tbuckley/cabot-search huggingface dataset:
AdvanTIG-203: A randomized phase 2 study comparing anti-TIGIT ociperlimab plus tislelizumab versus tislelizumab plus placebo as second-line treatment in patients with advanced or recurrent esophageal squamous cell carcinoma (ESCC) expressing programmed death-ligand 1 (PD-L1).
Authors: Rui-hua Xu, Sung-Bae Kim, David Tougeron, Yunxia Zuo, Haiyuan Yang, Juan Zhang, Jingwen Shi, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2022)

TPS370 Background: The programmed death-1 (PD-1)/PD-L1 pathway plays an important role in tumor induced immunosuppression. PD-L1 overexpression is observed in approximately 30–60% of esophageal cancers and is associated with poor prognosis. Anti-PD-1 agents demonstrate moderate efficacy in PD-L1-positive esophageal cancer in terms of response rate and overall survival, however, long-term outcomes remain poor due to primary and secondary resistance driven by tumor immune escape. The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is upregulated on T-cells and natural killer cells in multiple solid tumors, which can inhibit anticancer immune responses. Ociperlimab (BGB-A1217) is a novel, humanized, monoclonal antibody that binds TIGIT with high specificity and affinity, blocking the interaction with its ligands on tumor cells. Preclinical and clinical studies suggest that dual targeting with anti-TIGIT and anti-PD-1 antibodies produces synergistic immune cell activation and enhanced antitumor activity. Methods: AdvanTIG-203 is a Phase 2, global, randomized, double-blind, placebo-controlled study (NCT04732494) of patients with unresectable, locally advanced, recurrent or metastatic ESCC, who progressed on or after 1st line systemic therapy and whose tumors express PD-L1 (visually-estimated combined positive score ≥ 10%). After stratification by Eastern Cooperative Oncology Group performance status (0 or 1), number of metastatic sites (≤ 1 or ≥ 2) and region (Asian or non-Asian), 280 patients will be randomized (1:1) to either ociperlimab 900 mg intravenous (IV) plus tislelizumab 200 mg IV every 3 weeks (Q3W), or tislelizumab plus placebo Q3W, until disease progression (per RECIST v1.1), unacceptable toxicity, death or withdrawal of consent. Co-primary endpoints are investigator-assessed overall response rate (ORR) and overall survival (OS) in the intention-to-treat population. A sample size of 280 patients was estimated to provide approximately 94.8% power to detect a 20% difference in ORR at a one-sided significance level of 0.025. With 198 deaths, the study was estimated to provide approximately 86% power to detect a hazard ratio of 0.65 for OS. Secondary endpoints are ORR by independent review, progression-free survival, duration of response, disease control rate, and clinical benefit rate per investigator and independent assessment, cancer-specific health-related quality of life (HRQoL), and safety. Exploratory endpoints include but are not limited to expression of TIGIT, CD226, CD155, CD112, and PD-L1, pharmacokinetics, immunogenicity, and generic HRQoL measures. Clinical trial information: NCT04732494.
Abstract P038: Association Of Discordance Between Low-density Lipoprotein And High-density Lipoprotein Cholesterol Versus Particle Concentration With Incidence Of Type 2 Diabetes: Coronary Artery Risk Development In Young Adults Study
Authors: Jonathan J Ruiz-Ramie, Jacob Barber, Xuewen Wang, John T Wilkins, Janet Snell-bergeon, Don M Lloyd-Jones, Abbi Lane-cordova, Mark A Sarzynski
Journal: Circulation (2022)

Background: The body of literature on discordance between lipoprotein cholesterol and particle concentrations focuses primarily on the relationship between lipoprotein discordance and clinical and subclinical indices of cardiovascular disease. Data are sparse regarding associations between either high (HDL) or low (LDL) density lipoprotein discordance and incident type 2 diabetes (T2D). Purpose: To test the hypothesis that both HDL and LDL discordance status are associated with incident T2D. Methods: All included phenotypes were measured at the year 7 exam among 3891 participants of the CARDIA study. Diabetes status at each exam was classified as a fasting glucose above 126 mg/dL. Sex-specific median-based lipoprotein discordance groups were created and combined into four exclusive cholesterol/particle groups for both HDL and LDL: 1) low/low (below the median for both cholesterol and particle concentration), 2) low/high (below the median for cholesterol, at or above the median for particle concentration), 3) high/low, and 4) high/high. The association of incident T2D with lipoprotein discordance was assessed via sex-specific multivariable proportional hazards regression. All sex-specific models were adjusted for self-identified race and the time varying covariates of age, smoking, and BMI. In the instance of a significant race by discordance interaction term, race-specific models were utilized. The low cholesterol/low particle groups were used as the reference group for all analyses. Results: Approximately 27% of men and 34% of Women were discordant (either low/high or high/low) for HDL while around 15% of both men and women were discordant for LDL. In women only, both HDL and LDL discordance were associated with incident T2D with higher risk associated with lower HDL-C (Low HDL-C/High HDL-P at highest risk of incident T2D; Hazard Ratio [HR] 1.7, 95% confidence interval [CI] 1.1 to 2.6, p=0.01). Race-specific associations were found for LDL discordance with T2D risk, with the High LDL-C/High LDL-P group at higher risk (Black participants only: HR 1.5, 95%CI 1.03 to 2.4, p&lt;0.01). No significant relationships between lipoprotein discordance and T2D incidence were found for males. Conclusions: Lipoprotein concordance/discordance status is significantly associated with incident T2D in women only, although racial differences may be present. These data suggest that measurement of lipoprotein particle concentrations alongside cholesterol measures may provide novel insight into health risks and prevention needs.
Accuracy of a Factory-Calibrated Continuous Glucose Monitor in Individuals With Diabetes on Hemodialysis
Authors: Orianne Villard, Marc D. Breton, Swati Rao, Mary K. Voelmle, Morgan R. Fuller, Helen E. Myers, Ryan K. McFadden, Zander S. Luke, Christian A. Wakeman, Mary Clancy-Oliveri, Ananda Basu, Meaghan M. Stumpf
Journal: Diabetes Care (2022)

OBJECTIVE Continuous glucose monitoring (CGM) improves diabetes management, but its reliability in individuals on hemodialysis is poorly understood and potentially affected by interstitial and intravascular volume variations. RESEARCH DESIGN AND METHODS We assessed the accuracy of a factory-calibrated CGM by using venous blood glucose measurements (vBGM) during hemodialysis sessions and self-monitoring blood glucose (SMBG) at home. RESULTS Twenty participants completed the protocol. The mean absolute relative difference of the CGM was 13.8% and 14.4%, when calculated on SMBG (n = 684) and on vBGM (n = 624), and 98.7% and 100% of values in the Parkes error grid A/B zones, respectively. Throughout 181 days of CGM monitoring, the median time in range (70–180 mg/dL) was 38.5% (interquartile range 29.3–57.9), with 28.7% (7.8–40.6) of the time &amp;gt;250 mg/dL. CONCLUSIONS The overall performance of a factory-calibrated CGM appears reasonably accurate and clinically relevant for use in practice by individuals on hemodialysis and health professionals to improve diabetes management.
Abstract 10646: The Use of Beta Blockers and Renin Angiotensin System Inhibitors Among Patients with Concurrent HFrEF and Alzheimer’s Disease and Related Dementias (ADRD)
Authors: Lauren Gilstrap, Greg Ouellete, Andrew Cohen, Danette Flint, Barbara Gladders, Andrea Austin, Jonathan Skinner
Journal: Circulation (2021)

Introduction: Recent data suggests that patients with concurrent HFrEF and ADRD (HF+ADRD) have markedly higher mortality than HFrEF patients without ADRD. One of the proposed mechanisms for this is a lower rate of guideline directed medical therapy (GDMT) use in the HF+ADRD population. The aim of this study is to determine the change in GDMT use before and after HFrEF hospitalization for patients with HF+ADRD. Methods: We used 100% Medicare Parts A and B and a random 40% sample of Part D to create a cohort of 397,680 fee-for-service beneficiaries with ≥1 hospitalization for HFrEF between 2012 and 2018. We used previously validated ICD-9/10 codes to define ADRD. We created 4 exposure groups for both evidenced-based beta-blockers (BB) and renin angiotensin system inhibitors (RASI): “continued” (on drug before and after hospitalization); “initiated” (not on before, but on after); “discontinued” (on before, but not after) and “never started” (not on before or after). Results: Rates of BB continuation (42% vs. 37%, p&lt;0.001) and initiation (24% vs. 18%, p&lt;0.001) were higher among HFrEF patients without ADRD ( Table 1 ). Rates of BB discontinuation (13% vs. 10%, p&lt;0.001) and never starting (32% vs. 24%, p&lt;0.001) were higher among HF+ADRD patients. Similarly, rates of RASI continuation (33% vs. 26%, p&lt;0.001) and initiation (18% vs. 15%, p&lt;0.001) were higher among HFrEF patients without ADRD. Rates of RASI discontinuation (15% vs. 14%, p&lt;0.001) and never starting (44% vs. 35%, p&lt;0.001) were higher among HF+ADRD patients. Conclusions: Rates of BB/RASI continuation and initiation are higher among HFrEF patients without ADRD while rates of BB/RASI discontinuation and never starting are higher among HF+ADRD patients. Additional work is needed to understand why GDMT use is lower in patients with HF+ADRD and to determine whether, in this population, there are adverse outcomes associated with failing to receive GDMT, such as increased HFrEF symptoms, hospital admissions, and mortality.
Presacral Benign Schwannoma Mimics Malignancy on 18F-FDG and 68Ga-FAPI PET/CT
Authors: Yahua Zhu, Junhao Wu, Yingwei Wang, Jun Geng, Chunyin Zhang
Journal: Clinical Nuclear Medicine (2021)

We present findings of FDG PET/CT and FAPI PET/CT in a 55-year-old woman with a history of black stools and low-back pain. Pelvic CT detected a giant presacral mass that was suspected to be malignant. 18F-FDG and 68Ga-FAPI PET/CT showed that the mass had intense activity. Pathological examination confirmed the mass as a benign schwannoma.
NAD <sup>+</sup> Metabolism in Cardiac Health, Aging, and Disease
Authors: Mahmoud Abdellatif, Simon Sedej, Guido Kroemer
Journal: Circulation (2021)

Nicotinamide adenine dinucleotide (NAD + ) is a central metabolite involved in energy and redox homeostasis as well as in DNA repair and protein deacetylation reactions. Pharmacological or genetic inhibition of NAD + -degrading enzymes, external supplementation of NAD + precursors, and transgenic overexpression of NAD + -generating enzymes have wide positive effects on metabolic health and age-associated diseases. NAD + pools tend to decline with normal aging, obesity, and hypertension, which are all major risk factors for cardiovascular disease, and NAD + replenishment extends healthspan, avoids metabolic syndrome, and reduces blood pressure in preclinical models. In addition, experimental elevation of NAD + improves atherosclerosis, ischemic, diabetic, arrhythmogenic, hypertrophic, or dilated cardiomyopathies, as well as different modalities of heart failure. Here, we critically discuss cardiomyocyte-specific circuitries of NAD + metabolism, comparatively evaluate distinct NAD + precursors for their preclinical efficacy, and raise outstanding questions on the optimal design of clinical trials in which NAD + replenishment or supraphysiological NAD + elevations are assessed for the prevention or treatment of major cardiac diseases. We surmise that patients with hitherto intractable cardiac diseases such as heart failure with preserved ejection fraction may profit from the administration of NAD + precursors. The development of such NAD + -centered treatments will rely on technological and conceptual progress on the fine regulation of NAD + metabolism.
Abstract P151: Higher Gut Microbiota Diversity And Abundance Of Butyrogenic Species Are Associated With Lower Pulse Wave Velocity In The Baltimore Longitudinal Study Of Aging
Authors: Moira K Differding, Toshiko Tanaka, Curtis Tilves, Adam P Spira, Luigi Ferrucci, Noel T Mueller
Journal: Circulation (2022)

Background: Gut microbiota, particularly butyrogenic species, may affect risk of cardiovascular disease through effects on arterial stiffness. However, studies on gut microbiota and arterial stiffness in human population studies are sparse, with no prior studies having used shotgun metagenomic sequencing to identify species. Objective: To investigate associations of gut microbiota with measures of arterial stiffness as measured by pulse wave velocity (PWV). Methods: We studied 780 adults from the Baltimore Longitudinal Study of Aging who provided feces for shotgun metagenomic microbiome sequencing and at least 1 measure of carotid-femoral PWV between 2013 and 2017. We examined associations of PWV (continuous and as quartiles) with gut microbiome features using beta-binomial and linear regression models for microbiota relative abundances; linear regression models for microbial alpha diversity (Shannon index); and PERMANOVA for microbial beta diversity (Weighted Unifrac distance). We adjusted all models for age, sex and race. We used an FDR-threshold of q &lt;0.05 for abundance models. Results: Approximately 55% of our sample were female and 65% identified as white, with a mean age of 71 years. Microbial beta diversity was significantly associated with PWV (Weighted UniFrac p=0.003, R 2 =0.01), and a 1-SD increase in (Shannon index) alpha diversity was associated with a 0.21 decrease in PWV (p=0.002). Twelve species were associated with continuous PWV, including 4 key butyrate producers in dose-response fashion (Figure). These findings persisted after further adjustment for Mediterranean diet score. Conclusion: Higher microbial diversity and abundance of key butyrogenic bacteria were associated with lower arterial stiffness in a racially diverse cohort of US adults. Some of the species associated with arterial stiffness, e.g. F. prausnitzii and other taxa in Figure, have been previously associated with lower cardiovascular disease risk. Clinical trials are needed to determine if these relationships are causal.
Efficacy of 12-months oral itraconazole versus 6-months oral itraconazole to prevent relapses of chronic pulmonary aspergillosis: an open-label, randomised controlled trial in India
Authors: Inderpaul S Sehgal, Sahajal Dhooria, Valliappan Muthu, Kuruswamy T Prasad, Ashutosh N Aggarwal, Arunaloke Chakrabarti, Hansraj Choudhary, Mandeep Garg, Ritesh Agarwal
Journal: The Lancet Infectious Diseases (2022)
A Poem of Rivers and Trees
Authors: Thorsen Haugen
Journal: Annals of Internal Medicine (2022)

On Being a DoctorApril 2022A Poem of Rivers and TreesThorsen Haugen, MDThorsen Haugen, MDGeisinger Medical Center, Danville, PennsylvaniaSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M21-4789 Audio Reading - “A Poem of Rivers and Trees” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “A Poem of Rivers and Trees” by Thorsen Haugen, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Could a greater miracle take place than for us to look through each other's eyes for an instant?—Henry David ThoreauMy first job was in Humboldt County in Northern California. The town of Eureka, where we lived, was a weathered sea town frequently blanketed in fog and rain. This rural community was medically underserved and far from a major medical center, which meant my practice was busy and interesting. However, after 4 years, it became apparent a change was needed. I turned in my resignation and began looking for new opportunities.Leaving was bittersweet. Like a first love, a first ... Author, Article, and Disclosure InformationAffiliations: Geisinger Medical Center, Danville, PennsylvaniaCorresponding Author: Thorsen Haugen, MD, 100 N. Academy Avenue, Danville, PA 17822; e-mail, thorsen.[email protected]com. PreviousarticleNextarticle Advertisement Audio Reading - “A Poem of Rivers and Trees” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “A Poem of Rivers and Trees” by Thorsen Haugen, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics April 2022Volume 175, Issue 4Page: 610 ePublished: 19 April 2022 Issue Published: April 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Brain Responses to Propofol in Advance of Recovery from Coma and Disorders of Consciousness: A Preliminary Study
Authors: Catherine Duclos, Charlotte Maschke, Yacine Mahdid, Danielle Nadin, Alexander Rokos, Caroline Arbour, Mohamed Badawy, Justin Létourneau, Adrian M. Owen, Gilles Plourde, Stefanie Blain-Moraes
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Predicting recovery of consciousness in unresponsive, brain-injured individuals has crucial implications for clinical decision-making. Propofol induces distinctive brain network reconfiguration in the healthy brain as it loses consciousness. In patients with disorders of consciousness, the brain network’s reconfiguration to propofol may reveal the patient’s underlying capacity for consciousness. Objectives: To design and test a new metric for the prognostication of consciousness recovery in disorders of consciousness. Methods: Using a within-subject design, we conducted an anesthetic protocol with concomitant high-density EEG in 12 patients with a disorder of consciousness after a brain injury. We quantified the reconfiguration of EEG network hubs and directed functional connectivity before, during, and after propofol exposure and obtained an index of propofol-induced network reconfiguration: the adaptive reconfiguration index. We compared the index of patients who recovered consciousness 3 months after EEG (n = 3) to that of patients who did not recover or remained in a chronic disorder of consciousness (n = 7) and conducted a logistic regression to assess prognostic accuracy. Measurements and Main Results: The adaptive reconfiguration index was significantly higher in patients who later recovered full consciousness (U value = 21, P = 0.008) and able to discriminate with 100% accuracy whether the patient recovered consciousness. Conclusions: The adaptive reconfiguration index of patients who recovered from a disorder of consciousness at 3-month follow-up was linearly separable from that of patients who did not recover or remained in a chronic disorder of consciousness on the single-subject level. EEG and propofol can be administered at the bedside with few contraindications, affording the adaptive reconfiguration index tremendous translational potential as a prognostic measure of consciousness recovery in acute clinical settings.
Trispecifics Improve Immune-Cell Engagement
Journal: Cancer Discovery (2022)

As drug developers look for new ways to hone the precision of their off-the-shelf immunotherapeutics, a growing number of companies are turning to trispecific antibody designs that offer additional specificity for tumors or enhanced immune-cell activation. Trispecific constructs that engage either T cells or natural killer cells are now in clinical trials, each with their own mechanistic advantages over more conventional bispecific approaches.
Pembrolizumab Alone or With Chemotherapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma in KEYNOTE-048: Subgroup Analysis by Programmed Death Ligand-1 Combined Positive Score
Authors: Barbara Burtness, Danny Rischin, Richard Greil, Denis Soulières, Makoto Tahara, Gilberto de Castro Jr, Amanda Psyrri, Irene Brana, Neus Basté, Prakash Neupane, Åse Bratland, Thorsten Fuereder, Brett G.M. Hughes, Ricard Mesia, Nuttapong Ngamphaiboon, Tamara Rordorf, Wan Zamaniah Wan Ishak, Joy Ge, Ramona F. Swaby, Burak Gumuscu, Kevin Harrington
Journal: Journal of Clinical Oncology (2022)

The phase III KEYNOTE-048 (ClinicalTrials.gov identifier: NCT02358031) trial of pembrolizumab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) included planned efficacy analyses in the total population and in participants with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 1 and CPS ≥ 20. To further characterize the predictive value of PD-L1 expression on outcome, we conducted efficacy analyses in the PD-L1 CPS < 1 and CPS 1-19 subgroups in KEYNOTE-048.
Accumulation of 99mTc-DTPA in Lumbar Tuberculosis
Authors: Hongyan Yin, Haojun Yu, Dai Shi, Jing Lv, Hongcheng Shi
Journal: Clinical Nuclear Medicine (2022)

A 70-year-old woman with lumbar and renal tuberculosis underwent 99mTc-DTPA renal scintigraphy to evaluate renal function before lumbar lesion resection and nephrectomy. The images incidentally identified a focus of abnormal DTPA activity in the midline of the abdomen, which corresponded to lumbar tuberculosis revealed by CT images. Subsequent pathology after the resection of the lesions was consistent with lumbar and renal tuberculosis.
Racial Disparities and Gastrointestinal Cancer—How Structural and Institutional Racism in the US Health System Fails Black Patients
Authors: Shervin Assari, Helena Hansen
Journal: JAMA Network Open (2022)

Baylee F. Bakkila, BA, BS; Daniel Kerekes, MD; Marcella Nunez-Smith, MD, MHS; Kevin G. Billingsley, MD, MBA; Nita Ahuja, MD, MBA; Karen Wang, MD, MHS; Carol Oladele, PhD, MPH; Caroline H. Johnson, PhD; Sajid A. Khan, MD