tbuckley/cabot-search huggingface dataset:
AB0440 CLINICAL AND IMMUNOLOGICAL FEATURES OF THE SYSTEMIC SCLEROSIS-OVERLAP SYNDROMES
Authors: O. Desinova, M. Starovoytova, L. P. Ananyeva, O. Koneva, L. Garzanova, R. Shayakhmetova, O. Ovsyannikova
Journal: Annals of the Rheumatic Diseases (2021)

Background: Systemic Sclerosis (SSc) overlap syndromes (SSc with polymyositis / dermatomyositis (PM/DM), rheumatoid arthritis (RA), etc.) still remain a group of very heterogenous and not very well studied clinical variants of SSc that are characterized by certain clinical and immunological features. Objectives: Identify clinical and immunological features of the SSc-overlap syndromes Methods: 80 pts with SSc-PM/DM and 35 pts with SSc-RA undergoing standard clinical examination and laboratory immunological evaluation. Results: ANA Hep2 was positive in 98% of SSc-PM/DM pts; a-Scl-70 was in 34%, a - PM-Scl and RF were in 20%. ACA (6%), a-RNP (9%), and a - Jo-1 (5%) were significantly less common. Correlation analysis showed significant prevalence of conduction abnormalities in pts with a-Scl-70- (p&lt;0.03); PM-Scl was rarely associated with cardiac arrhythmia (p&lt;0.02) and pericarditis (p&lt;0.03), but there was an association between ACA and presence of digital ischemia (p&lt;0.04). Three pts with limited skin had Scl-70 and PM-Scl antibodies, two of them manifested clinical features of DM. A-Jo-1 was found in 3 pts with a longstanding disease (14,10 and 7 years), and one of these pts was also positive for a-Scl-70. All pts had limited skin and two had interstitial lung disease with FVC values of 79% and 74.8%. ANA Hep2 was positive in 96% of SSc-RA pts; a-Scl-70 – in 28%, and a-RNP - in 30%. RF-positivity was in 72% of pts, and Anti-CCP - in 27%. Simultaneous Anti-CCP and a-Scl-70 was found in one case, and Anti-CCP - anti-RNP – in another, both were associated with low RF titers. All pts had early joint involvement which became prevailing in subsequent years, and onset of the disease between 30 and 36 years. There was a correlation between laboratory signs of inflammatory activity and immunological disorders: ESR and a-Scl-70 (p&lt;0.03). Anti-CCP and a-Scl-70 co-positivity was a significantly less frequent phenomenon (p&lt;0.04). There was a remarkable 28% proportion of a-Scl-70 cases in SSc-RA with limited cutaneous which is usually characterized by ACA-positivity. Conclusion: SSc-PM/DM and SSc-RA appear to be an active disease from the immunological point of view, confirming therefore an important role of immune alterations in disease progression. Laboratory findings display specific pathogenetic features of SSc-overlap syndromes; laboratory abnormalities can be used to measure the activity and specify characteristics of the pathological process. Disclosure of Interests: None declared
Eliminating hypoxic tumor cells improves response to PARP inhibitors in homologous recombination–deficient cancer models
Authors: Manal Mehibel, Yu Xu, Caiyun G. Li, Eui Jung Moon, Kaushik N. Thakkar, Anh N. Diep, Ryan K. Kim, Joshua D. Bloomstein, Yiren Xiao, Julien Bacal, Joshua C. Saldivar, Quynh-Thu Le, Karlene A. Cimprich, Erinn B. Rankin, Amato J. Giaccia
Journal: Journal of Clinical Investigation (2021)

Hypoxia, a hallmark feature of the tumor microenvironment, causes resistance to conventional chemotherapy, but was recently reported to synergize with poly(ADP-ribose) polymerase inhibitors (PARPis) in homologous recombination–proficient (HR-proficient) cells through suppression of HR. While this synergistic killing occurs under severe hypoxia (<0.5% oxygen), our study shows that moderate hypoxia (2% oxygen) instead promotes PARPi resistance in both HR-proficient and -deficient cancer cells. Mechanistically, we identify reduced ROS-induced DNA damage as the cause for the observed resistance. To determine the contribution of hypoxia to PARPi resistance in tumors, we used the hypoxic cytotoxin tirapazamine to selectively kill hypoxic tumor cells. We found that the selective elimination of hypoxic tumor cells led to a substantial antitumor response when used with PARPi compared with that in tumors treated with PARPi alone, without enhancing normal tissue toxicity. Since human breast cancers with BRAC1/2 mutations have an increased hypoxia signature and hypoxia reduces the efficacy of PARPi, then eliminating hypoxic tumor cells should enhance the efficacy of PARPi therapy.
Covid-19: Antimicrobial use was high during first wave despite bacterial co-infections being rare, study finds
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Measures to prevent the unnecessary use of antimicrobials—such as by restricting prescriptions until a bacterial infection has been confirmed through testing—should be incorporated into covid-19 patient care to help prevent a long term rise of drug resistant infections, researchers have said.

In a paper published in the Lancet Microbe ,1 the research team found that bacterial co-infections among patients with covid-19 during the UK’s first peak were rare but that antimicrobial use was high.

Antonia Ho, clinical senior lecturer and consultant in infectious diseases at the University of Glasgow, said, “Given the unprecedented challenges posed by the pandemic—particularly during its early stages when admitted patients were very sick, effective treatments …
AB0744 HOW JUVENILE IDIOPATHIC ARTHRITIS PATIENTS PERCEIVE THEIR ILLNESS?
Authors: K. Maatallah, M. Yasmine, H. Ferjani, W. Triki, D. Ben Ncib, D. Kaffel, W. Hamdi
Journal: Annals of the Rheumatic Diseases (2021)

Background: Juvenile idiopathic arthritis (JIA) represents the most common inflammatory rheumatism of childhood. Because of a prolonged course of active disease, many patients experience physical and psychosocial limitations. Illness perceptions involve the personal beliefs that patients have about their illness and may influence health behaviors considerably. Objectives: The present study aimed to investigate the illness perception of patients with JIA. Methods: We conducted a cross-sectional study including children with JIA (according to the International League of Associations for Rheumatology (ILAR)). We recorded sociodemographic data and the subtype of the JIA. To assess a child’s perception of how arthritis affects their life, the Brief Illness Perception Questionnaire (IPQ) was completed by the parent (child age ≤10 years) or by the child (age ≥11 years). The Brief IPQ is a nine-item questionnaire rated using a 0-to10 response scale that assesses cognitive illness representations: consequences (Item 1), timeline (Item 2), personal control (Item 3), treatment control (Item 4), and identity (Item 5). Two of the items assess emotional representations: concern (Item 6) and emotions (Item 8). One item assesses illness comprehensibility (Item 7). Results: The study included 22 patients. The mean age was 15 ± 7 years [4-35], and the mean age at diagnosis was 9 ±3 years [3-14]. There was a female predominance (sex ratio= 2.1). The frequency of each JIA subset was at follows: polyarticular with rheumatoid factor (n= 1), polyarticular without rheumatoid factor (n=3), systemic (n= 2), enthesitis-related arthritis (n=9), oligoarthritis (n= 7), undifferentiated (n=1). Non-steroidal anti-inflammatory drugs were prescribed in 72% of cases, and Cs-DMARDs in 59% of patients. The most-reported causal factor in their illness was a history of traumatism (22%). Perceiving symptoms (identity) were significantly related to being affected by the disease (emotional response) (p= 0.01). Conversely, patients who had personal and treatment control expressed less emotional response ( r = −0.7, r=-0.2 respectively). Moreover, those who were concerned about the disease perceived more the consequences of their illness ( p=0.09 ) and understood it more (p=0.029). We also noted significant correlations between personal control and treatment control ( p = 0.033). A positive correlation was found between identity as well as consequences and timeline (p=0.011, p=0.024), showing that the perception of chronicity was associated with pain and the burden of the disease. Conclusion: Our study highlighted the importance of assessing illness perception in JIA patients. Patient education programs should be implemented since diagnosis for better disease management. Disclosure of Interests: None declared
Comfortable, lightly sedated colonoscopy
Authors: Roland Valori
Journal: Endoscopy (2021)

There are three components to a successful colonoscopy: intubation to the cecum, lesion recognition, and lesion excision. Each of these can be assessed using competencies and/or performance measures. Competency assessment is used to identify areas in need of improvement, or to determine competency to practice independently (such as a driving test). Performance measures determine the consequence of applying the competencies: does the driver get to her destination safely? There are other important nonprocedural measures to consider in a colonoscopy service such as efficiency, costs, consent, aftercare, patient satisfaction, etc. [1].
Assessment of SARS-CoV-2 Reinfection 1 Year After Primary Infection in a Population in Lombardy, Italy
Authors: Josè Vitale, Nicola Mumoli, Pierangelo Clerici, Massimo De Paschale, Isabella Evangelista, Marco Cei, Antonino Mazzone
Journal: JAMA Internal Medicine (2021)

This cohort study examines the rate of SARS-CoV-2 reinfection among people in Lombardy, Italy, who previously recovered from COVID-19.
Efficient and precise delivery of microRNA by photoacoustic force generated from semiconducting polymer-based nanocarriers
Authors: Tianyi Kang, Jen-Shyang Ni, Tingting Li, Jun Wang, Zeshun Li, Yaxi Li, Menglei Zha, Chen Zhang, Xue Wu, Heng Guo, Lei Xi, Kai Li
Journal: Biomaterials (2021)
AB0013 ASSOCIATION BETWEEN STAT4 POLYMORPHISM AND MANIFESTATIONS OF SLE
Authors: V. Agarwal, S. Kakati, P. Debbaruah
Journal: Annals of the Rheumatic Diseases (2021)

Background: SNP rs7574865, located within the third intron of STAT4 gene at chromosome 2, has been associated with susceptibility to SLE among different ethnic groups. 1,2 Interestingly, we recently have documented an association between this gene and susceptibility to systemic lupus erythematosus (SLE) in Indian population. 3 Objectives: To determine whether the STAT4 (rs7574865) SNP is associated with clinical and immunological manifestations in SLE. Methods: The study was carried out on 100 unrelated SLE (SLICC criteria 2012) patients from North-East India. Genotyping of STAT4 rs7574865 SNP was done using Taqman probe and Real-Time Polymerase chain reaction. An association study was performed between the alleles and genotypes of STAT4 rs7574865 with the clinical and immunological manifestations included in the SLE SLICC classification criteria. For all analysis, the statistical significance was fixed at 5% level of significance (p &lt; 0.05). Results: The mean duration of illness was 2.69±2.55 years. Cases and Controls remained in Hardy-Weinberg equilibrium.The occurrence of Photosensitivity and hyperpigmentation was significantly higher in TT genotype group (97.22% and 77.77%, respectively) with p &lt;0.001 in each case.SLE patients with nephritis (Albuminuria &gt;500mg/24 hours) and elevated serum creatinine were both significantly higher in TT genotype group as compared to GT and GG (p&lt; 0.001 and p=0.001 respectively).The Anti-dsDNA antibody was significantly associated with TT genotype (p &lt;0.001). Conclusion: Our study provides evidence regarding the association between STAT4 rs7574865 gene polymorphism is risk factor for cutaneous manifestations, Lupus nephritis and Anti ds-DNA positivity in SLE. So, our findings reinforce the need for further association studies including prospective studies with larger subjects in order to replicate such findings. References: [1]Graham RR, Ph D, Hom G, Ph D, Behrens TW, Bakker PIW De, et al. and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus. N Engl J Med. 2007;357(10):977–86. [2]Yuan H, Feng JB, Pan HF, Qiu LX, Li LH, Zhang N, et al. A meta-analysis of the association of STAT4 polymorphism with systemic lupus erythematosus. Mod Rheumatol. 2010;20(3):257–62. [3]Gupta V, Kumar S, Pratap A, Singh R, Kumari R, Kumar S, et al. Association of ITGAM, TNFSF4, TNFAIP3 and STAT4 gene polymorphisms with risk of systemic lupus erythematosus in a North Indian population. Lupus. 2018;27(12):1973–9. Disclosure of Interests: None declared
Predictors of surgical treatment burden, outcomes, and overall survival in older adults with basal cell carcinoma: Results from the prospective, multicenter BATOA cohort
Authors: Marieke E.C. van Winden, Ewald M. Bronkhorst, M. Birgitte Visch, Gertruud A.M. Krekels, Simone van der Geer, Godelieve W.J. A. Damen, Avital Amir, Katja K.H. Aben, Marie-Jeanne J.P. Gerritsen, Peter C.M. van de Kerkhof, Elke M.G. J. de Jong, Satish F.K. Lubeek
Journal: Journal of the American Academy of Dermatology (2021)

Background: Incorporating patient-related factors associated with treatment outcomes could improve personalized care in older patients with basal cell carcinoma (BCC).Objective: To evaluate and identify predictors of treatment burden, treatment outcomes, and overall survival in patients aged $70 years, surgically treated for BCC in the head and neck area. Methods:The data from the prospective, multicenter Basal Cell Carcinoma Treatment in Older Adults (BATOA) cohort study were extracted to evaluate the experienced treatment burden (visual analog scale, 0-10 cm; lower scores indicating higher treatment burden), treatment outcomes, and mortality.Results: A total of 539 patients were included (median age, 78 years).The patients experienced a low overall treatment burden (median, 8.6) and good cosmetic results.The predictors of higher treatment burden were instrumental activities of daily living (iADL) dependency, female sex, complications, larger tumor diameter, and polypharmacy.Thirty-five patients (6.5%) died (none of the deaths were due to BCC) within the follow-up period; the predictors of mortality were increasing comorbidity index and iADL dependency.No difference in these outcomes was seen between Mohs micrographic surgery and conventional excision after correction for covariates.Age was not significantly associated with any outcome.Limitations: A selection bias may exist owing to the observational design. Conclusion:BCC management decisions based on chronological age alone should be avoided, whereas more attention is recommended for patient-related factors.Based on these data, early BCC intervention is beneficial for robust and fit patients or those experiencing symptoms.(
Chronic T cell proliferation in brains after stroke could interfere with the efficacy of immunotherapies
Authors: Steffanie Heindl, Alessio Ricci, Olga Carofiglio, Qihui Zhou, Thomas Arzberger, Nikolett Lenart, Nicolai Franzmeier, Tibor Hortobagyi, Peter T. Nelson, Ann M. Stowe, Adam Denes, Dieter Edbauer, Arthur Liesz
Journal: The Journal of Experimental Medicine (2021)

Neuroinflammation is an emerging focus of translational stroke research. Preclinical studies have demonstrated a critical role for brain-invading lymphocytes in post-stroke pathophysiology. Reducing cerebral lymphocyte invasion by anti-CD49d antibodies consistently improves outcome in the acute phase after experimental stroke models. However, clinical trials testing this approach failed to show efficacy in stroke patients for the chronic outcome 3 mo after stroke. Here, we identify a potential mechanistic reason for this phenomenon by detecting chronic T cell accumulation—evading the systemic therapy—in the post-ischemic brain. We observed a persistent accumulation of T cells in mice and human autopsy samples for more than 1 mo after stroke. Cerebral T cell accumulation in the post-ischemic brain was driven by increased local T cell proliferation rather than by T cell invasion. This observation urges re-evaluation of current immunotherapeutic approaches, which target circulating lymphocytes for promoting recovery after stroke.
心機能測定装置による循環動態評価-スワンガンツカテーテル,心エコーとの比較-
Authors: 木村央, 平光伸也, 宮城島賢二, 森一真, 鈴木奈美, 山田晶, 依田竜二, 加藤茂, 加藤靖周, 植村晃久, 森本紳一郎, 菱田仁
Journal: Circulation (2006)
Olaparib vs Cabazitaxel in Metastatic Castration-Resistant Prostate Cancer
Authors: Christopher J. D. Wallis, Zachary Klaassen, William C. Jackson, Robert T. Dess, Zachery R. Reichert, Yilun Sun, Daniel E. Spratt
Journal: JAMA Network Open (2021)

This comparative effectiveness research compares survival end points and response rates among patients with metastatic castration-resistant prostate cancer (mCRPC) treated with olaparib and cabazitaxel using results from 2 phase 3 randomized clinical trials.
Improving Maternal Health
Authors: Rita Rubin
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Bile acid homeostasis in female mice deficient in Cyp7a1 and Cyp27a1
Authors: Daniel Rizzolo, Bo Kong, Rulaiha E. Taylor, Anita Brinker, Michael Goedken, Brian Buckley, Grace L. Guo
Journal: Acta Pharmaceutica Sinica B (2021)

Bile acids (BAs) are amphipathic molecules important for metabolism of cholesterol, absorption of lipids and lipid soluble vitamins, bile flow, and regulation of gut microbiome. There are over 30 different BA species known to exist in humans and mice, which are endogenous modulators of at least 6 different membrane or nuclear receptors. This diversity of ligands and receptors play important roles in health and disease; however, the full functions of each individual BA in vivo remain unclear. We generated a mouse model lacking the initiating enzymes, CYP7A1 and CYP27A1, in the two main pathways of BA synthesis. Because females are more susceptible to BA related diseases, such as intrahepatic cholestasis of pregnancy, we expanded this model into female mice. The null mice of Cyp7a1 and Cyp27a1 were crossbred to create double knockout (DKO) mice. BA concentrations in female DKO mice had reductions in serum (63%), liver (83%), gallbladder (94%), and small intestine (85%), as compared to WT mice. Despite low BA levels, DKO mice had a similar expression pattern to that of WT mice for genes involved in BA regulation, synthesis, conjugation, and transport. Additionally, through treatment with a synthetic FXR agonist, GW4064, female DKO mice responded to FXR activation similarly to WT mice.
High SARS-CoV-2 Viral Load in Urine Sediment Correlates with Acute Kidney Injury and Poor COVID-19 Outcome
Authors: Paulo S. Caceres, Gina Savickas, Shannon L. Murray, Kausik Umanath, Junior Uduman, Jerry Yee, Tang-Dong Liao, Steven Bolin, Albert M. Levin, Moomal N. Khan, Sarah Sarkar, Jamie Fitzgerald, Dipak Maskey, Adrian H. Ormsby, Yuvraj Sharma, Pablo A. Ortiz
Journal: Journal of the American Society of Nephrology (2021)

AKI is a complication of coronavirus disease 2019 (COVID-19) that is associated with high mortality. Despite documented kidney tropism of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are no consistent reports of viral detection in urine or correlation with AKI or COVID-19 severity. Here, we hypothesize that quantification of the viral load of SARS-CoV-2 in urine sediment from patients with COVID-19 correlates with occurrence of AKI and mortality.
Incidence of Venous Thromboembolism in Patients With Dermatologist-Diagnosed Chronic Inflammatory Skin Diseases
Authors: Maria C. Schneeweiss, Seoyoung C. Kim, Richard Wyss, Yinzhu Jin, Kristyn Chin, Joseph F. Merola, Arash Mostaghimi, Jonathan I. Silverberg, Sebastian Schneeweiss
Journal: JAMA Dermatology (2021)

Several studies have linked chronic inflammatory skin diseases (CISDs) with venous thromboembolism (VTE) in a range of data sources with mixed conclusions.To examine the incidence of VTE in patients with vs without CISD.A cohort study using commercial insurance claims data from a nationwide US health care database from January 1, 2004, through 2019 was conducted. A total of 158 123 patients with dermatologist-recorded psoriasis, atopic dermatitis, alopecia areata, vitiligo, or hidradenitis suppurativa were included. Risk-set sampling identified patients without a CISD. Patient follow-up lasted until the first of the following occurred: VTE, death, disenrollment, or end of data stream.Patients with vs without CISD.Venous thromboembolism events were identified with validated algorithms. Incidence rates were computed before and after 1:1 propensity-score matching to account for VTE risk factors. Hazard ratios were estimated to compare the incidence of VTE in the CISD vs non-CISD cohorts.A total of 158 123 patients were identified with CISD: with psoriasis (n = 96 138), atopic dermatitis (n = 30 418), alopecia areata (n = 17 889), vitiligo (n = 7735), or HS (n = 5934); 9 patients had 2 of these conditions. A total of 1 570 387 patients were without a CISD. The median follow-up time was 1.9 years (interquartile range, 0.8-4.0 years) in patients with CISD. The incidence rate (per 1000 person-years) of outpatient or inpatient VTE was 1.57 in psoriasis, 1.83 in atopic dermatitis, 0.94 in alopecia areata, 0.93 in vitiligo, 1.65 in HS and 1.53 in CISD overall, compared with 1.76 in patients without a CISD. Incidence rates increased in patients aged 50 years or older (2.3 per 1000 person-years) and decreased in those aged 18 to 49 years (0.8 per 1000 person-years). After propensity-score matching to patients without a CISD, the hazard ratio (HR) of VTE was 0.86 (95% CI, 0.75-0.99) in psoriasis, 1.19 (95% CI, 0.95-1.48) in atopic dermatitis, 0.97 (95% CI, 0.65-1.46) in alopecia areata, 0.90 (95% CI, 0.49-1.65) in vitiligo, 1.64 (95% CI, 0.82-3.27) in hidradenitis suppurativa, and 0.94 (95% CI, 0.84-1.05) in CISD overall.In this large-scale cohort study, CISDs were not associated with an increased incidence of VTE after controlling for relevant VTE risk factors in a representative dermatology patient population.