DAPK1 Promoter Methylation and Cervical Cancer Risk: A Systematic Review and a Meta-Analysis.

Objective: The Death-Associated Protein Kinase 1 (DAPK1) gene has been frequently investigated in cervical cancer (CC). The aim of the present study was to carry out a systematic review and a meta-analysis in order to evaluate DAPK1 promoter methylation as an epigenetic marker for CC risk. Methods A systematic literature search was carried out. The Cochrane software package Review Manager 5.2 was used. The fixed-effects or random-effects models, according to heterogeneity across studies, were used to calculate odds ratios (ORs) and 95% Confidence Intervals (CIs). Furthermore, subgroup analyses were conducted by histological type, assays used to evaluate DAPK1 promoter methylation, and control sample source. Results: A total of 20 papers, published between 2001 and 2014, on 1929 samples, were included in the meta-analysis. DAPK1 promoter methylation was associated with an increased CC risk based on the random effects model (OR: 21.20; 95%CI = 11.14–40.35). Omitting the most heterogeneous study, the between study heterogeneity decreased and the association increased (OR: 24.13; 95% CI = 15.83–36.78). The association was also confirmed in all the subgroups analyses. Conclusions: A significant strong association between DAPK1 promoter methylation and CC was shown and confirmed independently by histological tumor type, method used to evaluate methylation and source of control samples. Methylation markers may have value in early detection of CC precursor lesions, provide added reassurances of safety for women who are candidates for less frequent screens, and predict outcomes of women infected with human papilloma virus

La sorveglianza della tubercolosi in Sicilia

Obiettivi. Descrivere l’andamento dei casi di tubercolosi (TB) in Sicilia negli anni 2010-2013. Disegno e partecipanti. Indagine osservazionale delle notifiche di TB relative agli anni 2010-2013 mediante l’analisi dei dati del Sistema informativo delle malattie infettive (SIMI) e indagine epidemiologico-molecolare mediante tipizzazione spoligo- e 24- loci mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) dei ceppi di Mycobacterium tuberculosis complex (MTBC) isolati a Palermo negli anni 2012-2013. Risultati. Negli anni 2010-2013 sono stati notificati in Sicilia 876 casi di TB con un tasso medio annuale di notifica pari a 4,4 casi per 100.000 abitanti. La proporzione di casi di TB in soggetti nati all’estero è crescente e nel 2012 e 2013 supera quella nella popolazione autoctona. L’età mediana dei pazienti stranieri è risultata significativamente inferiore agli italiani (30,5 vs. 51,2 anni, p <0,001). La distribuzione per classi di età è stata significativamente differente nelle due subpopolazioni, con la proporzione più elevata di casi nelle fascia di età 15-44 anni tra gli stranieri e, al contrario, una distribuzione uniforme dei pazienti italiani tra le fasce di età 15-44, 45-64 e >64 anni. Nell’82,5% dei casi è stata diagnosticata una localizzazione polmonare. La tipizzazione molecolare è stata effettuata su 151 ceppi di MTBC. Mediante spoligotyping essi sono stati attribuiti a 14 differenti lineage e 33 sublineage rappresentati con frequenza diversa tra le due subpopolazioni di pazienti. Soltanto nove ceppi (6,2%) sono stati inclusi in quattro cluster. Sono stati identificati, infine, due ceppi multiresistenti. Conclusioni. L’epidemiologia della TB in Sicilia è complessa e in rapida evoluzione, con una crescente proporzione di casi in soggetti non italiani e una grande eterogeneità dei ceppi di MTBC circolanti. L’integrazione di strumenti convenzionali e molecolari è necessaria per una sorveglianza efficace e un’interpretazione accurata dell’epidemiologia della TB in Sicilia

Increase in the prevalence of the MTHFR 677 TT polymorphism in women born since 1959: potential implications for folate requirements

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Epidemiology of intensive care unit-acquired sepsis in Italy: results of the SPIN-UTI network

BACKGROUND: Sepsis is the major cause of mortality from any infectious disease worldwide. Sepsis may be the result of a healthcare associated infection (HAI): the most frequent adverse events during care delivery especially in Intensive Care Units (ICUs). The main aim of the present study was to describe the epidemiology of ICU-acquired sepsis and related outcomes among patients enrolled in the framework of the Italian Nosocomial Infections Surveillance in ICUs - SPIN-UTI project. STUDY DESIGN: Prospective multicenter study. METHODS: The SPIN-UTI network adopted the European protocols for patient-based HAI surveillance. RESULTS: During the five editions of the SPIN-UTI project, from 2008 to 2017, 47.0% of HAIs has led to sepsis in 832 patients. Overall, 57.0% episodes were classified as sepsis, 20.5% as severe sepsis and 22.5% as septic shock. The most common isolated microorganisms from sepsis episodes were Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa. The case fatality rate increased with the severity of sepsis and the mean length of ICU-stay was significantly higher in patients with ICU-acquired sepsis than in patients without. CONCLUSION: Our study provides evidence that ICU-acquired sepsis occurs frequently in Italian ICU patients and is associated with a high case fatality rate and increased length of stay. However, in order to explain these findings further analyses are needed in this population of ICU patient

A combined multidisciplinary intervention for health promotion in the workplace: a pilot study

The aim of this study was to assess the effects of a joint health promotion intervention on a cohort of healthcare workers (HCWs) who had at least one cardiovascular risk factor. The HCWs were assessed at three different times, i.e., time zero (T0), after 6 months (T6), and after 12 months (T12). The following parameters were measured at a medical examination: physical activity, blood pressure, waist circumference, body mass index (BMI), routine laboratory tests, plicometric analysis, work ability index (WAI), and body image dissatisfaction (BID). Among the 447 HCWs, 38 HCWs were included in the study; 45% (n = 17) were male. At T12, the average blood pressure, waist/hip ratio (WHR) index, BMI, total cholesterol, triglyceride level, and blood glucose values were reduced. The levels of physical activity and adherence to the Mediterranean diet had progressively increased. The WAI showed a significant shift from low to good work performance at T12, as well as BID score. This is the first study that has analyzed work performance in relation to a workplace health promotion through a multidisciplinary approach. This health promotion intervention that combined diet and sport activity has led to a significant change in HCWs’ lifestyles and body perceptions, as well as their ability to work. This project highlights the importance of using a multidisciplinary approach and the workplace setting in health promotion programs

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 653 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&nbsp;months. Secondary outcomes included mean BCVA change at 6&nbsp;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\u201316.8; 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\u201311.6; p &lt; 0.01), with no heterogeneity. At 6&nbsp;months, a non-significant but borderline difference in visual gain was shown between in the two groups (MD = 5.1; 95%CI = 120.3\u201310.5; p = 0.06), with no heterogeneity. Three-month analysis of CMT revealed a greater reduction in the DEX group (MD = 1280.2; 95%CI = 12149.1\u201311.2; 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 = 1250.0; 95%CI = 12106.2\u20136.2; p = 0.08). At 6&nbsp;months, no difference in CMT change was shown between the two groups (MD = 1248.5; 95%CI = 12120.5\u201323.5; 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

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&nbsp;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&nbsp;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&nbsp;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

Intravitreal Dexamethasone Implant for Postoperative Macular Oedema Secondary to Vitrectomy for Epiretinal Membrane and Retinal Detachment: A Systematic Review and Meta-Analysis

Purpose. To evaluate the efficacy of intravitreal dexamethasone implant (DEX) for the treatment of macular oedema secondary to vitrectomy for epiretinal membrane (ERM) and retinal detachment (RD) by conducting a systematic review with meta-analysis of published studies. Methods. Studies reporting clinical outcomes of DEX use for the treatment of macular oedema secondary to ERM and RD vitrectomy were searched on PubMed and Embase databases. The primary outcome was best-corrected visual acuity (BCVA) change between baseline and post-DEX treatment, reported as mean difference (MD) with 95% confidence interval (CI). Mean central macular thickness (CMT) change was assessed as a secondary outcome. Postimplant adverse events, including intraocular pressure rise and cataract development, were reported as well. Results. Five uncontrolled studies, 1 nonrandomized controlled study, and 1 randomized controlled study were included, with a total of 5 cohorts and 3 cohorts in the ERM group and RD group, respectively. Considering the last available follow-up, a significant improvement in postimplant BCVA was found in the overall population, irrespective of the indication for vitrectomy (MD = -0.28, 95% CI = -0.37, -0.20; p&lt;0.001), but with significant heterogeneity. In either group, mean BCVA significantly improved following the implant (in the ERM group, MD = -0.31, 95% CI = -0.40, -0.22; in the RD group, MD = -0.22, 95% CI = -0.41, -0.03), with no difference between the two groups (p=0.41). However, there was significant heterogeneity in both groups. Considering the last available follow-up, a significant CMT reduction was found in the overall population, irrespective of the indication for vitrectomy (MD = -129.75, 95% CI = -157.49, -102.01; p&lt;0.001). In the ERM group, a significant CMT reduction was shown following DEX (MD = -133.41, 95% CI = -155.37, -111.45; p&lt;0.001), with no heterogeneity. In the RD group, mean CMT reduction was borderline significant (MD = -128.37, 95% CI = -253.57, -3.18; p=0.040), with significant heterogeneity. No difference in CMT improvement was found between the two groups (p=0.94). Conclusion. This meta-analysis showed that DEX yielded a significant improvement in visual and anatomical outcomes, even if limited by significant heterogeneity. Dexamethasone implant represents an effective treatment for postoperative macular oedema secondary to ERM and RD vitrectomy

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 &lt; 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 &lt; 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