tbuckley/cabot-search huggingface dataset:
Comparative effectiveness of chemotherapy in elderly patients with metastatic colorectal cancer.
Authors: Sacha Satram-Hoang, Devi Ramanan, Luen F. Lee, Shui Yu, Carolina M. Reyes, Edward McKenna
Journal: Journal of Clinical Oncology (2012)

463 Background: The management of metastatic colorectal cancer (mCRC) has evolved considerably with advances in chemotherapeutic agents that have led to improved outcomes. Less is known about the benefits of newer agents in the real-world setting. The objective of this study was to evaluate treatment patterns and survival in older, demographically diverse mCRC patients. Methods: Using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we conducted a retrospective cohort analysis of 5931 stage IIIB, IIIC and IV CRC patients diagnosed between 1/1/ 2000 – 12/31/2007, who were &gt;66 years, enrolled in Medicare Parts A and B, and received first-line treatment with 5FU/LV (n=2907), CAP (capecitabine; n=963), FOLFOX (n=1856) or CAPOX (CAP + oxaliplatin; n=205). Date of last follow-up was 12/31/2009. Statistical comparisons were made between 5FU/LV vs. CAP and FOLFOX vs. CAPOX. Cox regression with backward elimination estimated the relative risk of death, adjusting for demographic and clinical factors. Results: Compared to 5FU/LV, patients treated with CAP were older (&gt;80 years) at diagnosis (36% vs. 22%; p&lt;.0001) and more likely female (59% vs. 53%; p=.0025), while patients receiving CAPOX were older (&gt;80 years: 12% vs 8%; p&lt;0.05) compared to FOLFOX. The mean time to chemotherapy initiation after diagnosis was similar between CAP and 5FU/LV (76 vs. 71 days) and between FOLFOX and CAPOX (75 vs. 70 days). The mean duration of treatment was longer for 5FU/LV (144 days) vs. CAP (122 days; p&lt;.0001) and comparable between CAPOX (144 days) and FOLFOX (150 days; p=0.2139). The incidence of adverse events (AE) within 180 days after initiation of treatment were higher in patients treated with 5FU/LV (37%) vs. CAP (9%); p&lt;.0001 and in FOLFOX (58%) vs. CAPOX (44%); p&lt;0.0001. In multivariate analysis there were no significant differences in risk of death between CAP and 5FU/LV, and between CAPOX and FOLFOX ( table ). Conclusions: Overall survival was comparable between CAP and 5FU/LV and between CAPOX and FOLFOX with fewer AEs associated with CAP and CAPOX. This provides real-world confirmation of clinical trial data. [Table: see text]
Access to lifesaving medical resources for African countries: COVID-19 testing and response, ethics, and politics
Authors: Matthew M Kavanagh, Ngozi A Erondu, Oyewale Tomori, Victor J Dzau, Emelda A Okiro, Allan Maleche, Ifeyinwa C Aniebo, Umunya Rugege, Charles B Holmes, Lawrence O Gostin
Journal: The Lancet (2020)

Coronavirus disease 2019 (COVID-19) has revealed how strikingly unprepared the world is for a pandemic and how easily viruses spread in our interconnected world. A governance crisis is unfolding alongside the pandemic as health officials around the world compete for access to scarce medical supplies. As governments of African countries, and those in low-income and middle-income countries around the world, seek to avoid potentially catastrophic epidemics and learn from what has worked in other countries, testing and other medical resources are of concern.
How Dermatologists Can Learn and Contribute at the Leading Edge of the COVID-19 Global Pandemic
Authors: Lauren M. Madigan, Robert G. Micheletti, Kanade Shinkai
Journal: JAMA Dermatology (2020)

Adrien Sanchez, MD; Pierre Sohier, MD, PhD; Sarah Benghanem, MD; Anne-Sophie L'Honneur, PharmD, PhD; Flore Rozenberg, MD, PhD; Nicolas Dupin, MD, PhD; Bethsabée Garel, MD
Mast cells are required for experimental oral allergen–induced diarrhea
Authors: Eric B. Brandt, Richard T. Strait, Dan Hershko, Quan Wang, Emily E. Muntel, Troy A. Scribner, Nives Zimmermann, Fred D. Finkelman, Marc E. Rothenberg
Journal: Journal of Clinical Investigation (2003)

Gastrointestinal allergic disorders represent a diverse spectrum of inflammatory diseases that are occurring with increasing incidence and severity. An essential question concerning these disorders is to determine the specific cells and mediators responsible for specific clinical manifestations. With this in mind, we developed a murine model of oral allergen–induced intestinal inflammation accompanied by strong Th2-associated humoral and cellular responses and focused on the immunopathogenesis of allergic diarrhea. Exposure of OVA/alum–sensitized mice to repeated doses of intragastric OVA induced genetically restricted, dose-dependent, acute diarrhea associated with increased intestinal permeability, eosinophilia, and mastocytosis. Mice developed limited systemic manifestations of anaphylaxis, even though they developed marked intestinal mucosal mast cell degranulation. Notably, experiments involving mast cell depletion (with anti–c-kit mAb), anti-IgE treatment, and FcεRI-deficient mice indicated a critical effector role for mast cells in mediating allergic diarrhea. Furthermore, allergic diarrhea was dependent upon synergistic signaling induced by serotonin and platelet-activating factor (PAF), but not histamine. These results demonstrate that oral allergen–induced diarrhea associated with experimental Th2 intestinal inflammation is largely mast cell, IgE, serotonin, and PAF dependent.
Periodontal diseases and association with atherosclerotic disease
Authors: David Herrera, Ana Molina, Kare Buhlin, Bjorn Klinge
Journal: Periodontology 2000 (2020)

Abstract Cardiovascular diseases still account for the majority of deaths worldwide, although significant improvements in survival, after being affected by cardiovascular disease, have been achieved in the last decades. Periodontal diseases are also a common global burden. Several studies have shown a link between cardiovascular disease and periodontitis, although evidence is still lacking regarding the direct cause‐effect relation. During the 2012 “Periodontitis and systemic diseases” workshop, the available evidence on the association between cardiovascular and periodontal diseases was discussed, covering biologic plausibility and clinical studies. The objective of the present narrative review was to update the previous reviews presented at the 2012 workshop, following similar methodological approaches, aiming to critically assess the available evidence. With regard to biologic plausibility, two aspects were reviewed: (a) for microbiologic mechanisms, assessing periodontal bacteria as a contributing factor to atherosclerosis based on seven “proofs,” substantial evidence was found for Proofs 1 through 6, but not for Proof 7 (periodontal bacteria obtained from human atheromas can cause atherosclerosis in animal models), concluding that periodontal pathogens can contribute to atherosclerosis; (b) mechanistic studies, addressing five different inflammatory pathways that could explain the links between periodontitis and cardiovascular disease with the addition of some extra pathways , suggest an association between both entities, based on the presence of higher levels of these inflammatory markers in patients with periodontitis and cardiovascular disease, vs healthy controls, as well as on the evidence that periodontal treatment reduces serum levels of these mediators. When evidence from clinical studies was analyzed, two aspects were covered: (a) epidemiologic studies support the estimation that the incidence of atherosclerotic disease is higher in individuals with periodontitis than in individuals with no reported periodontitis, irrespective of many common risk factors, but with a substantial variability in the definitions used in reporting of exposure to periodontal diseases in different studies; (b) intervention trials have shown that periodontal therapy can reduce serum inflammatory mediators, improve the lipids profile, and induce positive changes in other cardiovascular disease surrogate measures, but no evidence is available to support that adequate periodontal therapy is able to reduce the risk for cardiovascular diseases, or the incidence of cardiovascular disease events in periodontitis patients.
HIV Preexposure Prophylaxis Among Adolescents in the US
Authors: Hasiya Yusuf, Errol Fields, Renata Arrington-Sanders, David Griffith, Allison L. Agwu
Journal: JAMA Pediatrics (2020)

<h3>Importance</h3> Many adolescents and young adults in the US are disproportionately affected by HIV. Several others who are uninfected are at risk and in need of effective preventive strategies. The uptake rate of preexposure prophylaxis (PrEP) for HIV prevention has remained low among US adolescents. This review assesses the current status of PrEP uptake among at-risk adolescents aged 13 to 19 years and recommendations for improving PrEP access, uptake, and future needed directions, including specific recommendations for health care professionals. <h3>Observations</h3> Of the 37 377 new HIV diagnoses made in 2018, 7734 diagnoses (21%) occurred in adolescents and young adults aged 12 to 24 years; of these, 1707 diagnoses (22%) occurred in adolescents aged 13 to 19 years. The greatest burden of HIV is found among young African American men who have sex with men, accounting for two-thirds of all HIV infections in adolescents and young adults. Preexposure prophylaxis awareness and engagement are lowest in adolescents with the greatest risk for HIV. Adolescent primary care clinicians and specialists do not routinely offer HIV testing as recommended by the Centers for Disease Control and Prevention or routinely assess sexual risk exposures of patients through sexual history taking. Clinicians' decision to prescribe PrEP for adolescents is often guided by their perceptions of the patient's HIV risk and their knowledge and acceptance of PrEP guidelines. State laws on consent, confidentiality, and the rights of the adolescent to independently access PrEP outside of parental influence differ across jurisdictions, often limiting access and uptake. <h3>Conclusions and Relevance</h3> Use of PrEP in adolescents at risk for HIV is an important component of HIV prevention. Optimizing uptake includes improving clinicians' knowledge about HIV risk and prevention strategies, enhancing sexual history taking and risk assessment through training and retraining, and improving PrEP knowledge and acceptance of prescribing among clinicians. Leveraging the ubiquity of social media, encouraging family support, and performing research aimed at finding lifestyle-congruent formulations can help mitigate HIV transmission in adolescents at greatest risk for HIV.
Offspring of Depressed Parents: 20 Years Later
Authors: Myrna M Weissman, Priya Wickramaratne, Yoko Nomura, Virginia Warner, Daniel Pilowsky, Helen Verdeli
Journal: American Journal of Psychiatry (2006)

Objective: This study was a 20-year follow-up of offspring of depressed and nondepressed parents to determine the magnitude and continuity of the risk of parental depression to the offspring. Method: The authors followed 151 offspring of moderately to severely depressed parents or nonpsychiatrically ill comparison subjects for about 20 years, to a mean age of 35 years. Four interviews and diagnostic assessments from childhood or adolescence to adulthood were conducted by assessors blind to the parents’ clinical status or the offspring’s previous history. Final best-estimate diagnoses were also made by blinded psychologists or psychiatrists. Results: The risks for anxiety disorders, major depression, and substance dependence were approximately three times as high in the offspring of depressed parents as in the offspring of nondepressed parents. Social impairment was also greater. The period of highest incidence for major depressive disorder remained between ages 15 and 20 years, largely in females. The early onset of disorder seen in the high-risk group was not offset by a later onset in the low-risk group as they matured. Higher rates of medical problems and mortality in the offspring of depressed parents were beginning to emerge as the offspring entered middle age. Conclusions: The offspring of depressed parents constitute a high-risk group for psychiatric and medical problems, which begin early and continue through adulthood. Early detection seems warranted.
SAT0519 CLINICAL CHARACTERISTICS, TREATMENT AND OUTCOMES OF ENTHESITIS-RELATED ARTHRITIS IN TAIWAN
Authors: Yang-Jen Shih, Yao-Hsu Yang, Bor-Luen Chiang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Juvenile idiopathic arthritis (JIA) has been categorized into seven different subtypes according to International League of Associations for Rheumatology system (ILAR) criteria [1]. Enthesitis-related arthritis (ERA) has represented the largest subtype in Taiwanese cohort study [2]. <h3>Objectives</h3> The aim was to compare the clinical characteristics, treatments and outcomes of ERA in one of tertiary medical center in Taiwan to other subtypes of JIA. Further, to determine patients' characteristics and risk factors help to predict the development of active and non-active treatment outcomes in ERA. <h3>Methods</h3> Retrospective review of patients diagnosed with JIA between March 1993 and December 2018 at a pediatric rheumatology clinic in National Taiwan University Hospital (NTUH), Taipei, Taiwan were enrolled. The outcome assessments were based on Wallace criteria to categorize patient into active and non-active (inactive, remission on medication and remission off medication) group. <h3>Results</h3> One hundred and eighty-three patients were included for 8 years mean follow up duration. Distribution of JIA subtypes in Figure 1 shown ERA was the single largest category of JIA (39.89%) in Taiwan. The demographic details of ERA patients in Table 1 revealed: male predominant (86%), late onset age (11.1±3.2 yrs), majority with HLA-B27 positive (92%), sacroiliac join or lumbosacral involvement (16%) and anterior uveitis (10%). Category specific outcomes in Table 2 showed ERA and extensive oligoarthritis were less likely to achieve non-active treatment response compared to persistent oligoarthritis. Among risk factors contributed to poorer treatment response in ERA were any clinical signs of sacroiliitis with P value of significant (0.0057). <h3>Conclusion</h3> ERA has represented the most common subtype of JIA in Taiwanese cohort study and has poorer treatment responses when compared to other JIA subtypes. To identify risk factors that contributing to poorer ERA treatment response might help more aggressive therapeutic strategy and improve outcome of ERA. <h3>References</h3> [1] Ravelli, A. and A. Martini, Juvenile idiopathic arthritis. The Lancet, 2007. 369(9563): p. 767-778. [2] Shen, C.C., et al., Clinical features of children with juvenile idiopathic arthritis using the ILAR classification criteria: a community-based cohort study in Taiwan. J Microbiol Immunol Infect, 2013. 46(4): p.288-94. <h3>Disclosure of Interests</h3> None declared
Diagnostic value of fine-needle puncture of the gallbladder: Side effects, safety, and prognostic value
Authors: J TUDYKA
Journal: Hepatology (1995)

Bile sampling without the risk of contamination by pancreatic and duodenal secretions and avoiding unpredictable influences of general anesthesia during biliary surgery on biliary analytics are feasible with percutaneous puncture of the gallbladder. In 207 patients with gallstones, gallbladder puncture was performed under local anesthesia with a 22-gauge spinal needle under continuous real-time ultrasound guidance. Bile samples were investigated for biliary lipids and nucleation time. Complete aspiration of gallbladder bile could be achieved in all patients without complications such as bleeding, bile leak, or inflammation. Of these patients, 11.6% reported mild abdominal problems, 3.4% required analgetics, and in 1.0% biliary colics were observed. Elective cholecystectomy was performed in 1 patient. Of the bile samples, 10.1% were contaminated with bactobilia. Biliary lipids, cholesterol saturation index (CSI), total lipid concentration (TLC), and bacteriological contamination were independent of gallstone number, whereas patients with solitary gallbladder stones exhibited a significantly longer nucleation time (NT) in comparison with those with multiple stones. In patients with gallstones, fine-needle puncture of the gallbladder represents an important diagnostic procedure and can be performed within minutes without major side effects if performed by an experienced sonographer.
Adaptive changes induced by noble-metal nanostructures <i>in vitro</i> and <i>in vivo</i>
Authors: Qianqian Huang, Jinchao Zhang, Yuanyuan Zhang, Peter Timashev, Xiaowei Ma, Xing-Jie Liang
Journal: Theranostics (2020)

The unique features of noble-metal nanostructures (NMNs) are leading to unprecedented expansion of research and exploration of their application in therapeutics, diagnostics and bioimaging fields.With the ever-growing applications of NMNs, both therapeutic and environmental NMNs are likely to be exposed to tissues and organs, requiring careful studies towards their biological effects in vitro and in vivo.Upon NMNs exposure, tissues and cells may undergo a series of adaptive changes both in morphology and function.At the cellular level, the accumulation of NMNs in various subcellular organelles including lysosomes, endoplasmic reticulum, Golgi apparatus, mitochondria, and nucleus may interfere with their functions, causing changes in a variety of cellular functions, such as digestion, protein synthesis and secretion, energy metabolism, mitochondrial respiration, and proliferation.In animals, retention of NMNs in metabolic-, respiratory-, immune-related, and other organs can trigger significant physiological and pathological changes to these organs and influence their functions.Exploring how NMNs interact with tissues and cells and the underlying mechanisms are of vital importance for their future applications.Here, we illustrate the characteristics of NMNs-induced adaptive changes both in vitro and in vivo.Potential strategies in the design of NMNs are also discussed to take advantage of beneficial adaptive changes and avoid unfavorable changes for the proper implementation of these nanoplatforms.
Benefits and Harms of Oral Anticoagulant Therapy in Chronic Kidney Disease
Authors: Jeffrey T. Ha, Brendon L. Neuen, Lap P. Cheng, Min Jun, Tadashi Toyama, Martin P. Gallagher, Meg J. Jardine, Manish M. Sood, Amit X. Garg, Suetonia C. Palmer, Patrick B. Mark, David C. Wheeler, Vivekanand Jha, Ben Freedman, David W. Johnson, Vlado Perkovic, Sunil V. Badve
Journal: Annals of Internal Medicine (2019)

This meta-analysis of 45 trials compares the benefits and harms of vitamin K antagonists and non–vitamin K oral anticoagulants in patients with chronic kidney disease stages 3 to 5.
The association of innate and adaptive immunity, subclinical atherosclerosis, and cardiovascular disease in the Rotterdam Study: A prospective cohort study
Authors: Lana Fani, Kimberly D. van der Willik, Daniel Bos, Maarten J. G. Leening, Peter J. Koudstaal, Dimitris Rizopoulos, Rikje Ruiter, Bruno H. C. Stricker, Maryam Kavousi, M. Arfan Ikram
Journal: PLoS Medicine (2020)

Atherosclerotic cardiovascular disease (ASCVD) is driven by multifaceted contributions of the immune system. However, the dysregulation of immune cells that leads to ASCVD is poorly understood. We determined the association of components of innate and adaptive immunity longitudinally with ASCVD, and assessed whether arterial calcifications play a role in this association.Granulocyte (innate immunity) and lymphocyte (adaptive immunity) counts were determined 3 times (2002-2008, mean age 65.2 years; 2009-2013, mean age 69.0 years; and 2014-2015, mean age 78.5 years) in participants of the population-based Rotterdam Study without ASCVD at baseline. Participants were followed-up for ASCVD or death until 1 January 2015. A random sample of 2,366 underwent computed tomography at baseline to quantify arterial calcification volume in 4 vessel beds. We studied the association between immunity components with risk of ASCVD and assessed whether immunity components were related to arterial calcifications at baseline. Of 7,730 participants (59.4% women), 801 developed ASCVD during a median follow-up of 8.1 years. Having an increased granulocyte count increased ASCVD risk (adjusted hazard ratio for doubled granulocyte count [95% CI] = 1.78 [1.34-2.37], P < 0.001). Higher granulocyte counts were related to larger calcification volumes in all vessels, most prominently in the coronary arteries (mean difference in calcium volume [mm3] per SD increase in granulocyte count [95% CI] = 32.3 [9.9-54.7], P < 0.001). Respectively, the association between granulocyte count and incident coronary heart disease and stroke was partly mediated by coronary artery calcification (overall proportion mediated [95% CI] = 19.0% [-10% to 32.3%], P = 0.08) and intracranial artery calcification (14.9% [-10.9% to 19.1%], P = 0.05). A limitation of our study is that studying the etiology of ASCVD remains difficult within an epidemiological setting due to the limited availability of surrogates for innate and especially adaptive immunity.In this study, we found that an increased granulocyte count was associated with a higher risk of ASCVD in the general population. Moreover, higher levels of granulocytes were associated with larger volumes of arterial calcification. Arterial calcifications may explain a proportion of the link between granulocytes and ASCVD.
Preventing psychological injury during the covid-19 pandemic
Authors: Matthew Roycroft, Daniel Wilkes, Simon Fleming, Shriti Pattani, Anna Olsson-Brown
Journal: BMJ (2020)

Greenberg and colleagues rightly state that the development of psychological injury is “influenced by the way [staff] are supported before, during, and after a challenging incident.”1 But identifying, supporting, and treating people after they have developed moral injuries can be very difficult, so we need a greater focus on preventive measures. Healthcare organisations, with their duty to …
The nature of obligation's special force
Authors: David Olbrich
Journal: Behavioral and Brain Sciences (2020)

Abstract Tomasello's characterization of obligation as demanding and coercive is not an implication of the centrality of collaborative commitment. Not only is this characterization contentious, it appears to be falsified in some cases of personal conviction. The theory would be strengthened if the nature of obligation's force and collaborative commitment were directly linked, possibly through Tomasello's notions of identity and identification.