Performance of adenosine deaminase in synovial fluid for the diagnosis of tuberculous arthritis: A systematic review and meta-analysis / Rendimiento de la adenosina desaminasa en el líquido sinovial para el diagnóstico de la artritis tuberculosa: una revisión sistemática y metaanálisis

Objectives: Adenosine deaminase (ADA) activity has shown good performance in diagnosing pleural, peritoneal, and meningeal tuberculosis. This meta-analysis aimed to evaluate the performance of measuring ADA activity in synovial fluid for the early diagnosis of joint tuberculosis. Methods: We searched published information in MEDLINE, Embase, Cochrane Library, Web of Science, and MedRxiv databases, as well as unpublished information in the American College of Rheumatology and European League Against Rheumatism for conference abstracts (2012–2021). We also scanned the reference lists of articles. Two reviewers independently applied the criteria for selection, assessed quality, and extracted data (PROSPERO number CRD42021284472). Results: Seven independent studies (N=305 subjects) that compared ADA activity in synovial fluid with a composite reference diagnostic method for tuberculosis were included. Overall, the risk of bias was judged low. Studies were classified as high quality (n=3; 148 subjects) and low quality (n=4; 157 subjects). Pooled sensitivity and specificity of ADA activity was 94% (95% confidence interval [CI], 0.89–98; I2=23%) and 88% (95% CI, 83–92; I2=83%), respectively. The random-effects model for pooled diagnostic Odds ratio was 67.1 (95%CI, 20.3–222.2; I2=30%). The receiver operating characteristic curve area was 0.96 (95% CI, 0.92–0.99). Meta-regression did not identify the quality of the study, country of publication, or the type of assay as a source of heterogeneity. Conclusions: Measuring ADA activity in synovial fluid demonstrates good performance for the early diagnosis of joint tuberculosis.(AU)

Objetivos: La actividad de la adenosina desaminasa (ADA) ha mostrado un buen desempeño en el diagnóstico de la tuberculosis pleural, peritoneal y meníngea. Este metaanálisis tuvo como objetivo evaluar el rendimiento de la medición de la actividad de la ADA en el líquido sinovial para el diagnóstico precoz de la tuberculosis articular. Métodos: Se realizaron búsquedas de resúmenes de congresos en la información publicada en las bases de datos MEDLINE, Embase, Cochrane Library, Web of Science y MedRxiv, así como en información no publicada en el American College of Rheumatology y la European League Against Rheumatism (2012-2021). También se escanearon las listas de referencias de los artículos. Dos revisores aplicaron de forma independiente los criterios de selección, evaluaron la calidad y extrajeron los datos (número PROSPERO CRD42021284472). Resultados: Se incluyeron siete estudios independientes (n=305 sujetos) que compararon la actividad de la ADA en el líquido sinovial con un método diagnóstico compuesto de referencia para la tuberculosis. En general, el riesgo de sesgo se consideró bajo. Los estudios se clasificaron como de alta calidad (n=3; 148 sujetos) y de baja calidad (n=4; 157 sujetos). La sensibilidad y la especificidad agrupadas de la actividad de la ADA fueron del 94% (intervalo de confianza [IC] del 95%: 0,89-98; I2=23%) y del 88% (IC95%: 83-92; I2=83%), respectivamente. El modelo de efectos aleatorios para el odds ratio diagnóstico agrupado fue de 67,1 (IC95%: 20,3-222,2; I2=30%). El área de la curva característica de operación del receptor fue de 0,96 (IC95%: 0,92-0,99). La metarregresión no identificó la calidad del estudio, el país de publicación o el tipo de ensayo como fuente de heterogeneidad.Conclusiones: La medición de la actividad de ADA en el líquido sinovial demuestra un buen rendimiento para el diagnóstico precoz de la tuberculosis articular.(AU)

Performance of adenosine deaminase in synovial fluid for the diagnosis of tuberculous arthritis: A systematic review and meta-analysis.

OBJECTIVES: Adenosine deaminase (ADA) activity has shown good performance in diagnosing pleural, peritoneal, and meningeal tuberculosis. This meta-analysis aimed to evaluate the performance of measuring ADA activity in synovial fluid for the early diagnosis of joint tuberculosis. METHODS: We searched published information in MEDLINE, Embase, Cochrane Library, Web of Science, and MedRxiv databases, as well as unpublished information in the American College of Rheumatology and European League Against Rheumatism for conference abstracts (2012-2021). We also scanned the reference lists of articles. Two reviewers independently applied the criteria for selection, assessed quality, and extracted data (PROSPERO number CRD42021284472). RESULTS: Seven independent studies (N=305 subjects) that compared ADA activity in synovial fluid with a composite reference diagnostic method for tuberculosis were included. Overall, the risk of bias was judged low. Studies were classified as high quality (n=3; 148 subjects) and low quality (n=4; 157 subjects). Pooled sensitivity and specificity of ADA activity was 94% (95% confidence interval [CI], 0.89-98; I2=23%) and 88% (95% CI, 83-92; I2=83%), respectively. The random-effects model for pooled diagnostic Odds ratio was 67.1 (95%CI, 20.3-222.2; I2=30%). The receiver operating characteristic curve area was 0.96 (95% CI, 0.92-0.99). Meta-regression did not identify the quality of the study, country of publication, or the type of assay as a source of heterogeneity. CONCLUSIONS: Measuring ADA activity in synovial fluid demonstrates good performance for the early diagnosis of joint tuberculosis.

Glycemic control and prescription profiles in internal medicine inpatients: The role of frailty.

AIM: This work aims to characterize the clinical profile of individuals with frailty syndrome, diabetes mellitus (DM), and hyperglycemia during hospitalization in regard to glycemic control and treatment regimen. METHODS: This cross-sectional multicentric study included patients with DM or hyperglycemia at admission. Demographic data, blood glucose values, treatment administered during hospitalization, and treatment indicated at discharge were analyzed. The sample was divided into three groups according to score on a frailty questionnaire. Generalized additive models were used to describe the relationship between either glycemic variability (GV) or minimum capillary blood glucose and hypoglycemia. Models were adjusted for age, comorbidity, and sarcopenia. RESULTS: A total of 1,137 patients were analyzed. Patients with frailty syndrome had more comorbidity and sarcopenia, worse renal function, and lower albumin and lymphocyte levels. A GV between 21% and 60% was related to a higher probability of hypoglycemia, especially in patients with frailty. Regarding minimum capillary blood glucose, patients with frailty had the highest probability of hypoglycemia. This probability remained significant even in the group with frailty in which, with a reference value of 200 mg/dl, the adjusted odds ratio of a minimum capillary blood glucose of 151 mg/dL was 1.08 (95% confidence interval (1.12-1.05)). Baseline treatments showed a significant predominance of insulin use in the frailest groups. CONCLUSIONS: Patients with frailty had more sarcopenia and undernourishment. These patients were managed in a similar manner during hospitalization to patients without frailty, despite their higher risk of hypoglycemia according to GV or minimum capillary blood glucose levels.

Effect of semaglutide on fatty liver disease biomarkers in patients with diabetes and obesity.

AIM: This work aims to assess the effect of weekly subcutaneous semaglutide on biomarkers of metabolic-associated fatty liver disease (MAFLD), namely the hepatic steatosis index (HSI) and the fibrosis-4 (FIB-4) index, at 24 weeks in outpatients attended to in internal medicine departments. METHODS: This study analyzed patients in an ongoing, multicenter, prospective, pre-post, uncontrolled cohort registry that enrolls unique, consecutive patients with type 2 diabetes treated with weekly subcutaneous semaglutide. Steatosis/fibrosis were determined by HSI (<30 ruled out, >36 steatosis) and FIB-4 (<1.3 ruled out, >2.67 fibrosis), respectively. RESULTS: The sample included 213 patients (46.9% women) with a median age of 64 (19) years. The median baseline body mass index and weight were 36.1 (8.4) kg/m2 and 98 (26.9) kg, respectively. A total of 99.9% had HSI values indicating steatosis, with a mean HSI of 47.9 (8.2). Additionally, 10.8% had fibrosis (FIB-4 > 2.67) and 42.72% had values in intermediate ranges (FIB-4 1.3-2.67). At 24 weeks, there was a significant reduction in HSI (-2.36 (95%CI 1.83-2.9) p < 0.00001) and FIB-4 (-0.075 (95%CI 0.015-0.14) p < 0.016), mainly related to declines in body weight, triglyceride levels, insulin resistance (estimated by the triglyceride-glucose index), and liver enzymes. CONCLUSION: These results show that weekly subcutaneous semaglutide had a beneficial effect on liver steatosis that went beyond glucose control. Its effects were mainly related to weight loss, a decline in biomarkers, and improvements in insulin sensitivity. For many patients, early detection is essential for improving MAFLD outcomes and may allow for selecting the most efficient treatment options.

Therapeutic-dose anticoagulation or thromboprophylaxis with low-molecular-weight heparin for moderate Covid-19: meta-analysis of randomized controlled trials.

BACKGROUND: We carried out a meta-analysis since there is not enough evidence to recommend for or against therapeutic-dose anticoagulation compared with thromboprophylaxis in noncritically ill patients hospitalized with Covid-19. METHODS: We performed a systematic literature search using PubMed, Embase, Cochrane Library, and MedRxiv for randomized trials that included therapeutic-dose with low-molecular-weight heparin (LMW) or thromboprophylaxis with LMW heparin in noncritically ill patients admitted to the hospital with Covid-19. We identified five open-label studies for analysis with a total of 3220 patients. Two independent researchers selected, assessed, and extracted the data in duplicate. The outcomes evaluated were all-cause mortality, progression to invasive mechanical ventilation, incidence of venous thromboembolism, and major bleeding. The studies did not show risk for selection, detection, attrition, or reporting bias. RESULTS: Therapeutic-dose anticoagulation with LMW heparin compared with thromboprophylaxis with LMW heparin had no significant effect of all-cause death (risk ratio [RR] 0.85; 95% confidence interval [CI] 0.67-1.07; P = 0.16; I2 = 48%), or progression to invasive mechanical ventilation (RR 0.89; CI 0.73-1.08; P = 0.24; I2: 0%). Therapeutic-dose anticoagulation significantly reduced the risk of venous thromboembolic disease (RR 0.42; 95% CI 0.28-0.62; P = 0.0001; I2 = 0%) [Number needed to treat = 37]. Major bleeding occurred in 1.79% of the patients receiving therapeutic-dose anticoagulation and in 0.97% of those receiving thromboprophylaxis [Number needed to harm 125]. CONCLUSION: Therapeutic-dose anticoagulation in noncritically ill patients with Covid-19 could be indicated for patients at high risk of venous thromboembolic disease and low risk of bleeding.

High-Risk Obesity Phenotypes: Target for Multimorbidity Prevention at the ROFEMI Study.

Background: Describe the profile of patients with obesity in internal medicine to determine the role of adiposity and related inflammation on the metabolic risk profile and, identify various "high-risk obesity" phenotypes by means of a cluster analysis. This study aimed to identify different profiles of patients with high-risk obesity based on a cluster analysis. Methods: Cross-sectional, multicenter project that included outpatients attended to in internal medicine. A total of 536 patients were studied. The mean age was 62 years, 51% were women. Patients were recruited from internal medicine departments over two weeks in November and December 2021 and classified into four risk groups according to body mass index (BMI) and waist circumference (WC). High-risk obesity was defined as BMI > 35 Kg/m2 or BMI 30−34.9 Kg/m2 and a high WC (>102 cm for men and >88 cm for women). Hierarchical and partitioning clustering approaches were performed to identify profiles. Results: A total of 462 (86%) subjects were classified into the high-risk obesity group. After excluding 19 patients missing critical data, two profiles emerged: cluster 1 (n = 396) and cluster 2 (n = 47). Compared to cluster 1, cluster 2 had a worse profile, characterized by older age (77 ± 16 vs. 61 ± 21 years, p < 0.01), a Charlson Comorbidity Index > 3 (53% vs. 5%, p < 0.001), depression (36% vs. 19%, p = 0.008), severe disability (64% vs. 3%, p < 0.001), and a sarcopenia score ≥ 4 (79% vs. 16%, p < 0.01). In addition, cluster 2 had greater inflammation than cluster 1 (hsCRP: 5.8 ± 4.1 vs. 2.1 ± 4.5 mg/dL, p = 0.008). Conclusions: Two profiles of subjects with high-risk obesity were identified. Based on that, older subjects with obesity require measures that target sarcopenia, disability, psychological health, and significant comorbidities to prevent further health deterioration. Longitudinal studies should be performed to identify potential risk factors of subjects who progress from cluster 1 to cluster 2.

WHO Ordinal Scale and Inflammation Risk Categories in COVID-19. Comparative Study of the Severity Scales.

BACKGROUND: The WHO ordinal severity scale has been used to predict mortality and guide trials in COVID-19. However, it has its limitations. OBJECTIVE: The present study aims to compare three classificatory and predictive models: the WHO ordinal severity scale, the model based on inflammation grades, and the hybrid model. DESIGN: Retrospective cohort study with patient data collected and followed up from March 1, 2020, to May 1, 2021, from the nationwide SEMI-COVID-19 Registry. The primary study outcome was in-hospital mortality. As this was a hospital-based study, the patients included corresponded to categories 3 to 7 of the WHO ordinal scale. Categories 6 and 7 were grouped in the same category. KEY RESULTS: A total of 17,225 patients were included in the study. Patients classified as high risk in each of the WHO categories according to the degree of inflammation were as follows: 63.8% vs. 79.9% vs. 90.2% vs. 95.1% (p<0.001). In-hospital mortality for WHO ordinal scale categories 3 to 6/7 was as follows: 0.8% vs. 24.3% vs. 45.3% vs. 34% (p<0.001). In-hospital mortality for the combined categories of ordinal scale 3a to 5b was as follows: 0.4% vs. 1.1% vs. 11.2% vs. 27.5% vs. 35.5% vs. 41.1% (p<0.001). The predictive regression model for in-hospital mortality with our proposed combined ordinal scale reached an AUC=0.871, superior to the two models separately. CONCLUSIONS: The present study proposes a new severity grading scale for COVID-19 hospitalized patients. In our opinion, it is the most informative, representative, and predictive scale in COVID-19 patients to date.

Understanding Carbohydrate Metabolism and Insulin Resistance in Acute Intermittent Porphyria.

Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks associated with high production, accumulation and urinary excretion of heme precursors, δ-aminolevulinic acid (ALA) and porphobilinogen (PBG). The estimated clinical penetrance for AIP is extremely low (<1%), therefore it is likely that other factors may play an important role in the predisposition to developing attacks. Fasting is a known triggering factor. Given the increased prevalence of insulin resistance in patients and the large urinary loss of succinyl-CoA to produce ALA and PBG, we explore the impact of reduced availability of energy metabolites in the severity of AIP pathophysiology. Classic studies found clinical improvement in patients affected by AIP associated with the administration of glucose and concomitant insulin secretion, or after hyperinsulinemia associated with diabetes. Molecular studies have confirmed that glucose and insulin administration induces a repressive effect on hepatic ALA Synthase, the first and regulatory step of the heme pathway. More recently, the insulin-mimicking α-lipoic acid has been shown to improve glucose metabolism and mitochondrial dysfunction in a hepatocyte cell line transfected with interfering RNA targeting PBGD. In AIP mice, preventive treatment with an experimental fusion protein of insulin and apolipoprotein A-I improved the disease by promoting fat mobilization in adipose tissue, increasing the metabolite bioavailability for the TCA cycle and inducing mitochondrial biogenesis in the liver. In this review, we analyze the possible mechanisms underlying abnormal hepatocellular carbohydrate homeostasis in AIP.

The Use of Corticosteroids or Tocilizumab in COVID-19 Based on Inflammatory Markers.

BACKGROUND: The inflammatory cascade is the main cause of death in COVID-19 patients. Corticosteroids (CS) and tocilizumab (TCZ) are available to treat this escalation but which patients to administer it remains undefined. OBJECTIVE: We aimed to evaluate the efficacy of immunosuppressive/anti-inflammatory therapy in COVID-19, based on the degree of inflammation. DESIGN: A retrospective cohort study with data on patients collected and followed up from March 1st, 2020, to May 1st, 2021, from the nationwide Spanish SEMI-COVID-19 Registry. Patients under treatment with CS vs. those under CS plus TCZ were compared. Effectiveness was explored in 3 risk categories (low, intermediate, high) based on lymphocyte count, C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, and D-dimer values. PATIENTS: A total of 21,962 patients were included in the Registry by May 2021. Of these, 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ). MAIN MEASURES: The primary outcome of the study was in-hospital mortality. Secondary outcomes were the composite variable of in-hospital mortality, requirement for high-flow nasal cannula (HFNC), non-invasive mechanical ventilation (NIMV), invasive mechanical ventilation (IMV), or intensive care unit (ICU) admission. KEY RESULTS: A total of 5940 met the inclusion criteria for the present study (5332 were treated with CS and 608 with CS plus TCZ). No significant differences were observed in either the low/intermediate-risk category (1.5% vs. 7.4%, p=0.175) or the high-risk category (23.1% vs. 20%, p=0.223) after propensity score matching. A statistically significant lower mortality was observed in the very high-risk category (31.9% vs. 23.9%, p=0.049). CONCLUSIONS: The prescription of CS alone or in combination with TCZ should be based on the degrees of inflammation and reserve the CS plus TCZ combination for patients at high and especially very high risk.

Effect of newer antihyperglycemic drugs on liver steatosis indices in patients with diabetes and obesity.

AIM: To assess the efficacy of sodium-glucose cotransporter-2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptors agonist (GLP-1RA) therapy on liver steatosis measured by fatty liver index (FLI) and hepatic steatosis index (HSI) at 26 weeks in outpatients with diabetes and obesity. METHODS: Observational, prospective, multicenter study. Patients with steatosis determined by FLI (values <30 rule out and >60 indicate steatosis) and HIS (values <30 rule out and >36 indicate steatosis) who received combination therapy were included. Patients were stratified into three groups according to the sequential order of treatment. We used robust statistical methods. RESULTS: In our final report we included 174 patients (58.6% males), mean age 61.9 (10) years. Baseline body mass index, waist circumference and weight were 36.5 (6.8) kg/m2, 117.5 (15.1) cm and 99.4 (20.5) kg, respectively. One hundred percent of patients had altered biomarkers of fatty liver scores (FLI 96 [13] and HSI 49.2 [8.5]). At 26 weeks, significant reductions in FLI (-4.5 [95% CI 3.5-5.9] p < .001) and HSI (-2.4 [95% CI 1.6-3.2] p < .001) were found in the total sample and pre-specified treatment and FLI cut-off point subgroups. CONCLUSION: Our results show a beneficial effect of the combination of GLP-1RAs plus SGLT2is on liver steatosis that goes beyond glucose control, and it is related mainly to weight loss, a decline in biomarkers and reductions in abdominal circumference. For many patients, early detection is essential to improving outcomes in NAFLD and could allow us to select the most efficient treatment options.

Prior Treatment with Statins is Associated with Improved Outcomes of Patients with COVID-19: Data from the SEMI-COVID-19 Registry.

BACKGROUND: The impact of statins on COVID-19 outcomes is important given the high prevalence of their use among individuals at risk for severe COVID-19. Our aim is to assess whether patients receiving chronic statin treatment who are hospitalized with COVID-19 have reduced in-hospital mortality if statin therapy is maintained during hospitalization. METHODS: This work is a cross-sectional, observational, retrospective multicenter study that analyzed 2921 patients who required hospital admission at 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics and COVID-19 disease outcomes between patients receiving chronic statin therapy who maintained this therapy during hospitalization versus those who did not. Propensity score matching was used to match each statin user whose therapy was maintained during hospitalization to a statin user whose therapy was withdrawn during hospitalization. RESULTS: After propensity score matching, continuation of statin therapy was associated with lower all-cause mortality (OR 0.67, 0.54-0.83, p < 0.001); lower incidence of acute kidney injury (AKI) (OR 0.76,0.6-0.97, p = 0.025), acute respiratory distress syndrome (ARDS) (OR 0.78, 0.69- 0.89, p < 0.001), and sepsis (4.82% vs 9.85%, p = 0.008); and less need for invasive mechanical ventilation (IMV) (5.35% vs 8.57, p < 0.001) compared to patients whose statin therapy was withdrawn during hospitalization. CONCLUSIONS: Patients previously treated with statins who are hospitalized for COVID-19 and maintain statin therapy during hospitalization have a lower mortality rate than those in whom therapy is withdrawn. In addition, statin therapy was associated with a decreased probability that patients with COVID-19 will develop AKI, ARDS, or sepsis and decreases the need for IMV.

Evaluation of FilmArray ME panel for the rapid diagnosis of meningitis-encephalitis in emergency departments.

To assess the impact of a rapid diagnostic system based on nucleic acid amplification techniques (FilmArray ME) on the diagnosis and treatment of patients with meningitis or encephalitis admitted to our emergency department. Between November 2016, and June 2019 we studied 79 samples of cerebrospinal fluid from patients admitted to our emergency department with suspected diagnoses of meningitis or encephalitis. FilmArray ME panel was used routinely in addition to conventional laboratory methods for the identification of microorganisms in cerebrospinal fluid samples (CSF). A total of 46 (58%) patients had clinical and CSF results suggestive of meningitis or encephalitis, and 24 (30%) had a confirmed microbiological diagnosis. Patients' mean age was 41 years (range 2 months to 90 years) and 56% were male. Four patients had been partially treated with antibiotics. FilmArray ME identified 23 cases (1 fungal, 11 bacterial, and 11 viral). Gram staining showed microorganisms in 5 cases (1 fungal, 4 bacterial), and conventional microbiology cultures identified 8 cases (1 fungal and 7 bacterial). The time difference (95% confidence interval) between FilmArray ME and cerebrospinal fluid culture results was 3.2 days (95% CI 2.7-3.7; P < 0.001). FilmArray ME results induced modifications in antimicrobial treatment in 27 (59%) patients. The FilmArray ME panel provided a fast and reliable result in a large proportion of patients, even in those patients with culture-negative bacterial meningitis. Use of FilmArray ME can contribute to antimicrobial stewardship.

The Association Between Elevated Foot Skin Temperature and the Incidence of Diabetic Foot Ulcers: A Meta-Analysis.

Prior to the appearance of any foot ulcer, there is an increase in the local temperature due to the presence of an underlying inflammatory process. The use of thermometry to identify inflammation could make patients increase preventive measures until the inflammation disappears. We carried out a meta-analysis to determine the effectiveness of the daily measurement of the foot temperature in 6 points to prevent the occurrence of foot ulcers in patients with diabetes. Patients with temperature differences >4°F (2.2°C) between left and right corresponding sites should reduce activity and increase preventive measures until temperature is normalized. We searched the literature in MEDLINE, EMBASE, Cochrane Library, Web of Knowledge, and clinicaltrials.gov. We have only included randomized clinical trials where individuals were assigned to receive enhanced care (temperature measurement and standard care) versus standard care (education, self-care practices, and periodic clinical visits). We found 4 trials comprising 462 patients from the United States and Norway that met our inclusion criteria. The duration of follow-up varied from 4.5 to 15 months. Overall, 18 (7.9%) subjects in the enhanced foot care group and 53 (22.6%) in the standard foot care group developed foot ulcers (pooled risk ratio = 0.37; 95% confidence interval = 0.21-0.66; P = .0008; percentage of heterogeneity [I2], 25%; P = .26). The number needed to treat was 7 (95% confidence interval = 5-11). The results were robust after analysis by subgroups according to the potential risk of bias in the studies and the duration of follow-up.

Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study.

BACKGROUND: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. METHODS: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. RESULTS: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. CONCLUSIONS: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.

Efficacy and safety of insulin glargine 300 U/mL (Gla-300) during hospitalization and therapy intensification at discharge in patients with insufficiently controlled type 2 diabetes: results of the phase IV COBALTA trial.

INTRODUCTION: This study assessed the efficacy and safety of insulin glargine 300 U/mL (Gla-300) during hospitalization and therapy intensification at discharge in insufficiently controlled people with type 2 diabetes. RESEARCH DESIGN AND METHODS: COBALTA (for its acronym in Spanish, COntrol Basal durante la hospitalizacion y al ALTA) was a multicenter, open-label, single-arm, phase IV trial including 112 evaluable inpatients with type 2 diabetes insufficiently controlled (glycosylated hemoglobin (HbA1c) 8%-10%) with basal insulin and/or non-insulin antidiabetic drugs. Patients were treated with a basal-bolus-correction insulin regimen with Gla-300 during the hospitalization and with Gla-300 and/or non-insulin antidiabetics for 6 months after discharge. The primary endpoint was the HbA1c change from baseline to month 6 postdischarge. RESULTS: HbA1c levels decreased from 8.8%±0.6% at baseline to 7.2%±1.1% at month 6 postdischarge (p<0.001, mean change 1.6%±1.1%). All 7-point blood glucose levels decreased from baseline to 24 hours predischarge (p≤0.001, mean changes from 25.1±66.6 to 63.0±85.4 mg/dL). Fasting plasma glucose also decreased from baseline to 24 hours predischarge (p<0.001), month 3 (p<0.001) and month 6 (p<0.001) postdischarge (mean changes 51.5±90.9, 68.2±96.0 and 77.6±86.4 mg/dL, respectively). Satisfaction was high and hyperglycemia/hypoglycemia perception was low according to the Diabetes Treatment Satisfaction Questionnaire at month 6 postdischarge. The incidence of confirmed (glucose<70 mg/dL)/severe hypoglycemia was 25.0% during hospitalization and 59.1% 6 months after discharge. No safety concerns were reported. CONCLUSIONS: Inpatient and intensification therapy at discharge with Gla-300 improved significantly glycemic control of patients with type 2 diabetes insufficiently controlled with other basal insulin and/or non-insulin antidiabetic medication, with high treatment satisfaction. Gla-300 could therefore be a treatment choice for hospital and postdischarge diabetes management.

Efficacy and safety of bemiparin compared with enoxaparin: Meta-analysis of randomized controlled trials.

BACKGROUND: Potential advantages of bemiparin compared to enoxaparin are a longer half-life, once-a-day dosage, and possibly a better safety profile due to the more selective antagonistic action toward Xa coagulation factor. We evaluated the efficacy and safety of bemiparin compared with enoxaparin as prophylaxis or treatment of venous thromboembolic disease. MATERIALS AND METHODS: We searched PubMed, Embase, Cochrane Library, Clinical Trials.gov, Google academics, and Conference Abstracts (2014 - 2019) of the American Society of Hematology and the Spanish Society of Hematology and Hemotherapy. Randomized trials that included bemiparin and enoxaparin were included as treatment arms. The outcomes evaluated were the incidence of venous thromboembolic disease and the proportion of adverse events in each group. Two independent researchers selected, evaluated, and extracted the data in duplicate. Four studies with a total of 5,473 patients were included. RESULTS: Most patients were included in prevention studies (N = 5,161). Bemiparin proved the non-inferiority in terms of efficacy with respect to enoxaparin (relative risk: 0.76; 95% confidence interval (95% CI): 0.56 - 1.01; p = 0.06) (heterogeneity I2 = 34%). We recorded 222 adverse events in 2,742 patients treated with bemiparin and 288 adverse events in 2,731 patients treated with enoxaparin (8.1 vs. 10.5 adverse events per 100 patients, respectively; p = 0.003). However, the meta-analysis for safety showed a significant heterogeneity making not possible to pool the result across the trials. CONCLUSION: Bemiparin proved a non-inferior efficacy compared to enoxaparin with a significant reduction in adverse events per 100 patients treated.

Early biomarkers of diabetic kidney disease. A focus on albuminuria and a new combination of antidiabetic agents.

AIMS: We aimed to determine the efficacy and safety of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists to prevent worsening urinary albumin-to-creatinine ratio as an early biomarker of diabetes kidney disease. METHODS: A total of 178 patients with type 2 diabetes and obesity received combination treatment with SGLT2i added to GLP1ra (n = 76), GLP1ra added to SGLT2i (n = 50) or GLP1ra plus SGLT2i from start (n = 52), according to investigators´ best clinical judgement. Major outcomes assessed at 26 weeks were changes in urine albumintocreatinine-ratio (UACR), estimated glomerular filtration rate (eGFR), glycated haemoglobin, body weight and systolic blood pressure. RESULTS: All patients (58.6% men, mean age 61.9 ± 10.0 years) completed the study. Baseline HbA1c, weight and eGFR levels were 8.2 ± 0.9%, 109.9 ± 19 kg and 83.3 ± 19.6 mL/min/m2 , respectively. At 26 weeks, we found significant reductions in HbA1c (1.16%), weight (5.17 kg) and systolic blood pressure (8.13 mmHg). The reduction in UACR was 15.14 mg/g (95% CI 8.50-22.4) (-24.6 ± 64.7%), which was greatest in the group of patients with SGLT2i added on to GLP1ra therapy (116.7 mg/g; 95% CI: 54-296.5 mg/g; P < .001. Patients with urinary albumin-to-creatinine ratio ≥30 mg/g, showed a higher declines (63.18 mg/g [95% CI 44.5-104.99]) (-56 ± 65.9%). The greatest reduction in urinary albumin-to-creatinine ratio was obtained when SGLT2i was added to GLP1ra (116.7 mg/g). The eGFR did not significantly change along the study period. CONCLUSION: Our results show the beneficial effect of GLP1ra and SGLT2i combination therapy on early biomarkers of diabetes kidney disease such as albuminuria and in other significant outcomes for diabetes control.

Association between an elevated inter-arm systolic blood pressure difference, the ankle-brachial index, and mortality in patients with diabetes mellitus / Asociación entre una diferencia elevada de presión arterial sistólica entre brazos, el índice tobillo-brazo y la mortalidad en pacientes con diabetes mellitus

OBJECTIVES: To estimate the prevalence of an inter-arm blood pressure difference greater than 10mmHg in patients with type 2 diabetes, and the association of this measurement with the presence of a low ankle-brachial index and mortality at 5-year follow-up. METHOD: A validated blood pressure measurement protocol was used. The blood pressure was calculated for each arm to obtain mean systolic differences. Peripheral arterial disease was confirmed by an ankle-arm index less than 0.9. The medical history of the patient was reviewed in the computerized clinical notes after 5 years of follow-up. RESULTS: The study included 139 patients with a mean age of 70.1 years (49% male), and a mean duration of diabetes mellitus of 10.8 years. A total of 50 (36%) patients had an inter-arm systolic blood pressure difference greater than 10mmHg. Patients with an inter-arm systolic blood pressure greater than 10 mmHg had lower ankle-arm index (0.91 ± 0.30 vs. 1.04 ± 0.28, P = 0.005), and higher mortality rates from all causes (48.0% vs. 28.9%; hazard ratio 1.64; 95% confidence interval: 1.06-2.53; P = 0.03), compared with those with lower inter-arm systolic blood pressure difference. CONCLUSION: A high proportion of patients with type 2 diabetes have an elevated systolic blood pressure difference between arms. A significant relationship was found between elevated inter-arm systolic blood pressure difference, lower ankle-brachial index and greater all-cause mortality

OBJETIVOS: Estimar la prevalencia de una diferencia de presión arterial entre brazos superior a 10mmHg en pacientes con diabetes tipo 2, y su asociación con el índice tobillo-brazo y la mortalidad a los 5 años de seguimiento. MÉTODO: Se utilizó un protocolo validado de medición de presión arterial. La presión sanguínea se calculó para cada brazo para obtener diferencias sistólicas medias. La enfermedad arterial periférica fue confirmada por un índice tobillo-brazo inferior a 0,9. El estado vital del paciente se revisó en la historia clínica electrónica a los 5 años de seguimiento. RESULTADOS: Estudiamos a 139 pacientes con una edad media de 70,1 años (49% hombres) y una duración media de diabetes mellitus de 10,8 años. Un total de 50 (36%) pacientes tenía una diferencia de presión arterial sistólica entre brazos mayor de 10 mmHg. Los pacientes con diferencia elevada de presión arterial sistólica entre los brazos mostraron un menor índice tobillo-brazo (0,91 ± 0,30 vs. 1,04 ± 0,28; P = 0,005), y una mayor tasa de mortalidad por todas las causas (48,0% vs. 28,9%; cociente de riesgo 1,64; intervalo de confianza al 95%: 1,06-2,53; P = 0,03), respecto a los pacientes con menores diferencias de presión sistólica entre brazos. CONCLUSIÓN: Encontramos una alta proporción de pacientes con diabetes tipo 2 que tenían una diferencia elevada de presión arterial sistólica entre los brazos. Existe una asociación significativa entre la diferencia elevada de la presión arterial sistólica entre brazos, el índice tobillo-brazo y mortalidad

Association between an elevated inter-arm systolic blood pressure difference, the ankle-brachial index, and mortality in patients with diabetes mellitus.

OBJECTIVES: To estimate the prevalence of an inter-arm blood pressure difference greater than 10mmHg in patients with type 2 diabetes, and the association of this measurement with the presence of a low ankle-brachial index and mortality at 5-year follow-up. METHOD: A validated blood pressure measurement protocol was used. The blood pressure was calculated for each arm to obtain mean systolic differences. Peripheral arterial disease was confirmed by an ankle-arm index less than 0.9. The medical history of the patient was reviewed in the computerized clinical notes after 5 years of follow-up. RESULTS: The study included 139 patients with a mean age of 70.1 years (49% male), and a mean duration of diabetes mellitus of 10.8 years. A total of 50 (36%) patients had an inter-arm systolic blood pressure difference greater than 10mmHg. Patients with an inter-arm systolic blood pressure greater than 10mmHg had lower ankle-arm index (0.91±0.30 vs. 1.04±0.28, P=0.005), and higher mortality rates from all causes (48.0% vs. 28.9%; hazard ratio 1.64; 95% confidence interval: 1.06-2.53; P=0.03), compared with those with lower inter-arm systolic blood pressure difference. CONCLUSION: A high proportion of patients with type 2 diabetes have an elevated systolic blood pressure difference between arms. A significant relationship was found between elevated inter-arm systolic blood pressure difference, lower ankle-brachial index and greater all-cause mortality.