tbuckley/cabot-search huggingface dataset:
Comparative Effectiveness of Microdecompression Alone vs Decompression Plus Instrumented Fusion in Lumbar Degenerative Spondylolisthesis
Authors: Ivar Magne Austevoll, Rolf Gjestad, Tore Solberg, Kjersti Storheim, Jens Ivar Brox, Erland Hermansen, Frode Rekeland, Kari Indrekvam, Christian Hellum
Journal: JAMA Network Open (2020)

Conflicting evidence and large practice variation are present in the surgical treatment of degenerative spondylolisthesis. More than 90% of surgical procedures in the United States include instrumented fusion compared with 50% or less in other countries.To evaluate whether the effectiveness of microdecompression alone is noninferior to decompression with instrumented fusion in a real-world setting.This multicenter comparative effectiveness study with a noninferiority design assessed prospective data from the Norwegian Registry for Spine Surgery. From September 19, 2007, to December 21, 2015, 1376 patients at 35 Norwegian orthopedic and neurosurgical departments underwent surgery for lumbar spinal stenosis with degenerative spondylolisthesis without scoliosis. After excluding patients undergoing laminectomy alone, fusion without instrumentation, or surgery in more than 2 levels and those with a former operation at the index level, 794 patients were included in the analyses, regardless of missing or incomplete follow-up data, before propensity score matching. Data were analyzed from March 20 to October 30, 2018.Microdecompression alone or decompression with instrumented fusion.A reduction from baseline of 30% or greater in the Oswestry Disability Index at 12-month follow-up.After propensity score matching, 570 patients (413 female [72%]; mean [SD] age, 64.7 [9.5] years) were included for comparison, with 285 undergoing microdecompression (mean [SD] age, 64.6 [9.8] years; 205 female [72%]) and 285 undergoing decompression with instrumented fusion (mean [SD] age, 64.8 [9.2] years; 208 female [73%]). The proportion of each type of procedure varied between departments. However, changes in outcome scores varied within patients but not between departments. The proportion of patients with improvement in the Oswestry Disability Index of at least 30% was 150 of 219 (68%) in the microdecompression group and 155 of 215 (72%) in the instrumentation group. The 95% CI (-12% to 5%) for the difference of -4% was above the predefined margin of noninferiority (-15%). Microdecompression alone was associated with shorter operation time (mean [SD], 89 [44] vs 180 [65] minutes; P < .001) and shorter hospital stay (mean [SD], 2.5 [2.4] vs 6.4 [3.0] days; P < .001).Among patients with degenerative spondylolisthesis, the clinical effectiveness of microdecompression alone was noninferior to that of decompression with instrumented fusion. Microdecompression alone was also associated with shorter durations of surgery and hospital stay, supporting the suggestion that the less invasive procedure should be considered for most patients.
Safety of Anti–PD-L1 Inhibition in HIV-1–Infected Patients With Cancer
Authors: Tim Johannes Adrianus Dekker
Journal: JAMA Oncology (2020)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications 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 Oncology journal
Histologic Features of Colon Biopsies (Geboes Score) Associated With Progression of Ulcerative Colitis for the First 36 Months After Biopsy
Authors: Fernando Magro, Catarina Alves, Joanne Lopes, Susana Lopes, Helena Tavares de Sousa, José Cotter, Vitor Macedo da Silva, Paula Lago, Ana Vieira, Mariana Brito, Maria A.M. Duarte, Francisco Portela, João P. Silva, Paula Ministro, Bruno Arroja, Liliana Carvalho, Joana Torres, Mafalda Santiago, Maria Manuela Estevinho, Silvio Danese, Laurent Peyrin-Biroulet, Cláudia Camila Dias, Paula Borralho, Roger M. Feakins, Fátima Carneiro
Journal: Clinical Gastroenterology and Hepatology (2020)
Evolutionary Genomics of Niche-Specific Adaptation to the Cystic Fibrosis Lung in <i>Pseudomonas aeruginosa</i>
Authors: Jeremy R Dettman, Rees Kassen
Journal: Molecular Biology and Evolution (2020)

The comparative genomics of the transition of the opportunistic pathogen Pseudomonas aeruginosa from a free-living environmental strain to one that causes chronic infection in the airways of cystic fibrosis (CF) patients remain poorly studied. Chronic infections are thought to originate from colonization by a single strain sampled from a diverse, globally distributed population, followed by adaptive evolution to the novel, stressful conditions of the CF lung. However, we do not know whether certain clades are more likely to form chronic infections than others and we lack a comprehensive view of the suite of genes under positive selection in the CF lung. We analyzed whole-genome sequence data from 1,000 P. aeruginosa strains with diverse ecological provenances including the CF lung. CF isolates were distributed across the phylogeny, indicating little genetic predisposition for any one clade to cause chronic infection. Isolates from the CF niche experienced stronger positive selection on core genes than those derived from environmental or acute infection sources, consistent with recent adaptation to the lung environment. Genes with the greatest differential positive selection in the CF niche include those involved in core cellular processes such as metabolism, energy production, and stress response as well as those linked to patho-adaptive processes such as antibiotic resistance, cell wall and membrane modification, quorum sensing, biofilms, mucoidy, motility, and iron homeostasis. Many genes under CF-specific differential positive selection had regulatory functions, consistent with the idea that regulatory mutations play an important role in rapid adaptation to novel environments.
Retinoic acid–responsive CD8 effector T cells are selectively increased in IL-23–rich tissue in gastrointestinal GVHD
Authors: Jennifer A. Ball, Andrew Clear, James Aries, Sarah Charrot, Caroline Besley, Matt Mee, Andrew Stagg, James O. Lindsay, Jamie Cavenagh, Maria Calaminci, John G. Gribben, Jeff Davies
Journal: Blood (2020)
Efficacy and safety of once-daily single-inhaler triple therapy (FF/UMEC/VI) versus FF/VI in patients with inadequately controlled asthma (CAPTAIN): a double-blind, randomised, phase 3A trial
Authors: Laurie A Lee, Zelie Bailes, Neil Barnes, Louis-Philippe Boulet, Dawn Edwards, Andrew Fowler, Nicola A Hanania, Huib A M Kerstjens, Edward Kerwin, Robert Nathan, John Oppenheimer, Alberto Papi, Steven Pascoe, Guy Brusselle, Guy Peachey, Neal Sule, Maggie Tabberer, Ian D Pavord
Journal: The Lancet Respiratory Medicine (2020)
AB0063 Intensive therapy of system variant juvenile rheumatoid arthritis
Authors: TM Fomenko, GI Donov, IE Shahbazyan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Combined plasmapheresis (PP) with methotrexate was used in 39 children aged 2 – 15 with severe system variant juvenile rheumatoid arthritis. Juvenile rheumatoid arthritis accomponied persistence infection and septic complication. <h3>Methods</h3> PP was conducted every other day 5 times. After each PP followed by immunosupressants therapy (PIT) (bolus methylprednisolone, methotrexate). Total dose was at most 15 mg/week. Then patients received injections imunoglobulines every other day 3 times. Total dose imunoglobulines was 0,4 ? 0,6 mg/kg. 12 patients had herpes infection. Before intensive therapy patients received zovirax. <h3>Results</h3> During first week by used intensive methods of therapy used to disappear basic indication of disease. After 2 weeks state of patients was stably and not required intensive therapy. 9 patients from 39 had remission about 12 months. These patients used intensive methods of therapy repeatedly. 12 patients had exacerbation a year later after intensive therapy. These patients received only basic therapy. 1 died 2 years after the end of the treatment. 17 patients developed complete remission in 16 ? 36 months. All these patients received basic therapy (prednisolone, methotrexate).
Effectiveness of a high volume injection as treatment for chronic Achilles tendinopathy: randomised controlled trial
Authors: Arco C van der Vlist, Robert F van Oosterom, Peter L J van Veldhoven, Sita M A Bierma-Zeinstra, Jan H Waarsing, Jan A N Verhaar, Robert-Jan de Vos
Journal: BMJ (2020)

To study whether a high volume injection without corticosteroids improves clinical outcome in addition to usual care for adults with chronic midportion Achilles tendinopathy.Patient and assessor blinded, placebo controlled randomised clinical trial.Sports medicine department of a large district general hospital, the Netherlands.80 adults (aged 18-70 years) with clinically diagnosed chronic midportion Achilles tendinopathy and neovascularisation on ultrasonography. 39 were randomised to a high volume injection without corticosteroids and 41 to placebo.Participants were instructed to perform an exercise programme for 24 weeks (usual care) combined with one 50 mL high volume injection of saline and lidocaine (intervention group) or one 2 mL placebo injection of saline and lidocaine (placebo group) at baseline.Primary outcome was pain and function assessed using the validated Victorian Institute of Sports Assessment-Achilles (VISA-A) questionnaire at 24 weeks (analysed using a generalised estimation equations model). Secondary outcomes were patient satisfaction, return to sport, degree of ultrasonographic Doppler flow, visual analogue scale on 10 hop test, power and flexibility of the gastrocnemius and soleus muscles, pain detect questionnaire for neuropathic pain, and pain coping inventory. Participants were evaluated at baseline and at 2, 6, 12, and 24 weeks.Only one participant (1%) was lost to follow-up. The estimated mean VISA-A score improved significantly, from 40.4 (95% confidence interval 32.0 to 48.7) at baseline to 59.1 (50.4 to 67.8) at 24 weeks in the high volume injection group and from 36.9 (27.1 to 46.8) to 58.5 (47.9 to 69.1) in the placebo group. The VISA-A score over time did not differ between the groups (adjusted between group difference at 24 weeks 0.5 points, 95% confidence interval -17.8 to 18.8). No significant between group differences were found for patient satisfaction (21/37 (57%) v 19/39 (49%) patients, P=0.50) and return to desired sport (15/29 (52%) v 19/31 (61%) patients active in sports, P=0.65) at 24 weeks. None of the other secondary outcomes differed between the two groups.A high volume injection without corticosteroids in addition to usual care is not effective for symptom reduction in patients with chronic midportion Achilles tendinopathy. On the basis of our findings, we cannot recommend the use of a high volume injection in this patient group.ClinicalTrials.gov NCT02996409.
Cell-based artificial APC resistant to lentiviral transduction for efficient generation of CAR-T cells from various cell sources
Authors: Andrea Schmidts, Leah C Marsh, Ambike A Srivastava, Amanda A Bouffard, Angela C Boroughs, Irene Scarfò, Rebecca C Larson, Felipe Bedoya, Bryan D Choi, Matthew J Frigault, Stefanie R Bailey, Mark B Leick, Sonika Vatsa, Michael C Kann, Michelle S Prew, Benjamin P Kleinstiver, J Keith Joung, Marcela V Maus
Journal: Journal for ImmunoTherapy of Cancer (2020)

Adoptive cell therapy with chimeric antigen receptor T cells (CAR-T) has become a standard treatment for patients with certain aggressive B cell malignancies and holds promise to improve the care of patients suffering from numerous other cancers in the future. However, the high manufacturing cost of CAR-T cell therapies poses a major barrier to their broader clinical application. Among the key cost drivers of CAR-T production are single-use reagents for T cell activation and clinical-grade viral vector. The presence of variable amounts of contaminating monocytes in the starting material poses an additional challenge to CAR-T manufacturing, since they can impede T cell stimulation and transduction, resulting in manufacturing failure.We created K562-based artificial antigen-presenting cells (aAPC) with genetically encoded T cell stimulation and costimulation that represent an inexhaustible source for T cell activation. We additionally disrupted endogenous expression of the low-density lipoprotein receptor (LDLR) on these aAPC (aAPC-ΔLDLR) using CRISPR-Cas9 gene editing nucleases to prevent inadvertent lentiviral transduction and avoid the sink effect on viral vector during transduction. Using various T cell sources, we produced CD19-directed CAR-T cells via aAPC-ΔLDLR-based activation and tested their in vitro and in vivo antitumor potency against B cell malignancies.We found that lack of LDLR expression on our aAPC-ΔLDLR conferred resistance to lentiviral transduction during CAR-T production. Using aAPC-ΔLDLR, we achieved efficient expansion of CAR-T cells even from unpurified starting material like peripheral blood mononuclear cells or unmanipulated leukapheresis product, containing substantial proportions of monocytes. CD19-directed CAR-T cells that we produced via aAPC-ΔLDLR-based expansion demonstrated potent antitumor responses in preclinical models of acute lymphoblastic leukemia and B-cell lymphoma.Our aAPC-ΔLDLR represent an attractive approach for manufacturing of lentivirally transduced T cells that may be simpler and more cost efficient than currently available methods.
FcγRIIB engagement drives agonistic activity of Fc-engineered αOX40 antibody to stimulate human tumor-infiltrating T cells
Authors: Lucia Campos Carrascosa, Adriaan A van Beek, Valeska de Ruiter, Michail Doukas, Jie Wei, Timothy S Fisher, Keith Ching, Wenjing Yang, Karlijn van Loon, Patrick P C Boor, Yannick S Rakké, Lisanne Noordam, Pascal Doornebosch, Dirk Grünhagen, Kees Verhoef, Wojciech G Polak, Jan N M IJzermans, Irene Ni, Yik Andy Yeung, Shahram Salek-Ardakani, Dave Sprengers, Jaap Kwekkeboom
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background OX40 (CD134) is a costimulatory molecule of the tumor necrosis factor receptor superfamily that is currently being investigated as a target for cancer immunotherapy. However, despite promising results in murine tumor models, the clinical efficacy of agonistic αOX40 antibodies in the treatment of patients with cancer has fallen short of the high expectation in earlier-stage trials. Methods Using lymphocytes from resected tumor, tumor-free (TF) tissue and peripheral blood mononuclear cells (PBMC) of 96 patients with hepatocellular and colorectal cancers, we determined OX40 expression and the in vitro T-cell agonistic activity of OX40-targeting compounds. RNA-Seq was used to evaluate OX40-mediated transcriptional changes in CD4+ and CD8+ human tumor-infiltrating lymphocytes (TILs). Results Here, we show that OX40 was overexpressed on tumor-infiltrating CD4+ T cells compared with blood and TF tissue-derived T cells. In contrast to a clinical candidate αOX40 antibody, treatment with an Fc-engineered αOX40 antibody (αOX40_v12) with selectively enhanced FcγRIIB affinity, stimulated in vitro CD4+ and CD8+ TIL expansion, as well as cytokine and chemokine secretions. The activity of αOX40_v12 was dependent on FcγRIIB engagement and intrinsic CD3/CD28 signals. The transcriptional landscape of CD4+ and CD8+ TILs shifted toward a prosurvival, inflammatory and chemotactic profile on treatment with αOX40_v12. Conclusions OX40 is overexpressed on CD4+ TILs and thus represents a promising target for immunotherapy. Targeting OX40 with currently used agonistic antibodies may be inefficient due to lack of OX40 multimerization. Thus, Fc engineering is a powerful tool in enhancing the agonistic activity of αOX40 antibody and may shape the future design of antibody-mediated αOX40 immunotherapy.
Abstract 14920: Optimal Timing of Extracorporeal Membrane Oxygenation in Patients With Acute Myocardial Infarction Complicated by Profound Cardiogenic Shock After Resuscitated Cardiac Arrest
Authors: Youngkeun Ahn, Min Chul Kim, Jae Yeong Cho, Ki Hong Lee, Doo Sun Sim, Hyun Ju Yoon, Nam Sik Yoon, Kye Hun Kim, Young Joon Hong, Hyung Wook Park, Ju Han Kim, Myung Ho Jeong, Jeong Gwan Cho, Jong Chun Park
Journal: Circulation (2018)

Introduction: Mortality is very high in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) or cardiac arrest despite intensive use of percutaneous coronary interv...
E-cigarette Use Among Middle and High School Students — United States, 2020
Authors: Teresa W. Wang, Linda J. Neff, Eunice Park-Lee, Chunfeng Ren, Karen A. Cullen, Brian A. King
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

The use of any tobacco product by youths is unsafe, including electronic cigarettes (e-cigarettes) (1). Most e-cigarettes contain nicotine, which is highly addictive, can harm the developing adolescent brain, and can increase risk for future addiction to other drugs (1). E-cigarette use has increased considerably among U.S. youths since 2011 (1,2). Multiple factors have contributed to this increase, including youth-appealing flavors and product innovations (1-3). Amid the widespread use of e-cigarettes and popularity of certain products among youths, on February 6, 2020, the Food and Drug Administration (FDA) implemented a policy prioritizing enforcement against the manufacture, distribution, and sale of certain unauthorized flavored prefilled pod or cartridge-based e-cigarettes (excluding tobacco or menthol).
Rituximab Dose Adjusted EPOCH Improves Progression-Free Survival of Patients Affected By Diffuse Large Cell Lymphomas with Double Expression of MYC and BCL2 Proteins
Authors: Anna Dodero, Anna Guidetti, Alessandra Tucci, Alessio Pellegrinelli, Antonello Cabras, Liliana Franca Devizzi, Lucia Farina, Luca Pappalettera, Alberto Mussetti, Maria Chiara Di Chio, Rosa Jessica, Martina Soldarini, Angela Passi, Paola Matteucci, Stefano A. Pileri, Giuseppe Rossi, Paolo Corradini
Journal: Blood (2017)
Hospital errors led to patient’s death, finds coroner
Authors: Clare Dyer
Journal: BMJ (2020)

Hospital errors that were later exposed in a whistleblower’s letter contributed to the death of a woman five weeks after bowel surgery, a coroner has concluded.

Susan Warby, 57, was mistakenly given a glucose rather than a saline drip at West Suffolk Hospital after an operation for a perforated bowel in July 2018. Staff noticed a rise in blood sugar concentrations but gave her insulin to lower them rather than check the drip, which remained in place for 36 hours.

The Suffolk senior coroner …
Comorbid acne inversa and Dowling–Degos disease due to a single <i>NCSTN</i> mutation: is there enough evidence?
Authors: M.A. Hermasch, M.P. Schön, J. Frank
Journal: British Journal of Dermatology (2020)

Linked Article: Garcovich et al. Br J Dermatol 2020; 183:758–759.
Trends in Cardiovascular Mortality Among a Cohort of Children and Young Adults Starting Dialysis in 1995 to 2015
Authors: Elaine Ku, Charles E. McCulloch, Patrick Ahearn, Barbara A. Grimes, Mark M. Mitsnefes
Journal: JAMA Network Open (2020)

Survival of patients receiving dialysis has improved during the last 2 decades. However, few studies have examined temporal trends in the attributed causes of death (especially cardiovascular-related) in young populations.To determine temporal trends and risk of cause-specific mortality (ie, cardiovascular and infectious) for children and young adults receiving dialysis.This retrospective cohort study examined the records of children and young adults (aged <30 years) starting dialysis between 1995 and 2015 according to the United States Renal Data System database. Analyses were performed between June 2019 and June 2020. Fine-Gray models were used to examine trends in risk of different cardiovascular-related deaths. Models were adjusted for age, sex, race, neighborhood income, cause of end-stage kidney disease, insurance type, and comorbidities. Analyses were performed separately for children (ie, age <18 years) and young adults (between ages 18 and 30 years). Follow-up was censored at death or administratively, and transplantation was treated as a competing event.Calendar year.Cardiovascular cause-specific mortality.A total of 80 189 individuals (median [interquartile range] age, 24 [19-28] years; 36 259 [45.2%] female, 29 508 [36.8%] Black, and 15 516 [19.3%] Hispanic white) started dialysis and 16 179 experienced death during a median (interquartile range) of 14.3 (14.0-14.7) years of follow-up. Overall, 40.2% of deaths were from cardiovascular-related causes (6505 of 16 179 patients). In adjusted analysis, risk of cardiovascular-related death was stable initially but became statistically significantly lower after 2006 (vs 1995) in those starting dialysis as either children (subhazard ratio [SHR], 0.74; 95% CI, 0.55-1.00) or adults (SHR, 0.90; 95% CI, 0.83-0.98). Risk of sudden cardiac death improved steadily for all age groups, but to a greater degree in children (SHR, 0.31; 95% CI, 0.20-0.47) vs young adults (SHR, 0.64; 95% CI, 0.56-0.73) comparing 2015 vs 1995. Risk of stroke became statistically significantly lower around 2010 (vs 1995) for children (SHR, 0.40; 95% CI, 0.18-0.88) and young adults (SHR, 0.76; 95% CI, 0.59-0.99).In this study, the risk of cardiovascular-related death declined for children and young adults starting dialysis during the last 2 decades, but trends differed depending on age at dialysis initiation and the specific cause of death. Additional studies are needed to improve risk of cardiovascular disease in young populations.