tbuckley/cabot-search huggingface dataset:
Management of colonic diverticulitis
Authors: Anne F Peery
Journal: BMJ (2021)

ABSTRACT Left sided colonic diverticulitis is a common and costly gastrointestinal disease in Western countries, characterized by acute onset of often severe abdominal pain. Imaging is necessary to make an initial diagnosis and determine disease severity. Colonoscopy should be done six to eight weeks after diagnosis to rule out a missed colon malignancy. Antibiotic treatment is used selectively in immunocompetent patients with mild acute uncomplicated diverticulitis. The clinical course of diverticulitis commonly includes unpredictable recurrences and chronic gastrointestinal symptoms, which are a detriment to quality of life. A better understanding of prognosis has prompted a shift toward non-operative approaches. The decision to undergo prophylactic colon resection should be individualized to consider the severity of diverticulitis, the patient’s health and immune status, and the patient’s preferences and values, as well as benefits and risks. Because only a section of colon is removed, recurrent diverticulitis remains a risk. Acute diverticulitis with an abscess is treated with antibiotics that cover Gram negative and anaerobic bacteria, with or without percutaneous drainage. Acute diverticulitis with purulent or feculent contamination of the peritoneal cavity is managed with surgery; primary resection and anastomosis is the procedure of choice in stable patients.
Can Transcatheter Aortic Valve Replacement Cure Cardiorenal Syndrome?
Authors: Benjamin Z. Galper
Journal: JAMA Network Open (2021)

Guy Witberg, MD; Tali Steinmetz, MD; Uri Landes, MD; Rotem Pistiner Hanit, BSc; Hefziba Green, MD; Shira Goldman, MD; Hana Vaknin-Assa, MD; Pablo Codner, MD; Leor Perl, MD; Benaya Rozen-Zvi, MD; Ran Kornowski, MD
Interplay of Mineralocorticoid Receptor Antagonists and Empagliflozin in Heart Failure
Authors: João Pedro Ferreira, Faiez Zannad, Stuart J. Pocock, Stefan D. Anker, Javed Butler, Gerasimos Filippatos, Martina Brueckmann, Waheed Jamal, Dominik Steubl, Elke Schueler, Milton Packer
Journal: Journal of the American College of Cardiology (2021)

Mineralocorticoid receptor antagonists (MRAs) and sodium glucose co-transporter 2 inhibitors favorably influence the clinical course of patients with heart failure and reduced ejection fraction. This study sought to study the mutual influence of empagliflozin and MRAs in EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction). Secondary analysis that compared the effects of empagliflozin versus placebo in 3,730 patients with heart failure and a reduced ejection fraction, of whom 71% used MRAs at randomization. The effects of empagliflozin on the primary endpoint, on most efficacy endpoints, and on safety were similar in patients receiving or not receiving an MRA (interaction p > 0.20). For cardiovascular death, the hazard ratios for the effect of empagliflozin versus placebo were 0.82 (95% confidence interval [CI]: 0.65 to 1.05) in MRA users and 1.19 (95% CI: 0.82 to 1.71) in MRA nonusers (interaction p = 0.10); a similar pattern was seen for all-cause mortality (interaction p = 0.098). Among MRA nonusers at baseline, patients in the empagliflozin group were 35% less likely than those in the placebo group to initiate treatment with an MRA following randomization (hazard ratio: 0.65; 95% CI: 0.49 to 0.85). Among MRA users at baseline, patients in the empagliflozin group were 22% less likely than those in the placebo group to discontinue treatment with an MRA following randomization (hazard ratio: 0.78; 95% CI: 0.64 to 0.96). Severe hyperkalemia was less common in the empagliflozin group. In EMPEROR-Reduced, the use of MRAs did not influence the effect of empagliflozin to reduce adverse heart failure and renal outcomes. Treatment with empagliflozin was associated with less discontinuation of MRAs. (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction [EMPEROR-Reduced]; NCT03057977)
David Oliver: Improving DNACPR discussions, decisions, and documentation
Authors: David Oliver
Journal: BMJ (2021)

<h3>ABSTRACT</h3> To mitigate the unprecedented health, social, and economic damage of COVID-19, the Philippines is undertaking a nationwide vaccination program to mitigate the effects of the global pandemic. In this study, we interrogated COVID-19 vaccine hesitancy in the country by deploying a nationwide open-access online survey, two months before the rollout of the national vaccination program. The Health Belief Model (HBM) posits that people are likely to adopt disease prevention behaviors and to accept medical interventions like vaccines if there is sufficient motivation and cues to action. A majority of our 7,193 respondents (62.5%) indicated that they were willing to be vaccinated against COVID-19. Moreover, multivariable analysis revealed that HBM constructs were associated with vaccination intention in the Philippines. Perceptions of high susceptibility, high severity, and significant benefits were all good predictors for vaccination intent. We also found that external cues to action were important. Large majorities of our respondents would only receive the COVID-19 vaccines after many others had received it (72.8%) or after politicians had received it (68.2%). Finally, our study revealed that most (21%) were willing to pay an amount of PHP1,000 [USD20] for the COVID-19 vaccines with an average willing-to-pay amount of PHP1,892 [USD38].
The Airway Microbiota Modulates Effect of Azithromycin Treatment for Episodes of Recurrent Asthma-like Symptoms in Preschool Children: A Randomized Clinical Trial
Authors: Jonathan Thorsen, Jakob Stokholm, Morten Arendt Rasmussen, Martin Steen Mortensen, Asker Daniel Brejnrod, Mathis Hjelmsø, Shiraz Shah, Bo Chawes, Klaus Bønnelykke, Søren Johannes Sørensen, Hans Bisgaard
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Childhood asthma is often preceded by recurrent episodes of asthma-like symptoms, which can be triggered by both viral and bacterial agents. Recent randomized controlled trials have shown that azithromycin treatment reduces episode duration and severity through yet undefined mechanisms. Objectives: To study the influence of the airway microbiota on the effect of azithromycin treatment during acute episodes of asthma-like symptoms. Methods: Children from the COPSAC2010 (Copenhagen Prospective Studies on Asthma in Childhood 2010) cohort with recurrent asthma-like symptoms aged 12–36 months were randomized during acute episodes to azithromycin or placebo as previously reported. Before randomization, hypopharyngeal aspirates were collected and examined by 16S ribosomal RNA gene amplicon sequencing. Measurements and Main Results: In 139 airway samples from 68 children, episode duration after randomization was associated with microbiota richness (7.5% increased duration per 10 additional operational taxonomic units [OTUs]; 95% confidence interval, 1–14%; P = 0.025), with 15 individual OTUs (including several Neisseria and Veillonella), and with microbial pneumotypes defined from weighted UniFrac distances (longest durations in a Neisseria-dominated pneumotype). Microbiota richness before treatment increased the effect of azithromycin by 10% per 10 additional OTUs, and more OTUs were positively versus negatively associated with an increased azithromycin effect (82 vs. 58; P = 0.0032). Furthermore, effect modification of azithromycin was found for five individual OTUs (three OTUs increased and two OTUs decreased the effect; q < 0.05). Conclusions: The airway microbiota in acute episodes of asthma-like symptoms is associated with episode duration and modifies the effect of azithromycin treatment of the episodes in preschool children with recurrent asthma-like symptoms. Clinical trial registered with www.clinicaltrials.gov (NCT01233297).
NLRP3 inflammasome induces CD4+ T cell loss in chronically HIV-1–infected patients
Authors: Chao Zhang, Jin-Wen Song, Hui-Huang Huang, Xing Fan, Lei Huang, Jian-Ning Deng, Bo Tu, Kun Wang, Jing Li, Ming-Ju Zhou, Cui-Xian Yang, Qi-Wen Zhao, Tao Yang, Li-Feng Wang, Ji-Yuan Zhang, Ruo-Nan Xu, Yan-Mei Jiao, Ming Shi, Feng Shao, Rafick-Pierre Sékaly, Fu-Sheng Wang
Journal: Journal of Clinical Investigation (2021)

Chronic HIV-1 infection is generally characterized by progressive CD4+ T cell depletion due to direct and bystander death that is closely associated with persistent HIV-1 replication and an inflammatory environment in vivo. The mechanisms underlying the loss of CD4+ T cells in patients with chronic HIV-1 infection are incompletely understood. In this study, we simultaneously monitored caspase-1 and caspase-3 activation in circulating CD4+ T cells, which revealed that pyroptotic and apoptotic CD4+ T cells are distinct cell populations with different phenotypic characteristics. Levels of pyroptosis and apoptosis in CD4+ T cells were significantly elevated during chronic HIV-1 infection, and decreased following effective antiretroviral therapy. Notably, the occurrence of pyroptosis was further confirmed by elevated gasdermin D activation in lymph nodes of HIV-1-infected individuals. Mechanistically, caspase-1 activation closely correlated with the inflammatory marker expression and was shown to occur through NLRP3 inflammasome activation driven by virus-dependent and/or -independent ROS production, while caspase-3 activation in CD4+ T cells was more closely related to T cell activation status. Hence, our findings show that NLRP3-dependent pyroptosis plays an essential role in CD4+ T cell loss in HIV-1-infected patients and implicate pyroptosis signaling as a target for anti-HIV-1 treatment.
Safety and efficacy of tofacitinib up to 48 months in patients with active psoriatic arthritis: final analysis of the OPAL Balance long-term extension study
Authors: Peter Nash, Laura C Coates, Dona Fleishaker, Alan J Kivitz, Philip J Mease, Dafna D Gladman, Oliver FitzGerald, Cunshan Wang, Joseph Wu, Ming-Ann Hsu, Sujatha Menon, Lara Fallon, Keith S Kanik
Journal: The Lancet Rheumatology (2021)
A phase 2a randomized, placebo-controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24-week results
Authors: Brett King, Emma Guttman-Yassky, Elena Peeva, Anindita Banerjee, Rodney Sinclair, Ana B. Pavel, Linda Zhu, Lori Ann Cox, Brittany Craiglow, Linda Chen, Christopher Banfield, Karen Page, Weidong Zhang, Michael S. Vincent
Journal: Journal of the American Academy of Dermatology (2021)

BackgroundAlopecia areata (AA) is an autoimmune form of hair loss with limited treatments.ObjectiveTo evaluate the efficacy and safety of the Janus kinase inhibitors ritlecitinib and brepocitinib in patients who have AA with ≥ 50% scalp hair loss.MethodsPatients were randomized to once-daily ritlecitinib, brepocitinib, or placebo. The primary efficacy endpoint was a 24-week change from baseline in the Severity of Alopecia Tool (SALT) score. The key secondary efficacy endpoint was the proportion of patients achieving 30% improvement in SALT score (SALT30).ResultsThe ritlecitinib, brepocitinib, and placebo groups included 48, 47, and 47 patients, respectively. At week 24, least-squares mean difference from placebo in SALT score change from baseline was 31.1 (95% confidence interval [CI], 18.8-43.5) for ritlecitinib and 49.2 (95% CI, 36.6-61.7) for brepocitinib (P < .0001 for both comparisons with placebo). SALT30 was achieved by 50% (90% CI, 38%-62%) of patients receiving ritlecitinib, 64% (90% CI, 51%-75%) receiving brepocitinib, and 2% (90% CI, 0%-9%) receiving placebo. Two patients experienced a serious adverse event (rhabdomyolysis) in the brepocitinib group only.LimitationsOnly a single-dosage regimen of each study drug was included.ConclusionTreatment with ritlecitinib or brepocitinib for 24 weeks was efficacious and generally well tolerated. Alopecia areata (AA) is an autoimmune form of hair loss with limited treatments. To evaluate the efficacy and safety of the Janus kinase inhibitors ritlecitinib and brepocitinib in patients who have AA with ≥ 50% scalp hair loss. Patients were randomized to once-daily ritlecitinib, brepocitinib, or placebo. The primary efficacy endpoint was a 24-week change from baseline in the Severity of Alopecia Tool (SALT) score. The key secondary efficacy endpoint was the proportion of patients achieving 30% improvement in SALT score (SALT30). The ritlecitinib, brepocitinib, and placebo groups included 48, 47, and 47 patients, respectively. At week 24, least-squares mean difference from placebo in SALT score change from baseline was 31.1 (95% confidence interval [CI], 18.8-43.5) for ritlecitinib and 49.2 (95% CI, 36.6-61.7) for brepocitinib (P < .0001 for both comparisons with placebo). SALT30 was achieved by 50% (90% CI, 38%-62%) of patients receiving ritlecitinib, 64% (90% CI, 51%-75%) receiving brepocitinib, and 2% (90% CI, 0%-9%) receiving placebo. Two patients experienced a serious adverse event (rhabdomyolysis) in the brepocitinib group only. Only a single-dosage regimen of each study drug was included. Treatment with ritlecitinib or brepocitinib for 24 weeks was efficacious and generally well tolerated.
FP02.04 NSCLC with TPS&gt;90% could have Higher Possibility of Causing Severe irAE; Retrospective Investigation in one Institution
Authors: Y. Akazawa, A. Yoshikawa, T. Kuge, F. Okabe, Y. Yamamoto, M. Ishijima, T. Uenami, M. Kanazu, Y. Yano, T. Yamaguchi, M. Mori
Journal: Journal of Thoracic Oncology (2021)
An integrated epigenomic-transcriptomic landscape of lung cancer reveals novel methylation driver genes of diagnostic and therapeutic relevance
Authors: Xiwei Sun, Jiani Yi, Juze Yang, Yi Han, Xinyi Qian, Yi Liu, Jia Li, Bingjian Lu, Jisong Zhang, Xiaoqing Pan, Yong Liu, Mingyu Liang, Enguo Chen, Pengyuan Liu, Yan Lu
Journal: Theranostics (2021)

Background: Aberrant DNA methylation occurs commonly during carcinogenesis and is of clinical value in human cancers. However, knowledge of the impact of DNA methylation changes on lung carcinogenesis and progression remains limited. Methods: Genome-wide DNA methylation profiles were surveyed in 18 pairs of tumors and adjacent normal tissues from non-small cell lung cancer (NSCLC) patients using Reduced Representation Bisulfite Sequencing (RRBS). An integrated epigenomic-transcriptomic landscape of lung cancer was depicted using the multi-omics data integration method. Results: We discovered a large number of hypermethylation events pre-marked by poised promoter in embryonic stem cells, being a hallmark of lung cancer. These hypermethylation events showed a high conservation across cancer types. Eight novel driver genes with aberrant methylation (e.g., PCDH17 and IRX1) were identified by integrated analysis of DNA methylome and transcriptome data. Methylation level of the eight genes measured by pyrosequencing can distinguish NSCLC patients from lung tissues with high sensitivity and specificity in an independent cohort. Their tumor-suppressive roles were further experimentally validated in lung cancer cells, which depend on promoter hypermethylation. Similarly, 13 methylation-driven ncRNAs (including 8 lncRNAs and 5 miRNAs) were identified, some of which were co-regulated with their host genes by the same promoter hypermethylation. Finally, by analyzing the transcription factor (TF) binding motifs, we uncovered sets of TFs driving the expression of epigenetically regulated genes and highlighted the epigenetic regulation of gene expression of TCF21 through DNA methylation of EGR1 binding motifs. Conclusions: We discovered several novel methylation driver genes of diagnostic and therapeutic relevance in lung cancer. Our findings revealed that DNA methylation in TF binding motifs regulates target gene expression by affecting the binding ability of TFs. Our study also provides a valuable epigenetic resource for identifying DNA methylation-based diagnostic biomarkers, developing cancer drugs for epigenetic therapy and studying cancer pathogenesis.
MA08.10 LUNGMAP Master Protocol (LUNGMAP): Concordance Between Plasma ctDNA and Tissue Molecular Analysis
Authors: P. Mack, K. Minichielle, M. Redman, K. Tolba, D. Kozono, S. Waqar, A. Chowdhury, A. Dowlati, J. Neal, K. Dragnev, C. Aggarwal, F. Hirsch, K. Kelly, D. Gandara, R. Herbst
Journal: Journal of Thoracic Oncology (2021)
Facile Synthesis of a Croconaine‐Based Nanoformulation for Optoacoustic Imaging and Photothermal Therapy
Authors: Nian Liu, Patrick O'Connor, Vipul Gujrati, Dimitris Gorpas, Sarah Glasl, Andreas Blutke, Axel Walch, Karin Kleigrewe, Michael Sattler, Oliver Plettenburg, Vasilis Ntziachristos
Journal: Advanced Healthcare Materials (2021)

Near-infrared (NIR) light absorbing theranostic agents can integrate optoacoustic imaging and photothermal therapy for effective personalized precision medicine. However, most of these agents face the challenges of unstable optical properties, material-associated toxicity, and nonbiodegradability, all of which limit their biomedical application. Several croconaine-based organic agents able to overcome some of these limitations have been recently reported, but these suffer from complicated multistep synthesis protocols. Herein, the use of CR760, a croconaine dye with excellent optical properties, is reported for nanoparticle formulation and subsequent optoacoustic imaging and photothermal therapy. Importantly, CR760 can be conveniently prepared in a single step from commercially available materials. Furthermore, CR760 can be covalently attached, via a polyethylene glycol linker, to the α
P33.13 Prognostic and Predictive Value of Complete Blood Count Parameters in Patients with NSCLC Treated with PD-1 Inhibitors
Authors: I. Tourkantonis, D. Grapsa, A. Charpidou, I. Gkiozos, H. Gogas, D. Psyrri, K. Syrigos
Journal: Journal of Thoracic Oncology (2021)
<i>In vivo</i> fermentation production of humanized noncoding RNAs carrying payload miRNAs for targeted anticancer therapy
Authors: Peng-Cheng Li, Mei-Juan Tu, Pui Yan Ho, Neelu Batra, Michelle M.L. Tran, Jing-Xin Qiu, Theodore Wun, Primo N. Lara, Xiang Hu, Ai-Xi Yu, Ai-Ming Yu
Journal: Theranostics (2021)

Rationale: Noncoding RNAs (ncRNAs) such as microRNAs (miRs or miRNAs) play important roles in the control of cellular processes through posttranscriptional gene regulation. However, ncRNA research is limited to utilizing RNA agents synthesized in vitro. Recombinant RNAs produced and folded in living cells shall better recapitulate biologic RNAs. Methods: Herein, we developed a novel platform for in vivo fermentation production of humanized recombinant ncRNA molecules, namely hBERAs, carrying payload miRNAs or siRNAs. Target hBERAs were purified by anion exchange FPLC method. Functions of hBERA/miRNAs were investigated in human carcinoma cells and antitumor activities were determined in orthotopic osteosarcoma xenograft spontaneous lung metastasis mouse models. Results: Proper human tRNAs were identified to couple with optimal hsa-pre-miR-34a as new fully-humanized ncRNA carriers to accommodate warhead miRNAs or siRNAs. A group of 30 target hBERAs were all heterogeneously overexpressed (each accounting for >40% of total bacterial RNA), which facilitated large-scale production (8-31 mg of individual hBERAs from 1L bacterial culture). Model hBERA/miR-34a-5p and miR-124-3p were selectively processed to warhead miRNAs in human carcinoma cells to modulate target gene expression, enhance apoptosis and inhibit invasiveness. In addition, bioengineered miR-34a-5p and miR-124-3p agents both reduced orthotopic osteosarcoma xenograft tumor growth and spontaneous pulmonary metastases significantly. Conclusion: This novel ncRNA bioengineering technology and resulting recombinant ncRNAs are unique additions to conventional technologies and tools for basic research and drug development.
SARS-CoV-2 infection of human iPSC–derived cardiac cells reflects cytopathic features in hearts of patients with COVID-19
Authors: Juan A. Perez-Bermejo, Serah Kang, Sarah J. Rockwood, Camille R. Simoneau, David A. Joy, Ana C. Silva, Gokul N. Ramadoss, Will R. Flanigan, Parinaz Fozouni, Huihui Li, Pei-Yi Chen, Ken Nakamura, Jeffrey D. Whitman, Paul J. Hanson, Bruce M. McManus, Melanie Ott, Bruce R. Conklin, Todd C. McDevitt
Journal: Science Translational Medicine (2021)

Although coronavirus disease 2019 (COVID-19) causes cardiac dysfunction in up to 25% of patients, its pathogenesis remains unclear. Exposure of human induced pluripotent stem cell (iPSC)-derived heart cells to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed productive infection and robust transcriptomic and morphological signatures of damage, particularly in cardiomyocytes. Transcriptomic disruption of structural genes corroborates adverse morphologic features, which included a distinct pattern of myofibrillar fragmentation and nuclear disruption. Human autopsy specimens from patients with COVID-19 reflected similar alterations, particularly sarcomeric fragmentation. These notable cytopathic features in cardiomyocytes provide insights into SARS-CoV-2-induced cardiac damage, offer a platform for discovery of potential therapeutics, and raise concerns about the long-term consequences of COVID-19 in asymptomatic and severe cases.
Collaboration for the Management of Hydroxychloroquine
Authors: James T. Rosenbaum, Karen H. Costenbader, Julianna Desmarais, Ellen M. Ginzler, Nicole Fett, Susan M. Goodman, James R. O’Dell, Gabriela Schmajuk, Victoria P. Werth, Ronald B. Melles, Michael F. Marmor
Journal: Ophthalmology (2021)
Abstract 264: Automatic Detection of Ventilations Using the Thoracic Impedance Signal During Lucas Chest Compressions
Authors: Xabier Jaureguibeitia, Unai Irusta, Elisabete Aramendi, Pamela Owens, Henry E Wang, Ahamed H Idris
Journal: Circulation (2019)

Introduction: Resuscitation from out-of-cardiac arrest (OHCA) requires control of both chest compressions and lung ventilation. There are few effective methods for detecting ventilations during cardiopulmonary resuscitation. Thoracic impedance (TI) is sensitive to changes in lung air volumes and may allow detection of ventilations but has not been tested with concurrent mechanical chest compressions. Hypothesis: It is possible to automatically detect and characterize ventilations from TI changes during mechanical chest compressions. Methods: A cohort of 420 OHCA cases (27 survivors to hospital discharge) were enrolled in the Dallas-Fort Worth Center for Resuscitation Research cardiac arrest registry. These patients were treated with the LUCAS-2 CPR device and had concurrent TI and capnogram recordings from MRx (Philips, Andover, MA) monitor-defibrillators. We developed a signal processing algorithm to suppress chest compression artifacts from the TI signal, allowing identification of ventilations. We used the capnogram as gold standard for delivered ventilations. We determined the accuracy of the algorithm for detecting capnogram-indicated ventilations, calculating sensitivity, the proportion of true ventilations detected in the TI, and positive predictive value (PPV), the proportion of true ventilations within the detections. We calculated per minute ventilation rate and mean TI amplitude, as surrogate for tidal volume. Statistical differences between survivors and non-survivors were assessed using the Mann-Whitney test. Results: We studied 4331 minutes of TI during CPR. There were a median of 10 (IQR 6-14) ventilations per min and 52 (30-81) ventilations per patient. Sensitivity of TI was 95.9% (95% CI, 74.5-100), and PPV was 95.8% (95% CI, 80.0-100). The median ventilation rates for survivors and non-survivors were 7.75 (5.37-9.91) min -1 and 5.64 (4.46-7.15) min -1 (p&lt;10 -3 ), and the median TI amplitudes were 1.33 (1.03-1.75) Ω and 1.14 (0.77-1.66) Ω (p=0.095). Conclusions: An accurate automatic TI ventilation detection algorithm was demonstrated during mechanical CPR. The relation between ventilation rate during mechanical CPR and survival was significant, but it was not for impedance amplitude.