tbuckley/cabot-search huggingface dataset:
IgA‐mediated autoimmune hemolytic anemia
Authors: Eri Kawata, Ian Chin‐Yee, Cyrus Hsia, Ziad Solh
Journal: American Journal of Hematology (2019)

An eight-month-old previously healthy girl presented with a one-week history of fever, cough, rhinorrhea, and poor appetite. Initial laboratory findings revealed hemoglobin (Hb) 4.5 g/dL, hematocrit 12%, and mean cell volume (MCV) 121.8 fL with evidence of hemolysis; lactate dehydrogenase was elevated at 497 U/L (<300 U/L), total bilirubin 2.44 mg/dL, haptoglobin <10 mg/dL and absolute reticulocyte count 186 × 109/L (normal 10-100), reticulocyte percentage 23.3%. Peripheral blood film showed spherocytes and erythrocyte agglutination (Figure 1A, Wright-Giemsa stain, original magnification ×50), which falsely elevated the MCV.1-3 Direct antiglobulin test (DAT) was negative for IgG and C3d. The cold agglutinin screen and Donath-Landsteiner test were negative. Hb electrophoresis showed a normal pattern, and the screening test for hereditary spherocytosis was also negative. On ultrasound, her spleen was normal in size for age at 6.3 cm.4 As the blood film strongly suggested an immune mediated hemolytic etiology, further DAT investigation was carried out for IgM and IgA antibodies. It was strongly positive for IgA antiglobulin (Figure 1B), confirming a diagnosis of IgA-mediated autoimmune hemolytic anemia (AIHA). The patient was treated with prednisone to which she responded well, and her Hb improved significantly. The DAT plays a central role in diagnosing AIHA, detecting IgG and C3d on the surface of the red blood cells (RBC). Approximately 3-11% of patients with AIHA are estimated to be DAT-negative.5 There are three main causes of DAT-negative AIHA: (1) RBC-bound IgG immunoglobulin is below the detection limit of conventional DAT reagents, which contain anti-IgG and anti-C3d; (2) RBC-bound IgA or IgM immunoglobulin; and (3) low-affinity IgG autoantibodies.5-7 Although our investigations were sufficient, an eluate using monospecific antisera may detect IgA autoantibodies that are missed by DAT.8 Pure IgA-AIHA is a rare phenomenon and accounts for 0.03% to 4% of DAT-negative AIHA cases.4-7 Reported cases of IgA-AIHA vary in age, etiology, and severity.7, 9-11 Management strategies are similar to other types of AIHA: corticosteroids for the initial therapy with intravenous immunoglobulins, immunosuppressive drugs, rituximab, and splenectomy for refractory cases. In this case, the blood film findings of spherocytes and RBC agglutination were the initial clue to an immune mediated hemolytic mechanism, despite the initial DAT being negative. This case highlights the importance of the blood film interpretation in the investigation of DAT-negative hemolysis. The authors declare no potential conflict of interest. EK, ICY, CCH, and ZS collected and analyzed the data. EK and ZS wrote the manuscript. ICY and CCH reviewed the manuscript. We sincerely thank Jeff Kinney and Laura Aseltine for providing Figure 1B. All authors have reviewed and approved the manuscript.
Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes.
Authors: T. Bancroft, B.L. DeBuysscher, C. Weidle, A. Schwartz, A. Wall, Gray, J. Feng, H.R. Steach, K.S. Fitzpatrick, M.M. Gewe, P.D. Skog, C. Doyle-Cooper, T. Ota, R.K. Strong, D. Nemazee, M. Pancera, L. Stamatatos, A.T. McGuire, J.J. Taylor
Journal: The Journal of Experimental Medicine (2019)

Many tested vaccines fail to provide protection against disease despite the induction of antibodies that bind the pathogen of interest. In light of this, there is much interest in rationally designed subunit vaccines that direct the antibody response to protective epitopes. Here, we produced a panel of anti-idiotype antibodies able to specifically recognize the inferred germline version of the human immunodeficiency virus 1 (HIV-1) broadly neutralizing antibody b12 (iglb12). We determined the crystal structure of two anti-idiotypes in complex with iglb12 and used these anti-idiotypes to identify rare naive human B cells expressing B cell receptors with similarity to iglb12. Immunization with a multimerized version of this anti-idiotype induced the proliferation of transgenic murine B cells expressing the iglb12 heavy chain in vivo, despite the presence of deletion and anergy within this population. Together, our data indicate that anti-idiotypes are a valuable tool for the study and induction of potentially protective antibodies.
Improving Usability of Health Information Technology
Authors: Matthew E. Hirschtritt, Deirdre B. Hirschtritt
Journal: JAMA (2019)

To the Editor Dr Ratwani and colleagues1 summarized usability challenges in health information technology (HIT) and potential solutions to improve the design of electronic health records (EHRs). There are 2 additional points that should be addressed to design user-friendly EHRs.
The impact of immune status on clinical outcomes in patients with Merkel cell carcinoma.
Authors: Sean Donovan, Amy Weaver, Clark Otley, Richard Wayne Joseph
Journal: Journal of Clinical Oncology (2012)

8590 Background: Merkel Cell Carcinoma (MCC) is an aggressive cutaneous malignancy of neuroendocrine origin associated with immunosuppression presumably through infection with Merkel Cell Polyomavirus present in &gt;80% of patients (pts). The impact of immune status on clinical outcomes in pts with MCC is unknown. The primary objective of this study was to compare clinical characteristics and outcomes of pts with MCC who are immunosuppressed (ISP) versus non-immunosuppressed (non-ISP). Methods: We performed a retrospective chart review on pts with MCC diagnosed at the Mayo Clinic between 1981 and 2009. A dermatopathologist confirmed all cases. ISP was defined as pts diagnosed with chronic lymphocytic leukemia, HIV, solid organ transplant recipients, or chronic immunosuppressive medication. The association between ISP status and overall survival was summarized using the hazard ratio (HR) and 95% confidence interval (CI) estimated from a Cox regression model. Results: Of the 268 pts identified and included in the study, 38 (14%) were ISP. We found no differences in age, tumor size, tumor location, stage of disease, or recurrence rate in ISP vs Non-ISP. Among pts who had Stage 3-4 disease, there was no difference in the size of the primary between groups. Among pts with Stage 1-2 disease, ISP status was not significantly associated with poorer survival (HR 1.5, 95% CI 0.7-3.3). However, among pts with Stage 3-4 disease, ISP pts had significantly poorer survival compared to non-ISP pts (HR 2.7, 95% CI 1.2 - 6.2). Conclusions: Baseline clinical characteristics of pts with MCC do not differ based on immunosuppression, and outcomes do not differ in pts in regards to immunosuppression in early stage MCC (Stage 1-2). However, in pts with Stage III-IV MCC, ISP pts have a worse clinical outcome suggesting that metastatic MCC either behaves more aggressively in ISP pts either through intrinsic differences in the biology of the tumor or improved immune evasion in ISP pts. These results should be cautiously interpreted given the small number (n=12) of immunosuppressed pts with advanced stage MCC. The authors will update their data with an additional 58 patients by the date of presentation.
Response to Comment on Nanditha et al. Secular TRends in DiabEtes in India (STRiDE–I): Change in Prevalence in 10 Years Among Urban and Rural Populations in Tamil Nadu. Diabetes Care 2019;42:476–485
Authors: Ambady Ramachandran, Chamukuttan Snehalatha, Jonathan E. Shaw, Priscilla Susairaj, Mary Simon, Lakshminarayanan Vijaya, Krishnamoorthy Satheesh, Ramachandran Vinitha, Arun Raghavan, Arun Nanditha
Journal: Diabetes Care (2019)

We appreciate the interest shown by Tonnies et al. (1) in their comment on the prevalence data published by us and for having calculated the incidence based on the data provided in our article (2). In order to properly understand the causes of changes in the prevalence of diabetes, it is essential to assess incidence, as this, not prevalence, is the key index of population risk. Tonnies et al. (1) calculated the mean incidence across the 2006–2016 time period based on mathematical assumptions using the prevalence, temporal changes, mortality rate, etc. This calculation included a number of assumptions, since not all the actual data were available (1).

Taking a different analytical approach to the same problem, we have now used the data from …
Prospective Controlled Trial on Endurance Exercise Training in Adult Sickle Cell Disease Patients
Authors: Barnabas Gellen, Laurent Messonnier, Angele Merlet, Etienne Audureau, Thomas Rupp, Sandrine Peyrot, Cyril Martin, Jean-Antoine Ribeil, jean Benoit Arlet, Frédéric Galactéros, Leonard Feasson, Pablo Bartolucci
Journal: Blood (2017)
Validation of Zip Code–Based Estimates of Ambulance Driving Distance to Control for Access to Care in Emergency Surgery Research
Authors: Molly P. Jarman, Daniel Sturgeon, Ian Mathews, Tarsicio Uribe-Leitz, Adil H. Haider
Journal: JAMA Surgery (2019)

This study uses Medicaid data files to estimate the association of estimated driving distance and reported driven ambulance miles from an injury site to a hospital during emergency medical service calls as a means to assess data accuracy for use in future research.
Norursodeoxycholic acid versus placebo in the treatment of non-alcoholic fatty liver disease: a double-blind, randomised, placebo-controlled, phase 2 dose-finding trial
Authors: Stefan Traussnigg, Jörn M Schattenberg, Münevver Demir, Johannes Wiegand, Andreas Geier, Gerlinde Teuber, Wolf Peter Hofmann, Andreas E Kremer, Frank Spreda, Johannes Kluwe, Jörg Petersen, Tobias Boettler, Florian Rainer, Emina Halilbasic, Roland Greinwald, Markus Pröls, Michael P Manns, Peter Fickert, Michael Trauner, Wolfgang Vogel, Elmar Aigner, Christian Datz, Herbert Tilg, Guido Gerken, Christian Rust, Hans-Jörg Cordes, Christian Steib, Anita Pathil-Warth, Christian Prinz, MD, Frank Lammert, Christoph Antoni, Gerhard Klausmann, Dieter Häussinger, Alexander Zipprich
Journal: The Lancet. Gastroenterology & hepatology (2019)
Socioeconomic determinants of leprosy new case detection in the 100 Million Brazilian Cohort: a population-based linkage study
Authors: Joilda Silva Nery, Anna Ramond, Julia Moreira Pescarini, André Alves, Agostino Strina, Maria Yury Ichihara, Maria Lucia Fernandes Penna, Liam Smeeth, Laura C Rodrigues, Mauricio L Barreto, Elizabeth B Brickley, Gerson Oliveira Penna
Journal: The Lancet Global Health (2019)

Although leprosy is recognised as a disease of poverty, there is little evidence on the specific socioeconomic factors associated with disease risk. To inform targeted strategies for disease elimination, we investigated socioeconomic markers of leprosy risk in Brazil.
Assembling structurally customizable synthetic carriers of siRNA through thermodynamically self-regulated process
Authors: Guang Bai, Tong Xue, Xiaotao Dong, Uday Kumar Chinta, Jia Feng, Tuo Jin, Fei Wu
Journal: Asian Journal of Pharmaceutical Sciences (2019)

This study demonstrates that our previously reported polywraplex, a synthetic siRNA carrier consisting of a uni-molecular polyplex core of customizable size and a self-assembled tri-block copolymer envelop, may be constructed using dendrimers as the crosslinking junctions. Replacing the branched low molecular weight PEI with polyamidoamine (PAMAM) dendrimer in the zeta potential regulated polymerization resulted in the similar network structured cationic polymer with electron microscopically visible crosslinking junctions. This visibility may offer a convenient way to characterize the molecular structure of the rationally designed networked siRNA-packing cationic polymer without altering its chemical properties and biologic functions. A series of physical-chemical characterizations and biological assays, comprising size, zeta potential, pre-phagocytic siRNA leaking and degradation, and silencing of functional genes, confirmed that the advanced properties of polywraplexes remained with the dendrimer junctions. Although sixth generation PAMAM dendrimer was used as the crosslinking junctions in the size-customizable polymerization for electron microscopic observation, lower generation dendrimer should also work in case more practical and structurally defined cationic polymer is needed.
Impaired cell surface expression and digestive function of sucrase-isomaltase gene variants are associated with reduced efficacy of low FODMAPs diet in patients with IBS-D
Authors: Diab M Husein, Hassan Y Naim
Journal: Gut (2019)

Recent seminal reports in GUT 1 2 have proposed an association between gene variants of intestinal sucrase-isomaltase (SI) and the onset of irritable bowel syndrome (IBS).3 An increased risk of IBS-D (diarrhoea) symptoms in individuals harbouring the variant Val15Phe in the SI gene has been proposed due to partial trafficking impairment and reduced overall function of SI at the cell surface.1 2 These observations strongly suggested an association between Val15Phe and the onset of typical IBS-D symptoms (eg, diarrhoea and bloating4), which are similar to those in congenital SI deficiency.5 The presence of other SI gene variants (SIGVs) has been associated with poorer symptom response to a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet in IBS-D.2 However, molecular, cellular and functional analyses of these variants are required to explain their potential effects on the digestive function of SI and diminished efficacy of the low FODMAP diet in reducing symptoms in patients with these variants. We therefore generated mutants of SI that harbour these SIGVs, namely R774G [rs147207752], Y975H [rs146785675] and E1414K [rs145734588]), by site-directed mutagenesis, expressed them in …
Endoscopic ultrasound-guided ablation of pancreatic neuroendocrine tumors: with or without alcohol?
Authors: Michiel Bronswijk
Journal: Endoscopy (2019)

See also:Endoscopic ultrasound-guided fine needle injection of alcohol for ablation of an insulinoma: a well documented successful procedureEndoscopy eFirstDOI: 10.1055/a-0820-1053See also:Reply to BronswijkEndoscopy 2019; 51(08): 799-799DOI: 10.1055/a-0965-0545
Supplementary Anal Imaging by Magnetic Resonance Enterography in Patients with Crohn’s Disease Not Suspected of Having Perianal Fistulas
Authors: Pyeong Hwa Kim, Seong Ho Park, Kiok Jin, Byong Duk Ye, Yong Sik Yoon, Jong Seok Lee, Hyun Jin Kim, Ah Young Kim, Chang Sik Yu, Suk-Kyun Yang
Journal: Clinical Gastroenterology and Hepatology (2019)
Predictive value of clinical and laboratory findings for overt bone marrow metastasis in patients with solid tumor.
Authors: Kalman Filanovsky, Lev Shvidel, Efraim Idelevich, Edit Feldberg, Mordechai Shtalrid
Journal: Journal of Clinical Oncology (2012)

e19529 Background: Bone marrow (BM) involvement is not a rare finding in advanced stages of solid tumors, it may have a profound influence on prognosis and affect a treatment approach. Methods: 103 patients (pts) with an advanced metastatic solid tumor were included in retrospective study. BM metastasis were diagnosed in 72 cases according to Bone marrow biopsy (BMB) ; 31 other metastatic pts. didn't have a marrow spread. We analyzed a basic demographic characteristics, localization of primary tumors and metastasis, laboratory tests, blood smears, BM aspirates (BMA) and biopsies reports.Results: Pts in both groups had comparable median age, gender distribution, pattern of primary tumor and metastatic spread. Hematological parameters' strong correlated with marrow metastasis were: anemia 83% vs. 61% p=0.015 ,thrombocytopenia 55% vs.16% p&lt;0.001 with higher MPV p=0.01, hypocellular/ dry tap marrow aspirate 58% vs.14% p=0.001 and leukoerythroblastic blood smear 82% vs.0% p&lt;0.0001. Leukoerythroblastosis(LEB) in 92% reflected hypocellular aspirate was not included in final analysis because of low rate recorder blood smears. Analysis of biochemical finding showed higher increase by 2 upper limits (&gt;2ULN) of LDH and ALP in the metastatic BM cohort: 50% vs. 16% and 35% vs. 9%, p=0.002 and p=0.007 respectively. Factors predicted metastatic BM by multivariate analysis were: thrombocytopenia &lt;50x10 9 /L OR 14.4 95%CI (1.6-128), hypocellular BMA OR 7.0 95%CI (1.82-21.2) and alkaline phosphatase &gt;2ULN levels OR 6.5 95%CI ( 1.2-35.3). Causes which influenced the survival of pts with BM metastasis: thrombocytopenia &lt; 50X10 9 / L median survival 0.8 month 95% CI (0.1-1.5) vs. 4.1m 95%CI( 2.0-6.1), LDH level &gt;2ULN 1.8m 95%CI(0.5-3.0) vs.4.7m 95%CI(3.0-6.3) and tumor presenting with BM metastasis vs. previously recognized carcinoma with BM involvement 1.8m 95% CI(0.3-3.0) vs.4.0 m.95%CI(1.3-6.7).Conclusions: Our study demonstrated that thrombocytopenia , alkaline phosphatase level&gt;2ULN and probably LEB reflect hypoplastic BM predict BM metastasis in cancer patients; furthermore, thrombocytopenia, LDH&gt;2ULN and BM metastasis in a clinical presentation affect their survival.
Locally adapted QOF led to improvements in patient care for long term conditions
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The introduction of a local Quality and Outcomes Framework (QOF) alternative in Somerset led to more patient centred care and increased multidisciplinary team working, a new study has found.1

By removing unhelpful QOF components, the alternative scheme allowed GP practices to engage in other schemes aimed at improving care for people with long term conditions.

QOF has been criticised as a box ticking exercise, with both the NHS chief executive and the BMA’s GP Committee chair previously backing its removal. In 2014, NHS England …
Abstract 15727: LDL-C Monitoring Frequency After the Diagnosis of Diabetes or Atherosclerotic Cardiovascular Disease
Authors: Sarah S Cohen, Alanna M Chamberlain, Jill M Killian, Keri L Monda, Susan A Weston, Ted Okerson
Journal: Circulation (2017)

Background: After a cardiovascular event, ACC/AHA guidelines suggest a high intensity statin for most patients to achieve ≥50% reduction in LDL-C. However, it is not known how often clinicians asse...
Hepa systems in hematology clinic to ameliorate the increased fungal infection risk owing to environmental changing.
Authors: Gunhan Gurman, Mehmet Ozen, Gulden Yilmaz, Belgin Coskun, Pervin Topcuoglu, Bengi Ozturk, Muhit Ozcan, Onder Arslan, Osman Ilhan, Meral Beksac, Balik Ismail, Hamdi Akan
Journal: Journal of Clinical Oncology (2013)

e18009 Background: Building constructions around Hematology inpatient clinics are always a major concern for Aspergillus infections in immunocompromised patients. The use of HEPA (High Efficiency Particulate Arresting) filters can be helpful in reducing fungal infections. This quasi-experimental study was designed to measure the efficacy of HEPA filters in such a construction period. Methods: In May 2011, Portable HEPA filters have been placed in patient rooms where hematological malignancies were treated, because of the massive construction 10 meters from the clinic. Infection rates and survival 6 months before and after the installment were compared to see the effect of HEPA filters. A total of 413 patients were treated in the department during this 1-year period. Results: There were no statistical differences between antifungal prophylaxis or treatment regimens in groups. After HEPA filter installation the rates of fungal or non-fungal derived infection and pneumonia and length of hospital stay did not deteriorate in AML and ALL patients. Also, infection rates and infection-related mortality did not increase in AML group, moreover these rates decreased in ALL patients in the construction period. These findings were shown in Table. Conclusions: Despite the construction and the summer months, which environmental Aspergillus contamination is more frequently seen, there was no increase in fungal infections during Post-HEPA period. That may reflect a positive effect of HEPA usage even in AML patients. HEPA filters may be used as a protective system in hematology departments, in such a construction period. [Table: see text]
Proposed Key Characteristics of Female Reproductive Toxicants as an Approach for Organizing and Evaluating Mechanistic Data in Hazard Assessment
Authors: Ulrike Luderer, Brenda Eskenazi, Russ Hauser, Kenneth S. Korach, Cliona M. McHale, Francisco Moran, Linda Rieswijk, Gina Solomon, Osamu Udagawa, Luoping Zhang, Marya Zlatnik, Lauren Zeise, Martyn T. Smith
Journal: Environmental Health Perspectives (2019)

Background: Identification of female reproductive toxicants is currently based largely on integrated epidemiological and in vivo toxicology data and, to a lesser degree, on mechanistic data. A uniform approach to systematically search, organize, integrate, and evaluate mechanistic evidence of female reproductive toxicity from various data types is lacking. Objective: We sought to apply a key characteristics approach similar to that pioneered for carcinogen hazard identification to female reproductive toxicant hazard identification. Methods: A working group of international experts was convened to discuss mechanisms associated with chemical-induced female reproductive toxicity and identified 10 key characteristics of chemicals that cause female reproductive toxicity: 1) alters hormone receptor signaling; alters reproductive hormone production, secretion, or metabolism; 2) chemical or metabolite is genotoxic; 3) induces epigenetic alterations; 4) causes mitochondrial dysfunction; 5) induces oxidative stress; 6) alters immune function; 7) alters cell signal transduction; 8) alters direct cell–cell interactions; 9) alters survival, proliferation, cell death, or metabolic pathways; and 10) alters microtubules and associated structures. As proof of principle, cyclophosphamide and diethylstilbestrol (DES), for which both human and animal studies have demonstrated female reproductive toxicity, display at least 5 and 3 key characteristics, respectively. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), for which the epidemiological evidence is mixed, exhibits 5 key characteristics. Discussion: Future efforts should focus on evaluating the proposed key characteristics against additional known and suspected female reproductive toxicants. Chemicals that exhibit one or more of the key characteristics could be prioritized for additional evaluation and testing. A key characteristics approach has the potential to integrate with pathway-based toxicity testing to improve prediction of female reproductive toxicity in chemicals and potentially prevent some toxicants from entering common use. https://doi.org/10.1289/EHP4971