tbuckley/cabot-search huggingface dataset:
Association Between Low-Density Lipoprotein Cholesterol Levels and Risk for Sepsis Among Patients Admitted to the Hospital With Infection
Authors: QiPing Feng, Wei-Qi Wei, Sandip Chaugai, Barbara G. Carranza Leon, Jonathan D. Mosley, Daniel A. Carranza Leon, Lan Jiang, Andrea Ihegword, Christian M. Shaffer, MacRae F. Linton, Cecilia P. Chung, C. Michael Stein
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Whether low levels of low-density lipoprotein cholesterol (LDL-C) are associated with increased risk of sepsis and poorer outcomes is unknown. <h3>Objective</h3> To examine the association between LDL-C levels and risk of sepsis among patients admitted to the hospital with infection. <h3>Design, Setting, and Participants</h3> Cohort study in which deidentified electronic health records were used to define a cohort of patients admitted to Vanderbilt University Medical Center, Nashville, Tennessee, with infection. Patients were white adults, had a code indicating infection from the<i>International Classification of Diseases, Ninth Revision, Clinical Modification</i>, and received an antibiotic within 1 day of hospital admission (N = 61 502). Data were collected from January 1, 1993, through December 31, 2017, and analyzed from January 24 through October 31, 2018. <h3>Interventions</h3> Clinically measured LDL-C levels (excluding measurements &lt;1 year before hospital admission and those associated with acute illness) and a genetic risk score (GRS). <h3>Main Outcomes and Measures</h3> The primary outcome was sepsis; secondary outcomes included admission to an intensive care unit (ICU) and in-hospital death. <h3>Results</h3> Among the 3961 patients with clinically measured LDL-C levels (57.8% women; mean [SD] age, 64.1 [15.9] years) and the 7804 with a GRS for LDL-C (54.0% men; mean [SD] age, 59.8 [15.2] years), lower measured LDL-C levels were significantly associated with increased risk of sepsis (odds ratio [OR], 0.86; 95% CI, 0.79-0.94;<i>P</i> = .001) and ICU admission (OR, 0.85; 95% CI, 0.76-0.96;<i>P</i> = .008), but not in-hospital mortality (OR, 0.80; 95% CI, 0.63-1.00;<i>P</i> = .06); however, none of these associations were statistically significant after adjustment for age, sex, and comorbidity variables (OR for risk of sepsis, 0.96 [95% CI, 0.88-1.06]; OR for ICU admission, 0.94 [95% CI, 0.83-1.06]; OR for in-hospital death, 0.97 [95% CI, 0.76-1.22];<i>P</i>&gt; .05 for all). The LDL-C GRS correlated with measured LDL-C levels (<i>r</i>= 0.24;<i>P</i> &lt; 2.2 × 10<sup>−16</sup>) but was not significantly associated with any of the outcomes. <h3>Conclusions and Relevance</h3> Results of this study suggest that lower measured LDL-C levels were significantly associated with increased risk of sepsis and admission to ICU in patients admitted to the hospital with infection; however, this association was due to comorbidities because both clinical models adjusted for confounders, and the genetic model showed no increased risk. Levels of LDL-C do not appear to directly alter the risk of sepsis or poor outcomes in patients hospitalized with infection.
Effect of dupilumab on atopic manifestations in patients treated for atopic dermatitis in real‐life practice
Authors: M. Tauber, P.A. Apoil, C. Richet, J. Laurent, G. De Bonnecaze, E. Mouchon, M. Cassagne, M.C. Marguery, S. Hegazy, M.P. Konstantinou, M. Severino, C. Uthurriague, F. Giordano‐Labadie, A. Didier, C. Paul
Journal: British Journal of Dermatology (2019)
Clinical Efficacy of Prebiotics on Transplant-Related Complications
Authors: Kota Yoshifuji, Kyoko Inamoto, Kazuhiko Kakihana, Megumi Akiyama, Takashi Toya, Aiko Igarashi, Yuho Najima, Noriko Doki, Takeshi Kobayashi, Yuuko Kiridooshi, Kozue Takeshita, Wataru Suda, Atsushi Shiota, Masahira Hattori, Kenya Honda, Hisashi Sakamaki, Kazuteru Ohashi
Journal: Blood (2018)
New Insights into the Mechanism of NO3 - Selectivity in the Human Kidney Chloride Channel ClC-Ka and the CLC Protein Family
Authors: Laura Lagostena, Giovanni Zifarelli, Alessandra Picollo
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement The human chloride channels ClC-Ka and ClC-Kb, in complex with their accessory subunit barttin, are essential for NaCl reabsorption in the nephron. Mutations of ClC-Ka, ClC-Kb, or barttin cause type III and IV Bartter syndrome, characterized by renal salt wasting, hypokalemic metabolic alkalosis, and other effects. Using electrophysiologic techniques and mutational analysis, the authors show that the mechanism of discriminating Cl − versus NO 3 − anions in the human ClC-Ka channel is unique in the CLC protein family, and they identified previously unimplicated residues as responsible for anion selectivity. This represents significant progress in better understanding of the relationship between structure and function of kidney channels ClC-Ka and ClC-Kb and of CLC proteins in general. Background The mechanism of anion selectivity in the human kidney chloride channels ClC-Ka and ClC-Kb is unknown. However, it has been thought to be very similar to that of other channels and antiporters of the CLC protein family, and to rely on anions interacting with a conserved Ser residue (Ser cen ) at the center of three anion binding sites in the permeation pathway S cen . In both CLC channels and antiporters, mutations of Ser cen alter the anion selectivity. Structurally, the side chain of Ser cen of CLC channels and antiporters typically projects into the pore and coordinates the anion bound at S cen . Methods To investigate the role of several residues in anion selectivity of ClC-Ka, we created mutations that resulted in amino acid substitutions in these residues. We also used electrophysiologic techniques to assess the properties of the mutants. Results Mutations in ClC-Ka that change Ser cen to Gly, Pro, or Thr have only minor effects on anion selectivity, whereas the mutations in residues Y425A, F519A, and Y520A increase the NO 3 − /Cl − permeability ratio, with Y425A having a particularly strong effect. Conclusion s ClC-Ka’s mechanism of anion selectivity is largely independent of Ser cen , and it is therefore unique in the CLC protein family. We identified the residue Y425 in ClC-Ka—and the corresponding residue (A417) in the chloride channel ClC-0—as residues that contribute to NO 3 − discrimination in these channels. This work provides important and timely insight into the relationship between structure and function for the kidney chloride channels ClC-Ka and ClC-Kb, and for CLC proteins in general.
Long-Term Outcome of Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Mycosis Fungoides and Sézary Syndrome: The Milan Experience
Authors: Francesco Onida, Giorgia Saporiti, Silvia Alberti Violetti, Elena Tagliaferri, Federica Grifoni, Giorgia Levati, Daniele Fanoni, Nicola Orofino, Mariarita Sciumè, Agostino Cortelezzi, Emilio Berti
Journal: Blood (2018)
Prediction of incident heart failure by serum amino‐terminal pro‐B‐type natriuretic peptide level in a community‐based cohort
Authors: Duncan J. Campbell, Fei Fei Gong, Michael V. Jelinek, Julian M. Castro, Jennifer M. Coller, Michele McGrady, Umberto Boffa, Louise Shiel, Bing H. Wang, Danny Liew, Rory Wolfe, Simon Stewart, Alice J. Owen, Henry Krum, Christopher M. Reid, David L. Prior
Journal: European Journal of Heart Failure (2019)
Worldwide Incidence of Aneurysmal Subarachnoid Hemorrhage According to Region, Time Period, Blood Pressure, and Smoking Prevalence in the Population
Authors: Nima Etminan, Han-Sol Chang, Katharina Hackenberg, Nicolien K. de Rooij, Mervyn D. I. Vergouwen, Gabriel J. E. Rinkel, Ale Algra
Journal: JAMA Neurology (2019)

<h3>Importance</h3> Subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms is a subset of stroke with high fatality and morbidity. Better understanding of a change in incidence over time and of factors associated with this change could facilitate primary prevention. <h3>Objective</h3> To assess worldwide SAH incidence according to region, age, sex, time period, blood pressure, and smoking prevalence. <h3>Data Sources</h3> We searched PubMed, Web of Science, and Embase for studies on SAH incidence published between January 1960 and March 2017. Worldwide blood pressure and smoking prevalence data were extracted from the Noncommunicable Disease Risk Factor and Global Burden of Disease data sets. <h3>Study Selection</h3> Population-based studies with prospective designs representative of the entire study population according to predefined criteria. <h3>Data Extraction and Synthesis</h3> Two reviewers independently extracted data according to PRISMA guidelines. Incidence of SAH was calculated per 100 000 person-years, and risk ratios (RRs) including 95% CIs were calculated with multivariable random-effects binomial regression. The association of SAH incidence with blood pressure and smoking prevalence was assessed with linear regression. <h3>Main Outcomes and Measures</h3> Incidence of SAH. <h3>Results</h3> A total of 75 studies from 32 countries were included. These studies comprised 8176 patients with SAH were studied over 67 746 051 person-years. Overall crude SAH incidence across all midyears was 7.9 (95% CI, 6.9-9.0) per 100 000 person-years; the RR for women was 1.3 (95% CI, 0.98-1.7). Compared with men aged 45 to 54 years, the RR in Japanese women older than 75 years was 2.5 (95% CI, 1.8-3.4) and in European women older than 75 years was 1.5 (95% CI, 0.9-2.5). Global SAH incidence declined from 10.2 (95% CI, 8.4-12.5) per 100 000 person-years in 1980 to 6.1 (95% CI, 4.9-7.5) in 2010 or by 1.7% (95% CI, 0.6-2.8) annually between 1955 and 2014. Incidence of SAH declined between 1980 and 2010 by 40.6% in Europe, 46.2% in Asia, and 14.0% in North America and increased by 59.1% in Japan. The global SAH incidence declined with every millimeter of mercury decrease in systolic blood pressure by 7.1% (95% CI, 5.8-8.4) and with every percentage decrease in smoking prevalence by 2.4% (95% CI, 1.6-3.3). <h3>Conclusions and Relevance</h3> Worldwide SAH incidence and its decline show large regional differences and parallel the decrease in blood pressure and smoking prevalence. Understanding determinants for regional differences and further reducing blood pressure and smoking prevalence may yield a diminished SAH burden.
Intestinal microbes direct CX<sub>3</sub>CR1<sup>+</sup> cells to balance intestinal immunity
Authors: Myunghoo Kim, Andrea A. Hill, Wan-Jung Wu, Gretchen E. Diehl
Journal: Gut Microbes (2019)

Intestinal damage driven by unrestricted immune responses against the intestinal microbiota can lead to the development of inflammatory diseases including inflammatory bowel disease. How such breakdown in tolerance occurs alongside the mechanisms to reinforce homeostasis with the microbiota are a focus of many studies. Our recent work demonstrates coordinated interactions between intact microbiota and CX3CR1 expressing intestinal antigen presenting cells (APCs) that limits T helper 1 cell responses and promotes differentiation of regulatory T cells (Treg) against intestinal antigens including pathogens, soluble proteins and the microbiota itself. We find a microbial attachment to intestinal epithelial cells is necessary to support these anti-inflammatory immune functions. In this addendum, we discuss how our findings enhance understanding of microbiota-directed homeostatic functions of the intestinal immune system and implications of modulating this interaction in ameliorating inflammatory disease.
THU0436 Incidence, prevalence, mortality and chronic renal damage of anca-associated glomerulonephritis in a 20 year population-based cohort
Authors: A. Berti, E. Cornec-Le Gall, D. Cornec, E. Matteson, C.S. Crowson, S. Sethi, F. Fervenza, U. Specks
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> True population-based incidence rates of ANCA-associated glomerulonephritis (AAGN) are lacking. <h3>Objectives</h3> We aimed to estimate incidence, prevalence and mortality of AAGN, and to assess if the grade of chronic renal damage at presentation predicts renal and non-renal outcomes. <h3>Methods</h3> A population-based incident cohort of 57 Olmsted County residents diagnosed with ANCA-associated vasculitis (AAV) in 1996–2015 was identified by medical record review. AAGN was defined as an increase in creatinine &gt;30% and/or a decrease in estimated glomerular filtration rate &gt;25%, and/or the presence of urine red cell casts or hematuria and/or biopsy-proven necrotizing and/or crescentic glomerulonephritis. Incidence rates were age- and sex-adjusted to the 2010 US white population. Age- and sex-adjusted prevalence was calculated for January 1, 2015. Survival rates were compared with expected rates in Minnesota population. Chronic renal damage was assessed by chronicity score (CS) on biopsies performed at diagnosis. <h3>Results</h3> Thirty-four (60%) patients had AAGN. Of these, 65% had microscopic polyangiitis (MPA), and 74% were myeloperoxidase (MPO)-ANCA-positive. The annual incidence of AAGN was 2.0/100,000 population (95% CI:1.3–2.7), the overall prevalence was 35/100,000 (95%CI:24–47). Mortality for AAGN was increased (p&lt;0.001), whereas mortality for AAV without glomerulonephritis did not differ from the general population. Minimal/mild CS predicted recovery of renal function at 1 year (p=0.035; <b>figure 1A</b>); clinical diagnosis (granulomatosis with polyangiitis (GPA) <i>versus</i> MPA) and ANCA-specificity (proteinase 3(PR3)-AAV <i>versus</i> MPO-AAV) did not (<b>figure 1B-C</b>). <h3>Conclusions</h3> Annual incidence and prevalence of AAGN in Minnesota are 2.0/100,000 and 35/100,000, respectively. Mortality is worse compared to AAV patients without glomerulonephritis. More advanced renal damage at diagnosis predicts less renal recovery. <h3>References</h3> [1] Berti A, Cornec D, Crowson CS, Specks U, Matteson EL. The epidemiology of ANCA associated vasculitis in Olmsted County, Minnesota (USA): a 20 year population-based study. Arthritis &amp; rheumatology (Hoboken, NJ) 2017. [2] Sethi S, D'Agati VD, Nast CC, Fogo AB, De Vriese AS, Markowitz GS, et al. A proposal for standardized grading of chronic changes in native kidney biopsy specimens. Kidney international2017;91(4):787–9. <h3>Disclosure of Interest</h3> None declared
AB1234 What happens if it isn’t early inflammatory arthritis? a retrospective case note review of patients referred to our eia service who did not have eia
Authors: A.G. Pulikal, T. Ahmed, S. Levy
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Early inflammatory arthritis (EIA) has been a flagship subject for Rheumatology in the last few years. There has been a lot of interest in the patients diagnosed with EIA but less is known about those who enter the EIA pathway and are subsequently found not to have EIA. <h3>Objectives</h3> This study looks at the diagnoses and management of those discharged from the EIA pathway and what impact this has on resources, management and time. Croydon University Hospital Rheumatology Department has been running an Early Inflammatory Arthritis service incorporating ultrasound since 2014. In this study we are looking at patients that were referred to the EIA Pathway from August 2014 to August 2015. <h3>Methods</h3> To collect the data we looked at the patient records from our clinical system, Cerner Millennium. We recorded the clinical impression on first appointment, final diagnosis, additional investigations, referrals to therapies and other specialists and those that were discharged within the 6 weeks of referral. The data was analysed using .<sup>Microsoft Excel 2010</sup> <h3>Results</h3> Of the 368 patients who were referred to the EIA pathway 140 (38%) were not diagnosed with EIA. The final diagnosis of these patients was osteoarthritis 29 (26%), no rheumatological diagnosis 16 (14%), soft tissue abnormality 11 (9.8%), gout 7 (6.3%), fibromyalgia/hypermobility 7 (6.3%), SLE 5 (4.5%) and polymyalgia rheumatica 4 (3.6%). The remainder, 29 (26%), had miscellaneous rheumatological diagnoses. Of the 140 patients, 28 were thought to have possible EIA on the first consultation. The final diagnosis in this group was osteoarthritis 7 (25%), no rheumatological diagnosis 7 (25%), soft tissue/musculoskeletal injury 3 (11%) and fibromyalgia 2 (7%). The remainder had miscellaneous diagnosis 9 (32%). All patients had routine bloods and x-rays. In addition, musculoskeletal ultrasound was carried out in 22, MRI in 12, CT in 3, EMG in 4 and 3 patients underwent bone density scanning. 13 were referred on to physiotherapy (8 were to hand therapy). 5 were referred to other medical specialities. 30 patients were discharged within 6 weeks. <h3>Conclusions</h3> This is the first study looking at those who did not have EIA. The Best Practice Tariff for EIA states that those without EIA should be discharged back to the GP within 6 weeks. We have shown that these patients have a variety of rheumatological diagnoses that require investigation, referral and treatment with the majority (79%) remaining under our care at 6 weeks. This study highlights the resources needed to manage the patients attending rheumatology via the EIA pathway who do not have EIA and this should be taken into account when such a service is developed. <h3>Disclosure of Interest</h3> None declared
No causal effects of serum urate levels on the risk of chronic kidney disease: A Mendelian randomization study
Authors: Daniel M. Jordan, Hyon K. Choi, Marie Verbanck, Ruth Topless, Hong-Hee Won, Girish Nadkarni, Tony R. Merriman, Ron Do
Journal: PLoS Medicine (2019)

Background Studies have shown strong positive associations between serum urate (SU) levels and chronic kidney disease (CKD) risk; however, whether the relation is causal remains uncertain. We evaluate whether genetic data are consistent with a causal impact of SU level on the risk of CKD and estimated glomerular filtration rate (eGFR). Methods and findings We used Mendelian randomization (MR) methods to evaluate the presence of a causal effect. We used aggregated genome-wide association data (N = 110,347 for SU, N = 69,374 for gout, N = 133,413 for eGFR, N = 117,165 for CKD), electronic-medical-record-linked UK Biobank data (N = 335,212), and population-based cohorts (N = 13,425), all in individuals of European ancestry, for SU levels and CKD. Our MR analysis showed that SU has a causal effect on neither eGFR level nor CKD risk across all MR analyses (all P > 0.05). These null associations contrasted with our epidemiological association findings from the 4 population-based cohorts (change in eGFR level per 1-mg/dl [59.48 μmol/l] increase in SU: −1.99 ml/min/1.73 m2; 95% CI −2.86 to −1.11; P = 8.08 × 10−6; odds ratio [OR] for CKD: 1.48; 95% CI 1.32 to 1.65; P = 1.52 × 10−11). In contrast, the same MR approaches showed that SU has a causal effect on the risk of gout (OR estimates ranging from 3.41 to 6.04 per 1-mg/dl increase in SU, all P < 10−3), which served as a positive control of our approach. Overall, our MR analysis had >99% power to detect a causal effect of SU level on the risk of CKD of the same magnitude as the observed epidemiological association between SU and CKD. Limitations of this study include the lifelong effect of a genetic perturbation not being the same as an acute perturbation, the inability to study non-European populations, and some sample overlap between the datasets used in the study. Conclusions Evidence from our series of causal inference approaches using genetics does not support a causal effect of SU level on eGFR level or CKD risk. Reducing SU levels is unlikely to reduce the risk of CKD development.
FRI0648 Directly comparing latent functional ability in adolescents with jia using the chaq and haq: an item response theory analysis
Authors: S. J. W. Shoop-Worrall, M. O. Voshaar, M. van de Laar, W. Thomson, K. L. Hyrich, J. E. McDonagh, S. M. M. Verstappen
Journal: Annals of the Rheumatic Diseases (2018)

Rheumatoid Arthritis (RA) patients up to 50 years old supported by a charity program of the Belgian French speaking radio-television (RTBF).Objectives: The objectives of this cohort are to observe if a tight control favour remission at 6 months and to define synovial markers for severy and response to therapy.Methods: RA patients fulfilling the ACR/EULAR 2010 criteria and naïve to DMARDs therapy were recruited.Synovial biopsies before treatment were obtained using an ultrasound guided needle biopsy (US-NB) of the small joints or miniarthroscopy of the knee.RA disease activity measures including DAS28CRP domains were evaluated every 3 months and treatment was adapted by the treating physician.Tissues were assessed for quality.Retrieved tissue was fixed, stained and paraffin embedded for blinded tissue pathotype description.Results: A synovial biopsy was performed in 37 patients using US-NB in n patients.Patients were classified according 4 types of synovial histopathology findings.Baseline characteristics of the cohort is summarized in table 1.All patients in the diffuse lymphoïd group were ACPA negative and the majority of the ACPA positive patients were classified in the pauci immune and fibrous group.As shown in figure 1, the pauci immune ERA group showed lower DAS28-CRP response than the other groups.Table 1 All patients n=37 Group 'Diffuse' n=17 Group 'Nodules' n=7 Group 'Pauci-Immun' 'Fibrous' n=13 Age mean (SD) 34.4 (± 1.9) 31.3 (± 2.9) 36.1 (± 4.4) 33.0 (± 5.8) Gender 30F/7M 14F/3M 5F/2M 11F/2M ACPA % (n=) 37.8% (n= 14) 0% (n=0) 57.1% (n=4) 76.9% (n=10) RF % (n=) 48.6% (n=18) 11.8% (n=2) 85.7% (n=6) 76.9% (n=10) Erosion % (n=) 35.1% (n=13) 17.6% (n=3) 57.1% (n=4) 38.4% (n=5) Baseline DAS28-CRP 4.60 (± 0.23) 4.52 (± 1.50) 5.00 (± 1.37) 4.76 (± 1.44)Conclusions: Synovial tissue analysis could provide a step change towards personalized medicine in daily clinical practice for disease stratification and treatment selection of ERA.In the CAP48 cohort, a high number of these young and ERA patients achieved remission at 6 months but a lower response was observed in the pauci immune group.Further analyses are ongoing to define individual synovial markers of severity and response.