2020)

Abstract Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiographic diagnosis characterized by headache, confusion, visual disturbances, seizures and most commonly bilateral vasogenic edema. PRES during first trimester gestation is exceptional and in our report mimicking CNS tumor. An 18-year-old G1P0 Hispanic woman was admitted with headache, left-sided hemiparesis and left-sided visual loss for 4 days. Exam was consistent for drowsiness, dysarthria, left homonymous hemianopia, left facial droop and left hemiplegia with left hemi-sensory loss. By pelvic ultrasound she had a single 9-week intrauterine pregnancy with no detectable fetal heart tone. MRI brain: large area of increased T2 signal in the right parietal occipital and upper temporal and posterior right frontal lobe white matter with mass effect of 6mm midline shift and no evidence of hemorrhage. There was high suspicion for a glial neoplasm. MRA of head and neck and EEG were unremarkable. IR cerebral angiogram had no evidence of vascular abnormalities. Eventual MR spectroscopy, choline/NAA ratio was (&amp;lt; 2/1), elevated lactate/fat peak suggestive of inflammatory versus infectious process. She had D&amp;C for missed abortion and pathology was negative for malignancy. Further brain biopsy on day 5 demonstrated reactive astrogliosis with microglial activation, scattered macrophages with white matter vacuolation. Biopsy specimen was negative for infections. TPO Ab, NMO/AQP4, Ttg IgA and rheumatologic panel were negative. The pathology was most compatible with PRES. Repeat MRI had decreasing mass effect and increased patchy subcortical restricted diffusion in the right occipital and temporo-parietal lobes. She had inpatient rehabilitation leading to complete recovery.
BCG vaccination in health care providers and the protection against COVID-19
Authors: Mihai G. Netea, Jos W.M. van der Meer, Reinout van Crevel
Journal: Journal of Clinical Investigation (2020)

A number of coronavirus disease 2019 (COVID-19) vaccine candidates have shown promising results, but substantial uncertainty remains regarding their effectiveness and global rollout. Boosting innate immunity with bacillus Calmette Guérin (BCG) or other live attenuated vaccines may also play a role in the fight against the COVID-19 pandemic. BCG has long been known for its nonspecific beneficial effects that are most likely explained by epigenetic and metabolic reprogramming of innate immune cells, termed trained immunity. In this issue of the JCI, Rivas et al. add to these arguments by showing that BCG-vaccinated health care providers from a Los Angeles health care organization had lower rates of COVID-19 diagnoses and seropositivity compared with unvaccinated individuals. Prospective clinical trials are thus warranted to explore the effects of BCG vaccination in COVID-19. We posit that beyond COVID-19, vaccines such as BCG that elicit trained immunity may mitigate the impact of emerging pathogens in future pandemics.
High genetic contribution to anterior cruciate ligament rupture: Heritability ~69%
Authors: Karin Magnusson, Aleksandra Turkiewicz, Velocity Hughes, Richard Frobell, Martin Englund
Journal: British Journal of Sports Medicine (2020)

Objectives We aimed to determine the lifetime genetic risk for anterior cruciate ligament (ACL) rupture. Methods We used a twin study approach, linking the Swedish Twin Register with national healthcare data to form a 30 year, population wide, longitudinal twin cohort. We studied ACL rupture in this cohort of 88 414 identical and fraternal twins, aged ≥17 years, to determine the familial risk and heritability of ACL rupture. Results The incidence rate of ACL rupture was 70 (95% CI 66 to 74) per 100 000 person years. The familial risk, which is the excess risk ratio (RR) of the second twin having ACL rupture given that the first twin has had such a rupture, was higher in identical twin pairs (RR=8.6, 95% CI 6.2 to 11.0) than in fraternal twin pairs (RR=1.9, 95% CI 0.9 to 3.0). The overall heritability of ACL rupture was high, 69% (95% CI 47 to 91), increasing from 60% at age 17 years to 80% at age 60 years. Women and men had similar familial risk and heritability of ACL rupture. Conclusion The genetic contribution to ACL rupture of ~69% is high and suggests strong familial clustering. If clinicians recognise the high genetic risk of such injury, they may be better able to counsel athletes whose near relatives have had ACL rupture.