tbuckley/cabot-search huggingface dataset:
Effects of 13-valent pneumococcal conjugate vaccination of adults on lower respiratory tract infections and antibiotic use in primary care: secondary analysis of a double-blind randomized placebo-controlled study
Authors: Cornelis H. van Werkhoven, Marieke Bolkenbaas, Susanne M. Huijts, Theo J.M. Verheij, Marc J.M. Bonten
Journal: Clinical Microbiology and Infection (2020)

ObjectivesThe efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in adults to prevent community-acquired pneumonia (CAP) and lower respiratory tract infections (LRTI) not requiring hospitalization is unknown. We determined the effect of PCV13 on CAP, LRTI and antibiotic use in the primary care setting.MethodsCommunity-dwelling immunocompetent adults over 65 years of age were randomized to PCV13 or placebo as part of the double-blind Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA). CAP and LRTI episodes and antibiotic prescription data were extracted from general practitioner information systems of 40 426 individuals. Vaccine efficacy (VE) of PCV13 was determined using Poisson regression with robust standard errors, comparing CAP and non-CAP LRTI episodes, LRTI-specific and total antibiotic prescriptions.ResultsIn all, 20 195 participants received PCV13 and 20 231 received placebo. A total of 1564 and 1659 CAP episodes occurred in the PCV13 and placebo group, respectively; VE 5.5% (95% CI –2.6% to 13.0%). Non-CAP LRTI episodes occurred 7535 and 7817 times in the PCV13 and placebo groups, respectively; VE 3.4% (95% CI –2.0% to 8.5%). A total of 8835 and 9245 LRTI-related antibiotic courses were prescribed in the PCV13 and placebo arms, respectively; VE 4.2% (95% CI –1.0% to 9.1%). Antibiotic courses for any indication were prescribed 43 386 and 43 309 times, respectively; VE –0.4% (–4.9% to 3.9%).ConclusionsPCV13 vaccination in the elderly is unlikely to cause a relevant reduction in the incidence of CAP, LRTI, LRTI-related antibiotic use or total antibiotic use in primary care.
Clinical features of COVID-19 mortality: development and validation of a clinical prediction model
Authors: Arjun S Yadaw, Yan-chak Li, Sonali Bose, Ravi Iyengar, Supinda Bunyavanich, Gaurav Pandey
Journal: The Lancet Digital Health (2020)

The COVID-19 pandemic has affected millions of individuals and caused hundreds of thousands of deaths worldwide. Predicting mortality among patients with COVID-19 who present with a spectrum of complications is very difficult, hindering the prognostication and management of the disease. We aimed to develop an accurate prediction model of COVID-19 mortality using unbiased computational methods, and identify the clinical features most predictive of this outcome.
Application of bioactive hydrogels combined with dental pulp stem cells for the repair of large gap peripheral nerve injuries
Authors: Lihua Luo, Yan He, Ling Jin, Yanni Zhang, Fernando P. Guastaldi, Abdullkhaleg A. Albashari, Fengting Hu, Xiaoyan Wang, Lei Wang, Jian Xiao, Lingli Li, Jianming Wang, Akon Higuchi, Qingsong Ye
Journal: Bioactive Materials (2020)

Due to the limitations in autogenous nerve grafting or Schwann cell transplantation, large gap peripheral nerve injuries require a bridging strategy supported by nerve conduit. Cell based therapies provide a novel treatment for peripheral nerve injuries. In this study, we first experimented an optimal scaffold material synthesis protocol, from where we selected the 10% GFD formula (10% GelMA hydrogel, recombinant human basic fibroblast growth factor and dental pulp stem cells (DPSCs)) to fill a cellulose/soy protein isolate composite membrane (CSM) tube to construct a third generation of nerve regeneration conduit, CSM-GFD. Then this CSM-GFD conduit was applied to repair a 15-mm long defect of sciatic nerve in a rat model. After 12 week post implant surgery, at histologic level, we found CSM-GFD conduit could regenerate nerve tissue like neuron and Schwann like nerve cells and myelinated nerve fibers. At physical level, CSM-GFD achieved functional recovery assessed by a sciatic functional index study. In both levels, CSM-GFD performed like what gold standard, the nerve autograft, could do. Further, we unveiled that almost all newly formed nerve tissue at defect site was originated from the direct differentiation of exogeneous DPSCs in CSM-GFD. In conclusion, we claimed that this third-generation nerve regeneration conduit, CSM-GFD, could be a promising tissue engineering approach to replace the conventional nerve autograft to treat the large gap defect in peripheral nerve injuries.
Bioinspired Dopamine/Mucin Coatings Provide Lubricity, Wear Protection, and Cell‐Repellent Properties for Medical Applications
Authors: Jian Song, Theresa M. Lutz, Nora Lang, Oliver Lieleg
Journal: Advanced Healthcare Materials (2020)

Abstract Even though medical devices have improved a lot over the past decades, there are still issues regarding their anti‐biofouling properties and tribological performance, and both aspects contribute to the short‐ and long‐term failure of these devices. Coating these devices with a biocompatible layer that reduces friction, wear, and biofouling at the same time would be a promising strategy to address these issues. Inspired by the adhesion mechanism employed by mussels, here, dopamine is made use of to immobilize lubricious mucin macromolecules onto both manufactured commercial materials and real medical devices. It is shown that purified mucins successfully adsorb onto a dopamine pre‐coated substrate, and that this double‐layer is stable toward mechanical challenges and storage in aqueous solutions. Moreover, the results indicate that the dopamine/mucin double‐layer decreases friction (especially in the boundary lubrication regime), reduces wear damage, and provides anti‐biofouling properties. The results obtained in this study show that such dopamine/mucin double‐layer coatings can be powerful candidates for improving the surface properties of medical devices such as catheters, stents, and blood vessel substitutes.
Phase Ib Study of Chemoprevention with Green Tea Polyphenon E and Erlotinib in Patients with Advanced Premalignant Lesions (APL) of the Head and Neck
Authors: Dong M. Shin, Sreenivas Nannapaneni, Mihir R. Patel, Qiuying Shi, Yuan Liu, Zhengjia Chen, Amy Y. Chen, Mark W. El-Deiry, Jonathan J. Beitler, Conor E. Steuer, Steven M. Roser, Adam M. Klein, Taofeek K. Owonikoko, Suresh S. Ramalingam, Fadlo R. Khuri, Zhuo G. Chen, Nabil F. Saba
Journal: Clinical Cancer Research (2020)

On the basis of synergistic effects between green tea polyphenon E (PPE) and EGFR-tyrosine kinase inhibitor in preclinical studies, we conducted a phase Ib study of the PPE and erlotinib combination in patients with advanced premalignant lesions (APL) of the oral cavity and larynx.Patients were treated with a fixed dose of PPE (200 mg three times a day) and dose escalation of erlotinib (50, 75, 100 mg daily) for 6 months with tissue biopsy at baseline and 6 months. Primary endpoints were safety and toxicity; secondary endpoints were evaluation of pathologic response, cancer-free survival (CFS), overall survival (OS), and biomarker modulation.Among 21 enrolled patients, 19 began treatment and 17 completed 6 months of treatment with PPE and erlotinib. Main characteristics of treated patients: 15 severe dysplasia or carcinoma in situ and 17 oral cavity. Only skin rash was associated with dose-limiting toxicity and MTD. Recommended doses for phase II studies are PPE 600 mg daily plus erlotinib 100 mg daily for 6 months. Pathologic responses in 17 evaluable patients: pathologic complete response (47%) and pathologic partial response (18%). The 5-year CFS and OS were 66.3% and 93%, respectively. Among tested biomarkers, only phosphorylated ERK was correlated with response to treatment.Treatment with PPE and erlotinib combination was well tolerated in patients with APLs of the head and neck, and showed a high rate of pathologic response with excellent CFS. This combination deserves further investigation for the chemoprevention and/or prevention of second primary tumors in early-stage head and neck cancer.
18F-FDG PET/CT in Hyalinized Cholecystitis
Authors: Esra Arslan, Aytül Hande Yardimci, Enver Yarikkaya, Göksel Alçin, Tevfik Fikret Çermik
Journal: Clinical Nuclear Medicine (2020)

Hyalinizing cholecystitis is a rare type of chronic cholecystitis. Moderate patchy transmural especially perivascular lymphoplasmacytic inflammatory cell infiltration is observed in the gallbladder wall. We present the 18F-FDG PET/CT and MRI findings of this rare subtype of chronic cholecystitis. Hyalinizing cholecystitis should be kept in mind in the differential diagnosis of gallbladder wall thickening with intense 18F-FDG uptake.
Continuous Glucose Monitoring–Derived Data Report—Simply a Better Management Tool
Authors: Tadej Battelino, Richard M. Bergenstal
Journal: Diabetes Care (2020)

The introduction of A1C into routine diabetes care some 30 years ago provided the first reliable marker of glycemic control, clearly related to devastating chronic complications of diabetes. A1C became the standard metric to judge the quality of diabetes care and the primary outcome for all diabetes intervention trials investigating novel medications and new technologies. This dependence on A1C as our sole glycemic management guide and primary outcome measure was questioned by some investigators (1); however, the A1C was familiar and convenient and became the key diabetes pay-for-performance quality metric in the U.S. After decades of the “A1C era” in diabetes care, it is now evident that the management of diabetes guided by A1C has not yielded our desired results, and despite novel medicines and diabetes technology the mean A1C has actually deteriorated in the last decade (2–5). As national A1C levels were slipping, an impactful article entitled “Resurgence in Diabetes-Related Complications” was published (6), pointing out that while health care access, delivery, and preventive services are far from ideal, we also need to focus on innovative strategies to safely achieve glycemic targets. It seems fair to ask, what went wrong? Wasn’t the introduction of continuous glucose monitoring (CGM) going to transform diabetes management (7)?

While it often takes 17 years to get approved therapies or technology innovations adopted and implemented in clinical practice (8), we believe that in the case of CGM, effective implementation will also involve a refinement of our management philosophy. Our current training on use of the CGM glucose profile and data report is to always address any noted patterns of hypoglycemia first. This is a sound principle, and using CGM we have been extremely successful in minimizing hypoglycemia as demonstrated in randomized clinical trials …
Revealing the structure of pharmacobehavioral space through motion sequencing
Authors: Alexander B. Wiltschko, Tatsuya Tsukahara, Ayman Zeine, Rockwell Anyoha, Winthrop F. Gillis, Jeffrey E. Markowitz, Ralph E. Peterson, Jesse Katon, Matthew J. Johnson, Sandeep Robert Datta
Journal: Nature Neuroscience (2020)
Hybrid endoscopic submucosal dissection (ESD) compared with conventional ESD for colorectal lesions: a systematic review and meta-analysis
Authors: Thomas R. McCarty, Ahmad Najdat Bazarbashi, Christopher C. Thompson, Hiroyuki Aihara
Journal: Endoscopy (2020)

Abstract Background Hybrid endoscopic submucosal dissection (ESD) is increasingly utilized to overcome the complexity of conventional ESD. This systematic review and meta-analysis evaluated the efficacy and safety of hybrid ESD for treatment of colorectal lesions. Methods Search strategies were developed in accordance with PRISMA guidelines. Pooled proportions were calculated with rates estimated using random effects models. Measured outcomes included en bloc resection, procedure-associated complications, recurrence, and need for surgery. Subgroup analyses were performed to compare effectiveness of conventional versus hybrid ESD. Results 16 studies (751 patients) were included with a mean (standard deviation [SD]) lesion size of 27.96 (10.55) mm. En bloc resection rate was 81.63 % (95 % confidence interval [CI] 72.07 – 88.44; I2 = 80.89). Complications, recurrences, and need for surgery occurred in 7.74 % (95 %CI 4.78 – 12.31; I2 = 65.84), 4.52 % (95 %CI 1.40 – 13.65; I2 = 76.81), and 3.64 % (95 %CI 1.76 – 7.37; I2 = 15.52), respectively. Mean procedure duration was 48.83 (22.37) minutes. On subgroup analyses comparing outcomes for conventional (n = 1703) versus hybrid ESD (n = 497), procedure duration was significantly shorter for hybrid ESD (mean difference 18.45 minutes; P = 0.003), with lower complication rates (P = 0.04); however, hybrid ESD had lower en bloc resection rates (P &lt; 0.001). There was no difference in rates of recurrence or surgery (P &gt; 0.05). Conclusion While hybrid ESD was safe and effective for removal of colorectal lesions, with shorter procedure duration, fewer complications, and no difference in recurrence versus conventional ESD, hybrid ESD was associated with a lower en bloc resection rate.
<i>STAT3</i>Antisense Oligonucleotide Remodels the Suppressive Tumor Microenvironment to Enhance Immune Activation in Combination with Anti–PD-L1
Authors: Theresa A. Proia, Maneesh Singh, Richard Woessner, Larissa Carnevalli, Gayathri Bommakanti, Lukasz Magiera, Srimathi Srinivasan, Shaun Grosskurth, Mike Collins, Chris Womack, Matthew Griffin, Minwei Ye, Susan Cantin, Deanna Russell, Mingchao Xie, Adina Hughes, Nanhua Deng, Deanna A. Mele, Stephen Fawell, Simon Barry, Corinne Reimer, J. Carl Barrett, Patricia McCoon
Journal: Clinical Cancer Research (2020)

Danvatirsen is a therapeutic antisense oligonucleotide (ASO) that selectively targets STAT3 and has shown clinical activity in two phase I clinical studies. We interrogated the clinical mechanism of action using danvatirsen-treated patient samples and conducted back-translational studies to further elucidate its immunomodulatory mechanism of action.Paired biopsies and blood samples from danvatirsen-treated patients were evaluated using immunohistochemistry and gene-expression analysis. To gain mechanistic insight, we used mass cytometry, flow cytometry, and immunofluorescence analysis of CT26 tumors treated with a mouse surrogate STAT3 ASO, and human immune cells were treated in vitro with danvatirsen.Within the tumors of treated patients, danvatirsen uptake was observed mainly in cells of the tumor microenvironment (TME). Gene expression analysis comparing baseline and on-treatment tumor samples showed increased expression of proinflammatory genes. In mouse models, STAT3 ASO demonstrated partial tumor growth inhibition and enhanced the antitumor activity when combined with anti-PD-L1. Immune profiling revealed reduced STAT3 protein in immune and stromal cells, and decreased suppressive cytokines correlating with increased proinflammatory macrophages and cytokine production. These changes led to enhanced T-cell abundance and function in combination with anti-PD-L1.STAT3 ASO treatment reverses a suppressive TME and promotes proinflammatory gene expression changes in patients' tumors and mouse models. Preclinical data provide evidence that ASO-mediated inhibition of STAT3 in the immune compartment is sufficient to remodel the TME and enhance the activity of checkpoint blockade without direct STAT3 inhibition in tumor cells. Collectively, these data provide a rationale for testing this combination in the clinic.
Validation of a Machine Learning Model to Predict Childhood Lead Poisoning
Authors: Eric Potash, Rayid Ghani, Joe Walsh, Emile Jorgensen, Cortland Lohff, Nik Prachand, Raed Mansour
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Childhood lead poisoning causes irreversible neurobehavioral deficits, but current practice is secondary prevention. <h3>Objective</h3> To validate a machine learning (random forest) prediction model of elevated blood lead levels (EBLLs) by comparison with a parsimonious logistic regression. <h3>Design, Setting, and Participants</h3> This prognostic study for temporal validation of multivariable prediction models used data from the Women, Infants, and Children (WIC) program of the Chicago Department of Public Health. Participants included a development cohort of children born from January 1, 2007, to December 31, 2012, and a validation WIC cohort born from January 1 to December 31, 2013. Blood lead levels were measured until December 31, 2018. Data were analyzed from January 1 to October 31, 2019. <h3>Exposures</h3> Blood lead level test results; lead investigation findings; housing characteristics, permits, and violations; and demographic variables. <h3>Main Outcomes and Measures</h3> Incident EBLL (≥6 μg/dL). Models were assessed using the area under the receiver operating characteristic curve (AUC) and confusion matrix metrics (positive predictive value, sensitivity, and specificity) at various thresholds. <h3>Results</h3> Among 6812 children in the WIC validation cohort, 3451 (50.7%) were female, 3057 (44.9%) were Hispanic, 2804 (41.2%) were non-Hispanic Black, 458 (6.7%) were non-Hispanic White, and 442 (6.5%) were Asian (mean [SD] age, 5.5 [0.3] years). The median year of housing construction was 1919 (interquartile range, 1903-1948). Random forest AUC was 0.69 compared with 0.64 for logistic regression (difference, 0.05; 95% CI, 0.02-0.08). When predicting the 5% of children at highest risk to have EBLLs, random forest and logistic regression models had positive predictive values of 15.5% and 7.8%, respectively (difference, 7.7%; 95% CI, 3.7%-11.3%), sensitivity of 16.2% and 8.1%, respectively (difference, 8.1%; 95% CI, 3.9%-11.7%), and specificity of 95.5% and 95.1% (difference, 0.4%; 95% CI, 0.0%-0.7%). <h3>Conclusions and Relevance</h3> The machine learning model outperformed regression in predicting childhood lead poisoning, especially in identifying children at highest risk. Such a model could be used to target the allocation of lead poisoning prevention resources to these children.
Association of Medicare Mandatory Bundled Payment System for Hip and Knee Joint Replacement With Racial/Ethnic Difference in Joint Replacement Care
Authors: Hyunjee Kim, Thomas H. A. Meath, Felix W. Tran, Ana R. Quiñones, K. John McConnell, Said A. Ibrahim
Journal: JAMA Network Open (2020)

<h3>Importance</h3> There are marked racial/ethnic differences in hip and knee joint replacement care as well as concerns that value-based payments may exacerbate existing racial/ethnic disparities in care. <h3>Objective</h3> To examine changes in joint replacement care associated with Medicare's Comprehensive Care for Joint Replacement (CJR) model among White, Black, and Hispanic patients. <h3>Design, Setting, and Participants</h3> Retrospective cohort study of Medicare claims from 2013 through 2017 among White, Black, and Hispanic patients undergoing joint replacement in 67 treatment (selected for CJR participation) and 103 control metropolitan statistical areas. <h3>Exposures</h3> The CJR model holds hospitals accountable for spending and quality of joint replacement care during care episodes (index hospitalization through 90 days after discharge). <h3>Main Outcomes and Measures</h3> The primary outcomes were spending, discharge to institutional postacute care, and readmission during care episodes. <h3>Results</h3> Among 688 346 patients, 442 163 (64.2%) were women, and 87 286 (12.7%) were 85 years or older. Under CJR, spending decreased by $439 for White patients (95% CI, −$718 to −$161; from pre-CJR spending in treatment metropolitan statistical areas of $25 264) but did not change for Black patients and Hispanic patients. Discharges to institutional postacute care decreased for all groups (−2.5 percentage points; 95% CI, −4.7 to −0.4, from pre-CJR risk of 46.2% for White patients; −6.0 percentage points; 95% CI, −9.8 to −2.2, from pre-CJR risk of 59.5% for Black patients; and −4.3 percentage points; 95% CI, −7.6 to −1.0, from pre-CJR risk of 54.3% for Hispanic patients). Readmission risk decreased for Black patients by 3.1 percentage points (95% CI, −5.9 to −0.4, from pre-CJR risk of 21.8%) and did not change for White patients and Hispanic patients. Under CJR, Black-White differences in discharges to institutional postacute care decreased by 3.4 percentage points (95% CI, −6.4 to −0.5, from the pre-CJR Black-White difference of 13.3 percentage points). No evidence was found demonstrating that Black-White differences changed for other outcomes or that Hispanic-White differences changed for any outcomes under CJR. <h3>Conclusions and Relevance</h3> In this cohort study of patients receiving joint replacements, CJR was associated with decreased readmissions for Black patients. Furthermore, Black patients experienced a greater decrease in discharges to institutional postacute care relative to White patients, representing relative improvements despite concerns that value-based payment models may exacerbate existing disparities. Nonetheless, differences between White and Black patients in joint replacement care still persisted even after these changes.
Therapeutic vaccination against murine colon carcinoma by radiofrequency ablation in combination with intratumoral naive dendritic cell injection
Authors: Hisashi Saji, Harubumi Kato, Wenru Song, Edgar Engleman
Journal: Cancer Research (2006)

1852  Although the current treatment of radiofrequency ablation (RFA) for hepatic metastasis from colorectal cancer are safe and well-tolerated and successfully control local tumor recurrence, metastatic disease has developed at other sites. Because patients are at risk for the development of new metastatic disease after RFA, multimodality treatment approaches that include RFA in addition of a relevant systemic therapy should be highly investigated. In this present study, we evaluated the efficacy of additional injection of immature unpulsed dendritic cells (DCs) directly into tumor site following RFA treatment. Balb/c mice bearing CT26 murine colon carcinoma established simultaneously in both lower flanks were treated with RFA alone or in combination with intratumoral immature DCs (IT-DC) injection into only right side. Intratumoral DCs injection after RFA (RFA+IT-DC) led the systemic antitumor response against left distant tumors and decreased the rate of local tumor recurrence. This DCs-madiated antitumor effect was systemic and durable antitumor immune memory, therefore, completely protected against second tumor challenge into the lung site. Both CD4+ and CD8+ T cells are necessary for the antitumor effect. Furthermore, tumor milieu after RFA activated immature DCs to the mature subsets and induced DCs migration into regional lymph nodes, where DCs primes cytotoxic T lymphocytes (CTLs). Interestingly, established tumor itself deactivate DCs, rendering induction of tumor tolerance. These results show that RFA + IT-DC induces potent systemic anti-tumor immunity in mice and should be evaluated in the treatment of human cancer.