tbuckley/cabot-search huggingface dataset:
Surveillance and control of meningococcal disease in the COVID-19 era: A Global Meningococcal Initiative review
Authors: Mark R. Alderson, Peter D. Arkwright, Xilian Bai, Steve Black, Ray Borrow, Dominique A. Caugant, Ener Cagri Dinleyici, Lee H. Harrison, Jay Lucidarme, Lucy A. McNamara, Susan Meiring, Marco A.P. Sáfadi, Zhujun Shao, David S. Stephens, Muhamed-Kheir Taha, Julio Vazquez, Bingqing Zhu, GMI collaborators
Journal: Journal of Infection (2021)

This review article incorporates information from the 4th Global Meningococcal Initiative summit meeting. Since the introduction of stringent COVID-19 infection control and lockdown measures globally in 2020, there has been an impact on IMD prevalence, surveillance, and vaccination compliance. Incidence rates and associated mortality fell across various regions during 2020. A reduction in vaccine uptake during 2020 remains a concern globally. In addition, several Neisseria meningitidis clonal complexes, particularly CC4821 and CC11, continue to exhibit resistance to antibiotics, with resistance to ciprofloxacin or beta-lactams mainly linked to modifications of gyrA or penA alleles, respectively. Beta-lactamase acquisition was also reported through horizontal gene transfer (blaROB-1) involving other bacterial species. Despite the challenges over the past year, progress has also been made on meningococcal vaccine development, with several pentavalent (serogroups ABCWY and ACWYX) vaccines currently being studied in late-stage clinical trial programmes.
Abstract 10947: Sacubitril/Valsartan versus Spironolactone in Heart Failure with Preserved Ejection Fraction; A Cost per Outcome Analysis
Authors: Gal Tsaban, Hilmi Alnsasra, Ala Abu-Dogosh, Itai Weissberg, Yael Golan, Orit Barrett, Roi Westreich, Enis Aboalhasan, Joseph Azuri, Ariel Hammerman, Ronen Arbel
Journal: Circulation (2021)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is associated with frequent hospitalizations and an increased risk of death. There are no therapies with certain benefits for the treatment of HFpEF. Spironolactone and Sacubitril/Valsartan have shown marginal significance benefits in HFpEF and are approved to treat this condition. We aimed to compare the value for money of these treatments. Hypothesis: Spironolactone provides better value for money than Sacubitril/Valsartan for preventing HF events in patients with HFpEF. Methods: We compared the cost needed to treat (CNT) to prevent the composite outcome of HF hospitalization and CV death with Spironolactone or Sacubitril/Valsartan. The CNT was estimated by multiplying the annualized number needed-to-treat (aNNT) by the annual cost of therapy. The aNNTs were calculated based on data from the TOP-CAT and PARAGON trials. Costs were based on 2021 US prices. Scenario analyses were performed to attenuate the differences in the studies’ populations. Subgroup analyses were performed for mildly reduced EF. Results: The aNNT to prevent the composite outcome with Sacubitril/Valsartan in PARAGON was 53 [95% CI:28-∞] versus 107 (95% CI:51-∞), with spironolactone in TOPCAT. At an annual cost of $5,100 versus $1,353, The corresponding CNTs were $270,273 (95% CI:142,786-∞) for Sacubitril/Valsartan and $144,773 (95% CI:69,004-∞) for spironolactone. Figure 1 illustrates the results of the scenario and subgroup analysis. Conclusion: Despite lower clinical efficacy, spironolactone provides better value for money than Sacubitril/Valsartan in preventing HF hospitalizations and cardiovascular death among patients with HFpEF.
Regional Differences in Lymphomagenesis Identified through Quantification of AICDA-Mediated Subclonal Evolution in Follicular Lymphoma: Do Pesticides Play a Role?
Authors: Ash B Alpert, Nancy Eunice Torres, Eric Snyder, Philip J Rock, Diana G Adlowitz, Derick R. Peterson, Paula Cupertino, Carla Casulo, Richard Burack
Journal: Blood (2021)
Abstract 13269: Combination Therapy With Sodium Nitrite and Hydralazine Ameliorates the Severity of Heart Failure With Preserved Ejection Fraction
Authors: Kyle B Lapenna, Zhen Li, Thomas E Sharp, Hunter A Hidalgo, Huijing Xia, John S Wang, Karl H Moles, Kashyap Koul, Nikhilesh Alahari, Traci T Goodchild, David J Lefer
Journal: Circulation (2021)

Background: Recent studies suggest that nitrosative stress resulting from an imbalance in nitric oxide (NO) is the primary driver of heart failure with preserved ejection fraction (HFpEF); however, many of the comorbidities present in HFpEF patients are driven by oxidative stress. Due to the failure of nitric oxide (NO) based therapeutics in HFpEF clinical trials and the role of oxidative stress in each of the different HFpEF comorbidities, we sought to investigate the effects of sodium nitrite (NaNO2) therapy alone or in combination with the antioxidant and peroxynitrite scavenger, hydralazine, in a novel, “two-hit” murine model of HFpEF. Methods: HFpEF was induced in nine-week-old C57/BL6N mice (n = 13-15 per group) by high fat diet and L-NAME (0.5 g/L/day) via drinking water for 10 weeks. At 5 weeks, mice were treated with vehicle, sodium nitrite(75 mg/L) via drinking water, hydralazine (2 mg/kg/day B.I.D., I.P, or a combination of sodium nitrite + hydralazine. Cardiac structure and function via echocardiography and exercise capacity were measured at baseline, week 5 (prior to treatment), and week 10 (final endpoint). At week 10, invasive hemodynamic and in-vitro vascular reactivity studies were performed. Results: Sodium nitrite and hydralazine combination therapy resulted in significant (p &lt; 0.01) improvement inE/E’ that was superior to either therapy alone. Hydralazine as a monotherapy and in combination with NaNO2lowered the E/A ratio compared to NaNO2 monotherapy (p &lt;0.05). Aortic vasorelaxation maximal responses to acetylcholine were significantly improved in all study groups with the greatest improvement observed withNaNO2 + hydralazine. Left ventricular end-diastolic pressure (LVEDP) was significantly (p &lt; 0.01) reduced with either therapy alone, but our data indicate that combination therapy was superior to either drug alone. Conclusion: Our data suggest that antioxidant therapy is required in combination with NO based therapeutics in HFpEF.
Abstract P504: Transient Angiotensin Converting Enzyme Inhibition Protects Against Future Fibrogenic Responses Via Sex-specific Mechanisms
Authors: Alexandra M Garvin, Dana B Floyd, Wendy S Nunez, Amal W Altaf, Matthew M Siegel, Taben M Hale
Journal: Circulation Research (2021)

Following washout of angiotensin converting enzyme inhibitor (ACEi) treatment in hypertensive rats (SHR), there is an increase in the proportion of homeostatic cardiac fibroblasts (CFs) characterized by a less fibrogenic gene profile. The present study investigated the impact of this shift in CFs on subsequent Ang II-induced oxidative stress and fibrogenic responses in the left ventricle (LV). Male and female SHRs (11 wk old) underwent a 6-week treatment scheme: 2-week ACEi (enalapril, 30mg/kg/day) or vehicle treatment, followed by a 2-week washout period, and then a 2-week Ang II (400ng/kg/min, s.c.) or vehicle infusion (n=5-11/group/sex). RT-qPCR for collagens and immunoblotting for LOX, Postn, OPN, NOX2, SOD2, and catalase was performed. In males, Ang II-induced increases in ColI, III, and IV expression were significantly attenuated by prior ACEi. While in females, Ang II significantly increased the expression of ColI and III similarly, regardless of prior ACEi treatment; highlighting a sex-specific impact of ACEi. After Ang II infusion, both Postn and LOX are reduced in LV of male and female SHR previously treated with an ACEi - suggesting reduced collagen cross-linking. Oxidative stress induced by NOX2 has been linked to OPN in fibrotic tissue. Ang II-induced increases in NOX2 are attenuated in LV of both sexes, while OPN is only reduced in females previously treated with an ACEi. NOX2 is significantly positively correlated with OPN in males only suggesting a sex-specific link between OPN and oxidative stress. Antioxidant (SOD2, catalase) levels were positively correlated to NOX2 in females, but not males. This suggests that females more efficiently neutralize oxidative stress than males - regardless of prior ACEi. Taken together, the persistent genomic and phenotypic changes in CFs following transient ACEi render the heart resistant to future fibrotic and oxidative effects of Ang II, but the mechanisms of protection may differ by sex. Collectively, these data reveal that there are sex-specific processes that govern collagen production vs. cross-linking and oxidative stress. Future studies will elucidate the mechanistic underpinnings of sex-specific cellular memory following transient ACEi with a goal of identifying novel therapeutic targets.
Abstract 10667: Psychosocial Predictors of Cardiovascular Disease Risk Among Older Persons with HIV
Authors: Crista Irwin, Melinda Higgins, Drenna Waldrop, Rebecca Gary
Journal: Circulation (2021)

Introduction: People with HIV (PWH) are twice as likely to develop cardiovascular disease (CVD) at an average of 8 years earlier than persons without HIV independent of known risk factors; as a result, CVD is a major cause of morbidity and mortality in older PWH. Traditional CVD risk calculators do not reliably predict CVD in PWH. Psychosocial factors have been linked to higher rates of CVD in persons with and without HIV and PWH report higher rates of depression. Hypothesis: Clinical and psychosocial predictors were examined for associations with CVD risk scores among PWH. Methods: Clinical measures including blood pressure, cholesterol, CVD medications, smoking status and comorbidities were extracted from electronic medical records of PWH aged 40 years and older. CVD risk scores were calculated using the Atherosclerotic Cardiovascular Disease (ASCVD) calculator. Psychosocial factors were measured by the Perceived Stress Scale, the Internalized HIV Stigma Scale, Beck’s Depression Index-II, and the PROMIS-Sleep Disturbance and Emotional Support Scales. Multiple linear regression was used to examine associations between CVD risk scores and clinical/psychosocial variables. Covariates included age, gender, and race, and education. Results: Of the n=90 participants, the majority were male (n=52, 57.8%) and African American (n=77, 85.6%). Overall, the average CVD risk score for the total sample was low (mean 10.6, SD 7.0). Older age, which was significantly associated with higher CVD risk scores, is included in the ASCVD calculation, therefore, age was excluded from the model. Psychosocial variables and other covariates were examined with CVD risk scores and higher depressive symptom scores explained 6% of the variance (adj r 2 =0.061, p=0.01). No additional clinical or psychosocial variables were significant. Conclusions: The low ASCVD risk scores suggests that other factors such as chronic inflammation may contribute to higher CVD rates in this population and merits further research. Older age and higher depressive symptoms were significantly associated with CVD greater risk which may be bidirectional. Screening for depressive symptoms during routine clinic visits may provide a window of opportunity to reduce CVD burden in older PWH.
Abstract 10324: Characterization and Impact of Covid-19 on Heart Transplant Recipients
Authors: Christopher Kanaan, Jean Pierre Iskandar, Mohamed Gad, Nicholas Kondoleon, Maan Fares, Eileen M Hsich, Jerry Estep
Journal: Circulation (2021)

Introduction: Heart transplant recipients who subsequently acquire COVID-19 may be at an increased risk of severe disease and adverse outcomes, particularly in light of several comorbidities and chronic states of immunosuppression. Methods: In this retrospective case-control analysis, we compared the outcomes of heart transplant patients with confirmed COVID-19 to matched, COVID-19 positive, non-transplant patients at the Cleveland Clinic. The transplant group included adult patients who were hospitalized with COVID-19 between March 2020 and March 2021. The controls were matched 2:1 (24 heart transplant, 48 non-heart transplant) on different baseline characteristics. The primary outcome was in-hospital mortality and secondary outcomes were the length of hospital stay (LOS), need for mechanical ventilation, ICU admission, pressor requirements (norepinephrine, epinephrine, vasopressin), dialysis requirement, pneumonia incidence, and 30- day readmission within the COVID-19 diagnosis window. All tests had a 2-sided significance level of 0.05. Results: Of 11,505 patients with COVID-19 infection, 72 post-match were included in the final analysis. The mean age of hospitalized heart transplant recipients was 62 ±18, 70% were Caucasian, 87.5% were male, 47% had a smoking history, 17% had COPD, and 8% had asthma. Primary outcome of in-hospital mortality in the heart transplant COVID group vs. non-transplant COVID group was 12.5% and 14.6%, respectively (OR: 0.84; 95% CI 0.2-3.57). There was no statistically significant difference in median LOS (more than 7 days; 45.8% vs. 52.1%; OR: 0.78; 95% CI 0.29-2.08), need for mechanical ventilation (16.7% vs. 14.5%; OR: 1.17; 95% CI 0.31-4.47), ICU admissions (33.3% vs. 35.4%; OR: 0.91; 95% CI 0.32-2.57) pressor requirements (8.3% vs. 8.3%; OR: 1; 95% CI 0.17-5.89), dialysis needs (4.1% vs. 6.2%; OR: 0.65; 95% CI 0.06-6.63), pneumonia (4.2% vs. 8.5%; OR 0.48: 95% CI 0.05-4.53), or 30-day readmission (17.4% vs. 8.5%; OR: 2.26; 95% CI 0.51-10.02). Conclusion: Our study suggests that heart transplant recipients who acquire and are hospitalized for COVID-19 do not show worse in-hospital outcomes compared to those of their matched non-transplant cohorts. However, the study results are limited due to sample size.
Abstract 11100: Modified EDACS-ADP Score Using Derived 12-Lead Electrocardiogram and Cardiac Electrical Biomarker
Authors: David M Schreck, Robert D Fishberg, Noelle Bessette
Journal: Circulation (2021)

Introduction: The EDACS-ADP risk score includes 12-lead electrocardiogram (ECG) and troponin (cTn) to stratify patients presenting with chest pain. The ECG can be derived (dECG) from 3 measured leads with high correlation. A new cardiac electrical biomarker (CEB®) that correlates with cTn can be constructed in real-time from the dECG with reportedly high diagnostic accuracy for detection of acute myocardial infarction (AMI). Objective: Compare the EDACS-ADP to a modified risk score that includes substitution of dECG for ECG, and CEB® for cTn. Methods: This study included 138 consecutive patients presenting to an emergency facility with complaints of chest pain. The prevalence of AMI was 14.5% including 7 STEMI and 13 Non-STEMI. The dECG and CEB® were constructed from leads {I, II, V2} directly from an ECG device (VectraplexECG System, VectraCor Inc, Totowa, NJ). Each EDACS-ADP was calculated and compared to a modified score that utilized the dECG instead of the actual ECG, and CEB® instead of cTn. Sensitivities and specificities were calculated for the EDACS-ADP scores and respective modified scores. ROC curves were constructed to identify risk score cut-offs. Results: The CEB® showed high diagnostic accuracy for AMI with sensitivity 85%, specificity 95.8%, negative predictive value 97.4%, and positive predictive value 77.3%. The cTn showed sensitivity 100%, specificity 89.8%, negative predictive value 100%, and positive predictive value 62.5%. EDACS-ADP with ECG and cTn showed sensitivity 100%, specificity 88.1%, negative predictive value 100%, and positive predictive value 58.8% compared to the modified score with dECG and CEB that showed sensitivity 85%, specificity 94.9%, negative predictive value 97.4%, and positive predictive value 73.9%. The reported EDACS cut-off of 16 was validated by ROC curve analysis. Conclusions: The modified EDACS-ADP risk score based on substitution of the dECG for ECG and CEB® for cTn is comparable to the customary risk score. The modified risk score is easy to calculate and is available immediately allowing a shorter time to decision for possible admission. Also, the modified risk scores may be applicable in facilities where cTn is not immediately available such as in outpatient urgent care and post-acute care centers.
Effect of 7 vs 14 Days of Antibiotics Among Afebrile Men With Urinary Tract Infection—Reply
Authors: Dimitri M. Drekonja, Barbara Trautner, James R. Johnson
Journal: JAMA (2021)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 12856: Novel Four-Dimensional Ultrasound Metric Improves Detection of Heart Failure Progression in Hypertrophic Cardiomyopathy
Authors: Frederick W Damen, John P Salvas, Andrea S Pereyra, Jessica M Ellis, Craig J Goergen
Journal: Circulation (2021)

Introduction: Progression to heart failure is a known consequence of longstanding hypertrophic cardiomyopathy (HCM); however, routine function markers such as ejection fraction (EF) are often inadequate to predict dysfunction progression. The objective of this abstract was to create a novel metric, the Hybrid Strain Index (HSI), that can provide better characterization of heart failure progression. We hypothesized that longitudinal changes in a mouse model with known cardiac dysfunction could be more accurately differentiated with HSI than EF. Methods: Longitudinal 4D ultrasound (4DUS) data from mice with hypertrophic cardiomyopathy secondary to cardiac deletion of the carnitine palmitoyltransferase 2 enzyme ( Cpt2 M-/- ; n=12) and littermate controls (n=14) were analyzed using a custom MATLAB toolbox that derived both global volumetric (e.g., EF) and regional kinematic (e.g., circumferential and longitudinal strain) measurements. The circumferential and longitudinal regions most sensitive to disease progression were identified as the base (E θθ ) and posterior-wall (E LL ), respectively. The HSI metric was then calculated as the L2 norm of those peak-strain values. Results: To identify the earliest age of deviation between Cpt2 M-/- and controls, 95% confidence intervals from linear regression through HSI values intersected at 5.7 weeks old, compared to 7.1 weeks old using EF, suggesting HSI provides earlier sensitivity to cardiac dysfunction. Additionally, area-under-curve (AUC) measurements from ROC analysis of each metric, regardless of age, showed greater differentiation between cohorts using HSI (AUC = 0.91) than EF (AUC = 0.84). This further suggests enhanced diagnostic value of HSI compared to EF in the setting of cardiac dysfunction. Conclusions: The proposed HSI metric demonstrated greater sensitivity to detecting cardiac dysfunction and disease progression, compared to EF, in a mouse model of hypertrophic cardiomyopathy ( Cpt2 M-/- ).
Subsequent Anti-Myeloma Therapy after Idecabtagene Vicleucel (ide-cel, bb2121) Treatment in Patients with Relapsed/Refractory Multiple Myeloma from the KarMMa Study
Authors: Paula Rodriguez-Otero, Jesús F. San-Miguel, Larry D. Anderson, Sagar Lonial, Anna Truppel-Hartmann, Jill Sanford, Everton Rowe, Timothy B. Campbell, Nikhil C. Munshi
Journal: Blood (2021)
PATH-25. H3 K27M-MUTANT DIFFUSE NON-MIDLINE GLIOMA: REPORT OF A CASE WITH EXTENDED FOLLOW-UP
Authors: Kliment Donev, Vanitha Sundararajan, Derek Johnson, Cristiane Ida
Journal: Neuro-Oncology (2021)

Abstract H3 K27M-mutant diffuse gliomas without midline involvement are extremely rare and their clinical behavior remains elusive due to limited reported follow-up data. We describe an H3 K27M-mutant diffuse non-midline glioma patient with extended follow-up. A 34-year-old woman presented with headache, memory loss, periods of changes in taste and smell, and confusion. Imaging studies revealed an 2.3 cm expansile T2/flair hyperintensity with patchy postcontrast enhancement centered in the left amygdala without associated restricted diffusion and no involvement of the midline structures. The tumor was debulked and consisted of a mitotically active infiltrating astrocytic glioma without tumor necrosis or microvascular proliferation, consistent with anaplastic astrocytoma. Targeted 187-gene neuro-oncology NGS testing detected an H3F3A K27M mutation along with a PTPN11 and a PPM1D mutation. FISH 1p/19q-codeletion testing was negative. MGMT promoter was unmethylated. The patient was treated with chemoradiation with temozolomide for 6 weeks followed by 12 cycles of temozolomide. Four years after initial resection, an area of increased post-contrast enhancement indicating tumor recurrence/progression was noted. Partial resection of the recurrent tumor revealed a mitotically active infiltrating astrocytic glioma with tumor necrosis consistent with glioblastoma. Molecular profiling of the recurrent tumor by the neuro-oncology NGS panel detected similar mutational profile (identical H3F3A K27M and PTPN11 mutation; different PPM1D mutation) with an additional SOS1 mutation. The patient completed 4 cycles of Lomustine and although clinically stable, imaging studies showed slight increase in residual tumor size concerning for tumor progression. Lomustine was discontinued, Bevacizumab therapy was initiated and patient was enrolled in clinical trial (NCT02525692). Despite tumor progression, this patient has had a relatively long disease course (5 years) suggesting that H3 K27M-mutant non-midline diffuse gliomas although molecularly similar, may follow a more favorable clinical course than their midline counterparts possibly due to the hemispheric location, which is more amenable for surgical resection.
Laboratory Work in Bacteriology.
Journal: JAMA (1899)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Epigenetically Enhanced MED12L in ETO2-GLIS2 Positive Pediatric Acute Megakaryoblastic Leukemia Is Associated with Resistance to the CDK8 Inhibitors
Authors: Samrat Roy Choudhury, Jordan T Bird, Stephanie Byrum, Dane Jester, Troy Davidson, Giselle Almeida Gonzalez, David Becton, Jenny L. Smith, Rhonda E. Ries, Soheil Meshinchi, Jason E Farrar
Journal: Blood (2021)