tbuckley/cabot-search huggingface dataset:
Whether clean or dirty, endoscopic treatment is recommended for symptomatic walled-off necrosis
Authors: Rungsun Rerknimitr
Journal: Endoscopy (2021)

Walled-off necrosis (WON) is one of the stages in acute pancreatitis that develops weeks after the incidence of pancreatic and/or peripancreatic necrosis. WON is documented by cross-sectional imaging [1]. Typically, WON can be categorized into asymptomatic and symptomatic WON. Many small asymptomatic WONs may spontaneously resolve with conservative management, without the need for intervention. The most common presentation of symptomatic WON is infection. Cross-sectional imaging may show air bubbles inside the WON cavity. In cases with no air bubbles on cross-sectional imaging, a fine-needle aspiration from the WON may be needed to confirm bacterial contamination. In general, patients with infected WON show a wide clinical spectrum on presentation, ranging from uncontrolled fever to more severe cases with sepsis. Infected WON may herald spontaneous rupture either to the gastrointestinal lumen or to the skin [2]. The prognosis for spontaneously ruptured WON is unpredictable and could be fatal if the ruptured site is in the colon [3]. Therefore, drainage and/or necrosectomy either surgically or nonsurgically is recommended to avoid rupture of the infected WON [2] [4] [5].
Let's be skeptical about reconsolidation and emotional arousal in therapy
Authors: Lawrence Patihis
Journal: Behavioral and Brain Sciences (2015)

Abstract Lane et al. imply hypotheses that are questionable: that emotional arousal is a cause of positive change and reconsolidation research can be applied to therapy to alter memory. Given the history of problematic attempts to incorporate memory distortion or high emotional arousal into therapeutic techniques, both of which heralded premature optimism and hubris, I urge open-minded skepticism.
Beard loss in men with frontal fibrosing alopecia
Authors: Claudia Bernárdez, David Saceda-Corralo, Rocio Gil-Redondo, Oscar M. Moreno-Arrones, Ana Rita Rodrigues-Barata, Angela Hermosa-Gelbard, Sergio Vañó-Galvan
Journal: Journal of the American Academy of Dermatology (2021)
Reciprocal organ interactions during heart failure: a position paper from the ESC Working Group on Myocardial Function
Authors: Michele Ciccarelli, Dana Dawson, Inês Falcao-Pires, Mauro Giacca, Nazha Hamdani, Stéphane Heymans, Astrid Hooghiemstra, Annebet Leeuwis, Dorien Hermkens, Carlo Gabriele Tocchetti, Jolanda van der Velden, Serena Zacchigna, Thomas Thum
Journal: Cardiovascular Research (2021)

Abstract Heart failure—either with reduced or preserved ejection fraction (HFrEF/HFpEF)—is a clinical syndrome of multifactorial and gender-dependent aetiology, indicating the insufficiency of the heart to pump blood adequately to maintain blood flow to meet the body’s needs. Typical symptoms commonly include shortness of breath, excessive fatigue with impaired exercise capacity, and peripheral oedema, thereby alluding to the fact that heart failure is a syndrome that affects multiple organ systems. Patients suffering from progressed heart failure have a very limited life expectancy, lower than that of numerous cancer types. In this position paper, we provide an overview regarding interactions between the heart and other organ systems, the clinical evidence, underlying mechanisms, potential available or yet-to-establish animal models to study such interactions and finally discuss potential new drug interventions to be developed in the future. Our working group suggests that more experimental research is required to understand the individual molecular mechanisms underlying heart failure and reinforces the urgency for tailored therapeutic interventions that target not only the heart but also other related affected organ systems to effectively treat heart failure as a clinical syndrome that affects and involves multiple organs.
Abstract 11554: Atrial Fibrillation Ablation Outcome in Congenitally Corrected Transposition of Great Arteries
Authors: Pooneh Nabavizadeh, Richard J Czosek, Timothy K Knilans, Mehran Attari, Srinivas Rajsheker, David Spar
Journal: Circulation (2019)

Background: Ablation of atrial fibrillation (AF) in symptomatic patients unresponsive to medical therapy has become the standard of practice. However, the outcome of AF ablation in patients with co...
Repair cell first, then regenerate the tissues and organs
Authors: Xiao-Bing Fu
Journal: Military Medical Research (2021)

Abstract Wound healing, tissue repair and regenerative medicine are in great demand, and great achievements in these fields have been made. The traditional strategy of tissue repair and regeneration has focused on the level of tissues and organs directly; however, the basic process of repair at the cell level is often neglected. Because the cell is the basic unit of organism structure and function; cell damage is caused first by ischemia or ischemia-reperfusion after severe trauma and injury. Then, damage to tissues and organs occurs with massive cell damage, apoptosis and even cell death. Thus, how to achieve the aim of perfect repair and regeneration? The basic process of tissue or organ repair and regeneration should involve repair of cells first, then tissues and organs. In this manuscript, it is my consideration about how to repair the cell first, then regenerate the tissues and organs.
Comparison of Access to Primary Care Medical and Dental Appointments Between Simulated Patients Who Were Deaf and Patients Who Could Hear
Authors: Elizabeth Schniedewind, Ryan P. Lindsay, Steven Snow
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Primary medical and dental clinics may accept fewer people who are deaf as patients than persons who can hear, and clinics may deny requests by patients who are deaf for American Sign Language (ASL) interpretation at appointments when necessary, creating diminished access to primary medical and dental care. <h3>Objective</h3> To compare the rate at which patients who are deaf are offered primary care medical or dental appointments with the rate at which appointments are offered to patients who can hear in a real-world context. <h3>Design, Setting, and Participants</h3> This cross-sectional study used a simulated patient (SP) call audit method. Simulated patients (4 who could hear and 4 who were deaf) followed a call script in which an adult sought to establish care, requesting new patient appointments from a statewide stratified random sample of clinicians listed in the Idaho Medical and Dental Associations member databases at 445 clinics (334 primary care and 111 general dentistry) throughout Idaho. Simulated patients who were deaf also requested interpreting services at the appointment. Calls were made between June 7 and December 6, 2018. Data analysis was conducted from December 2019 to April 2020. <h3>Exposures</h3> Simulated patients who were deaf or could hear called primary care medical or dental clinics from the sampling frame and requested an appointment, supplying the same basic information. In addition, SPs who were deaf requested that an ASL interpreter be provided by the clinic for the appointment. <h3>Main Outcomes and Measures</h3> Rates of new appointments offered and, for SPs who were deaf, whether ASL interpreter services were confirmed for the appointment. <h3>Results</h3> Two male and 2 female SPs who could hear were successful on 210 occasions (64.4%) when requesting a new patient appointment compared with 2 male and 2 female SPs who were deaf who were successful on 161 occasions (49.1%) (<i>P</i> &lt; .001). Simulated patients who could hear were nearly 2 times more likely to secure appointments than were SPs who were deaf (adjusted odds ratio, 1.88; 95% CI, 1.27-2.79). For SPs who were deaf, 80 unsuccessful appointment requests (48.2%) were associated with a request for interpretation. <h3>Conclusions and Relevance</h3> The findings suggest that in a statewide representative sample, access to primary medical and dental care for patients who are deaf is significantly reduced. Patients who are deaf may not receive an appointment if they request interpreter services, even when such services are required to provide effective communication.
Chemo4MetPanc: A phase II study with combination chemotherapy (gemcitabine and nab-paclitaxel), chemokine (C-X-C) motif receptor 4 inhibitor (motixafortide), and immune checkpoint blockade (cemiplimab) in metastatic treatment naïve pancreas adenocarcinoma (PDAC).
Authors: Ilenia Pellicciotta, Emily Linda Alouani, Alexander Raufi, Samuel M Pan, Jianhua Hu, Gulam Abbas Manji
Journal: Journal of Clinical Oncology (2021)

TPS454 Background: Pancreas adenocarcinoma (PDAC) is an aggressive cancer projected to be the second leading cause of cancer-related death in the United States by 2030 for which improved treatment options are desperately needed. Immune checkpoint blockade (ICB) for PDAC has failed as monotherapy in early phase clinical trials likely due to a highly immunosuppressive tumor microenvironment. The CXCR4/CXCL12 axis is a key immune evasion mechanism thought to deter CD8+ T-cells (CTLs) from infiltrating the tumor. We performed a large seven arm survival and biopsy/necropsy study in KPC mice (Kras LSL.G12D/+ ;p53 R172H/+ ;Pdx1Cre tg/+ ) where we demonstrate that addition of gemcitabine to CXCR4 inhibition in combination with ICB, enhanced tumor stabilization and neoplastic cell death, and improved survival by 50 percent. Multiplex immunofluorescence indicated an increased CTL to regulatory T-cell ratio and clustering of CTLs around neoplastic cells. Presented here is a trial-in progress that will evaluate combination of a CXCR4 inhibitor, ICB, and chemotherapy in treatment naïve patients with PDAC. Methods: This is a multicenter, single arm, open-label phase 2 study of combination motixafortide 1.25mg/kg SC monotherapy for 5 days during priming followed by twice weekly, cemiplimab 350mg IV once every 21 days, gemcitabine 1000mg/m2 IV with nab-paclitaxel 125mg/m2 IV on days 1, 8, and 15 every 28 days. Patients with histologically confirmed metastatic PDAC who have not received prior therapy will be enrolled. The primary endpoint is overall response rate by 16 weeks. A response rate greater than 45% by 16 weeks is considered promising, whereas a response rate of less than 23% is considered not promising. We will use a Simon optimal 2-stage design, where we will enroll 10 patients in the first stage. If 3 or more patients meet the endpoint in the first stage, the study will be expanded to a total of 40 patients. If a total of 14 or more patients achieve CR or PR by 16 weeks, the agent will be considered promising and worthy of further study. Secondary endpoints include safety, mPFS, disease control rate (DCR), and mOS. Correlative aims include analyses of pre- and on-treatment biopsies with quantitative multiplex immunofluorescence, RNA-sequencing, and generation of patient derived organoids for association with clinical benefit and to determine mechanisms of action/resistance. An interim analysis will be performed at the conclusion of the stage I portion of the study. Clinical trial information: NCT04543071.
HP0032 Problems reported by persons with rheumatic diseases
Authors: MA Larsson, AM Andersson, M Aronsson, R Holtin, L Olausson, M Thyberg
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Since 1991, Apoteket AB (the national corporation of Swedish pharmacies) has conducted so called "theme years", focusing on one widespread disease each year, in order to improve drug use. In 2002, Swedish pharmacies will pay special attention to persons with Rheumatic disorders. To prepare for this, we wanted to learn more about the problems associated with these diseases. <h3>Objectives</h3> In order to identify disease-related difficulties in this group of patients, a Problem Detection Study (PDS) was performed. A PDS study not only identifies problems, it also ranks the problems according to how troublesome the patients find them. <h3>Methods</h3> Initially, interviews with individuals and groups of patients were performed in order to identify all problems. This qualitative step identified 116 different problems. A questionnaire based on the problems was distributed to 950 patients in Sweden. The patients were to give each problem a grade, from 0 (no problem at all) to 3 (large problem). The average grade for each problem was calculated and a list of all problems, ranked by their average grade, was generated. The problem with the highest average was the worst one. <h3>Results</h3> 75% of the 950 patients included answered the questionnaire. This large response rate may be due to an eager among these patients to improve their situation. Problems regarding everyday life were found most troublesome. The largest problem was "It is frustrating that I´m unable to do everything I wish to, due to my RD". The average grade for this problem was 2,5, which is very high compared to results from similar studies on other groups. The top 50 problems were further analysed, and divided into six categories. Many large problems were connected to everyday life. Problems regarding understanding, from others and from the community, were also important, as well as problems concerning the use of drugs and lack of information. The five subgroups, RA, Arthritis, SLE, Mb Bechterew, Fibromyalgia had very similar experiences, although the latter group differed to some extent. <h3>Conclusions</h3> These results are important in several ways. First, they indicate what measures pharmacists can take to solve some of these problems. For instance by counselling in the pharmacies or by information to relatives and others close to the patients. Second, the results will help pharmacists understand these patients better and thereby improve their ability to meet the patients professionally. The study is also of great value in the production of material for continuing education of the Swedish pharmacists.
Abstract 11639: “CKDPatch” to Incorporate Kidney Disease Measures Into the AHA/ACC Pooled Cohort Equation: An International Individual-level Data Study From the CKD Prognosis Consortium (CKD-PC)
Authors: Kunihiro Matsushita, Simerjot K Jassal, Elke Schaeffner, Josef Coresh
Journal: Circulation (2019)

Background: Major guidelines emphasize measures of chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR), as cardiovascular disease (...
Circulating tumor DNA in identifying resistant subclones post EGFR blockade: Implications for EGFR rechallenge.
Authors: Adithya Chennamadhavuni, Pashtoon Murtaza Kasi
Journal: Journal of Clinical Oncology (2021)

131 Background: For patients with metastatic RAS/RAF wild-type refractory colorectal cancer anti-EGFR therapy can be reused in subsequent lines of therapy. However, it is not entirely clear if all patients derive benefit. Increasingly it is been recognized that these patients acquire mechanisms of resistance which can be detected on circulating tumor DNA-based testing. We present a series of patients who had serial testing post EGFR therapy showing its feasibility and value. This would have implications for EGFR rechallenge. Methods: We reviewed records for patients who initially were noted to have tissue RAS/RAF Wild type who received prior anti-EGFR therapy and then subsequently had at least 1 circulating tumor DNA-based testing. Included a result of patients who had comprehensive NGS based profiling for both tissue as well as ctDNA. Results: Median duration of initial prior anti EGFR therapy was around 10 months. Table shows results of patient's tissue based genomic testing in parallel with the serial circulating tumor DNA-based testing that was done later when subsequent lines of therapy were being decided. As noted, known acquired mechanisms of resistance were noted in 100% of the cases. These included KRAS, NRAS, extracellular domain mutations in EGFR and BRAF mutations. Interestingly the levels of the sub-clones expressed as variant allele fraction percentage varied and decreased over time in relation to timing of the prior EGFR exposure. Additionally, these were noted to be polyclonal and the number of clones also varied including some disappearing over time during non-EGFR based therapy (EGFR holiday). Conclusions: Patient's post EGFR blockade may have multiple mechanisms of acquired resistance that can be easily detected on noninvasive liquid biopsies. These patients likely will not benefit from EGFR rechallenge based on the results of the recently reported CRICKET (NCT02296203) and CAVE (EudraCT number: 2017-004392-32) clinical trials. Rechecking liquid biopsy plasma RAS/RAF status is one thing that may be incorporated into practice with EGFR rechallenge only if acquired mechanisms of resistance are absent. [Table: see text]
TNFα induces endothelial dysfunction in rheumatoid arthritis via LOX-1 and arginase 2: reversal by monoclonal TNFα antibodies
Authors: Alexander Akhmedov, Margot Crucet, Branko Simic, Simon Kraler, Nicole R Bonetti, Caroline Ospelt, Oliver Distler, Adrian Ciurea, Luca Liberale, Matti Jauhiainen, Jari Metso, Melroy Miranda, Rose Cydecian, Lena Schwarz, Vera Fehr, Rita Zilinyi, Mohammad Amrollahi-Sharifabadi, Lydia Ntari, Niki Karagianni, Frank Ruschitzka, Reijo Laaksonen, Paul M Vanhoutte, George Kollias, Giovanni G Camici, Thomas F Lüscher
Journal: Cardiovascular Research (2021)

Abstract Aims Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting joints and blood vessels. Despite low levels of low-density lipoprotein cholesterol (LDL-C), RA patients exhibit endothelial dysfunction and are at increased risk of death from cardiovascular complications, but the molecular mechanism of action is unknown. We aimed in the present study to identify the molecular mechanism of endothelial dysfunction in a mouse model of RA and in patients with RA. Methods and results Endothelium-dependent relaxations to acetylcholine were reduced in aortae of two tumour necrosis factor alpha (TNFα) transgenic mouse lines with either mild (Tg3647) or severe (Tg197) forms of RA in a time- and severity-dependent fashion as assessed by organ chamber myograph. In Tg197, TNFα plasma levels were associated with severe endothelial dysfunction. LOX-1 receptor was markedly up-regulated leading to increased vascular oxLDL uptake and NFκB-mediated enhanced Arg2 expression via direct binding to its promoter resulting in reduced NO bioavailability and vascular cGMP levels as shown by ELISA and chromatin immunoprecipitation. Anti-TNFα treatment with infliximab normalized endothelial function together with LOX-1 and Arg2 serum levels in mice. In RA patients, soluble LOX-1 serum levels were also markedly increased and closely related to serum levels of C-reactive protein. Similarly, ARG2 serum levels were increased. Similarly, anti-TNFα treatment restored LOX-1 and ARG2 serum levels in RA patients. Conclusions Increased TNFα levels not only contribute to RA, but also to endothelial dysfunction by increasing vascular oxLDL content and activation of the LOX-1/NFκB/Arg2 pathway leading to reduced NO bioavailability and decreased cGMP levels. Anti-TNFα treatment improved both articular symptoms and endothelial function by reducing LOX-1, vascular oxLDL, and Arg2 levels.
Safety, tolerability and efficacy of transarterial chemoembolization using anthracyclines-loaded drug eluting microspheres for treatment of patients with unresectable hepatocellular carcinoma: Pooled analyses.
Authors: Thierry De Baere, Filipe Veloso Gomes, Gontran Verset, Gerardo Tovar-Felice, Katerina Malagari, Elia Coimbra, Jordi Bruix
Journal: Journal of Clinical Oncology (2021)

287 Background: Transarterial chemoembolization either with Lipiodol (cTACE) or with drug eluting microspheres (DEM-TACE) is indicated for the treatment of hepatocellular carcinoma (HCC) not amenable to curative treatments in patients with preserved liver function. Safety of TACE is becoming more important with its increased use as a bridge to transplant or downstaging to resection, but also for preservation of liver function in case of subsequent immuno-combination therapies. LifePearl microspheres is a novel DEM comprised of polyethylene-glycol with reported good safety profile and efficacy in smaller series. Our purpose was to assess safety and efficacy of TACE using anthracycline loaded LifePearl for the treatment of patients with unresectable HCC in a pooled analysis of studies with available more than 500 patient’s level data. Methods: We pooled patient level data from 5 single arm studies. Safety was assessed by close monitoring of adverse events according to CTCAE (v4.03). Tumor response was assessed, according to mRECIST and RECIST1.1 and analyzed as best overall response to account for differences in time of imaging follow-up between studies. The Kaplan-Meier method was used to estimate event rates for time to event outcomes: progression free survival (PFS), time to unTACEable progression (TTUP) and overall survival (OS) censoring patients at time of surgery or transplantation. Results: Out of 586 patients, 85.5%, 13.5% and 1.0% were Child Pugh A, B and C, respectively. BCLC stages 0, A, B and C were 13.6%, 43.4%, 41.1% and 1.9% respectively. The mean number of HCC lesions was 2.1±1.5 and mean sum of tumor diameters was 49.3±32.9mm. In 19% of patients alpha-feto protein level was &gt; 200ng/ml. A mean of 1.9±1.3 DEM-TACEs were performed per patient. A total of 197 events were reported including 2.6 % grade 4 and 1.5% grade 5, mostly related to post-embolization syndrome. Complete response, partial response and stable disease were 60.2%, 27.1% and 7.4% respectively providing an objective response and disease control rates of 87,3% and 94,7% respectively. 10% of patients were transplanted or resected. Median OS, PFS and TTUP is indicated in the table below. OS was 89.2%, 80.2% and 69.7% at 12, 18 and 24 months respectively. Conclusions: The treatment of patients with unresectable HCC with anthracycline loaded LifePearl showed good tolerance with acceptable toxicity and high tumor response rate that translated into promising PFS, TTUP and OS. [Table: see text]
Mandatory Extended Searches in All Genome Sequencing
Authors: Lainie Friedman Ross, Mark A. Rothstein, Ellen Wright Clayton
Journal: JAMA (2013)

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