CXCL10 levels at hospital admission predict COVID-19 outcome: hierarchical assessment of 53 putative inflammatory biomarkers in an observational study.

BACKGROUND: Host inflammation contributes to determine whether SARS-CoV-2 infection causes mild or life-threatening disease. Tools are needed for early risk assessment. METHODS: We studied in 111 COVID-19 patients prospectively followed at a single reference Hospital fifty-three potential biomarkers including alarmins, cytokines, adipocytokines and growth factors, humoral innate immune and neuroendocrine molecules and regulators of iron metabolism. Biomarkers at hospital admission together with age, degree of hypoxia, neutrophil to lymphocyte ratio (NLR), lactate dehydrogenase (LDH), C-reactive protein (CRP) and creatinine were analysed within a data-driven approach to classify patients with respect to survival and ICU outcomes. Classification and regression tree (CART) models were used to identify prognostic biomarkers. RESULTS: Among the fifty-three potential biomarkers, the classification tree analysis selected CXCL10 at hospital admission, in combination with NLR and time from onset, as the best predictor of ICU transfer (AUC [95% CI] = 0.8374 [0.6233-0.8435]), while it was selected alone to predict death (AUC [95% CI] = 0.7334 [0.7547-0.9201]). CXCL10 concentration abated in COVID-19 survivors after healing and discharge from the hospital. CONCLUSIONS: CXCL10 results from a data-driven analysis, that accounts for presence of confounding factors, as the most robust predictive biomarker of patient outcome in COVID-19.

Impact of diabetes on COVID-19 and other infection: Report from the 22nd Hong Kong Diabetes and Cardiovascular Risk Factors-East Meets West Symposium.

The coronavirus disease 2019 (COVID-19) pandemic has posed enormous challenges to healthcare systems worldwide. The negative impact of COVID-19 is widespread and includes not only people who contracted the disease but also those with chronic morbidities such as diabetes whose care is compromised due to diversion of medical resources. People with diabetes are generally more susceptible to infection as a result of altered immunity. People with diabetes have a worse prognosis from COVID-19 and there is evidence to suggest that severe acute respiratory syndrome coronavirus 2 may directly affect pancreatic function precipitating hyperglycaemic crises. In the United Kingdom, one of the most heavily affected countries, guidelines are in place to unify the management of people with diabetes hospitalized for COVID-19. Diabetes services are re-organized to ensure that medical care of people with diabetes is maintained despite resource and other practical constraints. Public health measures including social distancing, hand hygiene and the use of face masks are crucial in containing community transmission of the virus. Hong Kong, one of the most densely populated city in the world, is particularly vulnerable and has in place a stringent containment policy and aggressive contact tracing to ensure public safety during this pandemic.

Pneumococcal Vaccine Coverage in Adults Aged 19-64 Years, Newly Diagnosed With Chronic Conditions in the U.S.

INTRODUCTION: This study examined pneumococcal vaccine coverage in adults aged 19-64 years newly diagnosed with diabetes, chronic heart, lung, or liver disease. These conditions are indicated for pneumococcal vaccination by the Advisory Committee on Immunization Practices. METHODS: A retrospective cohort analysis was conducted in 2016 using the Truven Health MarketScan® database. The study population was adults aged 19-64 years with at least one new chronic condition during 2009-2013 and continuous health plan enrolment for 2 years before and 1 year after the initial diagnosis. Vaccine coverage by length of follow-up since diagnosis (ranging from 1 to 5 years) was summarized. Multivariate analyses were performed to understand factors associated with vaccination. RESULTS: A total of 552,942 adults aged 19-64 years with chronic conditions were identified. There were 8% of adults newly diagnosed with one of four chronic conditions that received a pneumococcal vaccination after 1 year of follow-up; the proportion increased to 20.1% among those with 5 years of follow-up data. Adults aged 50-64 years were more likely to be vaccinated than those aged 19-49 years. Adults with diabetes were more likely to be vaccinated than adults with chronic heart, lung, or liver disease. Adults enrolled in HMO plans were more likely to be vaccinated than adults in other plan types. A higher number of healthcare encounters increased the likelihood of vaccination. Adults who received influenza vaccination were also more likely to receive a pneumococcal vaccination. CONCLUSIONS: Vaccine coverage remains well below Healthy People 2020 targets. A substantial number of adults with chronic conditions remain unvaccinated and at risk for pneumococcal disease.

Immunogenicity, safety, and effectiveness of seasonal influenza vaccination in patients with diabetes mellitus: A systematic review.

Influenza is associated with an increased risk of complications, especially in diabetic mellitus patients who are more susceptible to influenza infection. Despite recommendations of the WHO and public health authorities, vaccination uptake in this population remains suboptimal. This systematic review identified 15 studies published between January 2000-March 2017 in PubMed, Embase and Cochrane Library, which provided data on immunogenicity, safety, effectiveness, and/or cost-effectiveness of seasonal influenza vaccination in diabetic patients. Immunogenicity of seasonal influenza vaccination in diabetic patients was generally comparable to that of healthy participants. One month after vaccination of diabetic patients, seroconversion rates and seroprotection ranged from 24.0-58.0% and 29.0-99.0%, respectively. Seasonal influenza vaccination reduced the risk of hospitalization and mortality in diabetic patients, particularly those aged ≥65 years. These review results demonstrate and reinforce the need and value of annual influenza vaccination in diabetic patients, particularly in alleviating severe complications such as hospitalization or death.

The spectrum, incidence, kinetics and management of endocrinopathies with immune checkpoint inhibitors for metastatic melanoma.

OBJECTIVE: Endocrine immune-related adverse events (endocrinopathies) are increasingly prevalent with the use of immune checkpoint inhibitors for the treatment of metastatic melanoma and other malignancies. There are no evidence-based guidelines for the screening or management of such patients. To describe the spectrum, incidence, kinetics and management of endocrinopathies with immune checkpoint inhibitors. DESIGN: A prospective study conducted at Melanoma Institute Australia between April 2014 and October 2015. METHODS: A total of 177 patients were treated with (a) ipilimumab (n = 15), (b) anti-PD-1 (nivolumab, pembrolizumab) (n = 103) or (c) combination ipilimumab and anti-PD-1 (n = 59) and were screened and managed for the subsequent endocrinopathies. The main outcome measures were the incidence and kinetics of endocrinopathy by immunotherapy drug class. RESULTS: Thirty-one patients (18%) developed an endocrine immune-related adverse event (thyroid dysfunction: 14%, hypophysitis: 6% and autoimmune diabetes: 0.6%). Combination immunotherapy was more likely to result in a single or multiple endocrinopathy compared to anti-PD-1 monotherapy (27% vs 9% and 7% vs 0% respectively, P < 0.01). Endocrinopathies occurred after a median of 8 weeks from treatment commencement (range: 12-225 days), with combination immunotherapy resulting in significantly earlier onset compared to ipilimumab (median: 30 vs 76 days, P = 0.046). The majority of endocrinopathies were identified in asymptomatic patients with hormonal screening. There were no baseline predictors for endocrinopathy. CONCLUSIONS: Combination immunotherapy has a greater risk of development of endocrinopathy compared to anti-PD-1 monotherapy. Regular biochemical profiling of patients, particularly within the first twelve weeks, results in early detection of endocrinopathy to minimise morbidity.

Zinc transporter 8 autoantibodies assessment in daily practice.

OBJECTIVES: Zinc transporter 8 (ZnT8) is specifically expressed in the pancreatic ß-cell and is more restricted in its tissue distribution than other auto-antigens as glutamic acid decarboxylase 65 (GAD65) and insulinoma-associated antigen-2 (IA2). ZnT8 autoantibodies (ZnT8A) assessment allows identifying rapid progression to clinical onset of the disease. We evaluated the prevalence of ZnT8A in adults of different ethnic and phenotypic groups and analyzed its potential utility as additional marker of autoimmunity in daily practice. METHODS: ZnT8A, GADA and IA2A were assessed using enzyme-linked immune-sorbent assay (ELISA) in 160 controls and 216 diabetic subjects. 105 were of type 1 diabetes (T1D), 17 had Latent Autoimmune Diabetes of Adults (LADA), 38 were type 2 diabetic (T2D) and 56 had ketosis-prone diabetes (KPD). 82 patients were newly diagnosed cases. RESULTS: ZnT8A were detected in 1% of controls and were not found in any of our 38 T2D subjects or 56 KPD subjects. In contrast, ZnT8A were detected in 18% of LADA subjects and in 38% of T1D subjects. A slight difference of percentage of ZnT8A positivity was found among our T1D ethnic groups. ZnT8A were positive in 41% of patients positive for GADA and 67% of patients positive for IA2A. The percentage of stratification achieved 91% when GADA, IA2A and ZnT8A were assessed simultaneously. CONCLUSIONS: Results obtained for ZnT8A measurement using ELISA were consistent with previous data. Such investigation could improve the risk stratification and would be integrated in our daily practice.

A practical, clinical approach to the assessment and management of suspected insulin allergy.

BACKGROUND: Although allergic reactions to insulin are uncommon, they can be difficult to diagnose and management may be very difficult in subjects with Type 1 diabetes with severe allergy. Access to allergists and specialist diagnostic tests is limited and few diabetes specialists are familiar with desensitization as a means of treating allergy. People with diabetes may develop symptoms which mimic insulin allergy but are attributable to other conditions. CASE REPORTS: Here we describe three cases of insulin allergy. One patient presented with severe, albeit localized, urticarial reactions at injection sites. The most severe case was a woman with recent-onset Type 1 diabetes who presented with grade 2 anaphylaxis. The third patient presented with generalized urticaria and angioedema. Insulin allergy was confirmed in all three cases. METHODS: Assessment involved measurement of immunoglobulin and anti-insulin antibody levels. Skin testing was performed in two cases. Treatments included desensitization in one case, alternative insulin preparations, antihistamines and continuous subcutaneous insulin infusion. In all three cases of insulin allergy there has been successful resolution of symptoms. CONCLUSIONS: The clinical assessment and investigation in cases of suspected insulin allergy is described, along with detailed algorithms for skin testing and desensitization. This case series demonstrates an approach to challenging cases of suspected insulin allergy which will be helpful for diabetes specialists.

Cost-effectiveness of hepatitis B vaccination in adults with diagnosed diabetes.

OBJECTIVE To examine the cost-effectiveness of a hepatitis B vaccination program for unvaccinated adults with diagnosed diabetes in the U.S. RESEARCH DESIGN AND METHODS We used a cost-effectiveness simulation model to estimate the cost-effectiveness of vaccinating adults 20-59 years of age with diagnosed diabetes not previously vaccinated for or infected by hepatitis B virus (HBV). The model estimated acute and chronic HBV infections, complications, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Data sources included surveillance data, epidemiological studies, and vaccine prices. RESULTS With a 10% uptake rate, the intervention will vaccinate 528,047 people and prevent 4,271 acute and 256 chronic hepatitis B infections. Net health care costs will increase by $91.4 million, and 1,218 QALYs will be gained, producing a cost-effectiveness ratio of $75,094 per QALY gained. Results are most sensitive to age, the discount rate, the hepatitis B incidence ratio for people with diabetes, and hepatitis B infection rates. Cost-effectiveness ratios rise with age at vaccination; an alternative intervention that vaccinates adults with diabetes 60 years of age or older had a cost-effectiveness ratio of $2.7 million per QALY. CONCLUSIONS Hepatitis B vaccination for adults with diabetes 20-59 years of age is modestly cost-effective. Vaccinating older adults with diabetes is not cost-effective. The study did not consider hepatitis outbreak investigation costs, and limited information exists on hepatitis progression among older adults with diabetes. Partly based on these results, the Advisory Committee on Immunization Practices recently recommended hepatitis B vaccination for people 20-59 years of age with diagnosed diabetes.

Avaliação da variabilidade da frequência cardíaca de idosos diabéticos e não diabéticos / Assessment of heart rate variability in elderly diabetic and nondiabetic patients

INTRODUÇÃO: O cenário de envelhecimento populacional e o aumento das Doenças Crônicas Não Transmissíveis (DCNT) requer o desenvolvimento e validação de métodos diagnóstico e de ferramentas não invasivas para identificação de fatores de risco e estadiamento destas doenças. Entre estes métodos evidencia-se a análise da modulação autonômica do coração por meio da Variabilidade da Frequência Cardíaca (VFC). OBJETIVO: Analisar a variabilidade da frequência cardíaca de idosos diabéticos (DM+) e não diabéticos (DM–) residentes em um município baiano; avaliar a resposta da variabilidade da frequência cardíaca na realização da manobra de levantar-se rapidamente. MÉTODOS: estudo epidemiológico transversal, de abordagem censitária. Desenvolvido com 205 idosos da zona urbana do munícipio de Aiquara-BA, após aplicação os critérios de inclusão e exclusão. Os dados da VFC foram coletados através do monitor Polar RS800CX...

INTRODUCTION: The scenario of population aging and the increase of Chronic Noncommunicable Diseases (NCDs) requires the development and validation of diagnostic methods and non-invasive tools for identification of risk factors and staging of these diseases.Among these methods, the analysis of autonomic modulation of the heart using the Heart Rate Variability (HRV) becomes evident. OBJECTIVE: To analyze the heart rate variability in diabetic (DM+) and nondiabetic (DM–) elderlies residents in a municipality of Bahia, and also to know the response of heart rate variability in performance of the quickly stand up maneuver. METHODS: cross-sectional study of censitary approach. Carried out with 205 elderlies in the urban area of the municipality of Aiquara-BA, after had applied the inclusion and exclusion criteria. HRV data were collected through the Polar RS800CX...

Custo-efetividade do tratamento da infecção pelo vírus da hepatite C em candidatos a transplante renal submetidos à diálise / Cost-effectiveness of hepatitis C treatment in patients on dialysis awaiting renal transplantation

O estudo tem como objetivo geral avaliar a razão de custo-utilidade do tratamento da infecção pelo vírus da hepatite C (VHC) em pacientes dialisados, candidatos a transplante renal, tendo como esquemas terapêuticos alternativos o interferon-a em monoterapia; o interferon peguilado em monoterapia; o interferon-a em terapia combinada com ribavirina e o interferon peguilado em terapia combinada com ribavirina, comparando-os com o não-tratamento. A perspectiva do estudo foi a do Sistema Único de Saúde(SUS), que também serviu de base para estimar o impacto orçamentário da estratégia de tratamento mais custo efetiva. Para o alcance dos objetivos, foi construído um modelo de Makov para simulação de custos e resultados de cada estratégia avaliada. Para subsidiar o modelo, foi realizada uma revisão de literatura, a fim de definir os estados de saúde relacionados à infecção pelo vírus da hepatite C em transplantados e a probabilidade de transição entre os estados. Medidas de utilidade foram derivadas de consultas a especialistas. Os custos foram derivados da tabela de procedimentos do SUS. Os resultados do estudo demonstraram que o tratamento da infecção pelo VHC antes do transplante renal é mais custo-efetivo que o não tratamento, apontando o interferon-a como a melhor opção. O impacto orçamentário para adoção dessa estratégia pelo SUS corresponde a 0,3 por cento do valor despendido pelo SUS com terapia renal substitutiva ao longo do ano de 2007.

Autoantibodies to IA-2beta improve diabetes risk assessment in high-risk relatives.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the prognostic significance of autoantibodies to IA-2beta (IA2betaA) in a large, well-characterised population of islet cell antibody (ICA)-positive relatives followed for 5 years in the European Nicotinamide Diabetes Intervention Trial. METHODS: Autoantibodies to insulin (IAA), glutamate decarboxylase (GADA) and IA-2 (IA2A) were measured in 549 participants at study entry, and IA2A-positive samples tested for IA2betaA. First-phase insulin response (FPIR) and oral glucose tolerance were determined at baseline. RESULTS: Of 212 ICA/IA2A-positive participants (median age 12.1 years; 57% male), 113 developed diabetes (5 year cumulative risk 56%), and 148 were also GADA-positive and IAA-positive (4Ab-positive). IA2betaA were detected in 137 (65%) ICA/IA2A-positive participants and were associated with an increased 5 year diabetes risk (IA2betaA-positive 65 vs 39% in IA2betaA-negative, p=0.0002). The effect was most marked in 4Ab-positive relatives (72% vs 52%, p=0.003). Metabolic testing further refined risk assessment. Among 101 4Ab-positive relatives with IA2betaA, the 5 year risk was 94% in those with a low FPIR (vs 50% in those with a normal FPIR, p<0.0001), and 95% in those with impaired glucose tolerance (IGT) (vs 66% in those with normal glucose tolerance, p<0.0001). The median time to diagnosis of 4Ab/IA2betaA-positive participants with a low FPIR was 1.5 years. Multivariate analysis confirmed IA2betaA status, antibody number, young age, FPIR and IGT as independent determinants of risk. CONCLUSIONS/INTERPRETATION: IA2betaA are associated with a very high risk of diabetes in ICA/IA2A-positive relatives. Testing for IA2A/IA2betaA compares favourably with the IVGTT in identifying a subgroup of autoantibody-positive relatives at increased risk. IA2betaA determination should be added to screening protocols of future intervention trials.

[Longitudinal assessment of IFN-gamma production in patients with pulmonary tuberculosis complicated with diabetes mellitus].

Patients with diabetes mellitus (DM) are more susceptible to bacterial infection including pulmonary tuberculosis. To define the immunopathologic mechanisms underlying pulmonary tuberculosis in patients with DM, the production of IFN-gamma by CD4+ T cells or PBMC were followed up longitudinally during antituberculous chemotherapy. At the time of diagnosis, IFN-gamma production by CD4+ T cells in either tuberculosis patients without DM (TB) or with DM was significantly lower than that in the healthy control. CD4+ T cells in tuberculosis patients with DM under poor control (DM(p)TB) produced significantly less IFN-gamma than did patients with DM under good control (DM(g)TB). In longitudinal studies, IFN-gamma production in both TB and DM(g)TB patients returned to the control level by 6 months, whereas the production in DM(p)TB patients remained depressed. There was no significant relation between regimens of antituberculous chemotherapy and the production of IFN-gamma by PBMC in all subject groups. IFN-gamma production was depressed in DM(p)TB patients treated with HREZ for 6 months. These results indicate that depressed production of IFN-gamma in DM(p)TB patients is prolonged not due to tuberculous infection but intrinsic defect presumably induced by poorly controlled DM.

[Nutritional status assessment in diabetes mellitus secondary to chronic alcoholic pancreatitis]. / Valoración del estado nutricional en la diabetes mellitus secundaria a pancreatitis crónica alcohólica.

BACKGROUND: Diabetes mellitus secondary to alcoholic chronic pancreatitis (DM-ACP) represents 0.5-2% of all cases of diabetes mellitus (DM) and shows predominantly symptoms related to malnutrition instead of cardinal clinical signs of diabetes. The aim of this study was to try to further characterize the features of the malnutrition in patients with pancreatic insufficiency. PATIENTS MATERIAL AND METHODS: We selected 40 patients (39 males and 1 female) meeting clinical, functional and morphological diagnostic criteria of DM-ACP which received a nutritional assessment that included estimation on fat and proteic body compartments being classified as caloric, proteic or mixed malnutrition. RESULTS: 29 patients (72.5%) showed some kind of malnutrition. The most frequent type was mixed (proteic-caloric) malnutrition found in 19 of them (47.5%). Caloric malnutrition was present in 6 (15%) and mainly proteic in 4 (10%). Only 11 patients with DM-ACP in our series showed a normal nourishment state. CONCLUSIONS: Large prevalence of mixed malnutrition in DM-ACP patients may be related to malabsorption of macronutrients (especially proteins and fat) due to exocrine insufficiency and misuse of nutrients as a result of the characteristic hypoinsulinemia showed by these patients.

[Autoimmune diseases--principles and selected examples]. / Autoimmunkrankheiten--Grundlagen und ausgewählte Beispiele.

Autoimmune diseases present themselves as syndromes of different dysfunctions of the immune system due to multiple disturbances of immuninformation and regulation. Because of the lifelong persistence of the auto-antigen, chronic progredient diseases develop with a variety of symptoms and different stages within the clinical course. It may be that at first glance symptoms of lesser importance, like skin disorders or proteinuria, can be markers of a systemic manifestation of an immunopathy. The underwriting of proposal ought to be based on information of the own and family history as well as on recent clinical and serological findings and on the possible involvement of other organs.

Performance of two agglutination techniques in the detection of thyroid antibodies and assessment of their clinical significance.

Two clinically most widely used agglutination tests, Thymune and Serodia distributed by Wellcome and Fjirebio/Ames, respectively, to determine thyroid autoantibodies were compared. The Serodia tests seemed to be considerably more sensitive than the corresponding Thymune tests; first, Serodia tests resulted in several new positive samples and second, 16% and 30% of positive thyroglobulin and thyroid microsomal antibodies by Serodia resulted in at least 16 times higher titres, respectively. Over 300 healthy blood donor sera were used to determine the occurrence of thyroid autoantibodies in normal population. Titre limits of 400 and 6400 in anti-thyroglobulin and anti-microsomal antibodies were adapted for clinical use, respectively, even though the results suggested that the lower titre limits could be applied for males and subjects younger than 40 years. These defined titre limits were applied to examine randomly selected clinical patient material gathered during 1 year. The main patient groups identified included patients with chronic thyroiditis, thyroid malignancy, diabetes. Graves' disease and rheumatoid diseases as well as patients with vaguely defined clinical conditions. Without the aid of antithyroglobulin antibodies only one patient with chronic thyroiditis would have been missed if thyroid microsomal antibodies were used alone. Thus, in general clinical practise thyroid microsomal antibodies can be used as a sole diagnostic test for autoimmune thyroid diseases.