tbuckley/cabot-search huggingface dataset:
Low titers of SARS-CoV-2 neutralizing antibodies after first vaccination dose in cancer patients receiving checkpoint inhibitors
Authors: Evangelos Terpos, Flora Zagouri, Michalis Liontos, Aimilia D. Sklirou, Konstantinos Koutsoukos, Christos Markellos, Alexandros Briasoulis, Eleni-Dimitra Papanagnou, Ioannis P. Trougakos, Meletios-Athanasios Dimopoulos
Journal: Journal of Hematology & Oncology (2021)

Abstract Vaccination for SARS-CoV-2 provides significant protection against the infection in the general population. However, only limited data exist for patients with cancer under systemic therapy. Based on this, our site has initiated a study evaluating safety and efficacy of SARS-CoV-2 vaccination in patients with solid and hematological malignancies under several systemic therapies. The initial results of the cohort of 59 patients receiving Immune Checkpoint Inhibitors are presented here. Despite no new safety issues have been noticed, the levels of SARS-CoV-2 neutralizing antibodies are significantly lower in comparison to matched healthy volunteers up to day 22 post the first dose. These results should be taken into consideration for the patients under treatment.
Microscopic Colitis and Risk of Colon Adenomas: A Multicenter Retrospective Cohort Study
Authors: Amrit K. Kamboj, Haley M. Zylberberg, Conor M. Lane, Elida Voth, June Tome, Nicole D. Cuir, Ryan J. Lennon, Sahil Khanna, Benjamin Lebwohl, Darrell S. Pardi
Journal: Clinical Gastroenterology and Hepatology (2021)
Reply to Chandnani et al.
Authors: Pier Alberto Testoni, Sabrina Testoni, Giorgia Mazzoleni, Giuseppe Pantaleo, Maria Bernadette Cilona, Giovanni Distefano, Lorella Fanti, Mario Antonelli, Sandro Passaretti
Journal: Endoscopy (2021)

See also: Transoral incisionless fundoplication with an ultrasonic surgical endostapler for the treatment of gastroesophageal reflux disease: 12-month outcomesEndoscopy 2020; 52(06): 469-473DOI: 10.1055/a-1124-3187 See also: Too early to aʼMUSE!Endoscopy 2021; 53(06): 664-664DOI: 10.1055/a-1327-2359
Transcatheter Heart Valves: A Biomaterials Perspective
Authors: Hieu T. Bui, Nipa Khair, Breandan Yeats, Shelley Gooden, Susan P. James, Lakshmi Prasad Dasi
Journal: Advanced Healthcare Materials (2021)

Abstract Heart valve disease is prevalent throughout the world, and the number of heart valve replacements is expected to increase rapidly in the coming years. Transcatheter heart valve replacement (THVR) provides a safe and minimally invasive means for heart valve replacement in high‐risk patients. The latest clinical data demonstrates that THVR is a practical solution for low‐risk patients. Despite these promising results, there is no long‐term (&gt;20 years) durability data on transcatheter heart valves (THVs), raising concerns about material degeneration and long‐term performance. This review presents a detailed account of the materials development for THVRs. It provides a brief overview of THVR, the native valve properties, the criteria for an ideal THV, and how these devices are tested. A comprehensive review of materials and their applications in THVR, including how these materials are fabricated, prepared, and assembled into THVs is presented, followed by a discussion of current and future THVR biomaterial trends. The field of THVR is proliferating, and this review serves as a guide for understanding the development of THVs from a materials science and engineering perspective.
In older patients with permanent AF and HF, digoxin and bisoprolol did not differ for QoL at 6 mo
Authors: Kaveh Karimzad, Anita Deswal
Journal: Annals of Internal Medicine (2021)

Source Citation Kotecha D, Bunting KV, Gill SK, et al. Effect of digoxin vs bisoprolol for heart rate control in atrial fibrillation on patient-reported quality of life: the RATE-AF randomized clinical trial. JAMA. 2020;324:2497-508. 33351042
AB0583 FRAILTY IN THE PATIENTS WITH OSTEOARTHRITIS OF THE KNEE WAS NOT CAUSED BY SARCOPENIA
Authors: K. Inui, K. Mandai, T. Ikawa, Y. Minami, K. Ueno, H. Ohashi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Osteoarthritis of the knee (knee OA) decreases mobility of the elderly, which function could be significantly improved with artificial joint replacement in many cases. Successful results of the surgery depend on several factors including preoperative muscle strength of lower limbs. Objectives: We assessed morbidity and skeletal muscle mass and strength in patients with knee OA immediately before undergoing arthroplasty and investigated the relationship between impairment of mobility and skeletal muscle function. Methods: All patients scheduled to undergo knee arthroplasty at our hospital after July 2020 were assessed for basic attributes, clinical assessment, blood tests, radiography, whole-body mode DXA, knee muscle strength by dynamometer with written consent (UMIN ID: 000040940). And Japanese Cardiovascular Health Study criteria for frailty, and sarcopenia by Asian Working Group for Sarcopenia 2019 criteria were evaluated. Results: Among 46 patients (40 women, mean age 75.4 years) the overall distribution in frailty is no: 15.9%, pre-frailty: 56.8%, and frailty: 27.3%. That in sarcopenia is no: 91.3%, yes: 2.2%, and severe: 4.3%. Ninety-one % of the patients with frailty did not suffer from sarcopenia. Between the patients with frailty and those without frailty there was a significant difference in walking speed (0.71±0.29m/sec, 1.12±0.29m/sec; p=0.004 adjusted by age and sex). Meanwhile, between those 2 groups of patients no significant differences were observed in skeletal muscle mass (6.40±0.87 kg/m 2 , 6.59±1.09 kg/m 2 ; p=0.35) and knee extension power (120.4±37.4 N, 143.7±67.9 N; p=0.88) adjusted by age and sex. Together with these results, decrease in lower limb motor functions of the patients with knee OA was not caused by sarcopenia. In other words, improvement of mobility in the patients with knee OA could be expected by surgical intervention because of pain relief and ROM improvement. Conclusion: In the patients with knee OA immediately before arthroplasty, frailty was not caused by sarcopenia. Disclosure of Interests: None declared.
PAC1 receptor–mediated clearance of tau in postsynaptic compartments attenuates tau pathology in mouse brain
Authors: Ari W. Schaler, Avery M. Runyan, Catherine L. Clelland, Eric J. Sydney, Stephanie L. Fowler, Helen Y. Figueroa, Seiji Shioda, Ismael Santa-Maria, Karen E. Duff, Natura Myeku
Journal: Science Translational Medicine (2021)

PAC1 receptor activation enhances proteasome-mediated clearance of tau from postsynaptic compartments in the tau transgenic mouse brain.
Novel dental implant modifications with two-staged double benefits for preventing infection and promoting osseointegration in vivo and in vitro
Authors: Xiaoyu Huang, Yang Ge, Bina Yang, Qi Han, Wen Zhou, Jingou Liang, Mingyun Li, Xian Peng, Biao Ren, Bangcheng Yang, Michael D. Weir, Qiang Guo, Haohao Wang, Xinxuan Zhou, Xugang Lu, Thomas W. Oates, Hockin H.K. Xu, Dongmei Deng, Xuedong Zhou, Lei Cheng
Journal: Bioactive Materials (2021)

Peri-implantitis are a major problem causing implant failure these days. Accordingly, anti-infection during the early stage and subsequent promotion of osseointegration are two main key factors to solve this issue. Micro-arc oxidation (MAO) treatment is a way to form an oxidation film on the surface of metallic materials. The method shows good osteogenic properties but weak antibacterial effect. Therefore, we developed combined strategies to combat severe peri-implantitis, which included the use of a novel compound, PD, comprising dendrimers poly(amidoamine) (PAMAM) loading dimethylaminododecyl methacrylate (DMADDM) as well as MAO treatment. Here, we explored the chemical properties of the novel compound PD, and proved that this compound was successfully synthesized, with the loading efficiency and encapsulation efficiency of 23.91% and 31.42%, respectively. We further report the two-stage double benefits capability of PD + MAO: (1) in the first stage, PD + MAO could decrease the adherence and development of biofilms by releasing DMADDM in the highly infected first stage after implant surgery both in vitro and in vivo; (2) in the second stage, PD + MAO indicated mighty anti-infection and osteoconductive characteristics in a rat model of peri-implantitis in vivo. This study first reports the two-staged, double benefits of PD + MAO, and demonstrates its potential in clinical applications for inhibiting peri-implantitis, especially in patients with severe infection risk.
The search for disease-modifying agents in decompensated cirrhosis: From drug repurposing to drug discovery
Authors: Paolo Caraceni, Juan G. Abraldes, Pere Ginès, Phil N. Newsome, Shiv K. Sarin
Journal: Journal of Hepatology (2021)

Patients with decompensated cirrhosis are currently managed through targeted strategies aimed at preventing or treating specific complications. In contrast, a disease-modifying agent should, by definition, be aimed at globally addressing 'decompensated cirrhosis'. To be defined as a disease-modifying agent in decompensated cirrhosis, interventions need to demonstrate an unequivocal benefit on the course of disease in well-designed and adequately powered randomised clinical trials with hard endpoints (i.e. patient survival). These trials also need to define the target population, dosage and timing of administration, factors guiding treatment, temporary or permanent stopping rules, transferability to daily clinical practice, cost-effectiveness, and global treatment access. By eliminating the underlying cause of cirrhosis, aetiologic treatments can still influence the course of decompensated disease by halting or slowing down disease progression or even inducing reversion to the compensated state. In contrast, there remains an unmet clinical need for disease-modifying agents which can antagonise key pathophysiological mechanisms of decompensated cirrhosis, such as portal hypertension, gut translocation, circulatory dysfunction, systemic inflammation, and immunological dysfunction. However, in the last few years, the repurposing of "old drugs" that have already been prescribed for more limited indications in hepatology or for other diseases has provided a few candidates, including human albumin, statins, and poorly absorbable oral antibiotics, which are under further evaluation in large-scale randomised clinical trials. New disease-modifying agents are also expected to be identified in the next decade through the systematic repurposing of existing drugs and the development of novel molecules which are currently undergoing pre-clinical or early clinical testing.
AB0741 PREVALENCE AND ASSOCIATED FACTORS OF ATLANTO-AXIAL INSTABILITY IN PATIENTS WITH JUVENILE IDIOPATHIC ARTHRITIS
Authors: H. Bettaieb, H. Ferjani, K. Maatallah, H. Boussaa, D. Kaffel, W. Hamdi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Atlanto-axial instability (AAI) is a serious complication during Juvenile Idiopathic Arthritis (JIA). It can lead to severe neurological morbidity or mortality if left untreated (1). Objectives: To determine the prevalence of AAI in patients with JIA and to identify factors associated with an increased risk of its occurrence. Methods: A retrospective monocentric study was carried out on JIA patients (ILAR criteria). Data, including age at disease onset, JIA type, disease activity at AAI diagnosis and treatment were collected. Disease activity at JIA diagnosis was evaluated by JADAS10 (Juvenile Arthritis Disease Activity Score) in poly and oligoarticular subtypes and by BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) in arthritis related enthesitis form. Standard radiographs of the cervical spine were analyzed. The data were analyzed using the SPSS statistical package. A p value &lt; 0.05 was considered significant. Results: We enrolled 48 JIA (31 male and 17 female) with a mean age at disease onset of 11.2 ± 3.8 years. The median disease duration was 84 months [2-408]. The median JIA diagnosis delay was 8 months [1-108]. The JIA subgroups were in decreasing order of frequency: Enthesitis-related Arthritis (n=32), Polyarticular RF- (n=4), Polyarticular RF+ (n=2), Oligoarticular (n=6), Systemic (n=2), Psoriatic Arthritis (n=1) and Undifferentiated (n=1). At diagnosis, median ESR and CRP were 44 mm/hour [2-100] and 24 mg/l [2-86] respectively. Median JADAS10 score was 4 [0-21]. Median BASDAI score was 6.2 [2-9.4]. At follow-up, five patients (10.4%) had atlantoaxial subluxation and 17 had coxitis (43.8%). At bone densitometry, 45% of patients had osteroposis and 27.5% had osteopenia. An agreement was assessed between a long diagnosis delay and the following parameters: male gender (p=0.04) and osteoporosis (p=0.018). A Significant positive correlation was found between delay in JIA diagnosis and BASDAI score (p=0.047, r=0.63). No association was found between JIA diagnosis delay and JADAS score (p=0.56). Neither ESR (p=0.19) nor CRP (p=0.42) was associated with JIA diagnosis delay. Finally, no link was observed with the occurrence of hip arthritis (p=0.281) or atlantoaxial subluxation (p=0.137). Conclusion: In our study, the prevalence of AAI was 10.4%. Prolonged corticosteroid use and elevated inflammatory markers were the major factors associated with an increased risk of upper cervical spine involvement. Hence, targeted treatments are required to prevent cervical spine instability. References: [1]Hospach T, Maier J, Müller-Abt P, Patel A, Horneff G, von Kalle T. Cervical spine involvement in patients with juvenile idiopathic arthritis - MRI follow-up study. Pediatr Rheumatol Online J . 2014;12:9. Disclosure of Interests: None declared
Nanoparticle-mediated convection-enhanced delivery of a DNA intercalator to gliomas circumvents temozolomide resistance
Authors: Yongheng Wang, Yuhang Jiang, Dengshuai Wei, Priya Singh, Yingjie Yu, Teresa Lee, Lingpu Zhang, Hanna K. Mandl, Alexandra S. Piotrowski-Daspit, Xinyuan Chen, Fan Li, Xing Li, Yiyu Cheng, Alexander Josowitz, Fan Yang, Yao Zhao, Fuyi Wang, Zhenwen Zhao, Anita Huttner, Ranjit S. Bindra, Haihua Xiao, W. Mark Saltzman
Journal: Nature Biomedical Engineering (2021)
Opening of the Blood–Brain Barrier Using Low-Intensity Pulsed Ultrasound Enhances Responses to Immunotherapy in Preclinical Glioma Models
Authors: Aria Sabbagh, Kevin Beccaria, Xiaoyang Ling, Anantha Marisetty, Martina Ott, Hillary Caruso, Emily Barton, Ling-Yuan Kong, Dexing Fang, Khatri Latha, Daniel Yang Zhang, Jun Wei, John DeGroot, Michael A. Curran, Ganesh Rao, Jian Hu, Carole Desseaux, Guillaume Bouchoux, Michael Canney, Alexandre Carpentier, Amy B. Heimberger
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The blood–brain barrier (BBB) inhibits adequate dosing/penetration of therapeutic agents to malignancies in the brain. Low-intensity pulsed ultrasound (LIPU) is a safe therapeutic method of temporary BBB disruption (BBBD) to enhance chemotherapeutic delivery to the tumor and surrounding brain parenchyma for treatment of glioblastoma. Experimental Design: We investigated if LIPU could enhance therapeutic efficacy of anti–PD-1 in C57BL/6 mice bearing intracranial GL261 gliomas, epidermal growth factor receptor variant III (EGFRvIII) chimeric antigen receptor (CAR) T cells in NSG mice with EGFRvIII-U87 gliomas, and a genetically engineered antigen-presenting cell (APC)-based therapy producing the T-cell attracting chemokine CXCL10 in the GL261-bearing mice. Results: Mice treated with anti–PD-1 and LIPU-induced BBBD had a median survival duration of 58 days compared with 39 days for mice treated with anti–PD-1, and long-term survivors all remained alive after contralateral hemisphere rechallenge. CAR T-cell administration with LIPU-induced BBBD resulted in significant increases in CAR T-cell delivery to the CNS after 24 (P &amp;lt; 0.005) and 72 (P &amp;lt; 0.001) hours and increased median survival by greater than 129%, in comparison with CAR T cells alone. Local deposition of CXCL10-secreting APCs in the glioma microenvironment with LIPU enhanced T-cell glioma infiltration during the therapeutic window (P = 0.004) and markedly enhanced survival (P &amp;lt; 0.05). Conclusions: LIPU increases immune therapeutic delivery to the tumor microenvironment with an associated increase in survival and is an emerging technique for enhancing novel therapies in the brain.
Nerve Guidance Conduits with Hierarchical Anisotropic Architecture for Peripheral Nerve Regeneration
Authors: Qingqing Lu, Feng Zhang, Weinan Cheng, Xiang Gao, Zhaozhao Ding, Xiaoyi Zhang, Qiang Lu, David L. Kaplan
Journal: Advanced Healthcare Materials (2021)

Nerve guidance conduits with multifunctional features could offer microenvironments for improved nerve regeneration and functional recovery. However, the challenge remains to optimize multiple cues in nerve conduit systems due to the interplay of these factors during fabrication. Here, a modular assembly for the fabrication of nerve conduits is utilized to address the goal of incorporating multifunctional guidance cues for nerve regeneration. Silk-based hollow conduits with suitable size and mechanical properties, along with silk nanofiber fillers with tunable hierarchical anisotropic architectures and microporous structures, are developed and assembled into conduits. These conduits supported improves nerve regeneration in terms of cell proliferation (Schwann and PC12 cells) and growth factor secretion (BDNF, brain-derived neurotrophic factor) in vitro, and the in vivo repair and functional recovery of rat sciatic nerve defects. Nerve regeneration using these new conduit designs is comparable to autografts, providing a path towards future clinical impact.
Prognostic Value of 18F-FDG PET in Neuroendocrine Neoplasm
Authors: Sangwon Han, Hyo Sang Lee, Sungmin Woo, Tae-Hyung Kim, Changhoon Yoo, Baek-Yeol Ryoo, Jin-Sook Ryu
Journal: Clinical Nuclear Medicine (2021)

Accurate assessment of the prognosis is critical for the rational treatment of neuroendocrine neoplasms (NENs). We performed a systematic review and meta-analysis of the prognostic value of 18F-FDG PET for NENs.PubMed and Embase databases were searched up to September 2020 for studies that evaluated 18F-FDG PET as prognostic factors in patients with NENs with overall survival (OS) and event-free survival (EFS) as outcomes. Hazards ratios (HRs) comparing high and low FDG uptakes were pooled using the DerSimonian-Laird method. Publication bias was assessed and adjusted for using the trim-and-fill method. Metaregression and subgroup analyses were performed to explore the cause of heterogeneity.Twenty-three studies (1799 patients) were included. The overall pooled HRs of high FDG uptake on EFS and OS were 2.84 (95% confidence interval [CI], 2.21-3.64) and 3.50 (95% CI, 2.42-4.12), respectively. Publication biases were present regarding both EFS and OS (P = 0.0342 and 0.0009, respectively). After adjustment, effect sizes remained significant for EFS and OS (adjusted HR, 2.26 [95% CI, 1.76-2.89]; 3.16 [95% CI, 2.42-4.12]). In metaregression analyses, the proportion of grade 3 tumors positively correlated with the HR of OS (adjusted P = 0.0422).18F-FDG PET is a significant prognostic factor in patients with NENs. 18F-FDG PET might be a useful prognostic biomarker in conjunction with the histologic grade and can help select the optimal treatment.
Identification of Novel, Immunogenic HLA–DR‐Presented <i>Prevotella copri</i> Peptides in Patients With Rheumatoid Arthritis
Authors: Annalisa Pianta, Geena Chiumento, Kristina Ramsden, Qi Wang, Klemen Strle, Sheila Arvikar, Catherine E. Costello, Allen C. Steere
Journal: Arthritis & Rheumatology (2021)

We previously identified HLA-DR-presented epitopes from a 27-kd protein of Prevotella copri (Pc) obtained from peripheral blood mononuclear cells (PBMCs) from 1 rheumatoid arthritis (RA) patient. Herein, we sought to identify other HLA-DR-presented Pc peptides and source proteins in PBMCs from additional patients to better understand Pc immune responses and RA disease pathogenesis.Using tandem mass spectrometry, we searched for HLA-DR-presented Pc peptides in PBMCs from RA and Lyme arthritis (LA) patients. The identified peptides and source proteins were tested for reactivity in RA patients, those with other arthritides, and the general population. These results were assessed for correlation with clinical findings.Including Pc-p27, we identified 5 HLA-DR-presented Pc peptides, each derived from a different Pc protein, in 3 of 4 RA patients, but none in 2 LA patients. When tested in our RA cohort, 14 of 19 patients (74%) had T cell responses, and 47 of 89 patients (53%) had IgG or IgA responses to ≥1 of the 5 Pc peptides or proteins, most commonly IgA reactivity with Pc-p27. Additionally, 74% of RA patients with IgA antibodies to ≥1 Pc protein had anti-citrullinated protein antibodies (ACPAs) compared with 49% of patients who lacked IgA Pc antibody responses (P = 0.05), and IgA Pc antibody levels correlated with ACPA values.The majority of the RA patients had Pc immune responses. The correlation of IgA Pc antibody responses, particularly to Pc-p27, with ACPA supports the hypothesis that specific microbial antigens in the mucosa have a role in shaping or amplifying immune responses in RA joints.
Glycemic Control, Diabetic Complications, and Risk of Dementia in Patients With Diabetes: Results From a Large U.K. Cohort Study
Authors: Bang Zheng, Bowen Su, Geraint Price, Ioanna Tzoulaki, Sara Ahmadi-Abhari, Lefkos Middleton
Journal: Diabetes Care (2021)

OBJECTIVE Type 2 diabetes is an established risk factor for dementia. However, the roles of glycemic control and diabetic complications in the development of dementia have been less well substantiated. This large-scale cohort study aims to examine associations of longitudinal HbA1c levels and diabetic complications with the risk of dementia incidence among patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Data of eligible patients with diabetes, aged ≥50 years in the U.K. Clinical Practice Research Datalink from 1987 to 2018, were analyzed. Time-varying Cox regressions were used to estimate adjusted hazard ratios (HRs) and 95% CIs for dementia risk. RESULTS Among 457,902 patients with diabetes, 28,627 (6.3%) incident dementia cases were observed during a median of 6 years’ follow-up. Patients with recorded hypoglycemic events or microvascular complications were at higher risk of dementia incidence compared with those without such complications (HR 1.30 [95% CI 1.22–1.39] and 1.10 [1.06–1.14], respectively). The HbA1c level, modeled as a time-varying exposure, was associated with increased dementia risk (HR 1.08 [95% CI 1.07–1.09] per 1% HbA1c increment) among 372,287 patients with diabetes with postdiagnosis HbA1c records. Similarly, a higher coefficient of variation of HbA1c during the initial 3 years of follow-up was associated with higher subsequent dementia risk (HR 1.03 [95% CI 1.01–1.04] per 1-SD increment). CONCLUSIONS Higher or unstable HbA1c levels and the presence of diabetic complications in patients with type 2 diabetes are associated with increased dementia risk. Effective management of glycemia might have a significant role in maintaining cognitive health among older adults with diabetes.