tbuckley/cabot-search huggingface dataset:
THU0153 TCZ MIGHT BE A RISK FACTOR FOR WORSENING OF ILD, PARTICULARLY OF CHRONIC ILD
Authors: A. Tanaka, T. Owada, A. Hasegawa, T. Hiyama, Y. Takamura, T. Miyao, R. Yamazaki, S. Arai, R. Maezawa, M. Arima, K. Kurasawa
Journal: Annals of the Rheumatic Diseases (2020)

Background: Interstitial lung disease (ILD), frequent lung involvement, determine the prognosis of patients with RA. The presence of ILD also influences the selection of RA therapy. However, it is not fully elucidated what groups of RA-ILD patients worsen ILD. Objectives: To identify the risk factors for worsening of ILD in RA patients under biological DMARD (bDAMARDs) therapy; particularly to determine whether types of bDMARDs are associated with exacerbation of ILD. Methods: A retrospective cohort study was conducted. Subjects were consecutive 91 RA-ILD patients who received HR-CT examination at starting and during bDMARDs therapy. Clinical data were collected by reviewing. ILD was diagnosed, when patients showed ground-glass opacity (GGO), consolidation, reticular pattern or honeycomb; the former two were acute and the latter two were chronic ILD lesions. The extent of each lesion was scored and recorded. When the score was increased, the lesion was judged as worsened. The incidence of exacerbation of ILD under an indicated agent was calculated as follows; the sum of (exposure period of the agent/exposure period of any agent) in patients with the exacerbation was divided by total exposure period of the agent. Results: Subjects were 36 males and 55 females with a mean age of 66.8 years. At the entry, GGO, consolidation, reticular and honeycomb were found in16, 20, 63 and 17, respectively. Acute and chronic ILD were observed in 34 and 68, respectively. ILD worsened in 35 (38.5%). Between patients with and without ILD exacerbation, no differences were found in demographics (sex, age, disease duration, the positivity for anti-CCP ab and RF) and radiographic findings of pulmonary abnormalities. Disease activities at as 1st and sequential CT examinations were similar in both groups. The incidences of the worsening of ILD varied according to bDMARDs (Fig 1). The incidence of total ILD worsening was high in TCZ compared to TNF and ABT. The incidence of acute ILD worsening was similar among the three groups. However, the worsening of chronic ILD was more frequently found in TCZ than other bDMARDs. The incidence of death by respiratory failure was similar in TNF, ABT, and TCZ (Fig. 2). Fig. 1 Conclusion: TCZ might be a risk factor for exacerbation of ILD, particularly of chronic ILD. Fig. 2 Disclosure of Interests: None declared
Effects of α-Cyclodextrin on Cholesterol Control and Hydrolyzed Ginseng Extract on Glycemic Control in People With Prediabetes
Authors: Erica Bessell, Nicholas R. Fuller, Tania P. Markovic, Namson S. Lau, Jessica Burk, Chelsea Hendy, Tegan Picone, Ang Li, Ian D. Caterson
Journal: JAMA Network Open (2020)

Effective strategies for preventing type 2 diabetes are needed. Many people turn to complementary medicines, but there is little well-conducted scientific evidence to support their use.To assess the efficacy of α-cyclodextrin for cholesterol control and that of hydrolyzed ginseng for glycemic control in people with prediabetes and overweight or obesity.This 6-month double-blind, placebo-controlled, randomized clinical trial, with a 2 × 2 factorial design, was conducted between July 2015 and October 2018 at 2 locations in Sydney, Australia. Eligible participants were aged 18 years or older, had a body mass index (weight in kilograms divided by height in meters squared) of 25 or higher, and had prediabetes within 6 months of study entry according to the American Diabetes Association guidelines. Data analysis was performed from May to August 2019.Participants were randomized to 1 of 4 groups to take active or placebo versions of each supplement (α-cyclodextrin plus hydrolyzed ginseng, α-cyclodextrin plus placebo, placebo plus hydrolyzed ginseng, or placebo plus placebo) for 6 months. All participants received dietetic advice for weight loss.The primary outcomes were the differences in total cholesterol and fasting plasma glucose between groups after 6 months. The primary analysis used the intention-to-treat principle. Multiple predetermined subsample analyses were conducted.A total of 401 participants were eligible for the study (248 women [62%]; mean [SD] age, 53.5 [10.2] years; mean [SD] body mass index, 34.6 [6.2]). One hundred one patients were randomized to receive α-cyclodextrin plus hydrolyzed ginseng, 99 were randomized to receive α-cyclodextrin plus placebo, 101 were randomized to receive placebo plus hydrolyzed ginseng, and 100 were randomized to receive placebo plus placebo. For 200 participants taking α-cyclodextrin compared with 201 participants taking placebo, there was no difference in total cholesterol after 6 months (-1.5 mg/dL; 95% CI, -6.6 to 3.5 mg/dL; P = .51). For 202 participants taking hydrolyzed ginseng compared with 199 participants taking placebo, there was no difference in fasting plasma glucose after 6 months (0.0 mg/dL; 95% CI, -1.6 to 1.8 mg/dL; P = .95). Use of α-cyclodextrin was associated with constipation (16 participants vs 4 participants; P = .006) and cough (8 participants vs 1 participant; P = .02). Use of hydrolyzed ginseng was associated with rash and pruritus (13 participants vs 2 participants; P = .006). Only 37 of 401 participants (9.2%) experienced these adverse events.Although they are safe for use, there was no benefit found for either α-cyclodextrin for cholesterol control or hydrolyzed ginseng for glycemic control in people with prediabetes and overweight or obesity.Australian New Zealand Clinical Trials Registry Identifier: ACTRN12614001302640.
Effect of testosterone on the mitochondrial aspartate aminotransferase in prostate cancer cell lines
Authors: Laure A. Bidaisee, Radhey S. Gupta, Gurmit Singh
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1940 

Epidemiological and experimental studies have shown that long chain fatty acids (LCFA) and testosterone influence the development and subsequent progression of prostate cancer. One possible link between LCFA and testosterone might be through a mitochondrial matrix protein—mitochondrial aspartate aminotransferase (mAAT) and a protein located on the plasma membrane—fatty acid binding protein (FABPpm). mAAT plays a role in amino acid metabolism and is a critical component of the malate/aspartate shuttle. Cells uptake LCFA via the FABPpm. Comparison of chemical and immunological properties led to the discovery that mAAT is identical to FABPpm and is coded for by a single nuclear gene. The mechanism by which this mitochondrial protein is targeted to two different locations within the cell has yet to be elucidated. It has been determined that mAAT is regulated by testosterone only in prostate secretory epithelial cells, a site where prostate cancer initially develops. It is hypothesized that since mAAT is regulated by testosterone in the prostate, FABPpm may also be regulated by testosterone. With an increase in testosterone, there should be an increase in the levels of FABPpm followed by an increase in the uptake of LCFA. The cell lines chosen for this study were the androgen sensitive LNCaP and the androgen insensitive CL1, which were derived from LNCaP. A synthetic androgen, R1881, was used in substitution of testosterone. Immunofluorescence microscopy data show a difference in the staining pattern on the plasma membrane between LNCaP cells treated with 0.1nM R1881 versus control. Conversely, CL1 cells demonstrated no change in the staining pattern. Western blots verified the immunofluorescence data. In order to visualize and quantify these results, uptake studies using fluorescently labeled LCFA were done using real time confocal laser scanning microscopy and flow cytofluorimetric analysis. In conclusion, this data suggests that testosterone regulates the uptake of LCFA into prostate cancer cells. Significantly, LCFA play an important role in steroidogenesis implying there could be a continuous cycle of stimulation, where a steroid stimulates LCFA uptake while a LCFA stimulates steroidogenesis. (Supported by the Canadian Institute of Health Research (CIHR) to G.S.)
Clarification of Definitions of Hyperprogressive Disease During Immunotherapy
Authors: Ignacio Matos, Elena Garralda
Journal: JAMA Oncology (2020)

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Differential effect on different immune subsets of neoadjuvant chemotherapy in patients with TNBC
Authors: Chiara Massa, Thomas Karn, Carsten Denkert, Andreas Schneeweiss, Claus Hanusch, Jens-Uwe Blohmer, Dirk-Michael Zahm, Christian Jackisch, Marion van Mackelenbergh, Jörg Thomalla, Frederik Marme, Jens Huober, Volkmar Müller, Christian Schem, Anja Mueller, Elmar Stickeler, Katharina Biehl, Peter A Fasching, Michael Untch, Sibylle Loibl, Karsten Weber, Barbara Seliger
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer (BC). Due to the absence of targets such as HER2 or hormone receptors, early TNBC is treated with surgery and chemotherapy. Since TNBC is also considered the most immunogenic type of BC with tumor infiltrating lymphocytes that are predictive for chemotherapy response and prognostic for patients′ survival, many different immunotherapeutic strategies are currently explored in clinical trials for the treatment of this disease. In order to efficiently combine chemotherapy with immunotherapy, it is important to evaluate the effect of chemotherapy on immune cells in vivo. Methods Peripheral blood was taken from 56 patients with TNBC undergoing neoadjuvant chemotherapy with nanoparticle albumin-bound paclitaxel (Nab-Pac) followed by epirubicin and cyclophosphamide (EC) at three different time points. Multicolor flow cytometry was used to characterize the immune cell composition and functional properties along neoadjuvant chemotherapy. Results Whereas the first phase of the neoadjuvant chemotherapy did not significantly alter the patients′ immune cell composition, after the second phase of chemotherapeutic administration most B cells (&gt;90%) were lost and the frequency of natural killer (NK) cells and CD4 + T lymphocytes decreased approximately to 50%. In contrast, the frequency of CD8 + T cells were less affected. Conclusions Despite late consequences of Nab-Pac cannot be ruled out, these data suggest that different chemotherapeutics might have distinct effects on the immune cell repertoire and that different immune cell populations exhibit a specific susceptibility to these chemotherapies with B and NK cells being more affected than T cells. This might also have an impact on the combination of chemotherapies with immunotherapies. Trial registration number NCT02685059 .
Abstract 13727: Mapping Analysis Clarifies the Correlation Between Distribution of Patient’s Home Address and Participation in Outpatient Cardiac Rehabilitation
Authors: Atsuko Nakayama, Masatoshi Nagayama, Hiroyuki Morita, Issei Komuro, Mitsuaki Isobe
Journal: Circulation (2020)

Introduction: Geographical analysis is developing as a powerful tool for evaluating the quality of medical service and acquiring the fundamental data for medical decision-making. Using a geographical analysis, we can evaluate the impact of the distance from patient’s home to the hospital on the participation in outpatient cardiac rehabilitation (CR). Methods: All patients hospitalized for percutaneous coronary intervention, coronary artery bypass grafting, valvular surgery, congestive heart failure and aortic diseases were recommended to participate in outpatient-CR program after discharge. In the dataset of prospective cohort study of CR from 2004 to 2015 (n=9,019), we investigated the impact of the distance from patient’s home to hospital on the participation in outpatient-CR program using the geographical analysis. Results: The total participation rate of outpatient-CR was 47% in our study population. The participation rate of outpatient-CR was highest (62%) in patients with road distance from home to hospital &lt; 10 km as compared with those with road distance of 10-20 km, 20-30 km and &gt;30km to hospital (51%, 39%, and 23%, respectively, p&lt;0.001). Patients whose road distance from home to hospital was &lt; 30 km more participated in outpatient-CR as compared with patients whose road distance was ≧30 km (Odds ratio 4.41, 95%CI 3.86 - 5.04). Expecially in patients with heart failure, the longer distance-the less participation rate relationship was menifest (p&lt;0.01). Conclusions: Using the geographical analysis, we could successfully evaluate the impact of road distance from patient’s home to hospital on the participation in outpatient-CR after discharge in patients with cardiovascular diseases. Especially in patients with heart failure, “the longer distance, the less participation” relationship was manifest. This geographical analysis will provide us with essential information for future epidemiological and clinical studies as well as medical decision-making, improving the healthcare service.
Abstract 13613: Combination of Atrial Fibrillation and Frailty: Association With All-cause Mortality in Older Veterans
Authors: Marlena Fernandez, Marie Pitteloud, Angelica Torres, Sergio Ruiz, Victor Cevallos, Michael J Mintzer, Alexis Rodriguez, Jorge Ruiz
Journal: Circulation (2020)

Background: Atrial fibrillation (AF), the commonest arrhythmia among older adults, is associated with increased mortality. Frailty constitutes a state of vulnerability to stressors resulting from multisystemic loss of physiological reserve. The study aim was to determine whether concurrent frailty and AF increases all-cause mortality in older Veterans. Methods: Retrospective cohort study of community-dwelling Veterans 60 years and older identified as having baseline AF (ICD codes) or frailty through a 30-item VA Frailty Index (VA-FI). The VA-FI was generated as a proportion of morbidity, function, sensory loss, cognition/mood and other variables. The VA-FI categorized Veterans into non-frail (robust FI≤.10, prefrail FI=&gt;.10,&lt;.21) and frail (FI≥.21). The combination resulted in 4 groups: Neither AF nor frailty (NoAF-F), atrial fibrillation (AF), frailty (F), and AF and frailty (AF-F). At the end of follow-up, data on mortality was aggregated and adjusted for age, gender, race, ethnicity, marital status, and BMI, the association of concurrent AF and/or frailty with all-cause mortality was determined using a Cox regression model including testing for interaction effects. Results: A total of 16391 Veterans were included, mean age 72.06 (SD=9.23) years 74.2% White, 86.7% non-Hispanic, and 97.9% male. There were 1534 (9.4%) Veterans with AF and the proportion of robust, pre-frail and frail patients was 44.3% (n=7255), 37.2% (n=6095) and 18.6% (n=3041) respectively. The 4 resulting groups were NoAF-F (12357, 75.4%), AF (993, 6.1%), F (2500, 15.3%) and AF-F (541, 3.3%). Over a median follow-up of 2025 days (IQR=245) 3917 deaths occurred. As compared with NoAF-F, AF-F, F and AF in that order had higher all-cause mortality, adjusted hazard ratio (HR)=3.24 (95%CI:2.88-3.66), p&lt;.0005; HR=2.06 (95%CI:1.90-2.22), p&lt;.0005; and HR=1.47 (95%CI:1.31-1.64), p&lt;.0005 respectively. When frailty and AF were considered jointly they did not interact. Conclusions: The combination of AF and frailty at baseline represents the group with highest risk for all-cause mortality in older Veterans. Further studies may be needed to assess the impact on mortality of clinical interventions targeting both conditions.
Letter to the Editor: Post–Liver Transplantation Sinusoidal Obstruction Syndrome and Immunosuppressive Drugs: Causality of Mycophenolate Mofetil or Tacrolimus?
Authors: Véronique Loustaud‐Ratti, Alicia Anneraud, Paul Carrier, Marilyne Debette‐Gratien, Anne De Muret, Mattias Tallegas, Hélène Barraud, Louise Barbier, Ephrem Salamé
Journal: Hepatology (2020)
Hereditary Diffuse Gastric Cancer: Approaches to Screening, Surveillance, and Treatment
Authors: Nastazja Dagny Pilonis, Marc Tischkowitz, Rebecca C. Fitzgerald, Massimiliano di Pietro
Journal: Annual Review of Medicine (2020)

Hereditary diffuse gastric cancer (HDGC) is a cancer syndrome associated with a significant lifetime risk of diffuse gastric cancer (DGC), a malignancy characterized by late clinical presentation and poor prognosis, as well as lobular breast cancer. HDGC is linked to germline pathogenic variants in the E-cadherin gene (CDH1) that are inherited in an autosomal dominant pattern; however, in many families with DGC clustering, no genetic cause has been identified. This review discusses key elements that allow risk assessment of potential inherited DGC susceptibility. We provide a practical overview of the recommendations for surveillance and treatment of individuals at risk and patients with early disease. The review also outlines future research avenues to improve our understanding of the genetic background and natural history of the disease, the endoscopic detection of early lesions, and the outcome of prophylactic surgery in young individuals.
Abstract 12211: Major Depressive Disorder’S Cost to US Taxpayers: Increased Thirty-day Readmission and Total Hospital Cost Among Depressed Patients Admitted With Acute Myocardial Infarction
Authors: Kam Sing Ho, Bharat Narasimhan, Lingling Wu, Shabnam Nasserifar, Jacqueline Sheehan, Eyal Herzog
Journal: Circulation (2019)

Introduction: Major depressive disorder (MDD) is associated with higher mortality, morbidity, and health care resource utilization in patients admitted to hospitals in the in the US with acute myoc...
Epidemiological situation, laboratory capacity and preparedness for carbapenem-resistant Acinetobacter baumannii in Europe, 2019
Authors: Felix Lötsch, Barbara Albiger, Dominique L. Monnet, Marc J. Struelens, Harald Seifert, Anke Kohlenberg
Journal: Eurosurveillance (2020)

To update information on the epidemiological situation and national capacity for detection, surveillance and containment of carbapenem-resistant Acinetobacter baumannii (CRAb) in Europe, we performed a survey in 37 countries. Nine countries reported regional or inter-regional spread and seven an endemic situation. Laboratories with a reference function, surveillance systems, and a national containment plan for CRAb existed in 30, 23 and eight countries, respectively. A pan-European molecular survey would provide in-depth understanding of the CRAb epidemiology.
Effect and Reach of Medical Articles Posted on Preprint Servers During the COVID-19 Pandemic
Authors: Ye Eun (Grace) Jung, Yifei Sun, Neil W. Schluger
Journal: JAMA Internal Medicine (2020)

These findings underscore the need for more balanced news stories about medical therapies.If published, anecdotes should also provide counterbalance that conveys the expected outcomes for most patients.There is a need for both greater investment in organizations that assess news articles based on their scientific rigor and articles from trusted, nonpartisan organizations that underscore the strengths and limitations of technologies, including ECMO.Finally, raising awareness of unrealistic popular perceptions of interventions, as Fernando and colleagues 6 have done, may improve physician awareness of unrealistic media portrayals so they and their professional organizations can present scientifically accurate information at the bedside.Physicians without conflicts of interest should present nuanced evidence to the public through print-based opinion pieces, television news shows, peer-reviewed academic journals with patientdirected content (eg, JAMA and JAMA Internal Medicine Patient Pages), and social media.By partnering with the media to provide realistic insights into current evidence and expected outcomes, physicians can advocate for the best interest of patients.With medicine squared centrally in the public eye, now more than ever we must encourage the media to accurately portray medical therapies.Public trust depends on it.
Abstract 16993: Impact of Donor and Recipient Cytomegalovirus Immune Status on Long-Term Graft Survival in Pediatric Heart Transplantation
Authors: Naveed Rabbani, Richard Kronmal, Erin L Albers, Joshua Friedland-Little, Borah Hong, Mariska Kemna, Yuk M Law
Journal: Circulation (2020)

Introduction: While CMV infection has been associated with graft loss in adult heart transplants, its role in children is less understood. We aim to better understand the effect of donor and recipient CMV immune status at transplant on survival in pediatric recipients. Methods: We analyzed 6,951 pediatric heart-only transplants in the Scientific Registry of Transplant Recipients (1987-2019). Patients were stratified by recipient and donor CMV status at transplant. The primary endpoint was freedom from graft loss. Results: Of the various donor and recipient CMV statuses, only CMV-positive recipients had decreased graft survival compared to CMV-negative ones (at 15-yrs: 47% vs. 53%, HR 1.14). However, when fully adjusted by Cox regression, recipient status was no longer a risk factor ( p = 0.12). In this model, anti-CMV treatment with ganciclovir or valganciclovir was associated with a lower risk of graft loss (HR 0.80, CI 0.71 - 0.90, p &lt; 0.005). When stratified by the four donor-recipient CMV status combinations, antiviral use was associated with improved survival in both donor-positive groups: most strongly in donor-positive/recipient-positive transplants (at 15-yrs: 51% vs. 39%, p &lt; 0.005) and to a lesser extent in donor-positive/recipient-negative transplants (at 15-yrs: 53% vs. 51%, p &lt; 0.005). The association is maintained when examined by era, such as with more frequent use of anti-CMV therapy after 1995. No association with antiviral use was observed in either donor-negative transplant group. Conclusion: CMV-positive recipients had greater long-term graft loss, although this may be confounded by other transplant characteristics. Anti-CMV therapy is associated with improved long-term graft survival in transplants with CMV-positive donors. This finding may explain the lack of association between donor CMV status and graft loss in that an association may be masked by antiviral use. Further investigation of anti-CMV therapy may mitigate risk of graft loss.