Prevalence and spectrum of germline BRCA1 and BRCA2 in a cohort of ovarian cancer patients from the Salento peninsula (Southern Italy): a matter of preventive health.

OBJECTIVES: The aim of this exploratory, descriptive study was to characterize the deleterious BRCA1 and BRCA2 variants evaluated by genetic testing in a group of Ovarian cancer patients living in the Salento peninsula (Southern Italy). METHODS: From June 2014 to July 2023, patients with histologically confirmed high-grade serous carcinoma, fallopian tube, or primary peritoneal cancer who were referred to Lecce Familial Cancer Clinic were considered. BRCA-mutation genetic testing was performed on these patients. Socio-demographic data and cancer epidemiology were assessed, and Next Generation Sequencing and Sanger DNA sequencing were performed. RESULTS: The median age at the diagnosis of 332 ovarian cancer patients collected was 57 years. The pedigree analyses showed that 28.6% had familial cases and 39.7% had sporadic cases. Of the 319 patients submitted to genetic testing, 29.8% were carriers of BRCA1/2 mutation, 75.8% at BRCA1 and 24.2% at BRCA2 gene. Of the 21 BRCA1 mutations, the variant c.5266dupC was the most frequent alteration (28.4%). With respect to BRCA2, 13 mutations were found and the variant c.9676delT was the most frequently recorded (6.3%). CONCLUSIONS: This study reveals that the prevalence of germline mutations in the BRCA1 and BRCA2 genes was higher than reported by other studies. A broader understanding of the prevalence and role of BRCA mutations in development, response to treatment, and prognosis represents an exciting and developing area of ovarian cancer treatment and prevention.

Insulin pump treatment vs. multiple daily insulin injections in patients with poorly controlled Type 2 diabetes mellitus: a comparison of cardiovascular effects.

AIMS: Both hyperglycaemia and large glycaemic variability are associated with worse outcomes in patients with Type 2 diabetes mellitus (T2DM), possibly causing sympatho-vagal imbalance and endothelial dysfunction. Continuous subcutaneous insulin injection (CSII) improves glycemic control compared to multiple daily insulin injections (MDI). We aimed to assess whether CSII may improve cardiac autonomic and vascular dilation function compared to MDI. METHODS: We enrolled T2DM patients without cardiovascular disease with poor glycaemic control, despite optimized MDI therapy. Patients were randomized to continue MDI (with multiple daily peripheral glucose measurements) or CSII; insulin dose was adjusted to achieve optimal target ranges of blood glucose levels. Patients were studied at baseline and after 6 months by: 1) flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the brachial artery; 2) heart rate variability (HRV) by 24-hour ECG Holter monitoring (HM). 7-day continuous glucose monitoring (CGM) was performed in 9 and 8 patients of Group 1 and 2, respectively. RESULTS: Overall, 21 patients were enrolled, 12 randomized to CSII (Group 1) and 9 to MDI (Group 2). The daily dose of insulin and Hb1AC did not differ significantly between the 2 groups, both at baseline and at follow-up. Glucose variability showed some significant improvement at follow-up in the whole population, but no differences were observed between the 2 groups. Both FMD and NMD, as well as HRV parameters, showed no significant differences between the 2 groups at 6-month follow-up. CONCLUSIONS: In this randomized small study we show that, in T2DM patients, CSII achieves a similar medium-term glycemic control compared to MDI, without any adverse effect on the cardiovascular system.

Gambling and internet addiction: a pilot study among a Population of Italian Healthcare : Gambling and Internet Addition in a Healthcare Group.

AIM: Measuring the phenomenon of gambling and Internet addiction, with analysis of attitudes and psychophysical consequences among nurses working in different care settings. METHODS: An observational, cross sectional, multicenter study was conducted from April to September 2020. Participants' socio-demographic information, the "Internet Addiction Test" (IAT) scale, and the "South Oaks Gambling Screen" (SOGS) were collected in order to assess the overuse of and whether an individual has a problematic relationship with gambling, respectively. RESULTS: 502 nurses were enrolled in the study. Significant correlations were found (p < .001) between the IAT score and gender, number of years of work experience, job role, educational qualification; and between the SOGS and gender, number of years of work experience, job role and regions of Italy. CONCLUSIONS: The study highlighted an emerging social problem, and the results may be just the tip of the iceberg. Given the lack of knowledge of these phenomena and a high percentage of people who suffer from them but are afraid to admit it and get help, this study could also be useful in expanding knowledge and allow more professionals to get help and learn about possible treatments and cures for the resolution of these addictions.

Effects of inhaled corticosteroids (ICS) on lung microbiota and local immune response in long-term treatment of chronic obstructive pulmonary disease (COPD): utility of titration and therapeutic index.

Administration of inhaled corticosteroids (ICS) is one of the most controversial issues in the treatment of stable chronic obstructive pulmonary disease (COPD). Associations between these drugs and increased incidence of severe pneumonia and other respiratory infections have already been reported in literature, as well as effects on the immune system and on the lung microbiota. ICS vary in their pharmacodynamic and pharmacokinetic properties, despite being widely considered therapeutically similar. The use of ICS requires, therefore, a deep knowledge of their pharmacokinetics and pharmacodynamics to obtain the maximum benefit and the least side effects. Defining new phenotypes-endotypes of COPD may lead to novel pharmacological and therapeutic scenarios while define the correct indications for prescription of ICS. Titration is certainly an important means by which these objectives can be achieved.

COVID-19 IgG/IgM patterns, early IL-6 elevation and long-term radiological sequelae in 75 patients hospitalized due to interstitial pneumonia followed up from 3 to 12 months.

BACKGROUND: COVID-19 pandemic resulted in about 165 million infections and 3.4 million deaths all over the world across 15 months. The most severe clinical presentation of COVID-19 diseases is interstitial pneumonia. METHODS: In this paper we describe clinical outcomes based on radiological features as well as the pattern of haematochemical parameters and IgG/IgM antibodies in 75 patients hospitalized due to COVID-related interstitial pneumonia not requiring intensive care assistance. Each patient underwent routine laboratory tests, including inflammatory markers and coagulation profile at baseline. Computed Tomography (CT) was performed at baseline and after 3 months to assess the persistence of radiological sequelae. A Generalized Linear Model (GLM) was used to test for each patient the association between individual haematochemical parameters at the time of hospital admission and the subsequent radiological features after three months. The presence of IgG antibodies was quantitatively determined in 70 patients at the time of hospital admission and after 3 months. A subgroup of 49 and 21 patients underwent additional dosage of IgG after 6 and 12 months, respectively. IgM serological antibodies were available for 17 patients at baseline and 61 at T3, with additional follow-up for 51 and 20 subjects after 6 and 12 months, respectively. RESULTS: Only 28 out of 75 patients discharged from the hospital were totally healed after 3 months, while 47 patients (62.7%) still presented radiological sequelae. According to the GLM model, specific haematochemical baseline parameters-such as IL-6, GPT, platelets and eosinophil count-showed a statistically significant association with the presence of radiological sequelae at month 3 highlighting an OR = 0.5, thus meaning that subjects completely healed after 3 months presented half levels of IL-6 at baseline compared to patients with sequelae. In general, IgG serum levels were always higher than IgM at the time of hospitalization (75% at T0; n = 12 out of 16 patients with data available in both visits), after 3 months (72.1%; n = 44 out of 61 pts.), after 6 months (56.8%; 25 out of 44 pts.), and one year after hospitalization (60%; 12 out of 20 pts.). Overall, IgG and IgM serum levels presented a statistically significant decreasing trend from the baseline to month 3, 6 and 12. One patient presented an increase in IgM between baseline and month 3 but negative PCR test for SARS-COV2 on throat swab. CONCLUSIONS: As supported by our findings on 75 patients, COVID-related interstitial pneumonia triggers early IgG levels (higher than IgM) that gradually decrease over 12 months. Mid-term sequelae are still detectable at lung Computed Tomography after 3 months from the hospital admission. Occasionally, it is possible to observe increase of IgM levels in presence of low concentrations of IgG and negative PCR ELISA tests for SARS-COV2 RNA. Baseline levels of IL-6 could be proposed as predictor of radiological mid/long-term sequelae after COVID-related interstitial pneumonia.

Heat waves and adaptation strategies in a mediterranean urban context.

BACKGROUND: Heat waves can be considered as an emerging challenge among the potential health risks generated by urbanization and climate changes. Heat waves are becoming more frequent, long and intense, and can be defined as meteorological extreme events consisting in prolonged time of extremely high temperatures in a particular region. The following paper addresses health threats due to heat waves presenting the case study of Lecce, a city located in Southern Italy; the Mediterranean area is already recognized in international literature as a hot-spot for climate changes. This work assesses the potential impact of two different adaptation strategies. METHODS: We have tested the effectiveness of cool surfaces and urban forestry as adaptation approaches to cope with heat waves. The microclimate computer-based model "ENVI-met" was adopted to predict thermal scenarios arising from the two proposed interventions. The parameters analysed consisted in temperature and relative humidity. RESULTS: Urban forestry approach seem to lower temperature (that represents the major cause of urban overheating) better than cool surfaces strategy, but relative humidity produced by the evapotranspiration processes of urban forestry has also negative influences on temperature perceived by pedestrians (thermal discomfort). CONCLUSION: Vegetation represents both an adaptation and a mitigation strategy to climate changes that guarantees an improvement of air quality, with consequent psychological and physical benefits. Wide campaigns aimed at planting trees and increasing the urban green coverage should be systematically planned and fostered by national, regional and local institutions preferably with the involvement of research departments, schools and citizens' associations.

Potential role of particulate matter in the spreading of COVID-19 in Northern Italy: first observational study based on initial epidemic diffusion.

OBJECTIVES: A number of studies have shown that the airborne transmission route could spread some viruses over a distance of 2 meters from an infected person. An epidemic model based only on respiratory droplets and close contact could not fully explain the regional differences in the spread of COVID-19 in Italy. On March 16th 2020, we presented a position paper proposing a research hypothesis concerning the association between higher mortality rates due to COVID-19 observed in Northern Italy and average concentrations of PM10 exceeding a daily limit of 50 µg/m3. METHODS: To monitor the spreading of COVID-19 in Italy from February 24th to March 13th (the date of the Italian lockdown), official daily data for PM10 levels were collected from all Italian provinces between February 9th and February 29th, taking into account the maximum lag period (14 days) between the infection and diagnosis. In addition to the number of exceedances of the daily limit value of PM10, we also considered population data and daily travelling information for each province. RESULTS: Exceedance of the daily limit value of PM10 appears to be a significant predictor of infection in univariate analyses (p<0.001). Less polluted provinces had a median of 0.03 infections over 1000 residents, while the most polluted provinces showed a median of 0.26 cases. Thirty-nine out of 41 Northern Italian provinces resulted in the category with the highest PM10 levels, while 62 out of 66 Southern provinces presented low PM10 concentrations (p<0.001). In Milan, the average growth rate before the lockdown was significantly higher than in Rome (0.34 vs 0.27 per day, with a doubling time of 2.0 days vs 2.6, respectively), thus suggesting a basic reproductive number R0>6.0, comparable with the highest values estimated for China. CONCLUSION: A significant association has been found between the geographical distribution of daily PM10 exceedances and the initial spreading of COVID-19 in the 110 Italian provinces.

An Approach to Diabetic Ketoacidosis in an Emergency Setting.

BACKGROUND: Diabetic Ketoacidosis (DKA) is one of the most commonly encountered diabetic complication emergencies. It typically affects people with type 1 diabetes at the onset of the disease. It can also affect people with type 2 diabetes, although this is uncommon. METHODS: Research and online content related to diabetes online activity is reviewed. DKA is caused by a relative or absolute deficiency of insulin and elevated levels of counter-regulatory hormones. RESULTS: Goals of therapy are to correct dehydration, acidosis, and to reverse ketosis, gradually restoring blood glucose concentration to near normal. CONCLUSION: It is essential to monitor potential complications of DKA and, if necessary, to treat them and any precipitating events.

Ivermectin, antiviral properties and COVID-19: a possible new mechanism of action.

Ivermectin is an antiparasitic drug that has shown also an effective pharmacological activity towards various infective agents, including viruses. This paper proposes an alternative mechanism of action for this drug that makes it capable of having an antiviral action, also against the novel coronavirus, in addition to the processes already reported in literature.

Water Quality Assessment: A Quali-Quantitative Method for Evaluation of Environmental Pressures Potentially Impacting on Groundwater, Developed under the M.I.N.O.Re. Project.

Background: At global level, the vulnerability of aquifers is deteriorating at an alarming rate due to environmental pollution and intensive human activities. In this context, Local Health Authority ASL Lecce has launched the M.I.N.O.Re. (Not Compulsory Water Monitoring Activities at Regional level) project, in order to assess the vulnerability of the aquifer in Salento area (Puglia Region) by performing several non-compulsory analyses on groundwater samples. This first paper describes the quali-quantitative approach adopted under the M.I.N.O.Re. project for the assessment of environmental pressures suffered by groundwater and determines the number of wells to be monitored in specific sampling areas on the basis of the local potential contamination and vulnerability of the aquifer. Methods: We created a map of the entire Lecce province, interpolating it with a grid that led to the subdivision of the study area in 32 quadrangular blocks measuring 10 km × 10 km. Based on current hydrogeological knowledge and institutional data, we used GIS techniques to represent on these 32 blocks the 12 different layers corresponding to the main anthropic or environmental type of pressures potentially impacting on the aquifer. To each kind of pressure, a score from 0 to 1 was attributed on the basis of the potential impact on groundwater. A total score was assigned to each of the 32 blocks. A higher number of wells was selected to be monitored in those blocks presenting higher risk scores for possible groundwater contamination due to anthropic/environmental pressures. Results: The range of total scores varied from 2.4 to 42.5. On the basis of total scores, the 10 km × 10 km blocks were divided into four classes of environmental pressure (1st class: from 0,1 to 10,00; 2nd class: from 10,01 to 20,00; 3rd class: from 20,1 to 30,00; 4th class: from 30,01 to 42,50). There were 11 areas in the 1st class, 9 areas in the 2nd class, 8 areas in the 3rd class and 4 areas in the 4th class. We assigned 1 monitoring well in 1st class areas, 2 monitoring wells in 2nd class areas, 3 monitoring wells in 3rd class areas and 4 monitoring wells in 4th class areas. Conclusion: The methodology developed under the M.I.N.O.Re. project could represent a useful model to be used in other areas to assess the environmental pressures suffered by aquifers and the quality of the groundwater.

Updated incidence and costs of hip fractures in elderly Italian population.

PURPOSE: We aimed at updating our previous researches about the burden of hip fractures in elderly Italian population. METHODS: We analyzed national hospitalizations records from 2000 to 2014 to compute age- and sex-specific standardized rates. RESULTS: 1,335,375 hospitalizations were recorded in people ≥ 65 (1,031,816 women: 77.27% and 303,559 men: 22.73%) over 15 years, passing from 73,493 in year 2000 to 94,525 in 2014, with an overall increase of 28.62% over the 15-year period (females: + 25.1%; males: + 41.2%). About 84.9% of total hip fractures were suffered by patients aged ≥ 75 years old. Direct hospitalization costs and rehabilitation costs increased from 343 to 457 million Euros and from 392 to 504 million Euros from year 2000 to 2014, respectively. Overall costs of hip fractures raised from 735 to 961 million Euros (+ 30.74% from 2000 to 2014). CONCLUSION: The number of hip fractures and related hospitalizations costs in Italian elderly population is still increasing due to the absolute number of fractures occurring in people ≥ 65 years old and particularly over 75 years old.

Air Pollution and Estimated Health Costs Related to Road Transportations of Goods in Italy: A First Healthcare Burden Assessment.

Background: The Italian Society of Environmental Medicine has performed a preliminary assessment of the health impact attributable to road freight traffic in Italy. Methods: We estimated fine particulate matter (PM10, PM2.5) and nitrogen oxides (NOx) generated by road transportation of goods in Italy considering the number of trucks, the emission factors and the average annual distance covered in the year 2016. Simulations on data concerning Years of Life Lost (YLL) attributable to PM2.5 (593,700) and nitrogen oxides NO2 (200,700) provided by the European Environmental Agency (EEA) were used as a proxy of healthcare burden. We set three different healthcare burden scenarios, varying from 1/5 to 1/10 of the proportion of the overall particulate matter attributable to road freight traffic in Italy (about 7% on a total of 2262 tons/year). Results: Road freight traffic in Italy produced about 189 tons of PM10, 147 tons of PM2.5 and 4125 tons of NOx in year 2016, resulting in annual healthcare costs varying from 400 million up to 1.2 billion EUR per year. Conclusion: Road freight traffic has a relevant impact on air pollution and healthcare costs, especially if considered over a 10-year period. Any solution able to significantly reduce the road transportation of goods could decrease avoidable mortality due to air pollution and related costs.

Incidence and costs of hip fractures in elderly Italian population: first regional-based assessment.

We analyzed for the first-time hospitalizations and costs for hip fractures in the elderly Italian population at the regional level from 2007 to 2014. The number of fractures and the overall costs increased, mainly due to people aged > 85 in all the Italian regions, although at different rates. OBJECTIVE: We aimed at evaluating the burden of hip fractures in elderly Italian population at the regional level. METHODS: We analyzed national hospitalizations records 2007-2014 to compute standardized hospitalizations rates (SHR) due to hip fractures per 10,000 inhabitants at the regional level and average annual percent change (AAPC), along with related costs. RESULTS: Hip fractures occurred in people over 65 years increased from 89,601 to 94,525 over 8 years. The overall increase in the number of hospitalizations is attributable only to people aged ≥85. Actually, in the 65-74 and 74-84 age groups, total hospitalizations decreased from 13,396 to 12,268 and from 40,733 to 37,786 respectively, while they increased from 35,472 to 44,471 in people aged ≥85 (women = 28,605 and men = 6,867 in 2007; women = 34,636 and men = 9,835 in 2014). Almost 50% of hip fractures were found to have been experienced by patients aged 85 or older in 2014 (with women ≥ 85 representing 36.6% of total fractures), in accordance with the higher prevalence of osteoporosis in this age group. Fractures increase in people aged ≥ 85 was two-folds higher in males (AAPC: + 5.0%; P > 0.05) than in females (AAPC: + 2.6%; P > 0.05). Increases in the number of hospitalizations and related costs were observed for all the regions, with the only exception of Lazio (AAPC: - 4.6%; P < 0.05) and Friuli Venezia Giulia (hip fractures AAPC: - 1.9%; P < 0.05). The most significant increases in hip fractures and related costs were recorded in Calabria (+ 2.7%), Campania (+ 2.2%), and Lombardia (+ 2.0%). At the national level, SHR per 10,000 inhabitants due to hip fractures decreased in all three examined age groups (65-74, 75-84, and ≥ 85), both in males and females during the 8-year period (P < 0.05). This reduction was confirmed also when looking at the regional dataset, with few exceptions concerning female population (AAPC not statistically significant). When looking at the SHR per 10,000 inhabitants for the entire nation, we recorded a decreasing trend also in females aged 85 years old and over but not in males ≥ 85. Actually, men aged ≥ 85 showed increased HR per 10,000 in 10 regions out of 20. Direct hospitalization and rehabilitation costs increased in all the regions over the 8-year period (although at different rates), except for Friuli Venezia Giulia (where costs decreased from 21 to 19 million Euros) and Lazio (from 107 to 87 million Euros). Lombardia and Piemonte were the regions spending the highest amount of money to treat hip fractures in elderly people (151 and 95 million Euros in the year 2014, respectively). CONCLUSION: Hip fractures in the elderly population remain a major public health issue in all Italian regions, especially in people aged 85 years old and over, although the problem is starting to become more controlled compared with the past. Women represent the majority of hip fractures, but the highest increasing rate has been observed in men. Pilot projects at regional level targeting elderly people at higher risk of fractures and treatment compliance are needed.

Effects of oral amino acid supplementation on Multidimensional Prognostic Index in hospitalized older patients: a multicenter randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: It is not known whether amino acid supplementations may influence health status in hospitalized older acutely ill patients. AIM: The aim of this study was to determine whether nutritional supplementation with amino acids (Aminoglutam®) is associated with multidimensional improvement assessed with the Multidimensional Prognostic Index (MPI). METHODS: In this randomized, double-blind, placebo-controlled pilot clinical trial, 126 patients aged ≥65 years were enrolled from 6 Italian geriatric wards. A multidimensional assessment to calculate the MPI was performed at baseline and after 4 weeks of treatment with nutritional supplementation (96 kcal, 12 g amino acids, 0.18 g fat, 11.6 g carbohydrate, and vitamins B1, B6, and C) or placebo administered twice a day. Logistic regression modeling was applied to determine the effect of treatment on the improvement of MPI (vs no-change/worsening), adjusting for gender, age, and MPI at baseline. Treatment's interactions with age, gender, and MPI at baseline were tested adding the appropriate interaction parameter in the regression models. RESULTS: Of the 126 patients included, 117 patients (93%) completed the study. A significant improvement in the MPI score was detected in the overall population (mean difference post-pretreatment: -0.03, p=0.001), with no differences between active and placebo arms. Men in the amino acid supplementation group had a significantly higher rate of improvement in MPI (81%) compared to the placebo group (46%) (Fisher's exact test p=0.03). Adjusting for age, diagnosis, and MPI at baseline, amino acid treatment was shown to be associated with an improvement in MPI in men (OR=4.82, 95% confidence interval [CI]: 0.87-26.7) and not in women (OR=0.70, 95% CI: 0.27-1.81). The interaction effect between active treatment and gender was significant (p=0.04). CONCLUSION: A 4-week amino acid supplementation improved the MPI significantly in hospitalized older male patients but not in female patients. Further studies are needed to confirm the gender effect of amino acid supplementation on MPI in older patients.