Gender differences in comorbidities of patients with COVID-19: An Italian local register-based analysis.

In the current COVID-19 pandemic scenario, it is still necessary to understand if differences exist between genders in terms of patients' characteristics and clinical outcomes. For this reason, we retrospectively analyzed data obtained from a local register-based dataset of all SARS-CoV-2 positive patients diagnosed in the province of Catania (Italy). The main aim of this analysis was to understand any differences between genders in the distribution of previous medical conditions, and to evaluate which of them posed individuals at higher risk of death. With this purpose, we analyzed data from 1424 patients with at least one underlying medical condition, who were tested positive for SARS-CoV-2 infection from February 2020 to December 2021. Overall, males were 59.5% of the total population and significantly younger than females (median ages: 68 years vs. 72 years; p = 0.011). The age distribution of cases by gender confirms that individuals from 70 to 79 years were the most affected in both genders. The comparison of underlying comorbidities by gender shows significant differences for diabetes (p < 0.001), other metabolic diseases (p = 0.006), and obesity (p = 0.019). Accordingly, multivariable logistic regression analysis confirmed that diabetes was more likely to be present in males than in females (p = 0.001), while other metabolic diseases and obesity were less likely to be present (p = 0.003 and p = 0.005, respectively). Although no difference in mortality was evident between genders (p = 0.141), both male and female COVID-19 patients had a significantly higher risk of death if they had comorbidities such as CVDs, kidney diseases, or chronic neurological diseases. Moreover, diabetes and chronic respiratory diseases were significant risk factors for COVID-19 mortality among men, whereas cancer was a significant contributor among women. Our findings confirm gender-differences in pre-existing medical conditions of COVID-19 patients, which may influence the risk of death. Further studies, however, are needed to understand physiological and pathological mechanisms underpinning these differences.

Anti-vascular endothelial growth factor monotherapy or combined with verteporfin photodynamic therapy for retinal angiomatous proliferation: a systematic review with meta-analysis.

Purpose: To assess functional and anatomical outcomes of intravitreal anti-Vascular Endothelial Growth Factor (anti-VEGF) monotherapy versus combined with verteporfin Photodynamic Therapy (PDT) for Retinal Angiomatous Proliferation (RAP). Methods: Studies reporting outcomes of intravitreal anti-VEGF monotherapy and/or in combination with verteporfin PDT in RAP eyes with a follow-up ≥ 12 months were searched. The primary outcome was the mean change in best corrected visual acuity (BCVA) at 12 months. Mean change in central macular thickness (CMT) and mean number of injections were considered as secondary outcomes. The mean difference (MD) between pre- and post-treatment values was calculated along with 95% Confidence Interval (95% CI). Meta-regressions were performed to assess the influence of anti-VEGF number of injections on BCVA and CMT outcomes. Results: Thirty-four studies were included. A mean gain of 5.16 letters (95% CI = 3.30-7.01) and 10.38 letters (95% CI = 8.02-12.75) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.01). A mean CMT reduction of 132.45 µm (95% CI = from -154.99 to -109.90) and 213.93 µm (95% CI = from -280.04 to -147.83) was shown in the anti-VEGF group and combined group, respectively (anti-VEGF group vs. combined group, p < 0.02). A mean of 4.9 injections (95% CI = 4.2-5.6) and 2.8 injections (95% CI = 1.3-4.4) were administered over a 12-month period in the anti-VEGF group and combined group, respectively. Meta-regression analyses showed no influence of injection number on visual and CMT outcomes. High heterogeneity was found across studies for both functional and anatomical outcomes. Conclusion: A combined approach with anti-VEGF and PDT could provide better functional and anatomical outcomes in RAP eyes compared with anti-VEGF monotherapy.

Comparison of Quantitative Real-Time PCR and Digital PCR to Detect the Polyomavirus in Merkel Cell Carcinoma.

Merkel cell polyomavirus (MCPyV) prevalence in Merkel cell carcinoma (MCC) cases is controversial. The detection and quantification of MCPyV DNA is mainly performed by PCR techniques using formalin-fixed, paraffin-embedded (FFPE) tissues. The aim of this study is to compare the performance of two different molecular techniques, specifically the quantitative Real-Time PCR (qPCR) and digital PCR (dPCR). Samples from 31 cases of MCC excisional surgical biopsies were analyzed. DNA extraction and purification from clinical samples were performed using the QIAcube Qiagen automated nucleic acid extractor. After the extraction, MCPyV was detected by qPCR and dPCR using specially designed primers and probes. Of the 31 MCC samples under study, the MCPyV genome was detected in 11 samples (35%) by qPCR compared with 20 samples (65%) detected by dPCR. Notably, 65% of primary tumors were positive for MCPyV (15/23). The viral genome was detected in 75% of tumors located at UV-exposed sites (6/8), 55% of tumors at partially UV-protected sites (5/9), and 67% of tumors at UV-protected sites (4/6). Our results showed a better sensitivity of dPCR in detecting the MCPyV genome in MCC samples compared with traditional qPCR techniques.

In-vitro NET-osis induced by COVID-19 sera is associated to severe clinical course in not vaccinated patients and immune-dysregulation in breakthrough infection.

Since neutrophil extracellular traps formation (NET-osis) can be assessed indirectly by treating healthy neutrophils with blood-derived fluids from patients and then measuring the NETs response, we designed a pilot study to convey high-dimensional cytometry of peripheral blood immune cells and cytokines, combined with clinical features, to understand if NET-osis assessment could be included in the immune risk profiling to early prediction of clinical patterns, disease severity, and viral clearance at 28 days in COVID-19 patients. Immune cells composition of peripheral blood, cytokines concentration and in-vitro NETosis were detected in peripheral blood of 41 consecutive COVID-19 inpatients, including 21 mild breakthrough infections compared to 20 healthy donors, matched for sex and age. Major immune dysregulation in peripheral blood in not-vaccinated COVID-19 patients compared to healthy subjects included: a significant reduction of percentage of unswitched memory B-cells and transitional B-cells; loss of naïve CD3+CD4+CD45RA+ and CD3+CD8+CD45RA+ cells, increase of IL-1ß, IL-17A and IFN-γ. Myeloid compartment was affected as well, due to the increase of classical (CD14++CD16-) and intermediate (CD14++CD16+) monocytes, overexpressing the activation marker CD64, negatively associated to the absolute counts of CD8+ CD45R0+ cells, IFN-γ and IL-6, and expansion of monocytic-like myeloid derived suppressor cells. In not-vaccinated patients who achieved viral clearance by 28 days we found at hospital admission lower absolute counts of effector cells, namely CD8+T cells, CD4+ T-cells and CD4+CD45RO+ T cells. Percentage of in-vitro NET-osis induced by patients' sera and NET-osis density were progressively higher in moderate and severe COVID-19 patients than in mild disease and controls. The percentage of in-vitro induced NET-osis was positively associated to circulating cytokines IL-1ß, IFN-γ and IL-6. In breakthrough COVID-19 infections, characterized by mild clinical course, we observed increased percentage of in-vitro NET-osis, higher CD4+ CD45RO+ and CD8+ CD45RO+ T cells healthy or mild-COVID-19 not-vaccinated patients, reduced by 24 h of treatment with ACE inhibitor ramipril. Taken together our data highlight the role of NETs in orchestrating the complex immune response to SARS-COV-2, that should be considered in a multi-target approach for COVID-19 treatment.

Reintervention rate in glaucoma filtering surgery: A systematic review and meta-analysis.

PURPOSE: Reintervention rate is an important factor impacting on patients, surgeons, and society. To date, only a few studies have focused on this topic. For this reason, a systematic review and meta-analysis was undertaken to assess the reintervention rate after glaucoma filtering surgery. MATERIALS AND METHODS: Prospective studies reporting the reintervention rate after glaucoma filtering surgery and with at least 12 months of follow-up were systematically searched on PubMed, Medline and Embase databases. The primary outcome was the total reintervention rate following surgery. Secondary outcomes were: the rate of manipulation, in-clinic and in-operating room reintervention; the reintervention rate for intraocular pressure (IOP) control and for complications; demographic, clinical and surgical variables associated with reintervention rate. RESULTS: Ninety-three studies with a total of 8345 eyes were eligible. The total reintervention rate was 1.84 (95% CI 1.57-2.13), with a lower rate for Baerveldt (0.53, 95% CI 0.29-0.83) and Preserflo (0.60, 95% CI 0.15-1.29), and a higher rate for Xen (4.26, 95% CI 2.59-6.31). The manipulation rate was 0.99 (95% CI 0.77-1.23), the in-clinic reintervention rate was 0.08 (95% CI 0.05-0.12) and the in-operating room reintervention rate was 0.28 (95% CI 0.22-0.35). The reintervention rate for IOP control was 1.26 (95% CI 1.04-1.51) and the reintervention rate for complications was 0.27 (95% CI 0.21-0.35). CONCLUSIONS: All types of surgery presented a total reintervention rate similar to the overall findings, except studies on Baerveldt and Preserflo Microshunt, with a lower rate, and Xen, with a higher rate. None of the variables evaluated were found to be directly associated with the explored outcomes.

Body mass index is related to short term retinal worsening in type 2 diabetes patients treated with anticancer drugs.

BACKGROUND: In cancer patients with diabetes, anticancer drugs (ADs) may negatively affect the course of diabetes vascular complications. The short-term effects of ADs on type 2 diabetes (T2D) retinopathy are poorly known. This study evaluated the short-term effects of different classes of ADs on diabetic retinopathy (DR) and clinical risk factors for retinal worsening (RW) in cancer patients affected by T2D. METHODS: Retrospective single-centre study evaluating 168 patients with T2D and cancer. The diagnosis of T2D preceded those of cancer in all patients. We evaluated the retinal short-term effects within the six months after the first-line ADs treatment. RESULTS: After ADs, 6% of patients had a short-term RW. BMI is positively associated with the risk of RW (OR 1.45, 95% confidence interval (CI) 1.1-1.9, p<0.005). Patients treated with alkylating agents and topoisomerase inhibitors have an increased risk of RW (p=0.049 and p=0.057, respectively) and a significantly higher HDL level (p<0.01). CONCLUSIONS: To our knowledge, this study is the first investigating the short-term impact of ADs on DR of T2D patients. Moreover, we provide information arose from a real-world setting. As confirmed by other studies, these findings could help to identify patients at risk for shortterm RW, who should be promptly referred to the ophthalmologist for the prevention of visual impairment.

Development of a Web-App for the Ecological Momentary Assessment of Dietary Habits among College Students: The HEALTHY-UNICT Project.

The transition from adolescence to adulthood is a critical period for the development of healthy behaviors. Yet, it is often characterized by unhealthy food choices. Considering the current pandemic scenario, it is also essential to assess the effects of coronavirus disease-19 (COVID-19) on lifestyles and diet, especially among young people. However, the assessment of dietary habits and their determinants is a complex issue that requires innovative approaches and tools, such as those based on the ecological momentary assessment (EMA). Here, we describe the first phases of the "HEALTHY-UNICT" project, which aimed to develop and validate a web-app for the EMA of dietary data among students from the University of Catania, Italy. The pilot study included 138 students (mean age 24 years, SD = 4.2; 75.4% women), who used the web-app for a week before filling out a food frequency questionnaire with validation purposes. Dietary data obtained through the two tools showed moderate correlations, with the lowest value for butter and margarine and the highest for pizza (Spearman's correlation coefficients of 0.202 and 0.699, respectively). According to the cross-classification analysis, the percentage of students classified into the same quartile ranged from 36.9% for vegetable oil to 58.1% for pizza. In line with these findings, the weighted-kappa values ranged from 0.15 for vegetable oil to 0.67 for pizza, and most food categories showed values above 0.4. This web-app showed good usability among students, assessed through a 19-item usability scale. Moreover, the web-app also had the potential to evaluate the effect of the COVID-19 pandemic on students' behaviors and emotions, showing a moderate impact on sedentary activities, level of stress, and depression. These findings, although interesting, might be confirmed by the next phases of the HEALTHY-UNICT project, which aims to characterize lifestyles, dietary habits, and their relationship with anthropometric measures and emotions in a larger sample of students.

Preoperative Risk Factors for Conversion from Laparoscopic to Open Cholecystectomy: A Systematic Review and Meta-Analysis.

Laparoscopic cholecystectomy is a standard treatment for patients with gallstones in the gallbladder. However, multiple risk factors affect the probability of conversion from laparoscopic cholecystectomy to open surgery. A greater understanding of the preoperative factors related to conversion is crucial to improve patient safety. In the present systematic review, we summarized the current knowledge about the main factors associated with conversion. Next, we carried out several meta-analyses to evaluate the impact of independent clinical risk factors on conversion rate. Male gender (OR = 1.907; 95%CI = 1.254−2.901), age > 60 years (OR = 4.324; 95%CI = 3.396−5.506), acute cholecystitis (OR = 5.475; 95%CI = 2.959−10.130), diabetes (OR = 2.576; 95%CI = 1.687−3.934), hypertension (OR = 1.931; 95%CI = 1.018−3.662), heart diseases (OR = 2.947; 95%CI = 1.047−8.296), obesity (OR = 2.228; 95%CI = 1.162−4.271), and previous upper abdominal surgery (OR = 3.301; 95%CI = 1.965−5.543) increased the probability of conversion. Our analysis of clinical factors suggested the presence of different preoperative conditions, which are non-modifiable but could be useful for planning the surgical scenario and improving the post-operatory phase.

Antioxidant and inflammatory potential of diet among women at risk of cervical cancer: findings from a cross-sectional study in Italy.

OBJECTIVE: To evaluate the association of Composite Dietary Antioxidant Index (CDAI) and Dietary Inflammatory Index (DII) with the prevalence of high-grade cervical intraepithelial neoplasia (CIN). DESIGN: A cross-sectional study was conducted on women with abnormal Papanicolaou test, who underwent high-risk human papillomavirus (HPV) screening and histological test through colposcopy. Dietary data were collected using a FFQ and used to assess both CDAI and DII. SETTING: Women were recruited from 2012 to 2015 at the Cervical Cancer Screening Unit of the 'Azienda Sanitaria Provinciale' of Catania (Italy). PARTICIPANTS: The study included 539 women with a mean age of 40·2 years, who were classified as cases (n 127 with CIN2 or more severe lesions) and controls (n 412 with normal cervical epithelium or CIN1). RESULTS: Although we observed a lower proportion of HPV-positive women among those with higher CDAI (P < 0·001), the index was not associated with the diagnosis of CIN2 or more severe lesions. By contrast, women with medium or high DII showed higher odds to be diagnosed with CIN2 or more severe lesions than those with low DII (OR = 2·15; 95 % CI 1·11, 4·17; P = 0·024 and OR = 3·14; 95 % CI 1·50, 6·56; P = 0·002, respectively), after adjusting for age, HPV status, educational level, BMI, smoking status, parity, use of oral contraceptives and supplements. CONCLUSIONS: Our findings suggested that a pro-inflammatory diet might be associated with an increased risk of CIN2 and more severe lesions. However, further prospective studies should be encouraged to support this evidence.

Intravitreal dexamethasone implant versus anti-vascular endothelial growth factor therapy combined with cataract surgery in patients with diabetic macular oedema: a systematic review with meta-analysis.

OBJECTIVE: To compare outcomes of cataract surgery combined with either anti-Vascular Endothelial Growth Factor (anti-VEGF) therapy or dexamethasone implant (DEX) in patients with diabetic macular oedema (DMO). METHODS: Pubmed and Embase databases were searched for studies reporting outcomes of diabetic cataract surgery combined with either anti-VEGF or DEX, with a follow-up ≥3 months. The primary outcome was the mean change in central macular thickness (CMT). Mean change in best corrected visual acuity (BCVA) was considered as a secondary outcome. The mean difference between baseline and post-treatment values (MD) with 95%-Confidence Interval (95%CI) was calculated and meta-analyses were performed. RESULTS: Nine-teen studies were included, 8 in the DEX group and 11 in the anti-VEGF group. A significant reduction of macular thickness was shown in the DEX group at 3 months (MD = -98.35 µm; 95% CI, -147.15/-49.54), while mean CMT change was non-significant in the anti-VEGF group (MD = -21.61 µm; 95% CI, -59.46/16.24; test of group differences, P < 0.001). At 3 months, no difference in visual gain was found between the two groups (P = 0.13). CONCLUSIONS: In DMO patients, cataract surgery combined with DEX seems to provide better anatomical outcomes compared with cataract surgery combined with anti-VEGF therapy. However, our evidence was limited by significant heterogeneity. Randomised trials comparing these two different combined approaches are warranted.

The Relationship between Body Mass Index, Obesity, and LINE-1 Methylation: A Cross-Sectional Study on Women from Southern Italy.

Uncovering the relationship between body mass index (BMI) and DNA methylation could be useful to understand molecular mechanisms underpinning the effects of obesity. Here, we presented a cross-sectional study, aiming to evaluate the association of BMI and obesity with long interspersed nuclear elements (LINE-1) methylation, among 488 women from Catania, Italy. LINE-1 methylation was assessed in leukocyte DNA by pyrosequencing. We found a negative association between BMI and LINE-1 methylation level in both the unadjusted and adjusted linear regression models. Accordingly, obese women exhibited lower LINE-1 methylation level than their normal weight counterpart. This association was confirmed after adjusting for the effect of age, educational level, employment status, marital status, parity, menopause, and smoking status. Our findings were in line with previous evidence and encouraged further research to investigate the potential role of DNA methylation markers in the management of obesity.

Epigenetic Mechanisms in Type 2 Diabetes Retinopathy: A Systematic Review.

Diabetic retinopathy (DR) is one of the main causes of vision loss in middle-aged economically active people. Modifiable (i.e., hyperglycaemia, hypertension, hyperlipidaemia, obesity, and cigarette smoke) and non-modifiable factors (i.e., duration of diabetes, puberty, pregnancy and genetic susceptibility) are involved in the development of DR. Epigenetic mechanisms, modulating the oxidative stress, inflammation, apoptosis, and aging, could influence the course of DR. Herein, we conducted a systematic review of observational studies investigating how epigenetics affects type 2 diabetes retinopathy (T2DR). A total of 23 epidemiological studies were included: 14 studies focused on miRNA, 4 studies on lnc-RNA, one study on both miRNA and lnc-RNA, and 4 studies on global or gene-specific DNA methylation. A direct relation between the dysregulation of miR-21, miR-93, and miR-221 and FPG, HbA1c, and HOMA-IR was identified. A panel of three miRNAs (hsa-let-7a-5p, hsa-miR-novel-chr5_15976, and hsa-miR-28-3p) demonstrated a good sensitivity and specificity for predicting T2DR. Little evidence is available regarding the possible role of the long non-coding MALAT1 dysregulation and MTHFR gene promoter hypermethylation. Despite these initial, encouraging findings potentially suggesting a role of epigenetics in T2DR, the use in clinical practice for the diagnosis and staging of this complication encounters several difficulties and further targeted investigations are still necessary.

Identification by MicroRNA Analysis of Environmental Risk Factors Bearing Pathogenic Relevance in Non-Smoker Lung Cancer.

MicroRNA and DNA adduct biomarkers may be used to identify the contribution of environmental pollution to some types of cancers. The aim of this study was to use integrated DNA adducts and microRNAs analyses to study retrospectively the contribution of exposures to environmental carcinogens to lung cancer in 64 non-smokers living in Sicily and Catania city near to the Etna volcano. MicroRNAs were extracted from cancer lung biopsies, and from the surrounding lung normal tissue. The expression of 2549 human microRNAs was analyzed by microarray. Benzo(a)Pyrene-DNA adducts levels were analyzed in the patients' blood by HPLC-fluorescence detection. Correlations between tetrols and environmental exposures were calculated using Pearson coefficients and regression variable plots. Compared with the healthy tissue, 273 microRNAs were downregulated in lung cancer. Tetrols levels were inversely related both with the distance from Etna and years since smoking cessation, but they were not significantly correlated to environmental exposures. The analysis of the microRNA environmental signatures indicates the contribution of environmental factors to the analyzed lung cancers in the following decreasing rank: (a) car traffic, (b) passive smoke, (c) radon, and (d) volcano ashes. These results provide evidence that microRNA analysis can be used to retrospectively investigate the contribution of environmental factors in human lung cancer occurring in non-smokers.

The Effect of Alcohol on Telomere Length: A Systematic Review of Epidemiological Evidence and a Pilot Study during Pregnancy.

Several studies-albeit with still inconclusive and limited findings-began to focus on the effect of drinking alcohol on telomere length (TL). Here, we present results from a systematic review of these epidemiological studies to investigate the potential association between alcohol consumption, alcohol-related disorders, and TL. The analysis of fourteen studies-selected from PubMed, Medline, and Web of Science databases-showed that people with alcohol-related disorders exhibited shorter TL, but also that alcohol consumption per se did not appear to affect TL in the absence of alcohol abuse or dependence. Our work also revealed a lack of studies in the periconceptional period, raising the need for evaluating this potential relationship during pregnancy. To fill this gap, we conducted a pilot study using data and samples form the Mamma & Bambino cohort. We compared five non-smoking but drinking women with ten non-smoking and non-drinking women, matched for maternal age, gestational age at recruitment, pregestational body mass index, and fetal sex. Interestingly, we detected a significant difference when analyzing relative TL of leukocyte DNA of cord blood samples from newborns. In particular, newborns from drinking women exhibited shorter relative TL than those born from non-drinking women (p = 0.024). Although these findings appeared promising, further research should be encouraged to test any dose-response relationship, to adjust for the effect of other exposures, and to understand the molecular mechanisms involved.

Epiretinal Membrane Vitrectomy With and Without Intraoperative Intravitreal Dexamethasone Implant: A Systematic Review With Meta-Analysis.

Purpose: To evaluate the efficacy of vitrectomy combined with intravitreal dexamethasone implant vs. vitrectomy without the implant in patients with epiretinal membrane (ERM) by conducting a systematic review and meta-analysis. Methods: Studies that compared ERM vitrectomy with and without intraoperative dexamethasone implant with a follow-up ≥3 months were included. The primary outcome was mean best corrected visual acuity (BCVA) change between eyes undergoing ERM vitrectomy combined with dexamethasone implant (DEX group) and eyes undergoing ERM vitrectomy alone (control group) at 3 months. Secondary outcomes included mean BCVA change at 6 months and mean optical coherence tomography central macular thickness (CMT) change at both 3-months and 6-months follow-up. Mean differences (MDs) with their 95% confidence interval (95%CI) were calculated. Meta-analyses were based either on random effect model or fixed effect model according to heterogeneity. Results: Four studies were included. At 3 months, ERM vitrectomy combined with dexamethasone implant yielded a greater visual gain compared to vitrectomy alone (MD = 9.7; 95%CI = 2.6-16.8; p = 0.01). However, significant heterogeneity was found. A sensitivity analysis excluding the only retrospective non-randomized study confirmed a greater visual gain in the DEX group (MD = 7.1; 95%CI = 2.7-11.6; p < 0.01), with no heterogeneity. At 6 months, a non-significant but borderline difference in visual gain was shown between in the two groups (MD = 5.1; 95%CI = -0.3-10.5; p = 0.06), with no heterogeneity. Three-month analysis of CMT revealed a greater reduction in the DEX group (MD = -80.2; 95%CI =-149.1-11.2; p = 0.02), but with significant heterogeneity. A sensitivity analysis excluding the only retrospective non-randomized study allowed to reduce heterogeneity, but no difference in 3-months CMT change was found between the two groups (MD = -50.0; 95%CI = -106.2-6.2; p = 0.08). At 6 months, no difference in CMT change was shown between the two groups (MD = -48.5; 95%CI = -120.5-23.5; p = 0.19), with significant heterogeneity. Conclusions: Intraoperative dexamethasone implant in eyes undergoing vitrectomy for ERM provided a better visual outcome at 3 months compared to ERM vitrectomy without the implant, with limited evidence of better anatomic outcome as well. Further studies are needed to ascertain whether dexamethasone implant would ensure a significant long-term visual benefit as a result of a faster reduction of macular thickening.

Relationship between the miRNA Profiles and Oncogene Mutations in Non-Smoker Lung Cancer. Relevance for Lung Cancer Personalized Screenings and Treatments.

Oncogene mutations may be drivers of the carcinogenesis process. MicroRNA (miRNA) alterations may be adaptive or pathogenic and can have consequences only when mutation in the controlled oncogenes occurs. The aim of this research was to analyze the interplay between miRNA expression and oncogene mutation. A total of 2549 miRNAs were analyzed in cancer tissue-in surrounding normal lung tissue collected from 64 non-smoking patients and in blood plasma. Mutations in 92 hotspots of 22 oncogenes were tested in the lung cancer tissue. MicroRNA alterations were related to the mutations occurring in cancer patients. Conversely, the frequency of mutation occurrence was variable and spanned from the k-ras and p53 mutation detected in 30% of patients to 20% of patients in which no mutation was detected. The prediction of survival at a 3-year follow up did not occur for mutation analysis but was, conversely, well evident for miRNA analysis highlighting a pattern of miRNA distinguishing between survivors and death in patients 3 years before this clinical onset. A signature of six lung cancer specific miRNAs occurring both in the lungs and blood was identified. The obtained results provide evidence that the analysis of both miRNA and oncogene mutations was more informative than the oncogene mutation analysis currently performed in clinical practice.

Comparison of aspiration with sclerotherapy and laparoscopic deroofing for the treatment of symptomatic simple renal cysts: a systematic review and meta-analysis.

There are currently several strategies for the treatment of symptomatic simple renal cysts, such as aspiration with sclerosants and laparoscopic deroofing. However, no clear indication exists for choosing between them. Here, we carried out a systematic review and a meta-analysis of studies, which compared symptomatic and radiological success between aspiration with sclerotherapy and laparoscopic deroofing. Results were reported as relative risk (RR) and 95% confidence interval (95% CI) using laparoscopic deroofing as control group. The symptomatic and radiological successes were evaluated by 6 and 3 studies, respectively. Notably, aspiration with sclerotherapy was associated with higher risk of failure than laparoscopic deroofing (RR = 2.82; 95% CI = 1.84-4.31 for symptomatic failure; RR = 8.31; 95% CI = 4.22-16.38 for radiological failure). On the other hand, however, aspiration with sclerotherapy was associated with less frequent complications, shorter treatment duration and post-treatment hospital stay, and lower costs. Thus, our work underlines benefits and drawbacks of each intervention, raising the need for further studies to design guidelines for the management of simple renal cysts.

Vaccination Status of Mothers and Children from the 'Mamma & Bambino' Cohort.

According to the evidence demonstrating vaccines' safety and effectiveness in anticipation of and during pregnancy, several countries have established immunization programs during the periconceptional period. Here, we evaluated vaccination status among 220 mother-child pairs, using data from the 'Mamma & Bambino' cohort. The self-reported data were evaluated at delivery, and with planned follow-ups at 1-2 years after delivery. In general, we noted that the vaccination status among the women was heterogeneous, ranging from 8.3% (vaccine against Human Papillomavirus, HPV) to 65.6% (vaccine against Diphtheria Tetanus and Pertussis, DTaP). Excluding the women who contracted the diseases in the past, the main ground for refusal was the lack of information. We also demonstrated that increasing age was associated with higher odds of not being vaccinated against Measles-Mumps-Rubella (MMR; OR = 1.12; 95% CI = 1.04-1.21; p = 0.004), HPV (OR = 1.20; 95% CI = 1.08-1.33; p = 0.001) and DTaP (OR =1.09; 95% CI = 1.01-1.18; p = 0.040). As expected, we showed that the proportion of newborns vaccinated with the Hexavalent and Pneumococcal vaccines was high (99.5% and 98.6%, respectively), while the vaccination coverage against MMRV did not reach the auspicated threshold (84.1%). Overall, these results underlined the need for the improvement of women's knowledge about the recommendations for vaccination, especially during pregnancy.

Pediatric Non-Alcoholic Fatty Liver Disease Is Affected by Genetic Variants Involved in Lifespan/Healthspan.

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in both adults and children. Along with obesity and metabolic syndrome, genetic predisposition influences the progression of NAFLD. Here, we investigated the effect of lifespan/healthspan-related single nucleotide polymorphisms (SNPs) on metabolically associated fatty liver disease in children. METHODS: We evaluated the impact of 10 SNPs involved in both human liver/metabolic diseases and healthspan (interleukin-6 [IL-6] rs1800795, antisense non coding RNA in the INK4 locus (ANRIL) rs1556516, SH2B3/ATXN2 rs7137828, FURIN rs17514846, TP53 rs1042522, APOC3 rs2542052, KL rs9536314, KL rs9527025, SIRT6 rs107251, FOXO3 rs2802292) on NAFLD-related metabolic and liver features in 177 pediatric patients with biopsy-proven NAFLD, by comparing them to 146 healthy controls. We then applied a multidimensional reduction (MDR) case-control analysis of SNP-SNP interactions, to identify the joint effect of analyzed SNPs in predicting NAFLD and associated features. RESULTS: Discrete SNPs were significantly associated with individual metabolic NAFLD features, but none of them significantly associated with NAFLD diagnosis. By testing potential synergies using the MDR approach, the best combination to diagnose NAFLD (P = 0.0011) resulted in the one encompassing IL-6 rs1800795 and ANRIL rs1556516. Consistently, the risk combinations suggested by SNP-SNP analysis strongly associated with a higher level of fasting plasma blood glucose level (P = 0.024). CONCLUSION: In conclusion, here we demonstrated a synergic interaction between IL-6 rs1800795 and ANRIL rs1556516 in the diagnosis of NAFLD, and NAFLD-associated hyperglycemia in children. Larger studies are required to confirm our findings and to elucidate mechanisms by which the genetic interaction between these two genes influences healthspan in pediatric NAFLD.

Fluocinolone acetonide vitreous insert for chronic diabetic macular oedema: a systematic review with meta-analysis of real-world experience.

We conducted a meta-analysis of real-world studies on the 0.19 mg Fluocinolone Acetonide (FAc) intravitreal implant for chronic diabetic macular oedema (DMO), comparing these findings with the Fluocinolone Acetonide for Diabetic Macular Edema (FAME) study. The primary outcome was mean change of best corrected visual acuity (BCVA) at 24 months. Secondary outcomes were 36-month mean BCVA, mean central macular thickness (CMT) change, rates of eyes receiving supplementary intravitreal therapy, cataract surgery, intraocular pressure (IOP)-lowering drops and glaucoma surgery. Mean differences (MDs) with 95% confidence intervals (CIs) were calculated. Nine real-world studies were included. The FAc implant yielded a significantly improved BCVA at 24 and 36 months (24-month MD = 4.52; 95% CI 2.56-6.48; 36-month MD = 8.10; 95% CI 6.34-9.86). These findings were comparable with the FAME study. The FAc implant yielded significantly reduced 24- and 36-month CMT. Pooled proportions of cataract surgery, IOP-lowering drops and glaucoma surgery were 39%, 27% and 3%, respectively, all lower than the FAME study. Pooled estimate of supplementary intravitreal therapy was 39%, higher than the 15.2% of the FAME study. This meta-analysis of real-world studies confirms favorable visual and anatomical outcomes following FAc insert for chronic DMO. In real-life studies more than one third of patients received supplementary intravitreal therapy, an issue that needs to be further explored.