tbuckley/cabot-search huggingface dataset:
Management of Chronic Low Back Pain—Reply
Authors: Kenneth R. Cohen
Journal: JAMA Internal Medicine (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
When I use a word . . . . Medical aphorisms
Authors: Jeffrey K Aronson
Journal: BMJ (2022)

An aphorism attributed to Albert Einstein—“Everything should be made as simple as possible, but not simpler”—appears to have been derived from a longer passage in his 1933 Herbert Spencer Lecture, given in Oxford and titled “On the Method of Theoretical Physics,” in which he suggested that theories should not be so simple as to “surrender the adequate representation of a single datum experience.” Aphorisms are supposed to illustrate truisms in short, pithy maxims. However, they are not always short or pithy and do not always illustrate truisms. For example, an aphorism attributed to William Osler begins with an important injunction (“Listen to the patient …”) but continues with a misleading assertion (“… he is telling you the diagnosis”). The patient’s tale is generally incomplete and needs to be supplemented by careful questioning and followed by careful observation, examination, and investigation. The aphorism might therefore be rewritten, less pithily but more accurately: “Listen to what the patient tells you, both spontaneously and on careful questioning; the patient’s tale is the first step on the road to a complete diagnosis.”
Global Transcriptomic Profiling Identifies Differential Gene Expression Signatures Between Inflammatory and Noninflammatory Aortic Aneurysms
Authors: Benjamin Hur, Matthew J. Koster, Jin Sung Jang, Cornelia M. Weyand, Kenneth J. Warrington, Jaeyun Sung
Journal: Arthritis & Rheumatology (2022)

To identify hallmark genes and biomolecular processes in aortitis using high-throughput gene expression profiling, and to provide a range of potentially new drug targets (genes) and therapeutics from a pharmacogenomic network analysis.Bulk RNA sequencing was performed on surgically resected ascending aortic tissues from inflammatory aneurysms (giant cell arteritis [GCA] with or without polymyalgia rheumatica, n = 8; clinically isolated aortitis [CIA], n = 17) and noninflammatory aneurysms (n = 25) undergoing surgical aortic repair. Differentially expressed genes (DEGs) between the 2 patient groups were identified while controlling for clinical covariates. A protein-protein interaction model, drug-gene target information, and the DEGs were used to construct a pharmacogenomic network for identifying promising drug targets and potentially new treatment strategies in aortitis.Overall, tissue gene expression patterns were the most associated with disease state than with any other clinical characteristic. We identified 159 and 93 genes that were significantly up-regulated and down-regulated, respectively, in inflammatory aortic aneurysms compared to noninflammatory aortic aneurysms. We found that the up-regulated genes were enriched in immune-related functions, whereas the down-regulated genes were enriched in neuronal processes. Notably, gene expression profiles of inflammatory aortic aneurysms from patients with GCA were no different than those from patients with CIA. Finally, our pharmacogenomic network analysis identified genes that could potentially be targeted by immunosuppressive drugs currently approved for other inflammatory diseases.We performed the first global transcriptomics analysis in inflammatory aortic aneurysms from surgically resected aortic tissues. We identified signature genes and biomolecular processes, while finding that CIA may be a limited presentation of GCA. Moreover, our computational network analysis revealed potential novel strategies for pharmacologic interventions and suggests future biomarker discovery directions for the precise diagnosis and treatment of aortitis.
TCTAP A-031 The Importance of Performing Final Kissing Balloon Dilation Before Final Proximal Optimization When Using Provisional Stenting Technique in Bifurcation Lesions: A Computational Fluid Dynamics Study
Authors: Hassan Ali Warda, Mai El Zayat, Hazem Mamdouh Warda, Osama Shoeib, Essam Wahba
Journal: Journal of the American College of Cardiology (2022)
Socioeconomic inequality, waiting time initiatives and austerity in Scotland: an interrupted time series analysis of elective hip and knee replacements and arthroscopies
Authors: Graham Kirkwood, Allyson M Pollock
Journal: Journal of the Royal Society of Medicine (2022)

National Health Service (NHS) waiting times have long been a political priority in Scotland. In 2002, the Scottish government launched a programme of investment and reform to reduce waiting times. The effect on waiting time inequality is unknown as is the impact of subsequent austerity measures.An interrupted time series analysis between the most and least socioeconomically deprived population quintiles since the introduction of waiting time initiative 1 July 2002 and austerity measures 1 April 2010.All NHS-funded elective primary hip replacement, primary knee replacement and arthroscopy patient data in Scotland from 1 April 1997 to 31 March 2019.NHS Scotland funded patients treated in Scotland.Trends and changes in mean waiting time.There were 135,176, 122,883 and 173,976 NHS funded hip replacement, knee replacement and arthroscopy patients, respectively, in Scotland between 1 April 1997 and 31 March 2019. From 1 July 2002 to 31 March 2010, waiting time inequality between the most and least deprived patients fell and increased thereafter. For hip replacements before 1 July 2002, waiting time inequality increased 1.07 days per quarter; this changed at 1 July 2002 with significant slope change of -2.32 (-3.53, -1.12) days resulting in a decreasing rate of inequality of -1.26 days per quarter. On 1 April 2010 the slope changed significantly by 1.84 (0.90, 2.78) days restoring increasing inequality at 0.58 days per quarter. Knee replacements and arthroscopies had similar results.The waiting time initiative in Scotland is associated with a reduction in waiting time inequality benefiting the most socioeconomically deprived patients. Austerity measures may be reversing these gains.
Safety and tolerability of AAV8 delivery of a broadly neutralizing antibody in adults living with HIV: a phase 1, dose-escalation trial
Authors: Joseph P. Casazza, Evan M. Cale, Sandeep Narpala, Galina V. Yamshchikov, Emily E. Coates, Cynthia S. Hendel, Laura Novik, LaSonji A. Holman, Alicia T. Widge, Preeti Apte, Ingelise Gordon, Martin R. Gaudinski, Michelle Conan-Cibotti, Bob C. Lin, Martha C. Nason, Olga Trofymenko, Shinyi Telscher, Sarah H. Plummer, Diane Wycuff, William C. Adams, Janardan P. Pandey, Adrian McDermott, Mario Roederer, Avery N. Sukienik, Sijy O’Dell, Jason G. Gall, Britta Flach, Travis L. Terry, Misook Choe, Wei Shi, Xuejun Chen, Florence Kaltovich, Kevin O. Saunders, Judy A. Stein, Nicole A. Doria-Rose, Richard M. Schwartz, Alejandro B. Balazs, David Baltimore, Gary J. Nabel, Richard A. Koup, Barney S. Graham, Julie E. Ledgerwood, John R. Mascola, Charla Andrews, Anita Arthur, Seemal F. Awan, Allison Beck, Eugeania Burch, Maria C. Burgos Florez, Nina M. Berkowitz, Eli A. Boritz, Kevin Carlton, Cora T. Cartagena, Christina Carter, Grace L. Chen, Pamela Costner, Jennifer Cunningham, Daniel C. Douek, Aba M. Eshun, Catina Evans, Renunda Hicks, Katherine V. Houser, Justine Jones, Brenda Larkin, Lam Le, Floreliz Mendoza, Stephen Migueles, John Misasi, Thuy A. Nguyen, Abidemi Ola, Karen Parker, Iris Pittman, La’ Shawn Requilman, Ro Shauna Rothwell, Gretchen L. Schieber, Jamie Saunders, Sandra Sitar, Colin Tran, Olga Trofymenko, Olga Vasilenko, Sana Waheed, Lingshu Wang, Xiaolin Wang, William Whalen, Pernell Williams, Richard L. Wu, Kathy Zephir
Journal: Nature Medicine (2022)
TCTAP C-039 Double Trouble: Complex Left Main Bifurcation With Ostial LAD Chronic Total Occlusion (CTO)
Authors: Azrina Abdul Kadir, Yu Ying Ong, Heng Shee Kim, Vicknesan Kulasingham, Doreen Sumpat, Hou Tee Lu
Journal: Journal of the American College of Cardiology (2022)
Adult brain tumors in Sub-Saharan Africa: A scoping review
Authors: Ulrick Sidney Kanmounye, Claire Karekezi, Arsene Daniel Nyalundja, Ahmed K Awad, Tsegazeab Laeke, James A Balogun
Journal: Neuro-Oncology (2022)

Abstract Background Sub-Saharan African (SSA) neuro-oncologists report high workloads and challenges in delivering evidence-based care; however, these reports contrast with modeled estimates of adult neuro-oncology disease burden in the region. This scoping review aimed to better understand the reasons for this discrepancy by mapping out the SSA adult brain tumor landscape based on published literature. Methods Systematic searches were conducted in OVID Medline, Global Index Medicus, African Journals Online, Google Scholar, and faculty of medicine libraries from database inception to May 31, 2021. The results were summarized quantitatively and narratively. English and French peer-reviewed articles were included (title, abstract, and full text). Results Of the 819 records identified, 119 articles by 24 SSA countries (42.9%) were included in the final review. Odeku published the first article in 1967, and nine of the ten most prolific years were in the 21st century. The greatest contributing region was Western Africa (n = 58, 48.7%) led by Nigeria (n = 37, 31.1%). Central Africa had fewer articles published later than the other SSA regions (P = .61). Most studies were nonrandomized (n = 75, 63.0%) and meningiomas (n = 50, 42.0%) were the most common brain tumors reported. Less than 30 studies reported on adjuvant treatment or patient outcomes. Conclusions Most publications were hospital-based, and there was significant heterogeneity in the quality of evidence and reporting. This study highlights the need for rapid and sustainable investments and brain tumor research capacity in SSA.
Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India
Authors: Valliappan Muthu, Ritesh Agarwal, Atul Patel, Soundappan Kathirvel, Ooriapadickal Cherian Abraham, Ashutosh Nath Aggarwal, Amanjit Bal, Ashu Seith Bhalla, Prashant N Chhajed, Dhruva Chaudhry, Mandeep Garg, Randeep Guleria, Ram Gopal Krishnan, Arvind Kumar, Uma Maheshwari, Ravindra Mehta, Anant Mohan, Alok Nath, Dharmesh Patel, Shivaprakash Mandya Rudramurthy, Puneet Saxena, Nandini Sethuraman, Tanu Singhal, Rajeev Soman, Balamugesh Thangakunam, George M Varghese, Arunaloke Chakrabarti
Journal: The Lancet Infectious Diseases (2022)
Evaluation of Outcomes Following Hospital-Wide Implementation of a Subcutaneous Insulin Protocol for Diabetic Ketoacidosis
Authors: Priya Rao, Sheng-fang Jiang, Patricia Kipnis, Divyesh M. Patel, Svetlana Katsnelson, Samineh Madani, Vincent X. Liu
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Standard diabetic ketoacidosis care in the US includes intravenous insulin treatment in the intensive care unit. Subcutaneous (SQ) insulin could decrease intensive care unit need, but the data are limited. <h3>Objective</h3> To assess outcomes after implementation of an SQ insulin protocol for treating diabetic ketoacidosis. <h3>Design, Setting, and Participants</h3> This cohort study is a retrospective evaluation of a prospectively implemented SQ insulin protocol. The study was conducted at an integrated health care system in Northern California. Participants included hospitalized patients with diabetic ketoacidosis at 21 hospitals between January 1, 2010, and December 31, 2019. The preimplementation phase was 2010 to 2015, and the postimplementation phase was 2017 to 2019. Data analysis was performed from October 2020 to January 2022. <h3>Exposure</h3> An SQ insulin treatment protocol for diabetic ketoacidosis. <h3>Main Outcomes and Measures</h3> Difference-in-differences evaluation of the need for intensive care, mortality, readmission, and length of stay at a single intervention site using an SQ insulin protocol from 2017 onward compared with 20 control hospitals using standard care. <h3>Results</h3> A total of 7989 hospitalizations for diabetic ketoacidosis occurred, with 4739 (59.3%) occurring before and 3250 (40.7%) occurring after implementation. The overall mean (SD) age was 42.3 (17.7) years, with 4137 hospitalizations (51.8%) occurring among female patients. Before implementation, SQ insulin was the first insulin used in 40 intervention (13.4%) and 651 control (14.7%) hospitalizations. After implementation, 98 hospitalizations (80.3%) received SQ insulin first at the intervention site compared with 402 hospitalizations (12.8%) at control sites. The adjusted rate ratio for intensive care unit admission was 0.43 (95% CI, 0.33-0.56) at the intervention sites, a 57% reduction compared with control sites, and was 0.50 (95% CI, 0.25-0.99) for 30-day hospital readmission, a 50% reduction. There were no significant changes in hospital length of stay and rates of death. <h3>Conclusions and Relevance</h3> These findings suggest that a protocol based on SQ insulin for diabetic ketoacidosis treatment was associated with significant decreases in intensive care unit need and readmission, with no evidence of increases in adverse events.
A clinically relevant formulation for direct administration of nerve specific fluorophores to mitigate iatrogenic nerve injury
Authors: Connor W. Barth, Vidhi M. Shah, Lei G. Wang, Anas M. Masillati, Adel Al-Fatease, Syed Zaki Husain Rizvi, Alexander L. Antaris, Jonathan Sorger, Deepa A. Rao, Adam W.G. Alani, Summer L. Gibbs
Journal: Biomaterials (2022)

Iatrogenic nerve injury significantly affects surgical outcomes. Although intraoperative neuromonitoring is utilized, nerve identification remains challenging and the success of nerve sparing is strongly correlated with surgeon experience levels. Fluorescence guided surgery (FGS) offers a potential solution for improved nerve sparing by providing direct visualization of nerve tissue intraoperatively. However, novel probes for FGS face a long regulatory pathway to achieve clinical translation. Herein, we report on the development of a clinically-viable, gel-based formulation that enables direct administration of nerve-specific probes for nerve sparing FGS applications, facilitating clinical translation via the exploratory investigational new drug (eIND) guidance. The developed formulation possesses unique gelling characteristics, allowing it to be easily spread as a liquid followed by rapid gelling for subsequent tissue hold. Optimization of the direct administration protocol with our gel-based formulation enabled a total staining time of 1-2 min for compatibility with surgical procedures and successful clinical translation.
Altered peripheral factors affecting the absorption, distribution, metabolism, and excretion of oral medicines in Alzheimer’s disease
Authors: Elka S. Waller, Ben J. Yardeny, Wan Yun Fong, Xue Yi Gan, Stephen V. Jimenez, Yijun Pan, Joshua H. Abasszade, Joseph A. Nicolazzo
Journal: Advanced Drug Delivery Reviews (2022)
National responsibility for ecological breakdown: a fair-shares assessment of resource use, 1970–2017
Authors: Jason Hickel, Daniel W O’Neill, Andrew L Fanning, Huzaifa Zoomkawala
Journal: The Lancet Planetary Health (2022)

Human impacts on earth-system processes are overshooting several planetary boundaries, driving a crisis of ecological breakdown. This crisis is being caused in large part by global resource extraction, which has increased dramatically over the past half century. We propose a novel method for quantifying national responsibility for ecological breakdown by assessing nations' cumulative material use in excess of equitable and sustainable boundaries.For this analysis, we derived national fair shares of a sustainable resource corridor. These fair shares were then subtracted from countries' actual resource use to determine the extent to which each country has overshot its fair share over the period 1970-2017. Through this approach, each country's share of responsibility for global excess resource use was calculated.High-income nations are responsible for 74% of global excess material use, driven primarily by the USA (27%) and the EU-28 high-income countries (25%). China is responsible for 15% of global excess material use, and the rest of the Global South (ie, the low-income and middle-income countries of Latin America and the Caribbean, Africa, the Middle East, and Asia) is responsible for only 8%. Overshoot in higher-income nations is driven disproportionately by the use of abiotic materials, whereas in lower-income nations it is driven disproportionately by the use of biomass.These results show that high-income nations are the primary drivers of global ecological breakdown and they need to urgently reduce their resource use to fair and sustainable levels. Achieving sufficient reductions will likely require high-income nations to adopt transformative post-growth and degrowth approaches.None.
TCTAP A-089 PREmier of Randomized COMparison of Bypass Surgery Versus AgnioplasTy -5 Biodegradable Polymer Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease: PRE-COMBAT-5 Trial
Authors: Jinho Lee, Do-Yoon Kang, Jung-Min Ahn, Duk-Woo Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2022)
Effectiveness and impact of the 4CMenB vaccine against invasive serogroup B meningococcal disease and gonorrhoea in an infant, child, and adolescent programme: an observational cohort and case-control study
Authors: Bing Wang, Lynne Giles, Prabha Andraweera, Mark McMillan, Sara Almond, Rebecca Beazley, Janine Mitchell, Noel Lally, Michele Ahoure, Emma Denehy, Ann Koehler, Louise Flood, Helen Marshall
Journal: The Lancet Infectious Diseases (2022)
Immunogenicity of the mRNA-1273 COVID-19 vaccine in adult patients with inborn errors of immunity
Authors: Leanne P.M. van Leeuwen, Corine H. GeurtsvanKessel, Pauline M. Ellerbroek, Godelieve J. de Bree, Judith Potjewijd, Abraham Rutgers, Hetty Jolink, Frank van de Veerdonk, Eric C.M. van Gorp, Faye de Wilt, Susanne Bogers, Lennert Gommers, Daryl Geers, Anke H.W. Bruns, Helen L. Leavis, Jelle W. van Haga, Bregtje A. Lemkes, Annelou van der Veen, S.F.J. de Kruijf-Bazen, Pieter van Paassen, Karina de Leeuw, Annick A.J.M. van de Ven, Petra H. Verbeek-Menken, Annelies van Wengen, Sandra M. Arend, Anja J. Ruten-Budde, Marianne W. van der Ent, P. Martin van Hagen, Rogier W. Sanders, Marloes Grobben, Karlijn van der Straten, Judith A. Burger, Meliawati Poniman, Stefan Nierkens, Marit J. van Gils, Rory D. de Vries, Virgil A.S.H. Dalm
Journal: Journal of Allergy and Clinical Immunology (2022)

Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective vaccination against COVID-19 is therefore of great importance in this group, but little is known about the immunogenicity of COVID-19 vaccines in these patients.We sought to study humoral and cellular immune responses after mRNA-1273 COVID-19 vaccination in adult patients with IEI.In a prospective, controlled, multicenter study, 505 patients with IEI (common variable immunodeficiency [CVID], isolated or undefined antibody deficiencies, X-linked agammaglobulinemia, combined B- and T-cell immunodeficiency, phagocyte defects) and 192 controls were included. All participants received 2 doses of the mRNA-1273 COVID-19 vaccine. Levels of severe acute respiratory syndrome coronavirus-2-specific binding antibodies, neutralizing antibodies, and T-cell responses were assessed at baseline, 28 days after first vaccination, and 28 days after second vaccination.Seroconversion rates in patients with clinically mild antibody deficiencies and phagocyte defects were similar to those in healthy controls, but seroconversion rates in patients with more severe IEI, such as CVID and combined B- and T-cell immunodeficiency, were lower. Binding antibody titers correlated well to the presence of neutralizing antibodies. T-cell responses were comparable to those in controls in all IEI cohorts, with the exception of patients with CVID. The presence of noninfectious complications and the use of immunosuppressive drugs in patients with CVID were negatively correlated with the antibody response.COVID-19 vaccination with mRNA-1273 was immunogenic in mild antibody deficiencies and phagocyte defects and in most patients with combined B- and T-cell immunodeficiency and CVID. Lowest response was detected in patients with X-linked agammaglobulinemia and in patients with CVID with noninfectious complications. The assessment of longevity of immune responses in these vulnerable patient groups will guide decision making for additional vaccinations.
STAT3 is a biologically relevant therapeutic target in H3K27M-mutant diffuse midline glioma
Authors: Liang Zhang, Cody L Nesvick, Charlie A Day, Jonghoon Choi, Victor M Lu, Timothy Peterson, Erica A Power, Jacob B Anderson, Feda H Hamdan, Paul A Decker, Renae Simons, John P Welby, Ruby Siada, Jizhi Ge, Tatiana Kaptzan, Steven A Johnsen, Edward H Hinchcliffe, David J Daniels
Journal: Neuro-Oncology (2022)

Abstract Background H3K27M-mutant diffuse midline glioma (DMG) is a lethal brain tumor that usually occurs in children. Despite advances in our understanding of its underlying biology, efficacious therapies are severely lacking. Methods We screened a library of drugs either FDA-approved or in clinical trial using a library of patient-derived H3K27M-mutant DMG cell lines with cell viability as the outcome. Results were validated for clinical relevance and mechanistic importance using patient specimens from biopsy and autopsy, patient-derived cell lines, inhibition by gene knockdown and small molecule inhibitors, and patient-derived xenografts. Results Kinase inhibitors were highly toxic to H3K27M-mutant DMG cells. Within this class, STAT3 inhibitors demonstrated robust cytotoxic activity in vitro. Mechanistic analyses revealed one form of activated STAT3, phospho-tyrosine- 705 STAT3 (pSTAT3), was selectively upregulated in H3K27M-mutant cell lines and clinical specimens. STAT3 inhibition by CRISPR/Cas9 knockout, shRNA or small molecule inhibition reduced cell viability in vitro, and partially restored expression of the polycomb repressive mark H3K27me3, which is classically lost in H3K27M-mutant DMG. Putative STAT3-regulated genes were enriched in an H3K27M-knockout DMG cell line, indicating relative gain of STAT3 signaling in K27M-mutant cells. Treatment of patient-derived intracranial xenografts with WP1066, a STAT3 pathway inhibitor currently in clinical use for pediatric brain tumors, resulted in stasis of tumor growth, and increased overall survival. Finally, pSTAT3(Y705) was detected in circulating plasma extracellular vesicles of patients with H3K27M-mutant DMG. Conclusions STAT3 is a biologically relevant therapeutic target in H3K27M-mutant DMG. STAT3 inhibition should be considered in future clinical trials.