المؤلفون: Jun Wang, Hongmin Zhu, Chunhui Yuan, Xin Shen, Yun Xiang, Wei Luo, Cong Yao, Huan Wu, Jianbo Shao

المصدر: JAMA Network Open

مصطلحات موضوعية: CD4-Positive T-Lymphocytes, Male, Neutrophils, Systemic inflammation, Gastroenterology, Severity of Illness Index, Pediatrics, Leukocyte Count, Interquartile range, Creatine Kinase, MB Form, Child, Original Investigation, B-Lymphocytes, biology, Alanine Transaminase, General Medicine, Hospitals, Pediatric, Anti-Bacterial Agents, Interleukin-10, Killer Cells, Natural, Interleukin 10, Online Only, C-Reactive Protein, Child, Preschool, Cytokines, Female, medicine.symptom, Coronavirus Infections, medicine.medical_specialty, China, Critical Illness, Pneumonia, Viral, Antiviral Agents, Interferon-gamma, Age Distribution, Internal medicine, Severity of illness, medicine, Humans, Aspartate Aminotransferases, Lymphocyte Count, Neutrophil to lymphocyte ratio, Sex Distribution, Interleukin 6, Pandemics, L-Lactate Dehydrogenase, business.industry, Interleukin-6, Tumor Necrosis Factor-alpha, Research, COVID-19, Infant, Alanine transaminase, biology.protein, Interleukin-2, Creatine kinase, Interleukin-4, business

الوصف: Key Points Question What are the immunologic features of pediatric patients with pneumonia caused by coronavirus disease 2019 (COVID-19)? Findings In this single-center case series involving 157 pediatric patients with COVID-19, systemic inflammation rarely occurred. Patients with moderate disease had higher interleukin 10 levels and lower neutrophil levels than patients with mild disease. Meaning The results of this study suggest that dysregulation of immune response may be involved in the pathologic process of COVID-19; gaining a deeper understanding of the role of neutrophils, CD4+ T cells, and B cells in the pathogenesis of severe acute respiratory syndrome coronavirus 2 infection could be important for the clinical management of COVID-19.
This case series delineates and compares the immunologic features of mild and moderate coronavirus disease 2019 (COVID-19) in pediatric patients.
Importance The epidemiologic and clinical characteristics of pediatric patients with coronavirus disease 2019 (COVID-19) have been reported, but information on immune features associated with disease severity is scarce. Objective To delineate and compare the immunologic features of mild and moderate COVID-19 in pediatric patients. Design, Setting, and Participants This single-center case series included 157 pediatric patients admitted to Wuhan Children’s Hospital with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Data were collected from January 25 to April 18, 2020. Exposures Documented SARS-CoV-2 infection. Main Outcomes and Measures Clinical and immunologic characteristics were collected and analyzed. Outcomes were observed until April 18, 2020. Results Of the 157 pediatric patients with COVID-19, 60 (38.2%) had mild clinical type with pneumonia, 88 (56.1%) had moderate cases, 6 (3.8%) had severe cases, and 3 (1.9%) were critically ill. The 148 children with mild or moderate disease had a median (interquartile range [IQR]) age of 84 (18-123) months, and 88 (59.5%) were girls. The most common laboratory abnormalities were increased levels of alanine aminotransferase (ALT) (median [IQR], 16.0 [12.0-26.0] U/L), aspartate aminotransferase (AST) (median [IQR], 30.0 [23.0-41.8] U/L), creatine kinase MB (CK-MB) activity (median [IQR], 24.0 [18.0-34.0] U/L), and lactate dehydrogenase (LDH) (median [IQR], 243.0 [203.0-297.0] U/L), which are associated with liver and myocardial injury. Compared with mild cases, levels of inflammatory cytokines including interleukin 6, tumor necrosis factor α, and interferon γ were unchanged, whereas the level of immune suppressive interleukin 10 was markedly increased in moderate cases compared with mild cases (median [IQR], 3.96 [3.34-5.29] pg/mL vs 3.58 [3.10-4.36] pg/mL; P = .048). There was no statistically significant difference in absolute number of lymphocytes (including T cells and B cells) between mild and moderate cases, but moderate cases were associated with a decrease in neutrophil levels compared with mild cases (median [IQR], 2310/μL [1680/μL-3510/μL] vs 3120/μL [2040/μL-4170/μL]; P = .01). Immunoglobin G and the neutrophil to lymphocyte ratio were negatively associated with biochemical indices related to liver and myocardial injury (immunoglobulin G, ALT: r, −0.3579; AST: r, −0.5280; CK-MB activity: r, −0.4786; LDH: r, −0.4984; and neutrophil to lymphocyte ratio, ALT: r, −0.1893; AST: r, −0.3912; CK-MB activity: r, −0.3428; LDH: r, −0.3234), while counts of lymphocytes, CD4+ T cells, and interleukin 10 showed positive associations (lymphocytes, ALT: r, 0.2055; AST: r, 0.3615; CK-MB activity: r, 0.338; LDH: r, 0.3309; CD4+ T cells, AST: r, 0.4701; CK-MB activity: r, 0.4151; LDH: r, 0.4418; interleukin 10, ALT: r, 0.2595; AST: r, 0.3386; CK-MB activity: r, 0.3948; LDH: r, 0.3794). Conclusions and Relevance In this case series, systemic inflammation rarely occurred in pediatric patients with COVID-19, in contrast with the lymphopenia and aggravated inflammatory responses frequently observed in adults with COVID-19. Gaining a deeper understanding of the role of neutrophils, CD4+ T cells, and B cells in the pathogenesis of SARS-CoV-2 infection could be important for the clinical management of COVID-19.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f232d73e20ad6d349d58f85aaa4f0fadTest

المؤلفون: Jason Hom, Jonathan H. Chen, Santhosh Balasubramanian, Song Xu, Shivaal Roy, Lee F. Schroeder, Nader Najafi

المصدر: JAMA Network Open

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Health Informatics, 030204 cardiovascular system & hematology, Sensitivity and Specificity, Blood Urea Nitrogen, Machine Learning, Hemoglobins, Leukocyte Count, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Predictive Value of Tests, Internal medicine, medicine, Humans, 030212 general & internal medicine, Original Investigation, Aged, Retrospective Studies, Glycated Hemoglobin, L-Lactate Dehydrogenase, Receiver operating characteristic, Clinical Laboratory Techniques, business.industry, Research, Troponin I, Correction, Diagnostic test, Retrospective cohort study, General Medicine, Middle Aged, University hospital, Predictive value, 3. Good health, Hospitalization, Online Only, Laboratory test, ROC Curve, chemistry, Area Under Curve, Predictive value of tests, Female, Other, Glycated hemoglobin, business

الوصف: This diagnostic study uses machine learning models to assess the prevalence of low-yield inpatient laboratory tests.
Key Points Question How prevalent are low-yield inpatient diagnostic laboratory tests for which results are predictable with machine learning models? Findings In this diagnostic study of 191 506 inpatients from 3 tertiary academic medical centers, common low-yield inpatient diagnostic laboratory test results were systematically identified through data-driven methods and personalized predictions. Meaning The findings suggest that data-driven methods can make explicit the level of uncertainty and expected information gain from diagnostic tests, with the potential to encourage useful testing and discourage low-value testing that can incur direct cost and indirect harm.
Importance Laboratory testing is an important target for high-value care initiatives, constituting the highest volume of medical procedures. Prior studies have found that up to half of all inpatient laboratory tests may be medically unnecessary, but a systematic method to identify these unnecessary tests in individual cases is lacking. Objective To systematically identify low-yield inpatient laboratory testing through personalized predictions. Design, Setting, and Participants In this retrospective diagnostic study with multivariable prediction models, 116 637 inpatients treated at Stanford University Hospital from January 1, 2008, to December 31, 2017, a total of 60 929 inpatients treated at University of Michigan from January 1, 2015, to December 31, 2018, and 13 940 inpatients treated at the University of California, San Francisco from January 1 to December 31, 2018, were assessed. Main Outcomes and Measures Diagnostic accuracy measures, including sensitivity, specificity, negative predictive values (NPVs), positive predictive values (PPVs), and area under the receiver operating characteristic curve (AUROC), of machine learning models when predicting whether inpatient laboratory tests yield a normal result as defined by local laboratory reference ranges. Results In the recent data sets (July 1, 2014, to June 30, 2017) from Stanford University Hospital (including 22 664 female inpatients with a mean [SD] age of 58.8 [19.0] years and 22 016 male inpatients with a mean [SD] age of 59.0 [18.1] years), among the top 20 highest-volume tests, 792 397 were repeats of orders within 24 hours, including tests that are physiologically unlikely to yield new information that quickly (eg, white blood cell differential, glycated hemoglobin, and serum albumin level). The best-performing machine learning models predicted normal results with an AUROC of 0.90 or greater for 12 stand-alone laboratory tests (eg, sodium AUROC, 0.92 [95% CI, 0.91-0.93]; sensitivity, 98%; specificity, 35%; PPV, 66%; NPV, 93%; lactate dehydrogenase AUROC, 0.93 [95% CI, 0.93-0.94]; sensitivity, 96%; specificity, 65%; PPV, 71%; NPV, 95%; and troponin I AUROC, 0.92 [95% CI, 0.91-0.93]; sensitivity, 88%; specificity, 79%; PPV, 67%; NPV, 93%) and 10 common laboratory test components (eg, hemoglobin AUROC, 0.94 [95% CI, 0.92-0.95]; sensitivity, 99%; specificity, 17%; PPV, 90%; NPV, 81%; creatinine AUROC, 0.96 [95% CI, 0.96-0.97]; sensitivity, 93%; specificity, 83%; PPV, 79%; NPV, 94%; and urea nitrogen AUROC, 0.95 [95% CI, 0.94, 0.96]; sensitivity, 87%; specificity, 89%; PPV, 77%; NPV 94%). Conclusions and Relevance The findings suggest that low-yield diagnostic testing is common and can be systematically identified through data-driven methods and patient context–aware predictions. Implementing machine learning models appear to be able to quantify the level of uncertainty and expected information gained from diagnostic tests explicitly, with the potential to encourage useful testing and discourage low-value testing that incurs direct costs and indirect harms.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e5b65545c3b7db61d1925b5c4ed5644Test
https://doi.org/10.1001/jamanetworkopen.2019.10967Test

المؤلفون: Nirit Grushko, Ali Yahia, Vera Belsky, Dana Ben-Hur, Gidon Berger, Ronen Zalts, Jasmin Khateeb

المصدر: JAMA Internal Medicine. 176:398

مصطلحات موضوعية: Models, Educational, Organizational efficiency, Cost effectiveness, Lactate dehydrogenase measurement, MEDLINE, L-Lactate dehydrogenase, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Natriuretic Peptide, Brain, Unnecessary Procedure, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Israel, Creatine Kinase, Diagnostic Techniques and Procedures, Inpatients, L-Lactate Dehydrogenase, business.industry, medicine.disease, Creatine kinase measurement, Troponin, Hospital care, Amylases, Patient Care, Medical emergency, business, Delivery of Health Care, Blood Chemical Analysis

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c1a82173ed3a9d31d0d3cb98218b8fffTest
https://doi.org/10.1001/jamainternmed.2015.7705Test

المؤلفون: Eric J. Dobratz, E. Stephen Buescher, Mark Boston, David H. Darrow

المصدر: Archives of Otolaryngology–Head & Neck Surgery. 129:660

مصطلحات موضوعية: Pathology, medicine.medical_specialty, Cell Survival, Neutrophils, medicine.medical_treatment, In Vitro Techniques, Sodium Chloride, Andrology, chemistry.chemical_compound, Benzalkonium chloride, In vivo, Lactate dehydrogenase, medicine, Humans, Prospective Studies, Viability assay, Sinusitis, Saline, Administration, Intranasal, Rhinitis, L-Lactate Dehydrogenase, business.industry, Preservatives, Pharmaceutical, General Medicine, Otorhinolaryngology, chemistry, Nasal spray, Surgery, Trypan blue, Nasal administration, Benzalkonium Compounds, business, medicine.drug

الوصف: Background Nasal saline spray (NSS) used in the treatment of rhinitis and sinusitis often contains the preservative benzalkonium chloride (BKC). Previous studies have shown that corticosteroid nasal sprays and topical decongestants containing BKC damage respiratory mucosa, decrease mucociliary activity, and inhibit neutrophil functions in vitro. Objective To evaluate the effects of NSS with BKC on human neutrophils. Design Prospective, basic science observations. Methods Human neutrophils were exposed to NSS with BKC or to phosphate-buffered saline (PBS) at varying times and concentrations. The cells were examined for morphologic changes by light microscopy and for viability as determined by trypan blue exclusion. Lactate dehydrogenase levels were measured to quantify neutrophil cell lysis. In vivo morphologic changes were studied in neutrophils obtained from the oral mucosa in human volunteers who rinsed their mouths with NSS or PBS. Results Neutrophils exposed to NSS concentrations as low as 15% showed near-total cell lysis, and neutrophils exposed to 20% NSS demonstrated no cell viability by trypan blue staining. Phosphate-buffered saline–exposed cells were unaffected. The release of lactate dehydrogenase from lysed neutrophils increased sharply at NSS concentrations higher than 10% but remained stable in PBS-exposed cells. All neutrophils isolated from NSS oral rinses were lysed, while a mean of 78% of neutrophils from PBS rinses showed normal morphologic structure. Conclusions Nasal saline spray with BKC is toxic to human neutrophils even at concentrations far lower than those found in commercially available preparations. Saline solutions without BKC appear to be safer alternatives, and additional studies are needed to determine the clinical significance of these findings.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::117455fb41f6d279032458b6202e7719Test
https://doi.org/10.1001/archotol.129.6.660Test

المؤلفون: Sunshine M. Dwojak, Michael J. Cunningham, Jennifer L. Hunt

المصدر: Archives of Otolaryngology–Head & Neck Surgery. 138:99

مصطلحات موضوعية: Mouth neoplasm, medicine.medical_specialty, Facial swelling, Psychological suppression, business.industry, General surgery, Lactate dehydrogenase measurement, General Medicine, Bimanual examination, Tomography x ray computed, Otorhinolaryngology, Reference values, Medicine, Surgery, Ultrasonography, business

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::b0474bf26b1b5ae0852acc8cc6942285Test
https://doi.org/10.1001/archoto.2011.220-aTest

المؤلفون: Gregory J. Kato, Mark T. Gladwin

المصدر: JAMA. 300:2638

مصطلحات موضوعية: Adult, Blood Platelets, Hemolytic anemia, Phosphodiesterase Inhibitors, Hypertension, Pulmonary, Vasodilator Agents, Hemoglobin, Sickle, Anemia, Sickle Cell, Nitric Oxide, Article, Nitric oxide, chemistry.chemical_compound, medicine, Humans, Vascular Diseases, Clinical Trials as Topic, Arginase, L-Lactate Dehydrogenase, biology, Vascular disease, business.industry, Leg Ulcer, Endothelial Cells, Free Radical Scavengers, General Medicine, Hydrogen-Ion Concentration, medicine.disease, Pulmonary hypertension, Sickle cell anemia, Stroke, Nitric oxide synthase, Apolipoproteins, chemistry, Heme Oxygenase (Decyclizing), Immunology, biology.protein, Female, Nitric Oxide Synthase, Asymmetric dimethylarginine, business, Niacin

الوصف: A 34-year-old African American woman with sickle cell disease and history of relatively severe hemolysis, chronic leg ulcers, and mild pulmonary hypertension presented with a new ischemic stroke. Recent research has suggested a syndrome of hemolysis-associated vasculopathy in patients with sickle cell disease, which features severe hemolytic anemia and leads to scavenging of nitric oxide and its biochemical precursor L-arginine. This diminished bioavailability of nitric oxide promotes a hemolysis-vascular dysfunction syndrome, which includes pulmonary hypertension, cutaneous leg ulceration, priapism, and ischemic stroke. Additional correlates of this vasculopathy include activation of endothelial cell adhesion molecules, platelets, and the vascular protectant hemeoxygenase-1. Some known risk factors for atherosclerosis are also associated with sickle cell vasculopathy, including low levels of apolipoprotein AI and high levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase. Identification of dysregulated vascular biology pathways in sickle vasculopathy has provided a focus for new clinical trials for therapeutic intervention, including inhaled nitric oxide, sodium nitrite, L-arginine, phosphodiesterase-5 inhibitors, niacin, inhaled carbon monoxide, and endothelin receptor antagonists. This article reviews the pathophysiology of sickle vasculopathy and the results of preliminary clinical trials of novel small-molecule therapeutics directed at abnormal vascular biology in patients with sickle cell disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7e7d5a832c42d72024c16276cea9dfafTest
https://doi.org/10.1001/jama.2008.598Test

المؤلفون: Daniel C. Randall, David L. Jones

المصدر: Archives of Internal Medicine. 157:1441

مصطلحات موضوعية: medicine.medical_specialty, business.industry, L-Lactate dehydrogenase, medicine.disease, Ldh isoenzymes, Utilization review, Coronary heart disease, Lactate dehydrogenase isoenzymes, Surgery, Telephone survey, chemistry.chemical_compound, chemistry, Lactate dehydrogenase, Emergency medicine, Internal Medicine, medicine, Myocardial infarction, business

الوصف: Background: Consensus recommendations call for the elimination of lactate dehydrogenase (LDH) tests from routine rule out myocardial infarction (ROMI) protocols. Methods: We conducted a utilization review project in which we evaluated the institutional impact of removing LDH and LDH isoenzyme tests from our hospital diagnostic panel. We then conducted a scripted telephone survey of 100 US hospitals to assess the generalizability of this project. Results: All our cardiology staff members supported this intervention. Lactate dehydrogenase isoenzyme test results did not add clinically useful data for any of 200 consecutive patients discharged with a diagnosis of acute myocardial infarction, and selective use of LDH isoenzyme testing in cases where it was clinically believed to be indicated cut costs 99% during the year after our intervention. Furthermore, our telephone survey demonstrated that 66% of US hospitals polled continue to test for LDH isoenzymes in every patient with possible myocardial infarction. Conclusions: Our results corroborate prior recommendations for the removal of LDH testing from the routine ROMI protocol. Such an intervention may be accomplished easily, with excellent staff acceptance and considerable savings. Most US hospitals continue to include LDH testing in their ROMI panels despite national guidelines recommending otherwise. Arch Intern Med. 1997;157:1441-1444

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::97b7786c0fe2ef9be60e3d99827bc375Test
https://doi.org/10.1001/archinte.1997.00440340069006Test

المؤلفون: Pol Boudes

المصدر: Archives of Internal Medicine. 151:198

مصطلحات موضوعية: medicine.medical_specialty, business.industry, Human immunodeficiency virus (HIV), medicine.disease_cause, medicine.disease, Original research, Gastroenterology, chemistry.chemical_compound, Pneumonia, chemistry, Pneumocystis carinii, Internal medicine, Lactate dehydrogenase, Immunology, Internal Medicine, medicine, Abnormal Liver Function Test, In patient, business, Serum lactate dehydrogenase

الوصف: In Reply.— We thank Dr Boudes for his interest in our article. 1 The role of serum lactate dehydrogenase (LDH) as a diagnostic or predictive tool in human immunodeficiency virus—associated Pneumocystis carinii pneumonia (PCP) has not been clearly defined. The two original research articles cited by Boudes that evaluated LDH 2,3 are insufficient alone to make a statement. Kawaga et al 2 reported only four patients as appropriate controls, making it difficult to draw statistically significant conclusions. Zaman and White 3 found significant overlap among controls and patients with PCP; furthermore, 7% of patients with PCP had normal LDH values. They stressed cautious interpretation of LDH values. Lactate dehydrogenase values are also of limited use in patients with abnormal liver function test results. We await with interest the publication by Boudes that prospectively evaluates LDH levels for the diagnosis of PCP. We strongly agree that specific presumptive treatment of PCP

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2039866bb2a399c6eeebf5bc27d96455Test
https://doi.org/10.1001/archinte.1991.00400010180031Test

المؤلفون: Greg S. Martin

المصدر: Archives of Internal Medicine. 158:544-544

مصطلحات موضوعية: chemistry.chemical_compound, Biochemistry, chemistry, Obsolescence, business.industry, Lactate dehydrogenase, Internal Medicine, Medicine, business

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::4e95175fa58c25b545af96e47e36d0bfTest
https://doi.org/10.1001/archinte.158.5.544Test

المؤلفون: Marcia Polansky, Mariusz A. Wasik, Robert D. Bigler, Rosa M. Martí, Eric C. Vonderheid, Marshall E. Kadin, Stuart R. Lessin

المصدر: Archives of Dermatology. 132:42

مصطلحات موضوعية: Interleukin 2, Pathology, medicine.medical_specialty, Mycosis fungoides, business.industry, Cutaneous T-cell lymphoma, Dermatology, General Medicine, medicine.disease, Pathophysiology, Lymphoma, chemistry.chemical_compound, chemistry, hemic and lymphatic diseases, Lactate dehydrogenase, Medicine, IL-2 receptor, business, Sezary Cell, medicine.drug

الوصف: Background and Design: The serum concentration of soluble α-chain receptor for interleukin-2 (sIL-2R) was determined in 101 patients with cutaneous T-cell lymphoma (CTCL). Results: The serum concentration of sIL-2R correlates positively with CTCL tumor burden as determined by several clinical parameters (ie, clinical subtype of disease, extent of skin involvement, T rating, and stage), by serum lactate dehydrogenase concentration, and by Sezary cell counts in erythrodermic disease. The median value of sIL-2R in erythrodermic CTCL was more than threefold higher than that of classic mycosis fungoides (MF). The proportion of patients with elevated sIL-2R concentration (>1000 U/mL) also increased in CTCL in a similar fashion according to the clinical type of disease (MF patch phase, 15%; MF plaque phase, 33%; MF tumor phase, 47%; and erythrodermic variants, 90%). However, no correlation was found between sIL-2R serum concentration and expression of membrane-bound IL-2R α chain (CD25) on lymphoid cells in skin lesions and peripheral blood. Significantly, multivariate analysis of various prognostic factors demonstrated that in erythrodermic CTCL, sIL-2R serum concentration correlated best with survival and was a better predictor of prognosis than stage, Sezary cell counts, or lactate dehydrogenase values. Conclusions: These findings document the usefulness of the measurement of the sIL-2R serum concentration to determine tumor burden and prognosis in patients with CTCL. (Arch Dermatol. 1996;132:42-47)

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::93a1d2ad596e027c7e2e0d6373b9beb6Test
https://doi.org/10.1001/archderm.1996.03890250052009Test