Granulicatella adiacens and Abiotrophia defectiva Native Vertebral Osteomyelitis: Three Cases and Literature Review of Clinical Characteristics and Treatment Approach

Granulicatella adiacens and Abiotrophia defectiva are an increasingly recognized cause of osteoarticular infections. We describe two cases of G. adiacens and one case of A. defectiva native vertebral osteomyelitis (NVO) and review all published cases. Nine cases of G. adiacens NVO and two cases of A. defectiva NVO were previously described. Patients were usually middle-aged men, and classical risk factors for NVO were present in half of the cases. Concomitant bacteremia was reported in 78.6% of cases, and concurrent infective endocarditis occurred in 36.4% of this sub-group of patients. Many different antibiotic schemes were recorded, with median treatment duration of 6weeks. In the most recent reports, glycopeptides represented the most frequent empirical therapy, possibly due to the increasing emergence of G. adiacens and A. defectiva penicillin-resistant strains. Stabilization surgery was rarely required (14.3% of cases), and clinical cure was generally achieved. In conclusion, Granulicatella spp. and Abiotrophia spp. NVO is rare but increasingly described. A total antibiotic course of six weeks seems to be appropriate for noncomplicated cases, and clinical outcome is generally favorable

A genome-wide scan for type 1 diabetes susceptibility genes in nuclear families with multiple affected siblings in Finland

<p>Abstract</p> <p>Background</p> <p>A genome-wide search for genes that predispose to type 1 diabetes using linkage analysis was performed using 900 microsatellite markers in 70 nuclear families with affected siblings from Finland, a population expected to be more genetically homogeneous than others, and having the highest incidence of type 1 diabetes in the world and, yet, the highest proportion in Europe of cases (10%) carrying neither of the highest risk <it>HLA </it>haplotypes that include DR3 or DR4 alleles.</p> <p>Results</p> <p>In addition to the evidence of linkage to the <it>HLA </it>region on 6p21 (nominal p = 4.0 × 10^-6), significant evidence of linkage in other chromosome regions was not detected with a single-locus analysis. The two-locus analysis conditional on the <it>HLA </it>gave a maximum lod score (MLS) of 3.1 (nominal p = 2 × 10^-4) on chromosome 9p13 under an additive model; MLS of 2.1 (nominal p = 6.1 × 10^-3) on chromosome 17p12 and MLS of 2.5 (nominal p = 2.9 × 10^-3) on chromosome 18p11 under a general model.</p> <p>Conclusion</p> <p>Our genome scan data confirmed the primary contribution of the <it>HLA </it>genes also in the high-risk Finnish population, and suggest that non-<it>HLA </it>genes also contribute to the familial clustering of type 1 diabetes in Finland.</p

Epidemiology and Outcomes of Bloodstream Infections in HIV-Patients during a 13-Year Period

No data on antibiotic resistance in bloodstream infection (BSI) in people living with HIV (PLWH) exist. The objective of this study was to describe BSI epidemiology in PLWH focusing on multidrug resistant (MDR) organisms. A retrospective, single-center, observational study was conducted including all positive blood isolates in PLWH from 2004 to 2017. Univariable and multivariable GEE models using binomial distribution family were created to evaluate the association between MDR and mortality risk. In total, 263 episodes (299 isolates) from 164 patients were analyzed; 126 (48%) BSI were community-acquired, 137 (52%) hospital-acquired. At diagnosis, 34.7% of the patients had virological failure, median CD4 count was 207/μL. Thirty- and 90-day mortality rates were 24.2% and 32.4%, respectively. Thirty- and 90-day mortality rates for MDR isolates were 33.3% and 46.9%, respectively (p < 0.05). Enterobacteriaceae were the most prevalent microorganisms (29.8%), followed by Coagulase-negative staphylococci (21.4%), and S. aureus (12.7%). In BSI due to MDR organisms, carbapenem-resistant K. pneumoniae and methicillin-resistant S. aureus were associated with mortality after adjustment for age, although this correlation was not confirmed after further adjustment for CD4 < 200/μL. In conclusion, BSI in PLWH is still a major problem in the combination antiretroviral treatment era and it is related to a poor viro-immunological status, posing the question of whether it should be considered as an AIDS-defining event

How well can blood pressure be controlled? Progress report on the Systolic Hypertension in Europe Follow-Up Study (Syst-Eur 2)

BACKGROUND: The randomised, double-blind, placebo-controlled Systolic Hypertension in Europe trial (Syst-Eur 1) proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in elderly patients with isolated systolic hypertension. In an attempt to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine, the Syst-Eur patients remained in open follow-up after the end of Syst-Eur 1. This paper presents the second progress report of this follow-up study (Syst-Eur 2). It describes BP control and adherence to study medications. METHODS: After the end of Syst-Eur 1 all patients, treated either actively or with placebo, were invited either to continue or to start antihypertensive treatment with the same drugs as previously used in the active treatment arm. In order to reach the target BP (sitting SBP <150 mmHg), the first line agent, nitrendipine, could be associated with enalapril and/or hydrochlorothiazide. RESULTS: Of the 3787 eligible patients, 3516 (93%) entered Syst-Eur 2. At the last available visit, 72% of the patients were taking nitrendipine. SBP/DBP at entry in Syst-Eur 2 averaged 160/83 mmHg in the former placebo group and 151/80 mmHg in the former active-treatment group. At the last follow-up visit SBP/DBP in the patients previously randomised to placebo or active treatment had decreased by 16/5 mmHg and 7/5 mmHg, respectively. The target BP was reached by 74% of the patients. CONCLUSION: Substantial reductions in systolic BP may be achieved in older patients with isolated systolic hypertension with a treatment strategy starting with the dihydropyridine calcium-channel blocker, nitrendipine, with the possible addition of enalapril and/or hydrochlorothiazide

Association Testing of Previously Reported Variants in a Large Case-Control Meta-analysis of Diabetic Nephropathy

We formed the GEnetics of Nephropathy–an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of Kidneys in Diabetes U.K. and Republic of Ireland (U.K.-R.O.I.) collection and the Finnish Diabetic Nephropathy Study (FinnDiane), combined with reanalyzed data from the Genetics of Kidneys in Diabetes U.S. Study (U.S. GoKinD). We found little evidence for the association of the EPO promoter polymorphism, rs161740, with the combined phenotype of proliferative retinopathy and end-stage renal disease in U.K.-R.O.I. (odds ratio [OR] 1.14, P = 0.19) or FinnDiane (OR 1.06, P = 0.60). However, a fixed-effects meta-analysis that included the previously reported cohorts retained a genome-wide significant association with that phenotype (OR 1.31, P = 2 × 10−9). An expanded investigation of the ELMO1 locus and genetic regions reported to be associated with DN in the U.S. GoKinD yielded only nominal statistical significance for these loci. Finally, top candidates identified in a recent meta-analysis failed to reach genome-wide significance. In conclusion, we were unable to replicate most of the previously reported genetic associations for DN, and significance for the EPO promoter association was attenuated

Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

New susceptibility loci associated with kidney disease in type 1 diabetes

WOS:000309817900008Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ∼2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2×10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0×10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-β1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1×10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.Peer reviewe

Epidemiology of stroke in the Finnish adult population : the Finmonica stroke Register : Incidence, mortality and case-fatality rates of stroke and their trends from 1983 to 1989

Väitöskirja ; liitteinä tutkijan alkuperäisjulkaisu

Determination of metals in species of commercial interest from marine wetlands, coastal and offshore areas influenced by Po River outflows

The impact of heavy metal pollution on estuaries and coastal environments is a matter of major concern worldwide because of their persistency and tendency to bioaccumulate in the aquatic ecosystems, in addition to their toxicity [1]. These elements can derive from natural sources, influenced by bedrock geology of the drainage catchment and by weathering. However, along the Italian Northern Adriatic coast, anthropogenic pressure, in particular agriculture, industrial and municipal discharges, significantly increased the naturally occurring amounts of metals in the aquatic environment [2]. At the same time, Po delta and neighboring areas are traditionally exploited for fishery and mollusks farming, providing many species commonly used in Italian diet. In this context, the aim of this study is to evaluate the concentration of several metals (Hg, As, Cd, V, Cr, Mn, Fe, Ni, Cu, Zn, Ba, Pb) in five marine species of commercial interest collected in different environments influenced by Po River outflow. Farmed mollusks come from both wetland (Tapes philippinarum) and coastal areas (Chamelea gallina), while native mussels (Mytilus galloprovincialis) and fish species (Solea solea and Squalus acanthias) were caught offshore. All species were sampled twice between 2018 and 2019. Furthermore, the metal content was measured also in surface sediments, to assess the environmental contamination of farming and capture areas. The analytical determination was carried out by different atomic spectroscopy techniques, which were selected based on their analytical figure of merit. In detail, graphite furnace atomic absorption, cold vapor atomic absorption spectrometry (mercury analyzer), inductively coupled plasma atomic emission spectroscopy (ICP-AES) and mass spectrometry (ICP-MS) were employed. Certified Reference Materials (CRMs) were employed for quality control purposes. The results highlighted a correlation between the environmental state of the sites and metals content in the selected samples. The metals distribution in sediments were compared with the lithogenic composition, to attempt to discriminate between natural and anthropic input sources. In addition, the concentrations found in the selected marine species were correlated with those in surface sediments, thus confirming the tendency to bioaccumulate of heavy metals. Finally, contamination levels of hazardous metals in sediments and biota were compared with Environmental Quality Standard (EQS) and threshold levels (TL) for human health