Epidemiology, pathogenesis, clinical presentation and management of TB in patients with HIV and diabetes.

Caused by Mycobacterium tuberculosis, TB is the leading cause of death from an infectious disease. HIV and diabetes are recognised risk factors for progression of TB disease and both have a strong impact on the diagnosis and management of TB, threatening efforts to end TB globally. Here we provide the latest data on the complex interplay between these conditions. TB patients with HIV present systemic immune activation, increased HIV viral load, more severe clinical presentations and reduced success of TB therapy. Similarly, TB patients with diabetes are characterised by an exaggerated adaptive immunity, worsening of the clinical presentations and a higher risk for multidrug resistance and treatment failure. It is important to strengthen resources to prevent these comorbidities from occurring and to implement screening, early diagnosis and appropriate management strategies.

Budget impact analysis of anakinra in the treatment of familial Mediterranean fever in Italy.

INTRODUCTION: Familial Mediterranean Fever (FMF) is a hereditary autoinflammatory disease that significantly reduces occupational productivity and quality-of-life in affected patients. Italy has an estimated FMF prevalence of 1 in 60,000 people. While colchicine is the primary treatment for FMF, biologics are administered to intolerant and non-responder patients. Anakinra and canakinumab are the only biologics approved and reimbursed for FMF in Italy. Both medicines have demonstrated efficacy in FMF patients yet differ in treatment costs. This study aimed to perform a budget impact analysis (BIA) following anakinra's reimbursement for FMF treatment, considering pharmaceutical costs from the Italian National Healthcare Service (NHS) perspective. METHODS: A 'Reference scenario' (all patients treated with canakinumab) was compared to an 'Alternative scenario', with increased anakinra market shares. The target population was estimated based on the Italian population, epidemiological and market research data. Drugs costs were estimated based on Summary of Product Characteristics and net ex-factory prices. Sensitivity analyses were implemented to test results' robustness. RESULTS: The base case analysis showed an overall cumulative expenditure of €30,586,628 for 'Reference scenario' and € 16,465,548 for 'Alternative scenario'. A cumulative savings of €14,121,080 (46.2%) was calculated over 3 years as a result of the reimbursement and increasing uptake of anakinra. The sensitivity analyses, even considering a discount of 50% for canakinumab, confirmed the base case results. CONCLUSIONS: Anakinra's introduction, in FMF treatment, provides a financially sustainable option for Italian patients, with savings increasing according to greater use of anakinra.

Assessment of trace element contamination and effects on Paracentrotus lividus using several approaches: Pollution indices, accumulation factors and biochemical tools.

Among the most common contaminants in marine ecosystems, trace elements are recognized as serious pollutants. In Corsica (NW Mediterranean Sea), near the old asbestos mine at Canari, trace elements from the leaching of mine residues have been discharged into the sea for several decades. The aim of this study was to assess the levels of contamination in this area and the potential effects on Paracentrotus lividus (Lamarck, 1816) using pollution indices, accumulation factors and biochemical tools. For this purpose, the concentration of 24 trace elements was measured in sea urchins (gonads and gut content), macroalgae, seawater column and sediment collected at 12 stations nearby the old asbestos mine and at a reference site. The bioaccumulation of trace elements occurs as follows: macroalgae > gut > gonads. TEPI contribute to highlight contamination gradients which are mainly due to the dominant marine currents allowing the migration of mining waste along the coastline. This hypothesis was supported by TESVI, which identified characteristic trace elements in the southern area of the mine. High hydrogen peroxide content, associated with elevated catalase and glutathione-S-transferase enzyme activities, were also identified at these sites and at the reference site. Trace elements contamination as well as several abiotic factors could explain these results (e.g. microbiological contamination, hydrodynamic events, etc.). The results obtained in this study suggest that oxidative stress induced by contamination does not affect the health of Paracentrotus lividus. This work has provided a useful dataset allowing better use of sea urchins and various tools for assessing trace element contamination in coastal ecosystems.

Post treatment imaging in patients with local advanced cervical carcinoma.

Cervical cancer (CC) is the fourth leading cause of death in women worldwide and despite the introduction of screening programs about 30% of patients presents advanced disease at diagnosis and 30-50% of them relapse in the first 5-years after treatment. According to FIGO staging system 2018, stage IB3-IVA are classified as locally advanced cervical cancer (LACC); its correct therapeutic choice remains still controversial and includes neoadjuvant chemo-radiotherapy, external beam radiotherapy, brachytherapy, hysterectomy or a combination of these modalities. In this review we focus on the most appropriated therapeutic options for LACC and imaging protocols used for its correct follow-up. We explore the imaging findings after radiotherapy and surgery and discuss the role of imaging in evaluating the response rate to treatment, selecting patients for salvage surgery and evaluating recurrence of disease. We also introduce and evaluate the advances of the emerging imaging techniques mainly represented by spectroscopy, PET-MRI, and radiomics which have improved diagnostic accuracy and are approaching to future direction.

Stress response to trace elements mixture of different embryo-larval stages of Paracentrotus lividus.

This study investigated for the first time the oxidative biomarkers responses in all larval stages of sea urchin. The contamination effects were reproduced by using contaminated seawater to concentrations measured in the area adjacent to an old asbestos mine at factors of 5 and 10. The results suggested that the concentrations were not sufficiently high to induce a major oxidative stress. The biometric differences make this method a more sensitive approach for assessing the effects on sea urchin larvae. Measurements of specific activities of antioxidant enzymes at each stage suggested a high capacity of the larvae to respond to oxidative stress. This normal activity of the organism must be considered in future research. This work also highlighted the importance of spawners provenance in ecotoxicological studies. These data are essential to better understand the stress responses of sea urchin larvae and provide baseline information for later environmental assessment research.

Levosimendan for acute right heart failure in COVID-19: another arrow in our quiver?

OBJECTIVE: SARS-CoV-2 infection is associated with a higher risk of acute right heart failure (RHF) due to primary right ventricle (RV) dilation and systemic inflammatory response, which in turn lead to microvascular and cardiomyocytes dysfunction, local hypoxia and multi-organ failure. In this clinical setting, levosimendan could be a viable therapy thanks to its right-heart tropism and its additional pleiotropic properties. CASE REPORT: We present the case of a 72 years-old man with positive nasopharyngeal swab for SARS-CoV-2 infection, mild pulmonary involvement and clinical signs of new-onset RHF. We started a 12-hour levosimendan cycle to improve RV performance and reduce cardiac filling pressures. RESULTS: We obtained a net clinical benefit in terms of acute RHF-related signs and symptoms, progressive renal and liver function improvement and concomitant reduction of high-sensitivity C-Reactive Protein and Interleukin-6 (IL-6) levels. CONCLUSIONS: Acute RHF during SARS-CoV-2 infection could be related to a convergent widespread systemic inflammatory response. Thanks to its anti-inflammatory and anti-remodeling properties, levosimendan might represent a viable therapy in this clinical setting, contributing to the dampening of the inflammatory response.

Effects of trace elements contaminations on the larval development of Paracentrotus lividus using an innovative experimental approach.

Several experiments were performed using larvae of Paracentrotus lividus (Lamarck, 1816) in order to determine the consequences of different chronic contamination with mixtures of (i) fifteen trace elements from concentrations measured in the world ocean seawater, and (ii) seven trace elements from contamination resulting from mining. To predict the impact of increased marine pollution, higher concentrations were also used. These bioassays were conducted using spawners collected from Calvi (reference site, Corsica), and Albo (mining area, Corsica). The effects of trace elements have been studied on the entire larval development. The results show wider arms and delayed development as the number and concentration of trace elements increases. Therefore, the synergy between the different trace elements is of paramount importance with regard to the impact on organisms. Probably due to a hormesis phenomenon, larvae contaminated with seven trace elements at average concentrations developed more quickly. This work also highlighted the importance of the origin of spawners in ecotoxicological studies. To our knowledge, this is the first study to investigate the effects of such a broad combination of trace elements for chronic contamination on the entire larval stage of Paracentrotus lividus.

Compositional and Morphological Characterization of 'Sorrento' and 'Chandler' Walnuts.

In Italy, most of the cultivated walnuts belong to the Sorrento ecotype, and they are considered commercially valuable due to their specific organoleptic characteristics. The aim of this study is to evaluate and compare the morphological and compositional characteristics of walnuts sampled from 'Sorrento' trees cultivated in different locations in Campania and trees of both the 'Chandler' and 'Sorrento' varieties derived from the same location. The results demonstrated that 'Sorrento' and 'Chandler' walnuts have different biometric characteristics and a different fat content, with the highest fat content being found in the 'Sorrento' variety. Regarding the fatty acid (FA) composition, the content of monounsaturated and saturated fatty acids (MUFAs and SFAs) was highest in the 'Sorrento' variety (from 13 to 15% for MUFAs and from 11 to 13% for SFAs), while the polyunsaturated fatty acids (PUFAs) content was highest in the 'Chandler' variety (77%). The total phenolics content (TPC) was highest in the 'Sorrento' variety (from 910 to 1230 mg GAE/100 g), while no difference in γ-tocopherol content was found. Furthermore, the influence of walnut area cultivation was shown for fat content, FA composition and TPC. Therefore, both walnut varieties demonstrated good nutritional properties considering the PUFAs and γ-tocopherol content.

Use of Levosimendan as bridge therapy to surgical correction of post-infarction ventricular septal defect: a case report.

OBJECTIVE: Ventricular septal defect (VSD) is an uncommon but frequently fatal complication following acute myocardial infarction. In medically treated patients, mortality rates exceed 90%, while the surgical repair is associated with better outcomes, even though optimal surgical timing is still under debate. CASE REPORT: We present the case of a 78-years-old man with no previous remarkable cardiological history admitted to our Emergency Department with the diagnosis of anterior ST-elevation myocardial infarction and significant reduction of left ventricular ejection fraction. The emergency coronary angiography showed sub-occlusion of the left anterior descending coronary artery, treated with stent implantation. The post-procedural echocardiography unveiled the presence of an apical VSD with a large left-to-right shunt, significant right ventricular overload and dysfunction. An intra-aortic balloon pump (IABP) was positioned and, after Heart Team evaluation, a delayed surgical approach was planned. As a bridge to the intervention Levosimendan infusion was administered, on top of IABP support, and a significant improvement in bi-ventricular function and pressure profiles was obtained. Cardiac surgery was successfully performed 9 days after the admission without periprocedural complications. CONCLUSIONS: This unique case supports the use of Levosimendan as a valid pharmacological strategy for perioperative management of VSD.

Combined molecular and mathematical analysis of long noncoding RNAs expression in fine needle aspiration biopsies as novel tool for early diagnosis of thyroid cancer.

PURPOSE: In presence of indeterminate lesions by fine needle aspiration (FNA), thyroid cancer cannot always be easily diagnosed by conventional cytology. As a consequence, unnecessary removal of thyroid gland is performed in patients without cancer based on the lack of optimized diagnostic criteria. Aim of this study is identifying a molecular profile based on long noncoding RNAs (lncRNAs) expression capable to discriminate between benign and malignant nodules. METHODS: Patients were subjected to surgery (n = 19) for cytologic suspicious thyroid nodules or to FNA biopsy (n = 135) for thyroid nodules suspicious at ultrasound. Three thyroid-specific genes (TG, TPO, and NIS), six cancer-associated lncRNAs (MALAT1, NEAT1, HOTAIR, H19, PVT1, MEG3), and two housekeeping genes (GAPDH and P0) were analyzed using Droplet Digital PCR (ddPCR). RESULTS: Based on higher co-expression in malignant (n = 11) but not in benign (n = 8) nodules after surgery, MALAT1, PVT1 and HOTAIR were selected as putative cancer biomarkers to analyze 135 FNA samples. Cytological and histopathological data from a subset of FNA patients (n = 34) were used to define a predictive algorithm based on a Naïve Bayes classifier using co-expression of MALAT1, PVT1, HOTAIR, and cytological class. This classifier exhibited a significant separation capability between malignant and benign nodules (P < 0.0001) as well as both rule in and rule out test potential with an accuracy of 94.12% and a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 91.67%. CONCLUSIONS: ddPCR analysis of selected lncRNAs in FNA biopsies appears a suitable molecular tool with the potential of improving diagnostic accuracy.

From angiotensin-converting enzyme 2 disruption to thromboinflammatory microvascular disease: A paradigm drawn from COVID-19.

We concisely review clinical, autopsy, experimental and molecular data of 2019 coronavirus disease (COVID-19). Angiotensin-converting enzyme 2 disruption and thromboinflammatory microangiopathy emerge as distinctive features. Briefly, entry of the virus into microvessels can profoundly disrupt the local renin-angiotensin system, cause endothelial injury, activate the complement cascade and induce powerful thromboinflammatory reactions, involving, in particular, von Willebrand factor, that, if widespread, may lead to microvascular plugging, ischemia and, ultimately, organ failure. We believe the current COVID-19 data consolidate a widely unrecognised paradigm of potentially fatal thromboinflammatory microvascular disease.

Transmission of viral pathogens in a social network of university students: the eX-FLU study.

Previous research on respiratory infection transmission among university students has primarily focused on influenza. In this study, we explore potential transmission events for multiple respiratory pathogens in a social contact network of university students. University students residing in on-campus housing (n = 590) were followed for the development of influenza-like illness for 10-weeks during the 2012-13 influenza season. A contact network was built using weekly self-reported contacts, class schedules, and housing information. We considered a transmission event to have occurred if students were positive for the same pathogen and had a network connection within a 14-day period. Transmitters were individuals who had onset date prior to their infected social contact. Throat and nasal samples were analysed for multiple viruses by RT-PCR. Five viruses were involved in 18 transmission events (influenza A, parainfluenza virus 3, rhinovirus, coronavirus NL63, respiratory syncytial virus). Transmitters had higher numbers of co-infections (67%). Identified transmission events had contacts reported in small classes (33%), dormitory common areas (22%) and dormitory rooms (17%). These results suggest that targeting person-to-person interactions, through measures such as isolation and quarantine, could reduce transmission of respiratory infections on campus.

Race/Ethnic and Educational Disparities in the Association Between Pathogen Burden and a Laboratory-Based Cumulative Deficits Index.

BACKGROUND: Disparities in adult morbidity and mortality may be rooted in patterns of biological dysfunction in early life. We sought to examine the association between pathogen burden and a cumulative deficits index (CDI), conceptualized as a pre-clinical marker of an unhealthy biomarker profile, specifically focusing on patterns across levels of social disadvantage. METHODS: Using the data from the National Health and Nutrition Examination Survey 2003-2004 wave (aged 20-49 years), we examined the association of pathogen burden, composed of seven pathogens, with the CDI. The CDI comprised 28 biomarkers corresponding to available clinical laboratory measures. Models were stratified by race/ethnicity and education level. RESULTS: The CDI ranged from 0.04 to 0.78. Nearly half of Blacks were classified in the high burden pathogen class compared with 8% of Whites. Among both Mexican Americans and other Hispanic groups, the largest proportion of individuals were classified in the common pathogens class. Among educational classes, 19% of those with less than a high school education were classified in the high burden class compared with 7% of those with at least a college education. Blacks in the high burden pathogen class had a CDI 0.05 greater than those in the low burden class (P < 0.05). Whites in the high burden class had a CDI only 0.03 greater than those in the low burden class (P < 0.01). DISCUSSION: Our findings suggest there are significant social disparities in the distribution of pathogen burden across race/ethnic groups, and the effects of pathogen burden may be more significant for socially disadvantaged individuals.

Persistent socioeconomic and racial and ethnic disparities in pathogen burden in the United States, 1999-2014.

The disproportionate burden of prevalent, persistent pathogens among disadvantaged groups may contribute to socioeconomic and racial/ethnic disparities in long-term health. We assessed if the social patterning of pathogen burden changed over 16 years in a U.S.-representative sample. Data came from 17 660 National Health and Nutrition Examination Survey participants. Pathogen burden was quantified by summing the number of positive serologies for cytomegalovirus, herpes simplex virus-1, HSV-2, human papillomavirus and Toxoplasma gondii and dividing by the number of pathogens tested, giving a percent-seropositive for each participant. We examined sex- and age-adjusted mean pathogen burdens from 1999-2014, stratified by race/ethnicity and SES (poverty-to-income ratio (PIR); educational attainment). Those with a PIR < 1.3 had a mean pathogen burden 1.4-1.8 times those with a PIR > 3.5, with no change over time. Educational disparities were even greater and showed some evidence of increasing over time, with the mean pathogen burden among those with less than a high school education approximately twice that of those who completed more than high school. Non-Hispanic Black, Mexican American and other Hispanic participants had a mean pathogen burden 1.3-1.9 times non-Hispanic Whites. We demonstrate that socioeconomic and racial/ethnic disparities in pathogen burden have persisted across 16 years, with little evidence that the gap is closing.

Colectomy for caecal and sigmoid volvulus: a national analysis of outcomes and risk factors for postoperative complications.

AIM: Colonic volvulus is a common entity encountered by colorectal surgeons, but there are few reports of national data regarding postoperative outcomes. The aim of this study was to describe the volvulus population, 30-day outcomes following right- and left-sided colectomy and risk factors for postoperative complications. METHOD: The American College of Surgeons National Surgical Quality Improvement Program Database from 2012 to 2015 was utilized to identify patients with the diagnosis of 'volvulus' who underwent right- or left-sided colectomy. Primary outcomes were overall morbidity and mortality. RESULTS: A total of 2175 patients were identified (661 right colectomy and 1514 left colectomy). Risk factors for complications following right-sided colectomy included: age, male gender, smoker, systemic inflammatory response syndrome, sepsis, septic shock and American Society of Anesthesiologsts class ≥ 4. Risk factors for complications following left-sided colectomy included: age, male gender, systemic inflammatory response syndrome, sepsis and septic shock. CONCLUSION: Several nonmodifiable risk factors were identified for complications following colectomy for volvulus. These risk factors can be used in patient/family counselling and discharge planning.

Ileal pouch revision vs excision: short-term (30-day) outcomes from the National Surgical Quality Improvement Program.

AIM: Ileal pouch-anal anastomosis (IPAA) failure occurs in approximately 5%-10% of patients. We aimed to compare short-term (30-day) postoperative outcomes associated with pouch revision and pouch excision using a large international database. Our null hypothesis was that there is no statistically significant difference in overall postoperative complications between patients selected for pouch revision vs pouch excision. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program Participant User File from 2005 to 2016 we identified patients who underwent either IPAA revision via the combined abdominoperineal approach [Current Procedural Terminology (CPT) 46712] or IPAA excision (CPT 45136). Differences in baseline characteristics and short-term outcomes between groups were assessed with univariate and matched analyses. RESULTS: We identified 593 reoperative IPAA procedures: revision group 78 (13%) and excision group 515 (86%). The groups had similar age and body mass index (kg/m2 ), but the revision group had more women (65.4% vs 51.8%, P = 0.02) and fewer were on chronic steroids (3.9% vs 17.9%, P = 0.0008) relative to the excision group. Revision IPAA patients were more likely to have received a preoperative transfusion (5.1% vs 0.97%, P = 0.02). Revision and excision were associated with similar postoperative length of stay (9.3 vs 8.6 days, 0.44), mortality (nil vs 0.58%, respectively; P = 0.99) and short-term morbidity (34.6% vs 40.2%, respectively; P = 0.88) at 30 days. CONCLUSIONS: Pouch revision and excision have comparable short-term postoperative outcomes, but pouch excision appears to be more commonly utilized. Increased awareness of the indications for pouch revision or referral to specialized centres may improve pouch revision rates.

The association of parental and offspring educational attainment with systolic blood pressure, fasting blood glucose and waist circumference in Latino adults.

OBJECTIVE: The objective of the study is to evaluate the association of intergenerational educational attainment with cardiovascular disease (CVD) risk factors among US Latinos. METHODS: We used cross-sectional data from the Niños Lifestyle and Diabetes Study, an offspring cohort of middle-aged Mexican-Americans whose parents participated in the Sacramento Latino Study on Aging. We collected educational attainment, demographic and health behaviours and measured systolic blood pressure (SBP), fasting glucose and waist circumference. We evaluated the association of parental, offspring and a combined parent-offspring education variable with each CVD risk factor using multivariable regression. RESULTS: Higher parental education was associated only with smaller offspring waist circumference. In contrast, higher offspring education was associated with lower SBP, fasting glucose and smaller waist circumference. Adjustment for parental health behaviours modestly attenuated these offspring associations, whereas adjustment for offspring health behaviours and income attenuated the associations of offspring education with offspring SBP and fasting glucose but not smaller waist circumference, even among offspring with low parental education. CONCLUSIONS: Higher offspring education is associated with lower levels of CVD risk factors in adulthood, despite intergenerational exposure to low parental education.

Investigating pathogen burden in relation to a cumulative deficits index in a representative sample of US adults.

Pathogen burden is a construct developed to assess the cumulative effects of multiple, persistent pathogens on morbidity and mortality. Despite the likely biological wear and tear on multiple body systems caused by persistent infections, few studies have examined the impact of total pathogen burden on such outcomes and specifically on preclinical markers of dysfunction. Using data from two waves of the National Health and Nutrition Examination Survey, we compared three alternative methods for measuring pathogen burden, composed of mainly persistent viral infections, using a cumulative deficits index (CDI) as an outcome: single pathogen associations, a pathogen burden summary score and latent class analyses. We found significant heterogeneity in the distribution of the CDI by age, sex, race/ethnicity and education. There was an association between pathogen burden and the CDI by all three metrics. The latent class classification of pathogen burden showed particularly strong associations with the CDI; these associations remained after controlling for age, sex, body mass index, smoking, race/ethnicity and education. Our results suggest that pathogen burden may influence early clinical indicators of poor health as measured by the CDI. Our results are salient since we were able to detect these associations in a relatively young population. These findings suggest that reducing pathogen burden and the specific pathogens that drive the CDI may provide a target for preventing the early development of age-related physiological changes.

Autoimmune diseases and 8.1 ancestral haplotype: An update.

The aim of the present review is to provide an update of the current research into the pathogenesis of autoimmune diseases associated with 8.1 ancestral haplotype. This is a common Caucasoid haplotype carried by most people who type for HLA-B8, DR3. Numerous genetic studies reported that individuals with certain HLA alleles have a higher risk of specific autoimmune disorders than those without these alleles. However, much remains to be learned about the heritability of autoimmune conditions. Recently, progress and advances in the field of genome-wide-association studies have revolutionized the capacity to perform large, economically feasible, and statistically robust analyses of HLA within 8.1 ancestral haplotype, and understand its contribute to autoimmune events. In this paper, the characteristic features of this haplotype that might give rise to diverse autoimmune phenotypes are reviewed, focusing on the contribution of the HLA-DRB1 gene, the most polymorphic sequence within the HLA II region.

Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability.

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.