High mitochondrial DNA copy number is a protective factor from vision loss in heteroplasmic leber’s hereditary optic neuropathy (LHON)

PURPOSE. Leber’s hereditary optic neuropathy (LHON) is a mitochondrial disease that typically causes bilateral blindness in young men. It is characterized by as yet undisclosed genetic and environmental factors affecting the incomplete penetrance. METHODS. We identified 27 LHON subjects who possess heteroplasmic primary LHON mutations. Mitochondrial DNA (mtDNA) copy number was evaluated. RESULTS. The presence of centrocecal scotoma, an edematous, hyperemic optic nerve head, and vascular tortuosity, as well as telangiectasia was recognized in affected subjects. We found higher cellular mtDNA content in peripheral blood cells of unaffected heteroplasmic mutation carriers with respect to the affected. CONCLUSIONS. The increase of cellular mtDNA content prevents complete loss of vision despite the presence of a heteroplasmic state of LHON primary mutation, suggesting that it is a key factor responsible for penetrance of LHON

Risk of SARS-CoV-2 infection and disease severity in people at socioeconomic disadvantage in Italy

BACKGROUND: Evidence accumulated in the past months indicating that COVID-19 affects people at socioeconomic (SE) disadvantage more strongly. This is embodied by the COVID-19 syndemic concept, i.e., the biological, economic, and social interactions between non-communicable diseases and COVID-19 increase a person's susceptibility to infection and worse health outcomes. Here, we explored the relationship among the SE position and the risk of Sars-CoV-2 infection and disease severity in Tuscany and Apulia, two Italian regions, during the 1st(Feb-Jun2020) and 2nd(Sep-Dec2020) epidemic waves. METHODS: We included all individuals tested (only for Apulia) and/or resulted positive for SARS-CoV2(for Tuscany and Apulia) and reported to regional surveillance system. We linked surveillance data with the deprivation index (DI)(1-5 scale; DI = 5 highest deprivation) of the area of living. We calculated the relative risk (RR) of acquiring Sars-CoV-2, COVID-19-related hospitalization, and death of deprived individuals compared with people in the highest SEP-we adjusted for gender and age. RESULTS: A total of 159507 (82897 F; 76610 M) individuals with prior or current Sars-CoV-2 infection were included in our study, 71320 from Apulia and 88187 from Tuscany. For people aged over 30, and with a DI > 2, the RR of acquiring the infection increased for individuals with higher DI. The RR of being hospitalized and of death, were significantly higher for people over 30 with DI = 5. In Apulia, test positivity rate was comparable across all population groups during the 1stwave, while it increased among individuals with higher DI during the 2ndwave. CONCLUSIONS: According to our results, SE disadvantage is associated with an increased risk of acquiring Sars-CoV-2, and to suffer from severe outcomes when infected. Based on available data, diagnostic test access was more equitable during 1stepidemic wave. This study calls for targeted health policies and actions to protect those with the greatest SE vulnerability. KEY MESSAGES: Available Italian data, indicate that higher socioeconomic disadvantage is associated with an increased risk of acquiring Sars-CoV-2, and to suffer from severe outcomes when infected. Our study highlights the importance of adopting targeted health policies and action to protect those with the greatest socioeconomic vulnerability and enhance equity

An integrated approach to evaluate PAH exposure

Introduction - An integrated evaluation of PAH exposure should consider different routes of absorption, reliability and specificity of biomarkers of dose, and individual susceptibility. Material and Methods - The present study investigated the exposure to PAHs in coke oven workers (n=100), asphalt pavers (n=98) and ground construction workers (n=47), by means of environmental exposure and biological monitoring. Results \u2013 Personal exposure to total airborne PAHs [from naphtalene to indeno(1,2,3-cd)pyrene] in coke oven workers (median 140 \ub5g/m3), was much higher than in pavers exposed to bitumen fumes (0.6 \ub5g/m3), or in construction workers (0.4 \ub5g/m3),. Urinary 1-hydroxypyrene (1-HOP) in end-shift samples was significantly higher in cokeoven workers (2.2 \ub5g/l) than in asphalt pavers (0.7 \ub5g/l) and in construction workers (0.4 \ub5g/l). An increasing trend in 1-HOP levels, over the workweek and the workshift was registered. A similar trend was observed for urinary 2-hydroxyfluorene (2-FLE) and 3-hydroxyphenanthrene (3-PHE) as well as for some unmetabolised PAH in urine. In smokers with low exposures an important contribution to biomarkers was given by tobacco smoking. PAH-DNA adducts in peripheral blood lymphocytes were not associated with external exposure. Genetic polymorphisms of metabolic and DNA repairing enzymes (CYP1A1, GSTM1, GSTT1, XPD) did not appear to influence the levels of biomarkers. Total dermal contamination of PAHs in pavers, assessed in a subgroup of workers (n=22), ranged from 23 to 623 \ub5g. Significant correlations between dermal phenanthrene or pyrene and 1-HOP (r = 0.41 and 0.55), suggest that dermal exposure significantly contributes to the internal dose of these compounds. Conclusion \u2013 Our results suggest that urinary biomarkers of PAHs, integrating exposure from all sources and routes, are reliable tools for risk assessment in occupational health

Covid-19 vaccination programme effectiveness against SARS-CoV-2 related infections, hospital admissions and deaths in the Apulia region of Italy: a one-year retrospective cohort study

: Studies reporting vaccine effectiveness against COVID-19 outcomes concentrate mainly on estimates of one single type of vaccine and variant, seldom considering waning effects. We aimed to estimate the effectiveness of the overall COVID-19 vaccination programme implemented in the Apulia region of Italy at preventing SARS-CoV-2 infections, COVID-19-related hospital admissions and deaths during alpha and delta variant dominant periods. We conducted a retrospective cohort study using electronic health records of persons 16 years and older resident in the Apulia region, assessing the effectiveness of the combined use of BNT162b2, mRNA-1273, ChAdOx1-S and Ad26.COV2.S vaccines against confirmed COVID-19 infections, hospitalisations and deaths, for fully and partially vaccinated persons as well as by time since vaccination and variants. Cox regression models yielding hazard ratios were used to calculate the overall vaccination programme effectiveness. From 1 January to 1 December 2021, we included 3,530,967 eligible persons in the cohort, of whom 2,770,299 were fully vaccinated and 158,313 were COVID-19 positive at the end of the study period. The effectiveness of the programme over the entire study period for fully vaccinated persons against COVID-19 infection, hospitalisation and death were 87.69% (CI95% 87.73-88.18), 94.08% (93.58-94.54) and 95.95% (CI95% 95.26-96.54), respectively. The effectiveness against COVID-19 infection of fully vaccinated subjects during the alpha and delta period was respectively 88.20% (CI95% 87.60-99.78) and 59.31% (CI95% 57.91-60.67), against hospitalisation 93.89% (CI95% 92.67-94.90) and 88.32% (CI95% 86.50-89.90) and against death 93.83% (CI95% 91.65-95.45) and 85.91 (CI95% 79.98-90.09). The waning effects of the programme regarding COVID-19 infection during the delta period were stronger than for alpha, with 75.85% (CI95% 74.38-77.24) effectiveness after 1-2 months and 8.35% (CI95% 3.45-13.01) after 5-6 months after full vaccination. The effectiveness against hospitalisation and death during the delta period waned rapidly and at 7-8-months after the full vaccination respectively decreased to 27.67% (CI95% 7.48-43.45) and 48.47 (CI95% 53.97-34.82). Our study suggests that the COVID-19 vaccination program in Apulia was strongly protective against COVID-19 infection, hospitalisation, and death due to alpha as well as delta variants, although its effectiveness is reduced over time

Predictor Analysis in Radiofrequency Ablation of Benign Thyroid Nodules: A Single Center Experience

PURPOSE: To confirm the efficacy of ultrasound (US) guided radiofrequency ablation (RFA) in the treatment of benign thyroid nodules, we evaluated as primary outcome the technical efficacy and clinical success in a single center dataset. The secondary outcome was to find a correlation between nodules’ pre-treatment features and volume reduction rate (VRR) ≥75% at 12 months after RFA and during follow-up period. METHODS: This retrospective study included 119 consecutive patients (99 females, 20 males, 51.5 ± 14.4 years) with benign thyroid nodules treated in our hospital between October 2014 and December 2018 with a mean follow-up of 26.8 months (range 3–48). Clinical and US features before and after RFA were evaluated by a US examination at 1, 3, 6, 12 months and annually thereafter up to 48 months. RESULTS: The median pre-treatment volume was 22.4 ml; after RFA we observed a statistically significant volume reduction from the first month (11.7 ml) to the last follow-up (p 22.4 ml (HR 0.54, p 0.036) were found to be independent positive and negative predictors of VRR ≥75% respectively. One-month post RFA VRR ≥50% represented the best positive predictor of technical success. CONCLUSIONS: This study confirmed the efficacy of RFA in the treatment of benign thyroid nodules. In particular we show that by selecting macrocystic nodules smaller than 22.4 ml better long-term response can be achieved, which is predicted by an early shrinkage of the nodule

Hospital admission and mortality rates for non-Covid diseases among residents of the long-term care facilities before and during the pandemic: a cohort study in two Italian regions

Aim: Long-term-care facility residents are a vulnerable population who experienced reduced healthcare access during the pandemic. This study aimed to assess the indirect impact of the COVID-19 pandemic, in terms of hospitalisation and mortality rates, among this population in two Italian Regions, Tuscany and Apulia, during 2020 in comparison with the pre-pandemic period. Subject and methods: We conducted a retrospective cohort study on people residing in long-term-care facilities from 1 January 2018 to 31 December 2020 (baseline period: 1 January 2018-8 March 2020; pandemic period: and 9 March-31 December 2020). Hospitalisation rates were stratified by sex and major disease groups. Standardised weekly rates were estimated with a Poisson regression model. Only for Tuscany, mortality risk at 30 days after hospitalisation was calculated with the Kaplan-Meier estimator. Mortality risk ratios were calculated using Cox proportional regression models. Results: Nineteen thousand two hundred and fifty individuals spent at least 7 days in a long-term-care facility during the study period. The overall mean non-Covid hospital admission rate per 100 000 residents/week was 144.1 and 116.2 during the baseline and pandemic periods, with a decrease to 99.7 and 77.3 during the first (March-May) and second lockdown (November-December). Hospitalisation rates decreased for all major disease groups. Thirty-day mortality risk ratios for non-Covid conditions increased during the pandemic period (1.2, 1.1 to 1.4) compared with baseline. Conclusion: The pandemic resulted in worse non-COVID-related health outcomes for long-term-care facilities' residents. There is a need to prioritise these facilities in national pandemic preparedness plans and to ensure their full integration in national surveillance systems. Supplementary information: The online version contains supplementary material available at 10.1007/s10389-023-01925-1

Incidence, mortality, and survival of hematological malignancies in Northern Italian patients: an update to 2020

BackgroundHematological malignancies (HMs) represent a heterogeneous group of diseases with diverse etiology, pathogenesis, and prognosis. HMs' accurate registration by Cancer Registries (CRs) is hampered by the progressive de-hospitalization of patients and the transition to molecular rather than microscopic diagnosis. Material and methodsA dedicated software capable of automatically identifying suspected HMs cases by combining several databases was adopted by Reggio Emilia Province CR (RE-CR). Besides pathological reports, hospital discharge archives, and mortality records, RE-CR retrieved information from general and biomolecular laboratories. Incidence, mortality, and 5-year relative survival (RS) reported according to age, sex, and 4 HMs' main categories, were noted. ResultsOverall, 7,578 HM cases were diagnosed from 1996 to 2020 by RE-CR. HMs were more common in males and older patients, except for Hodgkin Lymphoma and Follicular Lymphoma (FL). Incidence showed a significant increase for FL (annual percent change (APC)=3.0), Myeloproliferative Neoplasms (MPN) in the first period (APC=6.0) followed by a significant decrease (APC=-7.4), and Myelodysplastic Syndromes (APC=16.4) only in the first period. Over the years, a significant increase was observed in 5-year RS for Hodgkin -, Marginal Zone -, Follicular - and Diffuse Large B-cell-Lymphomas, MPN, and Acute Myeloid Leukemia. The availability of dedicated software made it possible to recover 80% of cases automatically: the remaining 20% required direct consultation of medical records. ConclusionsThe study emphasizes that HM registration needs to collect information from multiple sources. The digitalization of CRs is necessary to increase their efficiency

Genetic heterogeneity in Italian families with IgA nephropathy: suggestive linkage for two novel IgA nephropathy loci.

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, but its etiologic mechanisms are still poorly understood. Different prevalences among ethnic groups and familial aggregation, together with an increased familial risk, suggest important genetic influences on its pathogenesis. A locus for familial IgAN, called "IGAN1," on chromosome 6q22-23 has been described, without the identification of any responsible gene. The partners of the European IgAN Consortium organized a second genomewide scan in 22 new informative Italian multiplex families. A total of 186 subjects (59 affected and 127 unaffected) were genotyped and were included in a two-stage genomewide linkage analysis. The regions 4q26-31 and 17q12-22 exhibited the strongest evidence of linkage by nonparametric analysis (best P=.0025 and .0045, respectively). These localizations were also supported by multipoint parametric analysis, in which peak LOD scores of 1.83 ( alpha =0.50) and 2.56 ( alpha =0.65) were obtained using the affected-only dominant model, and by allowance for the presence of genetic heterogeneity. Our results provide further evidence for genetic heterogeneity among families with IgAN. Evidence of linkage to multiple chromosomal regions is consistent with both an oligo/polygenic and a multiple-susceptibility-gene model for familial IgAN, with small or moderate effects in determining the pathological phenotype. Although we identified new candidate regions, replication studies are required to confirm the genetic contribution to familial IgA

Metastatic melanoma in an esophagus demonstrating Barrett esophagus with high grade dysplasia

BACKGROUND: Metastatic melanoma involving the esophagus is rare; the occurrence of metastatic melanoma in a background of Barrett esophagus is rarer still. We report a case of an 80 year-old male who presented to our institution for workup of Barrett esophagus with high-grade dysplasia and who proved to have metastatic melanoma occurring in the background of Barrett esophagus, the first report of this kind, to our knowledge, in the English literature. CASE PRESENTATION: An 80 year-old Caucasian male was diagnosed at an outside institution with Barrett’s esophagus with high grade dysplasia and presented to our institution for therapy. The patient underwent endoscopic mucosal resection using a band ligation technique of an area of nodularity within the Barrett esophagus. Microscopic examination demonstrated extensive Barrett esophagus with high-grade dysplasia as well as a second tumor which was morphologically different from the surrounding high-grade dysplasia and which was positive for S-100, HMB 45 and Melan-A on immunohistochemistry, consistent with melanoma. Further workup of the patient demonstrated multiple radiologic lesions consistent with metastases. Molecular studies demonstrated that the melanoma was positive for the 1799T>A (V600E) mutation in the BRAF gene. The overall features of the tumor were most consistent with metastatic melanoma occurring in a background of Barrett esophagus with high-grade dysplasia. CONCLUSION: This case demonstrates a unique intersection between a premalignant condition (Barrett esophagus with high grade dysplasia) and a separate malignancy (melanoma). This report also shows the utility of molecular testing to support the hypothesis of primary versus metastatic disease in melanoma