tbuckley/cabot-search huggingface dataset:
Abstract P093: Subclinical Thyroid Dysfunction And Fracture Risk In The Atherosclerosis Risk In Communities Study (ARIC)
Authors: Natalie Daya Malek, Anna E Fretz, Seth S Martin, Pamela L Lutsey, Anna Kottgen, Justin Echouffo Tcheugui, Elizabeth Selvin, Stephen P Juraschek
Journal: Circulation (2022)

Introduction: Overt thyroid dysfunction is a risk factor for bone-related outcomes. Clinical hyperthyroidism accelerates bone resorption without compensatory bone formation, reducing bone density. The link between subclinical hyperthyroidism and fracture risk is less clear. Methods: ARIC participants who were not on thyroid medication and had no history of fracture at visit 2 (1990-92) were included. Incident fracture was ascertained using ICD-9/10 codes from hospitalizations and linkage to inpatient and outpatient Medicare claims. We used Cox regression to examine the associations of subclinical hyperthyroidism (TSH&lt;0.56 mIU/L, with normal FT4) and subclinical hypothyroidism (TSH&gt;5.1mIU/L, with normal FT4, 0.85-1.4 ng/dL) with incident fracture. Euthyroidism (reference) was defined as TSH 0.56-5.1 mIU/L and normal FT4. We also modeled TSH using splines to characterize the continuous association of TSH with fracture risk. Results: There were 11,287 participants (mean age 57; 54% female; 25% black) of which 93% were euthyroid, 2.6% had subclinical hyperthyroidism, and 4.4% had subclinical hypothyroidism. Over a median follow-up of 21 years, there were 3,664 incident fractures (168.1 per 10,000 person-years). The adjusted hazard ratios of fracture were 1.33 (95% CI: 1.09, 1.63) for subclinical hyperthyroidism and 0.89 (0.76, 1.04) for subclinical hypothyroidism. When TSH was modeled as a spline, lower than normal range TSH was significantly associated with increased fracture risk (Figure). Fracture risk was highest for TSH levels &lt;0.56 mIU/L, however, there was also an increased risk of fracture for TSH levels 0.56-0.75 mIU/L. Conclusion: Subclinical hyperthyroidism was an independent risk factor for fracture. The increased risk for fracture in individuals with a TSH&lt;0.56 mIU/L highlights the need for more aggressive screening and potential treatment of patients with subclinical hyperthyroidism for bone mineral disease.
Inhaled Corticosteroids and Long-Acting β2 Receptor Agonists for Preterm-Born Children—New Insights but Still Many Questions—Reply
Authors: Nia Goulden, Iolo Doull, Sailesh Kotecha
Journal: JAMA Pediatrics (2022)

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Semantic memory before episodic memory: How memory research can inform knowledge and belief representations
Authors: R. Shayna Rosenbaum, Julia G. Halilova, Thanujeni Pathman
Journal: Behavioral and Brain Sciences (2021)

Abstract Knowledge and belief attribution are discussed in the context of episodic and semantic memory theory and research, with reference to patient-lesion and developmental studies under naturalistic conditions. Consideration of how episodic and semantic memory relate to each other and intersect in the real world, including how they fail, can illuminate the approach to studying how people represent others' minds.
Genetic Profile–Guided Therapy for Stroke?
Authors: Steven K. Feske
Journal: New England Journal of Medicine (2021)

The late 20th and early 21st centuries have seen a reduction in stroke risk resulting from lifestyle changes such as widespread smoking cessation and more regular exercise, advances in the treatment of hypertension and hyperlipidemia, and better control of the vascular complications of diabetes.1 Antiplatelet agents have played a major role as well. According to a meta-analysis from the Antithrombotic Trialists' Collaboration, antiplatelet therapies reduce the relative risk of stroke by approximately 25%, or the absolute risk by 3.6 percentage points, over a period of 2 years.2 The medical cost for this benefit is a slightly increased risk of major . . .
Cabozantinib in Combination With Atezolizumab for Advanced Renal Cell Carcinoma: Results From the COSMIC-021 Study
Authors: Sumanta K. Pal, Bradley McGregor, Cristina Suárez, Che-Kai Tsao, William Kelly, Ulka Vaishampayan, Lance Pagliaro, Benjamin L. Maughan, Yohann Loriot, Daniel Castellano, Sandy Srinivas, Rana R. McKay, Robert Dreicer, Thomas Hutson, Sarita Dubey, Scott Werneke, Ashok Panneerselvam, Dominic Curran, Christian Scheffold, Toni K. Choueiri, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2021)

COSMIC-021 is evaluating cabozantinib plus atezolizumab in patients with solid tumors. We report results from patients with advanced clear cell (cc) and non-clear cell (ncc) renal cell carcinoma (RCC).This phase Ib study (NCT03170960) enrolled patients age ≥ 18 years with advanced RCC. A dose-escalation stage was followed by expansion cohorts. For cohort expansion, prior systemic therapy was not permitted for ccRCC but allowed for nccRCC. Patients received oral cabozantinib 40 mg once a day (ccRCC and nccRCC) or 60 mg once a day (ccRCC only) plus atezolizumab (1,200 mg intravenously, once every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1; the secondary end point was safety.A total of 102 patients were enrolled. Median follow-up was 25.8, 15.3, and 13.3 months for the 40-mg ccRCC, 60-mg ccRCC, and nccRCC groups, respectively. ORR was 53% (80% CI, 41 to 65) in the 40-mg ccRCC group (n = 34) and 58% (80% CI, 46 to 70) in the 60-mg ccRCC group (n = 36), 3% and 11%, respectively, with complete response; median progression-free survival (exploratory end point) was 19.5 and 15.1 months, respectively. In nccRCC (n = 32), ORR was 31% (80% CI, 20 to 44), all partial responses; median progression-free survival was 9.5 months. Grade 3 or 4 treatment-related adverse events (TRAEs) were reported by 71% of patients in the 40-mg ccRCC group, 67% in the 60-mg ccRCC group, and 38% in the nccRCC group; TRAEs leading to discontinuation of both agents occurred in 15%, 6%, and 3% of patients, respectively. There were no grade 5 TRAEs.The novel combination of cabozantinib plus atezolizumab demonstrated encouraging clinical activity and acceptable tolerability in patients with advanced ccRCC and nccRCC. Disease control was observed across dose levels and histologic subtypes.
The resolvin D1 receptor GPR32 transduces inflammation resolution and atheroprotection
Authors: Hildur Arnardottir, Silke Thul, Sven-Christian Pawelzik, Glykeria Karadimou, Gonzalo Artiach, Alessandro L. Gallina, Victoria Mysdotter, Miguel Carracedo, Laura Tarnawski, April S. Caravaca, Roland Baumgartner, Daniel F.J. Ketelhuth, Peder S. Olofsson, Gabrielle Paulsson-Berne, Göran K. Hansson, Magnus Bäck
Journal: Journal of Clinical Investigation (2021)

Chronic inflammation is a hallmark of atherosclerosis and results from an imbalance between proinflammatory and proresolving signaling. The human GPR32 receptor, together with the ALX/FPR2 receptor, transduces biological actions of several proresolving mediators that stimulate resolution of inflammation. However, since no murine homologs of the human GPR32 receptor exist, comprehensive in vivo studies are lacking. Using human atherosclerotic lesions from carotid endarterectomies and creating a transgenic mouse model expressing human GPR32 on a Fpr2×ApoE double-KO background (hGPR32myc×Fpr2–/–×Apoe–/–), we investigated the role of GPR32 in atherosclerosis and self-limiting acute inflammation. GPR32 mRNA was reduced in human atherosclerotic lesions and correlated with the immune cell markers ARG1, NOS2, and FOXP3. Atherosclerotic lesions, necrotic core, and aortic inflammation were reduced in hGPR32mycTg×Fpr2–/–×Apoe–/– transgenic mice as compared with Fpr2–/–×Apoe–/– nontransgenic littermates. In a zymosan-induced peritonitis model, the hGPR32mycTg×Fpr2–/–×Apoe–/– transgenic mice had reduced inflammation at 4 hours and enhanced proresolving macrophage responses at 24 hours compared with nontransgenic littermates. The GPR32 agonist aspirin-triggered resolvin D1 (AT-RvD1) regulated leukocyte responses, including enhancing macrophage phagocytosis and intracellular signaling in hGPR32mycTg×Fpr2–/–×Apoe–/– transgenic mice, but not in Fpr2–/–×Apoe–/– nontransgenic littermates. Together, these results provide evidence that GPR32 regulates resolution of inflammation and is atheroprotective in vivo.
Pomalidomide in Patients With Relapsed and/or Refractory Multiple Myeloma: A Prospective Study Within the Nationwide Netherlands Cancer Registry
Authors: Ruth Wester, Avinash G. Dinmohamed, Bronno van der Holt, Sonja Zweegman, Monique Minnema, Sandra Croockewit, Mark-David Levin, Eduard Libourel, Esther de Waal, Pieter Sonneveld, Jan Cornelissen, Nicole Blijlevens, Annemiek Broijl
Journal: HemaSphere (2022)

Patients with relapsed and/or refractory multiple myeloma (RRMM) generally have limited treatment options and a poor prognosis. Previous trials demonstrated that pomalidomide combined with low-dose dexamethasone (Pd) is effective in these patients with significant responses and improved progression-free survival (PFS). Pd has been approved in RRMM patients who received ≥2 prior lines of therapy. Here, we present the results of a population-based study of patients with RRMM treated with Pd in The Netherlands from time of pomalidomide approval. Using the nationwide Netherlands Cancer Registry, data from all nontrial patients with RRMM treated with Pd were collected. Data were analyzed of response, PFS, and overall survival (OS). A total of 237 patients were included in this analysis. Previous treatment consisted of a proteasome inhibitor in 227 patients (96%) and/or an immune-modulating agent in 235 patients (99%). One hundred forty patients (59%) were refractory to an immune-modulating agent in their last line of therapy. Median time from diagnosis to treatment with Pd was 4.9 years (interquartile range, 2.7-7.9), and the median number of prior treatments was 4 (interquartile range, 3-5). Median PFS and OS for all patients were 3.6 months (95% confidence interval [CI], 3.1-3.8) and 7.7 months (95% CI, 5.7-9.7), respectively. For patients achieving ≥PR, median PFS and OS were 10.6 months (95% CI, 8.3-12.9) and 16.3 months (95% CI, 13.6-23.2), respectively. This nationwide, population-based registry study confirms data shown in pivotal clinical trials on Pd. PFS in this analysis is comparable to PFS observed in those clinical trials.
COVID-19 wastewater epidemiology: a model to estimate infected populations
Authors: Christopher S McMahan, Stella Self, Lior Rennert, Corey Kalbaugh, David Kriebel, Duane Graves, Cameron Colby, Jessica A Deaver, Sudeep C Popat, Tanju Karanfil, David L Freedman
Journal: The Lancet Planetary Health (2021)
Abstract P027: COVID-19-Related Mortality And A Decline In U.S. Kidney Transplantation During The Second Year Pandemic
Authors: Ekamol Tantisattamo, Natchaya Polpichai, Pornthira Mutirangura, Manasawee Tanariyakul
Journal: Circulation (2022)

Background: Since COVID-19 treatment and immunization have been implemented, effects of COVID-19pandemic on kidney transplantations (KT) may be altered from the prior year. We aim to examine the association of COVID-19 cases and deaths with the change in the number of KT in 2022. Method: A cross-sectional study examined data of COVID-19 cases and death, and adult KT in the United States, retrieved from the CDC and the OPTN/SRTR, respectively. The association of the cumulative COVID-19 cases and deaths between 1/21/2020 and 10/11/2021 among 52 states in the United States and the difference in the number of KT between the year 2020 and 2021 (ΔKT) was examined by multiple linear regression. Results: Of 44,377,493 COVID-19 cases, 713,950 had COVID-19-realted death during the study period. Of all 52 states, 38,947 and 31,273 KT were performed in 2020 and 2021, respectively (mean difference ±SEM 148±27, 95%CI 93, 202). Median (IQR) ΔKT 2020 - 2021 was 93 (26, 167). Compared to year 2020, every 10,000 increased COVID-19 cases and deaths were associated with a decrease in 2 and 102 KTs in year 2021, respectively (COVID-19 cases: β coeff 0.00018, 95%CI 0.00016, 0.00021; Figure 1A and COVID-19 deaths: β coeff 0.01020, 95%CI 0.00839, 0.01202; Figure 1B). After adjusted for categorized KT in 2020 (&lt; or ≥ median KT in 2020 of 468), COVID-19 cases (&lt; or ≥ median cases of 586,869) or COVID-19 deaths (&lt; or ≥ median deaths of 16,635), and the interaction term between KT in 2020 and COVID-19 cases or deaths, the states with a higher COVID-19 cases (≥586,869 cases) had a decrease in 53 KT in 2021; whereas, there was a decrease in 212 KT among states with greater COVID-19 deaths (≥16,635 deaths; COVID-19 cases: β coeff 53, 95%CI -291, 397, p interaction 0.874 and COVID-19 deaths: β coeff 212, 95%CI 96, 329, p interaction NS). Conclusion: The decline of KT in 2021 compared to 2020 is positively associated with COVID-19-related deaths, but not COVID-19 cases. This association is not modified by the number of KTs in 2020 and COVID-19 deaths in different states.
The Patchwork U.S. Public Health System
Authors: Megan Wallace, Joshua M. Sharfstein
Journal: New England Journal of Medicine (2022)

Interview with Dr. Joshua Sharfstein on the haphazard organization of U.S. public health at the local, state, and federal levels. (08:53)Download The U.S. public health system is an uneven patchwork. In the shadow of a pandemic, understanding this haphazard architecture is a step toward elucidating the U.S. paradox of enormous health expenditures but poor outcomes for population health.
Abstract MP10: Risk Factors For Diabetic Foot Infection: The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Michael Fang, Jiaqi Hu, Kuni Matsushita, Elizabeth Selvin, Caitlin W Hicks
Journal: Circulation (2022)

Introduction: Foot infections occur frequently among people with diabetes and significantly elevate the risk of lower-extremity amputations. However, risk factors for the onset of diabetic foot infection (DFI) in the community remain poorly characterized. Methods: We conducted a prospective cohort analysis of incident DFI using data from the Atherosclerosis Risk in Communities (ARIC) Study. We used Cox regression models to evaluate associations of demographics, cardiometabolic measures, prevalent complications, diabetes duration, and glycemic control with DFI. Incident DFI was ascertained from ICD-9/10 codes from hospital records and Medicare claims, with follow-up to December 31, 2018. Results: We included 1,451 participants with diabetes (mean age, 63 years; 33% black; 47% female, median duration of diabetes 6.2 years). During a median follow-up of 14.4 years, there were 332 incident DFIs (16.8 per 1,000 person-years). Independent risk factors for DFI included older age at baseline (HR: 1.41 per 5 year, 95% CI: 1.11, 1.80), chronic kidney disease (HR: 1.39, 95% CI: 1.08, 1.78), glycemic control (poor vs good, HR: 1.66, 95% CI: 1.24, 2.21), long diabetes duration ( &gt; 9 years vs &lt;9 years, HR: 1.61, 95% CI: 1.28, 2.03), retinopathy (HR: 1.75, 95% CI: 1.33, 2.31), subclinical cardiovascular disease (vs no cardiovascular disease, HR: 1.95, 95% CI: 1.23, 3.08), and clinical cardiovascular disease (vs no cardiovascular disease, HR: 1.36, 95% CI: 1.06, 1.74) (Figure) . Conclusion: Our results suggest that older adults with poor glycemic control, long standing diabetes, and cardiovascular, renal, or retinal complications are at increased risk of developing DFIs. Individualized foot care education, frequent foot screenings, and access to specialized footwear are warranted to reduce foot-related complications for these high-risk populations.
Muscle Involvement Caused by Chronic Active Epstein-Barr Virus Infection on 18F-FDG PET/CT in a Pediatric Patient
Authors: Xu Yang, Xia Lu, Ying Kan, Wei Wang, Jigang Yang
Journal: Clinical Nuclear Medicine (2021)

A 7-year-old girl with chronic active EBV (CAEBV) infection-associated hemophagocytic lymphohistiocytosis presented with fever. 18F-FDG PET/CT revealed heterogeneous FDG uptake in multiple muscle groups without significant abnormal activity elsewhere. On repeat FDG PET/CT scan 1 year later after therapy, the abnormal activity in muscles disappeared. Skeletal muscle involvement by CAEBV infection should be included as differential diagnosis for increased muscle activity on FDG PET/CT study.
RAF1 amplification drives a subset of bladder tumors and confers sensitivity to MAPK-directed therapeutics
Authors: Raie T. Bekele, Amruta S. Samant, Amin H. Nassar, Jonathan So, Elizabeth P. Garcia, Catherine R. Curran, Justin H. Hwang, David L. Mayhew, Anwesha Nag, Aaron R. Thorner, Judit Börcsök, Zsofia Sztupinszki, Chong-Xian Pan, Joaquim Bellmunt, David J. Kwiatkowski, Guru P. Sonpavde, Eliezer M. Van Allen, Kent W. Mouw
Journal: Journal of Clinical Investigation (2021)

Bladder cancer is a genetically heterogeneous disease, and novel therapeutic strategies are needed to expand treatment options and improve clinical outcomes. Here, we identified a unique subset of urothelial tumors with focal amplification of the RAF1 (CRAF) kinase gene. RAF1-amplified tumors had activation of the RAF/MEK/ERK signaling pathway and exhibited a luminal gene expression pattern. Genetic studies demonstrated that RAF1-amplified tumors were dependent upon RAF1 activity for survival, and RAF1-activated cell lines and patient-derived models were sensitive to available and emerging RAF inhibitors as well as combined RAF plus MEK inhibition. Furthermore, we found that bladder tumors with HRAS- or NRAS-activating mutations were dependent on RAF1-mediated signaling and were sensitive to RAF1-targeted therapy. Together, these data identified RAF1 activation as a dependency in a subset making up nearly 20% of urothelial tumors and suggested that targeting RAF1-mediated signaling represents a rational therapeutic strategy.
HIP FRACTURES RISKS IN EDOXABAN VERSUS WARFARIN USERS: A PROPENSITY SCORE-MATCHED POPULATION-BASED COHORT STUDY WITH COMPETING RISK ANALYSES
Authors: Danish Iltaf Satti, Jiandong Zhou, Sharen Lee, Xuejin Liu, Teddy Tai Loy Lee, Oscar Hou In Chou, Carlin Chang, Leonardo Roever, Wing Tak Wong, Abraham Ka Chung Wai, Tong Liu, Qingpeng Zhang, Gary Tse
Journal: Journal of the American College of Cardiology (2022)
Dual X-ray Absorptiometry Screening for Men Receiving Androgen Deprivation Therapy—Hiding in Plain (Film) Sight
Authors: Amar U. Kishan, Sophia C. Kamran, Simon J. C. Soerensen, John T. Leppert
Journal: JAMA Network Open (2022)

Maria E. Suarez-Almazor, MD, PhD; Xerxes Pundole, MD, PhD; Gerardo Cabanillas, MD; Xiudong Lei, PhD; Hui Zhao, PhD; Linda S. Elting, DrPH; Maria A. Lopez-Olivo, MD, PhD; Sharon H. Giordano, MD, MPH
Immunoglobulin light chain amyloidosis: 2022 update on diagnosis, prognosis, and treatment
Authors: Morie A. Gertz
Journal: American Journal of Hematology (2022)

Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS)."Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis. Invasive organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy.N-terminal pro-brain natriuretic peptide (NT-proBNP or BNP), serum troponin T (or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 73, 35, 15, and 5 months.All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first-line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a complete response (CR). In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine.Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. Trials of antibodies to catabolize deposited fibrils are underway.
Quantitative texture-based analysis of pulmonary parenchymal features on chest CT: comparison with densitometric indices and short-term effect of changes in smoking habit
Authors: Chiara Romei, Roberto Castellana, Barbara Conti, Pietro Bemi, Alessandro Taliani, Francesco Pistelli, Ronald A. Karwoski, Laura Carrozzi, Annalisa De Liperi, Brian Bartholmai
Journal: European Respiratory Journal (2022)

Purpose To investigate the correlations between densitometric and Computer Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER)-derived indices of pulmonary emphysema and their change in the short-term period for groups of patients with different smoking habits. Method This retrospective study included 284 subjects from the ITALUNG trial (198 men and 86 women; mean± sd age 60±4 years) who underwent low-dose chest computed tomography at baseline and 2-year follow-up. Subjects were divided into four groups (persistent smokers, restarters, quitters and former smokers) according to their smoking habit at baseline and follow-up. Densitometric and texture analyses were performed, using CALIPER software. A correlation analysis was conducted between CALIPER-derived low-attenuation areas (LAAs) and densitometric indices, including the 15th percentile of the whole-lung attenuation histogram (Perc 15 ) and the relative areas with density ≤−950 HU (RA 950 ). Densitometric indices and LAAs were evaluated at baseline and variation assessed longitudinally with comparisons between groups with different smoking habit. Further analysis of parenchymal changes per pulmonary zone was performed. Results LAAs were strongly correlated with Perc 15 (r s =0.81; p&lt;0.001) and RA 950 (r s =0.905; p&lt;0.001). At baseline, the group of smokers showed higher Perc 15 , lower RA 950 , lower LAAs (particularly mild sub-class of LAAs) than the group of ex-smokers (p&lt;0.001). At 2-year follow-up, densitometric indices and LAAs increased in persistent smokers, former smokers and quitters (p&lt;0.05). The progression was larger and statistically more significant in quitters (p&lt;0.001). Conclusion CALIPER texture analysis provides an objective measure comparable to traditional density/histogram features to assess the lung parenchymal changes in relation to different smoking habits.