Relationship between renal capacity to reabsorb glucose and renal status in patients with diabetes

AimsInterindividual variability in capacity to reabsorb glucose at the proximal renal tubule could contribute to risk of diabetic kidney disease. Our present study investigated, in patients with diabetes, the association between fractional reabsorption of glucose (FR_GLU) and degree of renal disease as assessed by urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR).MethodsFR_GLU [1-(glucose clearance/creatinine clearance)] was assessed in 637 diabetes patients attending our tertiary referral centre, looking for correlations between FR_GLU and UAE (normo-, micro-, macro-albuminuria) and Kidney Disease: Improving Global Outcomes (KDIGO) eGFR categories: >90 (G1); 90–60 (G2); 59–30 (G3); and < 30–16 (G4) mL/min/1.73 m². Patients were stratified by admission fasting plasma glucose (FPG) into three groups: low (<6 mmol/L); intermediate (6–11 mmol/L); and high (>11 mmol/L).ResultsMedian (interquartile range, IQR) FR_GLU levels were blood glucose-dependent: 99.90% (0.05) for low (n = 106); 99.90% (0.41) for intermediate (n = 288); and 96.36% (12.57) for high (n = 243) blood glucose categories (P < 0.0001). Also, FR_GLU increased with renal disease severity in patients in the high FPG group: normoalbuminuria, 93.50% (17.74) (n = 135); microalbuminuria, 96.56% (5.94) (n = 77); macroalbuminuria, 99.12% (5.44) (n = 31; P < 0.001); eGFR G1, 94.13% (16.24) (n = 111); G2, 96.35% (11.94) (n = 72); G3 98.88% (7.59) (n = 46); and G4, 99.11% (2.20) (n = 14; P < 0.01). On multiple regression analyses, FR_GLU remained significantly and independently associated with UAE and eGFR in patients in the high blood glucose group.ConclusionHigh glucose reabsorption capacity in renal proximal tubules is associated with high UAE and low eGFR in patients with diabetes and blood glucose levels > 11 mmol/L.     

Association between specific plasma ceramides and high-sensitivity C-reactive protein levels in postmenopausal women with type 2 diabetes

AimEmerging evidence suggests that specific plasma ceramides are involved in the pathophysiology of cardiovascular disease (CVD) and other inflammation-associated diseases. However, scarce information is currently available on the association between distinct plasma ceramides (that have been associated with increased cardiovascular morbidity and mortality) and plasma high-sensitivity C-reactive protein (hs-CRP) concentrations in patients with type 2 diabetes mellitus (T2DM), a group of individuals at high risk of developing CVD and other chronic inflammation-related conditions.MethodsWe measured six previously identified high-risk plasma ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), Cer(d18:1/24:1)] in 92 postmenopausal women with T2DM attending the diabetes outpatient service over a 3-month period. Plasma ceramide levels were measured using targeted liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay.ResultsPlasma hs-CRP levels were positively associated with all measured ceramides in univariable linear regression analyses. However, only plasma Cer(d18:1/16:0) (standard β coefficient: 0.27, P = 0.015), Cer(d18:1/22:0) (standard β coefficient: 0.25, P = 0.032) and Cer(d18:1/24:1) (standard β coefficient: 0.30, P = 0.007) remained significantly associated with increased plasma hs-CRP levels after adjusting for age, adiposity measures, diabetes duration, HbA_1c, insulin resistance, smoking, hypertension, plasma LDL cholesterol, estimated glomerular filtration rate, preexisting ischaemic heart disease and use of lipid-lowering, antihypertensive, antiplatelet or hypoglycaemic drugs.ConclusionIn postmenopausal women with T2DM, elevated levels of specific plasma ceramides are associated with higher plasma hs-CRP levels independent of established cardiovascular risk factors, diabetes-related variables and other potential confounding factors.     

Prolongation of the heart rate-corrected QT interval is associated with cardiovascular diseases: Systematic review and meta-analysis

BackgroundConflicting findings have described the association between prolonged heart rate-corrected QT interval (QTc) and cardiovascular disease.AimsTo identify articles investigating the association between QTc and cardiovascular disease morbidity and mortality, and to summarize the available evidence for the general and type 2 diabetes populations.MethodsA systematic search was performed in PubMed and Embase in May 2022 to identify studies that investigated the association between QTc prolongation and cardiovascular disease in both the general and type 2 diabetes populations. Screening, full-text assessment, data extraction and risk of bias assessment were performed independently by two reviewers. Effect estimates were pooled across studies using random-effect models.ResultsOf the 59 studies included, 36 qualified for meta-analysis. Meta-analysis of the general population studies showed a significant association for: overall cardiovascular disease (fatal and non-fatal) (hazard ratio [HR] 1.68, 95% confidence interval [CI] 1.33–2.12; I² = 69%); coronary heart disease (fatal and non-fatal) in women (HR 1.27, 95% CI 1.08–1.50; I² = 38%; coronary heart disease (fatal and non-fatal) in men (HR 2.07, 95% CI 1.26–3.39; I² = 78%); stroke (HR 1.59, 95% CI 1.29–1.96; I² = 45%); sudden cardiac death (HR 1.60, 95% CI 1.14–2.25; I² = 68%); and atrial fibrillation (HR 1.55, 95% CI 1.31–1.83; I² = 0.0%). No significant association was found for cardiovascular disease in the type 2 diabetes population.ConclusionQTc prolongation was associated with risk of cardiovascular disease in the general population, but not in the type 2 diabetes population.     

Association between increased plasma ceramides and chronic kidney disease in patients with and without ischemic heart disease

AimPlasma levels of certain ceramides are increased in patients with ischemic heart disease (IHD). Many risk factors for IHD are also risk factors for chronic kidney disease (CKD), but it is currently uncertain whether plasma ceramide levels are increased in patients with CKD.MethodsWe measured six previously identified high-risk plasma ceramide concentrations [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] in 415 middle-aged individuals who attended our clinical Cardiology and Diabetes services over a period of 9 months.ResultsA total of 97 patients had CKD (defined as e-GFR_CKD-EPI < 60 ml/min/1.73 m² and/or urinary albumin-to-creatinine ratio ≥ 30 mg/g), 117 had established IHD and 242 had type 2 diabetes. Patients with CKD had significantly (P = 0.005 or less) higher levels of plasma Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) compared to those without CKD. The presence of CKD remained significantly associated with higher levels of plasma ceramides (standardized beta coefficients ranging from 0.124 to 0.227, P < 0.001) even after adjustment for body mass index, smoking, hypertension, diabetes, prior IHD, plasma LDL-cholesterol, hs-C-reactive protein levels and use of any lipid-lowering medications. Notably, more advanced stages of CKD and abnormal albuminuria were both associated (independently of each other) with increased levels of plasma ceramides. These results were consistent in all subgroups considered, including patients with and without established IHD or those with and without diabetes.ConclusionIncreased levels of plasma ceramides are associated with CKD independently of pre-existing IHD, diabetes and other established cardiovascular risk factors.     

Metabolic and psychological effects of short-term increased consumption of less-processed foods in daily diets: A Pilot Study

AimThis study evaluated whether the consumption of locally produced food without additives might have a positive effect on known risk factors for non-communicable diseases (NCDs) such as hypertension, and levels of fasting glucose and visceral adipose tissue (VAT). Attention was focused on various types of cheese, sausages, fresh pasta, pastries, biscuits and chocolate without additives to make them palatable and durable for transport.MethodsHealthy volunteers were randomized to purchase the foods under study from either local producers not using additives (group 1) or supermarkets (group 2). At baseline and after 6 months, both groups underwent evaluation for weight, blood pressure, VAT, serum sodium, potassium, fasting glucose, insulin, C-peptide and creatinine levels, and also the State-Trait Anxiety Inventory (STAI) and Beck Depression Inventory (BDI-II) by examiners blinded to group allocation. At baseline, the state part of the STAI and Wechsler Adult Intelligence Scale IV were also performed, and body mass index, HOMA index and estimated glomerular filtration rate calculated.ResultsData for 159 subjects (89 in group 1, 70 in group 2) were analyzed. Baseline evaluations did not differ between groups. At 6 months, HOMA scores and fasting glucose levels were lower in group 1 than in group 2 (P < 0.01). Also, in group 1, VAT (P = 0.006), systolic blood pressure (P = 0.001) and BDI-II score (P = 0.0005) were decreased, whereas serum fasting glucose (P = 0.04) and C-peptide (P = 0.03) levels, and diastolic blood pressure (P = 0.02), were increased in group 2.ConclusionConsumption of the locally produced food under study improved some of the major risk factors for NCDs after 6 months.     

Higher liver stiffness scores are associated with early kidney dysfunction in patients with histologically proven non-cirrhotic NAFLD

AimThe association between Liver fibrosis (LF), as assessed by either histology or Liver stiffness measurement (LSM), and the presence of Early kidney dysfunction (EKD) was investigated in this study, as was also the diagnostic performance of LSM for identifying the presence of EKD in patients with Non-alcoholic fatty liver disease (NAFLD).Materials and methodsA total of 214 adults with non-cirrhotic biopsy-proven NAFLD were recruited from two independent medical centres. Their histological stage of LF was quantified using Brunt's criteria. Vibration-controlled Transient elastography (TE), using M-probe (FibroScan®) ultrasound, was performed in 154 patients and defined as significant when LSM was ≥ 8.0 kPa. EKD was defined as the presence of microalbuminuria with an estimated glomerular filtration rate ≥ 60 mL/min/1.73 m². Logistic regression modelling was used to estimate the likelihood of having EKD with NAFLD (LSM–EKD model).ResultsThe prevalence of EKD was higher in patients with vs without LF on histology (22.14% vs 4.82%, respectively; P < 0.001) and, similarly, EKD prevalence was higher in patients with LSM ≥ 8.0 kPa vs LSM < 8.0 kPa (23.81% vs 6.59%, respectively; P < 0.05). The area under the ROC curve of the LSM–EKD model for identifying EKD was 0.80 (95% CI: 0.72–0.89). LF detected by either method was associated with EKD independently of established renal risk factors and potential confounders.ConclusionLF was independently associated with EKD in patients with biopsy-proven NAFLD. Thus, TE-measured LSM, a widely used technique for quantifying LF, can accurately identify those patients with NAFLD who are at risk of having EKD.     

Clustering of patients with inconclusive non-invasive stress testing referred for vasodilator stress cardiovascular magnetic resonance

BackgroundInconclusive non-invasive stress testing is associated with impaired outcome. This population is very heterogeneous, and its characteristics are not well depicted by conventional methods.AimsTo identify patient subgroups by phenotypic unsupervised clustering, integrating clinical and cardiovascular magnetic resonance data to unveil pathophysiological differences between subgroups of patients with inconclusive stress tests.MethodsBetween 2008 and 2020, consecutive patients with a first inconclusive non-invasive stress test referred for stress cardiovascular magnetic resonance were followed for the occurrence of major adverse cardiovascular events (defined as cardiovascular death or myocardial infarction). A cluster analysis was performed on clinical and cardiovascular magnetic resonance variables.ResultsOf 1402 patients (67% male; mean age 70 ± 11 years) who completed the follow-up (median 6.5 years, interquartile range 5.6–7.5 years), 197 experienced major adverse cardiovascular events (14.1%). Three distinct phenogroups were identified based upon unsupervised hierarchical clustering of principal components: phenogroup 1 = history of percutaneous coronary intervention with viable myocardial infarction and preserved left ventricular ejection fraction; phenogroup 2 = atrial fibrillation with preserved left ventricular ejection fraction; and phenogroup 3 = coronary artery bypass graft with non-viable myocardial scar and reduced left ventricular ejection fraction. Using survival analysis, the occurrence of major adverse cardiovascular events (P = 0.007), cardiovascular mortality (P = 0.002) and all-cause mortality (P < 0.001) differed among the three phenogroups. Phenogroup 3 presented the worse prognosis. In each phenogroup, ischaemia was associated with major adverse cardiovascular events (phenogroup 1: hazard ratio 2.79, 95% confidence interval 1.61–4.84; phenogroup 2: hazard ratio 2.59, 95% confidence interval 1.69–3.97; phenogroup 3: hazard ratio 3.16, 95% confidence interval 1.82–5.49; all P < 0.001).ConclusionsCluster analysis of clinical and cardiovascular magnetic resonance variables identified three phenogroups of patients with inconclusive stress testing, with distinct prognostic profiles.     

Diferencias clínicas y genéticas de los pacientes con hipercolesterolemia familiar heterocigota con y sin diabetes mellitus tipo 2

Introduction and objectivesThe lower prevalence of type 2 diabetes mellitus (T2DM) in patients with heterozygous familial hypercholesterolemia (HeFH) could explain why T2DM has not always been identified as an independent predictor of cardiovascular disease (CVD) in different familial hypercholesterolemia cohort studies. The aim of the present study was to evaluate clinical and genetic aspects of HeFH patients with T2DM in the dyslipidemia registry of the Spanish Arteriosclerosis Society.MethodsHeFH patients were classified according to the presence or absence of T2DM. The clinical, biochemical and genetic characteristics of the 2 groups were compared.ResultsOf the 2301 patients with primary hypercholesterolemia included in the registry, 1724 with a probable or definite diagnosis according to the Dutch Lipid Clinic Network score were finally included. HeFH patients with T2DM had a higher rate of CVD and a less favorable lipid profile, with higher total cholesterol (366.9 ± 86.7 mg/dL vs 342.0 ± 74.7 mg/dL; mean difference 24.894; 95%CI, 5.840-43.949) and non–high-density lipoprotein cholesterol (316.9 ± 87.8 mg/dL vs 286.4 ± 75.4 mg/dL; mean difference 30.500; 95%CI, 11.211-49.790) levels. No significant differences were found between the groups concerning the specific type of HeFH-causing mutation (P = .720). After adjustment for major risk factors, logistic regression analysis confirmed a relationship between T2DM and the presence of CVD (OR, 2.01; 95%CI, 1.18-3.43; P = .010).ConclusionsHeFH patients with T2DM have a higher rate of CVD and a less favorable lipid profile, regardless of genetic mutation type. In these patients, T2DM is associated with the presence of CVD.     

The relationship of family history and risk of type 2 diabetes differs by ancestry

AimType 2 diabetes (T2DM) in a first-degree relative is a risk factor for incident diabetes. Americans of African ancestry (AA) have higher rates of T2DM than Americans of European ancestry (EA). Thus, we aimed to determine whether the presence, number and kinship of affected relatives are associated with race-specific T2DM incidence in a prospective study of participants from the Genetic Study of Atherosclerosis Risk (GeneSTAR), who underwent baseline screening including a detailed family history.MethodsNondiabetic healthy siblings (n = 1405) of patients with early-onset coronary artery disease (18–59 years) were enrolled (861 EA and 544 AA) and followed for incident T2DM (mean 14 ± 6 years).ResultsBaseline age was 46.2 ± 7.3 years and 56% were female. T2DM occurred in 12.3% of EA and 19.1% of AA. Among EA, 32.6% had ≥ 1 affected first-degree relatives versus 53.1% in AA, P < 0.0001. In fully adjusted Cox proportional hazard analyses, any family history was related to incident T2DM in EA (HR = 2.53, 95% CI: 1.58–4.06) but not in AA (HR = 1.01, 0.67–1.53). The number of affected relatives conferred incremental risk of T2DM in EA with HR = 1.82 (1.08–3.06), 4.83 (2.15–10.85) and 8.46 (3.09–23.91) for 1, 2, and ≥ 3 affected, respectively. In AA only ≥ 3 affected increased risk (HR = 2.45, 1.44–4.19). Specific kinship patterns were associated with incident T2DM in EA but not in AA.ConclusionsThe presence of any first-degree relative with T2DM does not discriminate risk in AA given the high race-specific prevalence of diabetes. Accounting for the number of affected relatives may more appropriately estimate risk for incident diabetes in both races.     

PNPLA3 polymorphism influences the association between high-normal TSH level and NASH in euthyroid adults with biopsy-proven NAFLD

AimWe aimed to evaluate the association between serum thyroid stimulating hormone (TSH) levels, within the reference range, and the histological severity of nonalcoholic fatty liver disease (NAFLD), and whether this association was modulated by the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism.Materials and methodsWe enrolled 327 euthyroid individuals with biopsy-proven NAFLD, who were subdivided into two groups, i.e., a ‘strict-normal’ TSH group (TSH level 0.4 to 2.5 mIU/L; n = 283) and a ‘high-normal’ TSH group (TSH level 2.5 to 5.3 mIU/L with normal thyroid hormones; n = 44). Logistic regression analyses were performed to assess the association between TSH status and presence of nonalcoholic steatohepatitis (NASH) after stratifying subjects by PNPLA3 genotypes.ResultsCompared to strict-normal TSH group, patients with high-normal TSH levels were younger and had a greater prevalence of NASH and higher histologic NAFLD activity score. After stratifying by PNPLA3 genotypes, the significant association between high-normal TSH levels and presence of NASH was restricted only to carriers of the PNPLA3 G risk allele and remained significant even after adjustment for potential confounding factors (adjusted-odds ratio: 3.279; 95% CI: 1.298–8.284; P = 0.012).ConclusionIn euthyroid individuals with biopsy-proven NAFLD, we found a significant association between high-normal TSH levels and NASH. After stratifying by PNPLA3 rs738409 genotypes, this association was observed only among carriers of the PNPLA3 G risk allele.     

Predictive model of persistent choledocholithiasis in patients with acute biliary pancreatitis

BackgroundCholedocholithiasis causing acute biliary pancreatitis (ABP) may migrate to the duodenum or persist in the common bile duct (CBD). We developed a model for predicting persistent choledocholithiasis (PC) in patients with ABP.MethodsThis retrospective cohort study included 204 patients, age ≥18 years (mean age: 73 years, 65.7% women), admitted for ABP in 2013–2018, with at least a magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasonography (EUS), and/or endoscopic retrograde cholangiopancreatography (ERCP). Epidemiological, analytical, imaging, and endoscopic variables were compared between patients with and without PC. Multivariate logistic regression analyses were performed to develop a predictive model of PC.ResultsPatients underwent MRCP (n = 145, 71.1), MRCP and ERCP (n = 44, 21.56%), EUS and ERCP (n = 1, 0.49%), or ERCP (n = 14, 6.86%). PC was detected in 49 patients (24%). PC was strongly associated with CBD dilation, detected in the emergency ultrasound (p < 0.001; OR = 27; 95% CI: 5.8–185.5), increased blood levels of gamma glutamyl transpeptidase, detected at 72 h (p = 0.008; OR = 3.4; 95% CI: 1.5–8.9); and biliary sludge in the gallbladder (p = 0.008; OR = 0.03; 95% CI: 0.001–0.3).ConclusionsThe predictive model showed a validated area under the curve (AUC) of 0.858 for detecting PC in patients with ABP. A nomogram was developed based on model results.ConclusionsThe predictive model was highly effective in detecting PC in patients with ABP. Therefore, this model could be useful in clinical practice.     

The MEFV gene and its association with familial Mediterranean fever,severe atopy,and recurrent respiratory tract infections

BackgroundFamilial Mediterranean fever (FMF) is the most common auto-inflammatory disease and is characterized by self-limiting episodes of fever and polyserositis. The aim of this study was to determine the atopic clinical findings associated with the MEFV gene.MethodsA retrospective chart review was conducted of pediatric patients who had received a diagnosis of familial Mediterranean fever between August 2015 and November 2018.ResultsA total of 454 patients with familial Mediterranean fever were evaluated. The median age of diagnosis was 60 months (min–max: 6–228) and the percentage of patients who were male was 57.5%. A MEFV gene mutation was determined in 310 (68.3%) children. The most frequent genetic mutation was a R202Q heterozygote mutation, which was found in 95 patients (20.9%). When compared with MEFV-negative patients, elevation of serum amyloid A and fibrinogen levels during an episode of FMF was found to occur more frequently in MEFV-positive patients (p = 0.019 and 0.027, respectively). Male gender, cigarette exposure, and a younger diagnosis age were seen more frequently in patients who had episodes with fever (p = 0.039, 0.022, and 0.001, respectively). Chronic cough with sputum and persistent purulent rhinitis were more frequent in the group which did not experience fever episodes (p = 0.003 and 0.002, respectively).ConclusionsWhile being a periodic fever syndrome, familial Mediterranean fever also presents as a multisystemic disease with heterogeneous clinical symptoms. Severe atopic diseases and recurrent respiratory tract infections are characteristic features of this disease.     

Platelet activation and coronavirus disease 2019 mortality: Insights from coagulopathy,antiplatelet therapy and inflammation

BackgroundCoronavirus disease 2019 (COVID-19) is associated with an inflammatory cytokine burst and a prothrombotic coagulopathy. Platelets may contribute to microthrombosis, and constitute a therapeutic target in COVID-19 therapy.AimTo assess if platelet activation influences mortality in COVID-19.MethodsWe explored two cohorts of patients with COVID-19. Cohort A included 208 ambulatory and hospitalized patients with varying clinical severities and non-COVID patients as controls, in whom plasma concentrations of the soluble platelet activation biomarkers CD40 ligand (sCD40L) and P-selectin (sP-sel) were quantified within the first 48 hours following hospitalization. Cohort B was a multicentre cohort of 2878 patients initially admitted to a medical ward. In both cohorts, the primary outcome was in-hospital mortality.ResultsIn cohort A, median circulating concentrations of sCD40L and sP-sel were only increased in the 89 critical patients compared with non-COVID controls: sP-sel 40,059 (interquartile range 26,876–54,678) pg/mL; sCD40L 1914 (interquartile range 1410–2367) pg/mL (P < 0.001 for both). A strong association existed between sP-sel concentration and in-hospital mortality (Kaplan-Meier log-rank P = 0.004). However, in a Cox model considering biomarkers of immunothrombosis, sP-sel was no longer associated with mortality, in contrast to coagulopathy evaluated with D-dimer concentration (hazard ratio 4.86, 95% confidence interval 1.64–12.50). Moreover, in cohort B, a Cox model adjusted for co-morbidities suggested that prehospitalization antiplatelet agents had no significant impact on in-hospital mortality (hazard ratio 1.05, 95% CI 0.80–1.37; P = 0.73).ConclusionsAlthough we observed an association between excessive biomarkers of platelet activation and in-hospital mortality, our findings rather suggest that coagulopathy is more central in driving disease progression, which may explain why prehospitalization antiplatelet drugs were not a protective factor against mortality in our multicentre cohort.     

Insulin secretion and sensitivity before and after surgical treatment for aldosterone-producing adenoma

AimPrimary aldosteronism, which is usually caused by an aldosterone-producing tumour, affects glucose metabolism. The effects of this condition on insulin secretion and insulin sensitivity have remained unclear, however. To gain insight into the influence of primary aldosteronism on glucose tolerance, various parameters related to insulin secretion or insulin sensitivity in patients with an aldosterone-producing tumour were comprehensively analyzed.MethodsTo assess 14 patients with an aldosterone-producing tumour, hyperglycaemic and hyperinsulinaemic–euglycaemic clamp tests as well as oral glucose tolerance tests (OGTTs) were performed before and after tumour excision. Time between presurgical analysis and surgery was 27–559 (194 ± 132) days, and 14–142 (51 ± 38) days between surgery and postsurgical analysis. Various parameters related to insulin secretion or sensitivity as determined by OGTT as well as hyperglycaemic and hyperinsulinaemic–euglycaemic clamp analyses were evaluated.ResultsSurgical treatment of tumours ameliorated hypokalaemia and reduced plasma aldosterone levels. First and second phases of insulin secretion during the hyperglycaemic clamp, as well as the insulinogenic index and total insulin secretion measured during OGTT, were also improved after surgery. In addition, the insulin sensitivity index determined during the hyperinsulinaemic–euglycaemic clamp was reduced after surgery.ConclusionPrimary aldosteronism impairs insulin secretion.     

The impact of antiviral therapy for HCV on kidney disease: a systematic review and meta-analysis

BackgroundControversy persists about the role of hepatitis C as a risk factor for developing kidney disease in the general population. Some authors have evaluated the effect of antiviral therapy for HCV on the risk of kidney disease.Study Aims and DesignA systematic review of the published medical literature was performed to assess whether antiviral therapy for HCV has an independent impact on kidney survival in the adult general population. A random effects model was used to generate an overall estimate of the risk of kidney disease after anti-HCV therapy across the published studies. Meta-regression and stratified analysis were also carried out.ResultsFifteen studies were eligible (n = 356, 285 patients) and separate meta-analyses were conducted according to the outcome. Pooling studies based on viral responses (n = 7; 34,763 individual patients) demonstrated a relationship between sustained viral response and lower frequency of kidney disease; the overall estimate for adjusted risk of kidney disease was 2.50 (95% CI, 1.41; 4.41) (p = 0.0016) and between-study heterogeneity was found (p-value by Q test = 0.004). Aggregation of studies comparing treated vs untreated cohorts (n = 8, n = 333,312 patients) revealed an association between anti-HCV therapy and lower risk of kidney disease. The overall estimate for adjusted risk of kidney disease across the eight studies was 0.39 (95% CI, 0.25; 0.612) (p = 0.0001). Meta-regression showed that the effectiveness of antiviral therapy in reducing the frequency of kidney disease diminishes as cirrhosis (p = 0.02) and HBV infection (p = 0.0001) increase among HCV-infected individuals.ConclusionsAntiviral therapy for HCV lowers the risk of kidney disease among HCV-infected individuals. Studies to understand the mechanisms underlying this association are ongoing.     

Five-year mortality in patients with diabetic foot ulcer during 2009–2010 was lower than expected

AimMortality rates are decreasing in patients with diabetes. However, as this observation also concerns patients with diabetic foot ulcer (DFU), additional data are needed. For this reason, our study evaluated the 5-year mortality rate in patients with DFU during 2009–2010 and identified risk factors associated with mortality.MethodsConsecutive patients who attended a clinic for new DFU during 2009–2010 were followed until healing and at 1 year. Data on mortality were collected at year 5. Multivariate Cox proportional-hazards model was used to identify mortality risk factors.ResultsA total of 347 patients were included: mean age was 65 ± 12 years, diabetes duration was 16 [10; 27] years; 13% were on dialysis; and 7% had an organ transplant. At 5 years, 49 patients (14%) were considered lost to follow-up. Total mortality rate at 5 years was 35%, and 16% in patients with neuropathy. On multivariate analyses, mortality was positively associated with: age [hazard ratio (HR): 1.05 (1.03–1.07), P < 0.0001]; duration of diabetes [HR: 1.02 (1.001–1.03], P = 0.03]; PEDIS perfusion grade 2 vs. 1 [HR: 2.35 (1.28–4.29), P = 0.006)]; PEDIS perfusion grade 3 vs. 1 [HR: 3.14 (1.58–6.24), P = 0.001); and ulcer duration at year 1 [HR 2.09 (1.35–3.22), P = 0.0009].ConclusionMortality rates were not as high as expected despite the large number of comorbidities, suggesting that progress has been made in the health management of these patients. In particular, patients with neuropathic foot ulcer had a survival rate of 84% at 5 years.     

Impact of left atrial and diastolic ventricular dysfunction on mortality in patients with aortic stenosis

BackgroundDiastolic dysfunction (DD) is common in severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF ≥ 50%).AimTo determine the impact of American Society of Echocardiography/European Association of Cardiovascular Imaging-recommended DD grading and left atrial strain on mortality in a cohort of patients with severe AS and preserved LVEF.MethodsWe studied patients with severe AS (aortic valve area indexed < 0.6 cm²/m² and/or aortic valve area < 1 cm²), LVEF ≥ 50% and no or mild AS-related symptoms. The endpoint was all-cause mortality.ResultsA total of 387 patients (median age 76 years; 53% women) were studied. During a median follow-up of 57 (interquartile range 37; 83) months, 158 patients died. After adjustment for prognostic factors, patients with grade II or III DD had an increased mortality risk versus patients with grade I DD (adjusted hazard ratio (aHR) 1.62, 95% confidence interval (CI) 1.11–2.38; P = 0.013; aHR 4.73, 95% CI 2.49–8.99; P < 0.001; respectively). Adding peak atrial longitudinal strain (PALS) ≤ 14% to a multivariable model including DD grade improved predictive performance, with better global model fit, reclassification and discrimination. Patients with grade III DD or grade II DD + PALS ≤ 14% displayed an increased mortality risk versus patients with grade I DD + PALS > 14% (aHR 4.17, 95% CI 2.46–7.06; P < 0.0001). Those with grade I DD + PALS ≤ 14% or grade II DD + PALS > 14% were at intermediate risk (aHR 1.63, 95% CI 1.07–2.49; P = 0.024).ConclusionsOur results demonstrate the strong relationship between DD and mortality in patients with severe AS and preserved LVEF. Patients with grade III or grade II DD and impaired PALS are at very high risk. These data demonstrate the importance of a comprehensive assessment of diastolic function in patients with severe AS.     

Effect of maternal lifestyle intervention on metabolic health and adiposity of offspring: Findings from the Finnish Gestational Diabetes Prevention Study (RADIEL)

AimTo assess in women at high risk of gestational diabetes mellitus (GDM) the effect of a lifestyle intervention on the metabolic health of their offspring around 5 years after delivery.MethodsFor the original Finnish gestational diabetes prevention study (RADIEL), 720 women with a prepregnancy body mass index (BMI) ≥ 30 kg/m² and/or previous GDM were enrolled before or during early pregnancy and allocated to either an interventional (n = 126) or conventional (n = 133) care group. The present 5-year follow-up substudy assessed the metabolic health outcomes of their offspring. Age- and gender-standardized residuals of metabolic health components (waist circumference, mean arterial pressure, high-density lipoprotein and triglyceride levels, and fasting insulin/glucose ratio) were also combined to determine the accumulation of metabolic effects. Body composition was assessed by electrical bioimpedance.ResultsOffspring of women in the intervention group had a less optimal metabolic profile after the 5-year follow-up compared with offspring in the usual care group (P = 0.014). This difference in metabolic health was primarily related to lipid metabolism, and was more prominent among boys (P = 0.001) than girls (P = 0.74). Neither GDM, gestational weight gain, prepregnancy BMI, offspring age nor timing of randomization (before or during pregnancy) could explain the detected difference, which was also more pronounced among the offspring of GDM pregnancies (P = 0.010). Offspring body composition was similar in both groups (P > 0.05).ConclusionThe lifestyle intervention aimed at GDM prevention was associated with unfavourable metabolic outcomes among offspring at around 5 years of age.     

Disease burden and costs for patients with hip and knee osteoarthritis and chronic moderate-to-severe refractory pain on treatment with strong opioids in Spain

Introduction and objectivesTo determine the disease burden and costs in patients with hip or knee OA and chronic moderate-to-severe refractory pain, receiving strong opioids in Spain.Materials and methodsThis was a 36-month longitudinal secondary analysis of the real-word OPIOIDS study. Patients aged ≥18 years with hip or knee OA and chronic moderate-to-severe refractory pain receiving strong opioids were considered. The disease burden included analgesia assessments (NRS scale), cognitive functioning (MMSE scale), basic activities of daily living (Barthel index), and comorbidities (severity and frequency). Costs due to the use of healthcare resources and productivity loss were estimated.Results2832 patients were analyzed; age was 72.0 years (SD = 14.3), 76.8% were women. Patients had mainly been treated with fentanyl (n = 979; 37.6%), tapentadol (n = 625; 24.0%), oxycodone (n = 572; 22.0%), and buprenorphine (n = 425; 16.3%). Pain intensity decreased by 1 point (13.7%), with a 2.6-point decline in the cognitive scale (14.3%, with a 5.3%-increase in patients with cognitive deficit) over a mean treatment period of 384.6 days (SD: 378.8). Barthel scores decreased significantly yielding to a slightly increase in proportion of patients with severe-to-total dependency; 1.2%–2.9%. In the first year of treatment, average healthcare costs were €2013/patient, whereas the average productivity loss cost was €12,227/working-active patient.Discussion and conclusionsStrong opioids resulted in high healthcare costs with a limited reduction in pain, an increase in cognitive deficit, and a slight increase of patients with severe to total dependency over 36 months of treatment.