tbuckley/cabot-search huggingface dataset:
Intercellular transfer of miR-200c-3p impairs the angiogenic capacity of cardiac endothelial cells
Authors: Lara Ottaviani, Rio P. Juni, Ricardo C. de Abreu, Marida Sansonetti, Vasco Sampaio-Pinto, Julie Halkein, Jana C. Hegenbarth, Nadja Ring, Kevin Knoops, Jordy M.M. Kocken, Carlos de Jesus, Auriane C. Ernault, Hamid el Azzouzi, Frank Rühle, Servé Olieslagers, Hugo Fernandes, Lino Ferreira, Luca Braga, Monika Stoll, Diana S. Nascimento, Leon J. de Windt, Paula A. da Costa Martins
Journal: Molecular Therapy (2022)

As mediators of intercellular communication, extracellular vesicles containing molecular cargo, such as microRNAs, are secreted by cells and taken up by recipient cells to influence their cellular phenotype and function. Here we report that cardiac stress-induced differential microRNA content, with miR-200c-3p being one of the most enriched, in cardiomyocyte-derived extracellular vesicles mediates functional cross-talk with endothelial cells. Silencing of miR-200c-3p in mice subjected to chronic increased cardiac pressure overload resulted in attenuated hypertrophy, smaller fibrotic areas, higher capillary density, and preserved cardiac ejection fraction. We were able to maximally rescue microvascular and cardiac function with very low doses of antagomir, which specifically silences miR-200c-3p expression in non-myocyte cells. Our results reveal vesicle transfer of miR-200c-3p from cardiomyocytes to cardiac endothelial cells, underlining the importance of cardiac intercellular communication in the pathophysiology of heart failure. As mediators of intercellular communication, extracellular vesicles containing molecular cargo, such as microRNAs, are secreted by cells and taken up by recipient cells to influence their cellular phenotype and function. Here we report that cardiac stress-induced differential microRNA content, with miR-200c-3p being one of the most enriched, in cardiomyocyte-derived extracellular vesicles mediates functional cross-talk with endothelial cells. Silencing of miR-200c-3p in mice subjected to chronic increased cardiac pressure overload resulted in attenuated hypertrophy, smaller fibrotic areas, higher capillary density, and preserved cardiac ejection fraction. We were able to maximally rescue microvascular and cardiac function with very low doses of antagomir, which specifically silences miR-200c-3p expression in non-myocyte cells. Our results reveal vesicle transfer of miR-200c-3p from cardiomyocytes to cardiac endothelial cells, underlining the importance of cardiac intercellular communication in the pathophysiology of heart failure.
IS LEFT VENTRICULAR ASSIST DEVICE ASSOCIATED WITH ADVERSE PERIPROCEDURAL OUTCOMES IN PATIENTS UNDERGOING CARDIAC TRANSPLANTATION?
Authors: Neelkumar Patel, Birendra Amgai, Adrija Hajra, Sandipan Chakraborty, Sriram Chowdary, Dhrubajyoti Bandyopadhyay, Zeel Patel, Sagar Ranka, Nikhil Cordeiro, Mazin Khalid
Journal: Journal of the American College of Cardiology (2022)
Multicenter, single-arm, phase II trial of camrelizumab and chemotherapy as neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma
Authors: Jun Liu, Yang Yang, Zhichao Liu, Xiaolong Fu, Xiaoyue Cai, Hongxuan Li, Li Zhu, Yan Shen, Hong Zhang, Yifeng Sun, Hezhong Chen, Bentong Yu, Renquan Zhang, Jinchen Shao, Ming Zhang, Zhigang Li
Journal: Journal for ImmunoTherapy of Cancer (2022)

Camrelizumab and chemotherapy demonstrated durable antitumor activity with a manageable safety profile as first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the safety and efficacy of camrelizumab plus neoadjuvant chemotherapy, using pathologically complete response (pCR) as primary endpoint, in the treatment for locally advanced ESCC.Patients with locally advanced but resectable thoracic ESCC, staged as T1b-4a, N2-3 (≥3 stations), and M0 or M1 lymph node metastasis (confined to the supraclavicular lymph nodes) were enrolled. Eligible patients received intravenous camrelizumab (200 mg, day 1) plus nab-paclitaxel (100 mg/m2, day 1, 8, 15) and carboplatin (area under curve of 5 mg/mL/min, day 1) of each 21-days cycle, for two cycles before surgery. The primary endpoint is pCR rate in the per-protocol population. Safety was assessed in the modified intention-to-treat population that was treated with at least one dose of camrelizumab.From November 20, 2019 to December 22, 2020, 60 patients were enrolled. 55 (91.7%) patients completed the full two-cycle treatment successfully. 51 patients underwent surgery and R0 resection was achieved in 50 (98.0%) patients. pCR (ypT0N0) was identified in 20 (39.2%) patients and 5 (9.8%) patients had complete response of the primary tumor but residual disease in lymph nodes alone (ypT0N+). 58 patients (96.7%) had any-grade treatment-related adverse events (TRAEs), with the most common being leukocytopenia (86.7%). 34 patients (56.7%) had adverse events of grade 3 or worse, and one patient (1.7%) occurred a grade 5 adverse event. There was no in-hospital and postoperative 30-day as well as 90-day mortality.The robust antitumor activity of camrelizumab and chemotherapy was confirmed and demonstrated without unexpected safety signals. Our findings established camrelizumab and chemotherapy as a promising neoadjuvant treatment for locally advanced ESCC.ChiCTR1900026240.
IMPACT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE ON SHORT-TERM OUTCOME IN PATIENTS WITH ST-ELEVATION MYOCARDIAL INFARCTION DURING COVID-19 PANDEMIC: INSIGHTS FROM THE INTERNATIONAL MULTICENTER ISACS-STEMI REGISTRY
Authors: Giuseppe De Luca, Matteo Nardin, Magdy Algowhary, Berat Uguz, Dinaldo Cavalcanti Oliveira, Vladimir Ganyukov, Zan Dimitar Zimbakov, Miha Cercek, Lisette Okkels Jensen, Poay Huan Loh, Lucian Calmac, Gerard Roura, Alexandre Schaan Quadros, Marek Milewski, Fortunato Scotto di Uccio, Clemens von Birgelen, Gustavo Pessah, Bernardino Tuccillo, Giuliana Cortese, Guido Parodi, Mohammed Bouragdha, Elvin Kedhi, Pablo Lamelas, Harry Suryapranata, Monica Verdoia
Journal: Journal of the American College of Cardiology (2022)
SEX DIFFERENCES IN NATRIURETIC PEPTIDE TESTING IN PATIENTS HOSPITALIZED WITH HEART FAILURE
Authors: Parul U. Gandhi, Tessa Runels, Melissa Skanderson, Lori Bastian, Cynthia Brandt, Ronald G. Hauser, Shelli Leore Feder, Benjamin Rodwin, Melissa Farmer, Bevanne Bean-Mayberry, Kathleen Akgun
Journal: Journal of the American College of Cardiology (2022)
Metabolic adaptation of ovarian tumors in patients treated with an IDO1 inhibitor constrains antitumor immune responses
Authors: Kunle Odunsi, Feng Qian, Amit A. Lugade, Han Yu, Melissa A. Geller, Steven P. Fling, Judith C. Kaiser, Andreanne M. Lacroix, Leonard D’Amico, Nirasha Ramchurren, Chihiro Morishima, Mary L. Disis, Lucas Dennis, Patrick Danaher, Sarah Warren, Van Anh Nguyen, Sudharshan Ravi, Takemasa Tsuji, Spencer Rosario, Wenjuan Zha, Alan Hutson, Song Liu, Shashikant Lele, Emese Zsiros, A. J. Robert McGray, Jessie Chiello, Richard Koya, Thinle Chodon, Carl D. Morrison, Vasanta Putluri, Nagireddy Putluri, Donald E. Mager, Rudiyanto Gunawan, Martin A. Cheever, Sebastiano Battaglia, Junko Matsuzaki
Journal: Science Translational Medicine (2022)

To uncover underlying mechanisms associated with failure of indoleamine 2,3-dioxygenase 1 (IDO1) blockade in clinical trials, we conducted a pilot, window-of-opportunity clinical study in 17 patients with newly diagnosed advanced high-grade serous ovarian cancer before their standard tumor debulking surgery. Patients were treated with the IDO1 inhibitor epacadostat, and immunologic, transcriptomic, and metabolomic characterization of the tumor microenvironment was undertaken in baseline and posttreatment tumor biopsies. IDO1 inhibition resulted in efficient blockade of the kynurenine pathway of tryptophan degradation and was accompanied by a metabolic adaptation that shunted tryptophan catabolism toward the serotonin pathway. This resulted in elevated nicotinamide adenine dinucleotide (NAD + ), which reduced T cell proliferation and function. Because NAD + metabolites could be ligands for purinergic receptors, we investigated the impact of blocking purinergic receptors in the presence or absence of NAD + on T cell proliferation and function in our mouse model. We demonstrated that A2a and A2b purinergic receptor antagonists, SCH58261 or PSB1115, respectively, rescued NAD + -mediated suppression of T cell proliferation and function. Combining IDO1 inhibition and A2a/A2b receptor blockade improved survival and boosted the antitumor immune signature in mice with IDO1 overexpressing ovarian cancer. These findings elucidate the downstream adaptive metabolic consequences of IDO1 blockade in ovarian cancers that may undermine antitumor T cell responses in the tumor microenvironment.
FEASIBILITY STUDY OF PERCUTANEOUSLY OCCLUDING LEFT ATRIAL APPENDAGES FENESTRATIONS DUE TO INCOMPLETE OR FAILED SURGICAL LIGATION USING VARIOUS AMPLATZER OCCLUDER DEVICES
Authors: Safwan Kassas, Peter Fattal, Brenda Wagner, Jennifer Thurston, Brandi Horgan
Journal: Journal of the American College of Cardiology (2022)
A FATAL COMPLICATION OF PERIPARTUM CARDIOMYOPATHY IN A HISPANIC WOMAN
Authors: Erica G. Otero-Cardenas, Hector E. Sepulveda Alemany, Andres Cordova Toro, Carla Colón-Nuñez, Hillarie Rios Torres, Maria A. Rodriguez Santiago, Marcel Mesa Pabon
Journal: Journal of the American College of Cardiology (2022)
Health System Approach to Improve Chronic Obstructive Pulmonary Disease Care after Hospital Discharge: Stepped-Wedge Clinical Trial
Authors: David H. Au, Margaret P. Collins, Douglas B. Berger, Paula G. Carvalho, Karin M. Nelson, Lynn F. Reinke, Richard B. Goodman, Rosemary Adamson, Deborah M. Woo, Peter J. Rise, Scott S. Coggeshall, Robert B. Plumley, Eric M. Epler, Brianna R. Moss, Jennifer A. McDowell, William G. Weppner
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Patients discharged from the hospital for chronic obstructive pulmonary disease (COPD) exacerbation have impaired quality of life and frequent readmission and death. Clinical trials to reduce readmission demonstrate inconsistent results, including some demonstrating potential harms. Objectives: We tested whether a pragmatic proactive interdisciplinary and virtual review of patients discharged after hospitalization for COPD exacerbation would improve quality of life, using the Clinical COPD Questionnaire, and reduce all-cause 180-day readmission and/or mortality. Methods: We performed a stepped-wedge clinical trial. We enrolled primary care providers and their patients after hospital discharge for COPD at two Department of Veterans Affairs medical centers and 10 outpatient clinics. A multidisciplinary team reviewed health records and developed treatment recommendations delivered to primary care providers via E-consult. We facilitated uptake by entering recommendations as unsigned orders that could be accepted, modified, or canceled. Providers and patients made all final treatment decisions. Measurements and Main Results: We enrolled 365 primary care providers. Over a 30-month period, 352 patients met eligibility criteria, with 191 (54.3%) patients participating in the control and 161 (45.7%) in the intervention. The intervention led to clinically significant better Clinical COPD Questionnaire scores (-0.47; 95% confidence interval [CI], -0.85 to -0.09; 52.6% missing) but did not reduce 180-day readmission and/or mortality (adjusted odds ratio, 0.83; 95% CI, 0.49 to 1.38), in part because of wide CIs. Among the 161 patients in the intervention group, we entered 519 recommendations as unsigned orders, of which 401 (77.3%) were endorsed. Conclusions: A pragmatic health system-level intervention that delivered proactive specialty supported care improved quality of life but did not reduce 180-day readmission or death. Clinical trial registered with www.clinicaltrials.gov (NCT02021955).
Variability in serum creatinine is associated with waitlist and post–liver transplant mortality in patients with cirrhosis
Authors: Giuseppe Cullaro, Chi‐yuan Hsu, Jennifer C. Lai
Journal: Hepatology (2022)

Abstract Background and Aims Kidney function in patients with cirrhosis is dynamic. After controlling for the presence of chronic kidney disease (CKD) and acute kidney injury (AKI), we investigated the impact of variation in clinical function on pre–liver transplantation (LT) and post‐LT outcomes. Approach and Results We included adults listed for LT from 2011 through 2018. We excluded those with any exceptions, those on hemodialysis at listing, and those with fewer than three clinical updates in the United Network for Organ Sharing database. Our primary exposure was the serum creatinine coefficient of variation (sCr CoV). Logistic regression determined the associations between our exposures and higher sCr CoV. Competing risk regression determined the associations between our exposures and waitlist mortality, accounting for LT as a competing risk. Cox regression determined the associations between our exposures and either listing for kidney transplant or death. We divided our cohort into tertiles of sCr CoV: low variability, 8.8% (interquartile range [IQR], 6.6%–10.8%); intermediate variability, 17.4% (IQR, 14.8%–20.4%); high variability, 36.8% (IQR, 29.5%–48.8%). We demonstrate that women, those with CKD, and those with advanced liver disease were more likely to have a greater sCr CoV. Compared to those with low variability, those with high variability had significantly higher waitlist mortality (34.7% vs. 19.6% vs. 11.7%, p &lt; 0.001). We highlight that the sCr CoV was associated with higher waitlist and post‐LT mortality—an association independent of baseline sCr, the degree of underlying liver disease, the presence of AKI, or the presence of CKD. Conclusion This study informs the long‐term impact of the variation in kidney function we all see in clinical practice. These data highlight that all fluctuations in sCr are associated with worse pre‐LT and post‐LT outcomes.
Microfluidics-based strategies for molecular diagnostics of infectious diseases
Authors: Xin Wang, Xian-Zhe Hong, Yi-Wei Li, Ying Li, Jie Wang, Peng Chen, Bi-Feng Liu
Journal: Military Medical Research (2022)

Abstract Traditional diagnostic strategies for infectious disease detection require benchtop instruments that are inappropriate for point-of-care testing (POCT). Emerging microfluidics, a highly miniaturized, automatic, and integrated technology, are a potential substitute for traditional methods in performing rapid, low-cost, accurate, and on-site diagnoses. Molecular diagnostics are widely used in microfluidic devices as the most effective approaches for pathogen detection. This review summarizes the latest advances in microfluidics-based molecular diagnostics for infectious diseases from academic perspectives and industrial outlooks. First, we introduce the typical on-chip nucleic acid processes, including sample preprocessing, amplification, and signal read-out. Then, four categories of microfluidic platforms are compared with respect to features, merits, and demerits. We further discuss application of the digital assay in absolute nucleic acid quantification. Both the classic and recent microfluidics-based commercial molecular diagnostic devices are summarized as proof of the current market status. Finally, we propose future directions for microfluidics-based infectious disease diagnosis.
<i>Lacticaseibacillus paracasei sh2020</i> induced antitumor immunity and synergized with anti-programmed cell death 1 to reduce tumor burden in mice
Authors: Shi-Long Zhang, Bing Han, Yu-Qin Mao, Zheng-Yan Zhang, Zhan-Ming Li, Chao-Yue Kong, You Wu, Guo-Qiang Chen, Li-Shun Wang
Journal: Gut Microbes (2022)

The gut microbiota was emerging as critical regulatory elements in shaping the outcome of cancer immunotherapy. However, the underlying mechanisms by which the gut commensal species enhance antitumor immunity remain largely unexplored. Here, we show that the gut microbiota from healthy individuals conferred considerable sensitivity to anti-PD-1 in the colorectal cancer (CRC) tumor-bearing mice, whereas gut microbiota from CRC patients failed to do so. By 16S rRNA gene sequencing, we identified Lactobacillus that was significantly increased in the mice with good response to anti-PD-1, and significantly correlated with anti-tumor immunity. After a series of screening, we isolated a novel Lacticaseibacillus strain, named L. paracasei sh2020. L. paracasei sh2020 showed the most notable anti-tumor immunity in the mice with gut dysbiosis. Mechanistically, the antitumor immune response elicited by L. paracasei sh2020 was dependent on CD8+ T cell. In vitro and in vivo studies revealed that L. paracasei sh2020 stimulation triggered the upregulated expression of CXCL10 in the tumors and subsequently enhanced CD8+ T cell recruitment. Meanwhile, the modulation of gut microbiota caused by L. paracasei sh2020 enhanced its antitumor effect and gut barrier function. Overall, our study offered novel insights into the mechanism by which gut microbiota shaped the outcome of cancer immunotherapy and, more importantly, the novel strain L. paracasei sh2020 might serve as an easy and effective way to promote anti-PD-1 effect in clinical practice.
Acute Cholecystitis
Authors: Jared R. Gallaher, Anthony Charles
Journal: JAMA (2022)

Gallbladder disease affects approximately 20 million people in the US. Acute cholecystitis is diagnosed in approximately 200 000 people in the US each year.Gallstone-associated cystic duct obstruction is responsible for 90% to 95% of the cases of acute cholecystitis. Approximately 5% to 10% of patients with acute cholecystitis have acalculous cholecystitis, defined as acute inflammation of the gallbladder without gallstones, typically in the setting of severe critical illness. The typical presentation of acute cholecystitis consists of acute right upper quadrant pain, fever, and nausea that may be associated with eating and physical examination findings of right upper quadrant tenderness. Ultrasonography of the right upper quadrant has a sensitivity of approximately 81% and a specificity of approximately 83% for the diagnosis of acute cholecystitis. When an ultrasound result does not provide a definitive diagnosis, hepatobiliary scintigraphy (a nuclear medicine study that includes the intravenous injection of a radiotracer excreted in the bile) is the gold standard diagnostic test. Following diagnosis, early (performed within 1-3 days) vs late (performed after 3 days) laparoscopic cholecystectomy is associated with improved patient outcomes, including fewer composite postoperative complications (11.8% for early vs 34.4% for late), a shorter length of hospital stay (5.4 days vs 10.0 days), and lower hospital costs. During pregnancy, early laparoscopic cholecystectomy, compared with delayed operative management, is associated with a lower risk of maternal-fetal complications (1.6% for early vs 18.4% for delayed) and is recommended during all trimesters. In people older than 65 years of age, laparoscopic cholecystectomy is associated with lower mortality at 2-year follow-up (15.2%) compared with nonoperative management (29.3%). A percutaneous cholecystostomy tube, in which a drainage catheter is placed in the gallbladder lumen under image guidance, is an effective therapy for patients with an exceptionally high perioperative risk. However, percutaneous cholecystostomy tube placement in a randomized trial was associated with higher rates of postprocedural complications (65%) compared with laparoscopic cholecystectomy (12%). For patients with acalculous acute cholecystitis, percutaneous cholecystostomy tube should be reserved for patients who are severely ill at the time of diagnosis; all others should undergo a laparoscopic cholecystectomy.Acute cholecystitis, typically due to gallstone obstruction of the cystic duct, affects approximately 200 000 people in the US annually. In most patient populations, laparoscopic cholecystectomy, performed within 3 days of diagnosis, is the first-line therapy for acute cholecystitis.
HEALTHCARE RESOURCE USE, INTENSITY AND COSTS AMONG PATIENTS WITH HEART FAILURE WITH REDUCED EJECTION FRACTION TREATED WITH OMECAMTIV MECARBIL IN GALACTIC-HF
Authors: Nihar R. Desai, Rafael Diaz, Michael Felker, Marco Metra, Scott D. Solomon, Gary Binder, Punag Divanji, Daniel Gomes, Robb D. Kociol, Lisa Meng, John R. Teerlink
Journal: Journal of the American College of Cardiology (2022)
DIAGNOSIS-TO-ABLATION TIME AS A PREDICTOR OF ATRIAL FIBRILLATION RECURRENCE
Authors: Ibrahim El Masri, Sharif Kayali, Mark Heckle, Issa Pour-Ghaz, Ike Ifedili, Courtland Blount, Eva Ingram, Kristina Mouksian, Sunil K. Jha, Rajesh Kabra, Yehoshua Levine
Journal: Journal of the American College of Cardiology (2022)
Type 1 Diabetes Mellitus
Authors: Fatima Z. Syed
Journal: Annals of Internal Medicine (2022)

Type 1 diabetes mellitus (T1DM) is an endocrine disorder in which pancreatic β cells stop producing insulin, typically due to autoimmune destruction. This results in hyperglycemia and ketosis; thus, insulin replacement is vital to management. Incidence peaks in puberty and early adulthood, but onset can occur at any age. However, prevalence is highest among adults because persons with T1DM live for many years. Symptoms include polyuria, polydipsia, and weight loss. Acute complications include diabetic ketoacidosis, which requires urgent management. Long-term complications include microvascular and macrovascular disease. Patients with T1DM are at higher risk for other autoimmune diseases and psychosocial issues. Management should focus on optimizing glucose control to reduce acute and long-term complications.
Prognostic and Predictive Value of Fibroblast Growth Factor Receptor Alterations in High-grade Non–muscle-invasive Bladder Cancer Treated with and Without Bacillus Calmette-Guérin Immunotherapy
Authors: Roman Mayr, Markus Eckstein, Ralph M. Wirtz, Ademi Santiago-Walker, Mahadi Baig, Ramesh Sundaram, Jenna Cody Carcione, Robert Stoehr, Arndt Hartmann, Christian Bolenz, Maximilian Burger, Wolfgang Otto, Philipp Erben, Johannes Breyer
Journal: European Urology (2022)

Limited data are available on the prognostic and predictive value of fibroblast growth factor receptor alterations (FGFRa) relative to clinical outcomes in patients with non-muscle-invasive bladder cancer (NMIBC).To determine whether FGFRa may be clinically useful in stratifying for treatment response in a real-world cohort of patients with pT1 NMIBC treated and untreated with bacillus Calmette-Guérin (BCG) instillation therapy.A pooled dataset of matched clinical and genomic data (1992-2015) for pT1 NMIBC patients was assessed by the Bladder Cancer Research Initiative for Drug Targets in Germany consortium.Key efficacy outcomes were recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS), which were estimated by Kaplan-Meier analysis, with hazard ratios calculated using a multivariate Cox proportional-hazard model.In this retrospective study of 263 patients with high-grade NMIBC, at a median follow-up of 63 mo, 32% showed recurrence and 15% progressed to muscle-invasive bladder cancer. FGFRa were found in 43% of patients, including 39% mutations and 5.7% fusions. FGFRa were associated with lower rates of concomitant carcinoma in situ. Among patients with or without FGFRa, there was no significant difference in PFS, RFS, and DSS in those who were BCG treated or BCG naive, or in the overall population. Limitations include the retrospective design from a single-center setting.In patients with high-risk NMIBC, FGFRa were frequently observed. Patients with FGFRa who often exhibit recurrence/relapse after BCG treatment have a high unmet need.Our retrospective study suggests that fibroblast growth factor receptor alterations (FGFRa) occur frequently in non-muscle-invasive bladder cancer (NMIBC). Outcomes were similar with or without FGFRa in patients with NMIBC, both overall and for standard bacillus Calmette-Guérin (BCG) treatment.