Role of BRCA2 mutation status on overall survival among breast cancer patients from Sardinia

Background: Germline mutations in BRCA1 or BRCA2 genes have been demonstrated to increase the risk of developing breast cancer. Conversely, the impact of BRCA mutations on prognosis and survival of breast cancer patients is still debated. In this study, we investigated the role of such mutations on breast cancer-specific survival among patients from North Sardinia. Methods: Among incident cases during the period 1997–2002, a total of 512 breast cancer patients gave their consent to undergo BRCA mutation screening by DHPLC analysis and automated DNA sequencing. The Hakulinen, Kaplan-Meier, and Cox regression methods were used for both relative survival assessment and statistical analysis. Results: In our series, patients carrying a germline mutation in coding regions and splice boundaries of BRCA1 and BRCA2 genes were 48/512 (9%). Effect on overall survival was evaluated taking into consideration BRCA2 carriers, who represented the vast majority (44/48; 92%) of mutation-positive patients. A lower breast cancer-specific overall survival rate was observed in BRCA2 mutation carriers after the first two years from diagnosis. However, survival rates were similar in both groups after five years from diagnosis. No significant difference was found for age of onset, disease stage, and primary tumour histopathology between the two subsets. Conclusion: In Sardinian breast cancer population, BRCA2 was the most affected gene and the effects of BRCA2 germline mutations on patients' survival were demonstrated to vary within the first two years from diagnosis. After a longer follow-up observation, breast cancer-specific rates of death were instead similar for BRCA2 mutation carriers and non-carriers

Computer-assisted navigation for intramedullary nailing of intertrochanteric femur fractures: a preliminary result

Aim To demonstrate a reduction of risk factors ray-depending in proximal femur nailing of intertrochanteric femur fractures, comparing standard technique with computer-assisted navigation system. Methods One hundred patients hospitalised between October 2021 and June 2022 with intertrochanteric femur fractures type 31-A1 and 31-A2 were prospectively enrolled and divided randomly into two groups. A study group was treated with computer-assisted navigation system ATLAS (Masmec Biomed, Modugno, Bari, Italy) (20 patients), while a control group received the standard nailing technique. The same intertrochanteric nail was implanted by a single senior surgeon, Endovis BA 2 (EBA2, Citieffe, Calderara di Reno, Bologna, Italy). The following data were recorded: the setup time of operating room (STOR; minutes); surgical time (ST; minutes); radiation exposure time (ETIR; seconds) and dose area product (DAP; cGy·cm2). Results Patients underwent femur nailing with computer-assisted navigation system reported more set-up time of operating room (24.87±4.58; p<0.01), less surgical time (26.15±5.80; p<0.01), less time of radiant exposure (4.84±2.07; p<0.01) and lower dose area product (16.26±2.91; p<0.01). Conclusion The preliminary study demonstrated that computerassisted navigation allowed a better surgical technique standardization, significantly reduced exposure to ionizing radiation, including a reduction in surgical time. The ATLAS system could also play a key role in residents improving learning curve

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P &lt; 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6+/-9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; pPeer reviewe

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Cumulative incidence estimation in the presence of competing risks

When competing risks are present, the appropriate estimate of the failure probabilities is the cumulative incidence. stcompet creates new variables containing the estimate of this function, its standard error, and ln(−ln) transformed confidence bounds. Two examples are presented to illustrate the use of the new command and some key features of the cumulative incidence

Cumulative incidence estimation in the presence of competing risks

When competing risks are present, the appropriate estimate of the failure probabilities is the cumulative incidence. stcompet creates new variables containing the estimate of this function, its standard error, and ln(-ln) transformed confidence bounds. Two examples are presented to illustrate the use of the new command and some key features of the cumulative incidence. Copyright 2004 by StataCorp LP.stcompet, survival analysis, competing risks, cumulative incidence

Recent Developments in Plasmonic Alloy Nanoparticles: Synthesis, Modelling, Properties and Applications

Despite the traditional plasmonic materials are counted on one hand, there are a lot of possible combinations leading to alloys with other elements of the periodic table, in particular those renowned for magnetic or catalytic properties. It is not a surprise, therefore, that nanoalloys are considered for their ability to open new perspectives in the panorama of plasmonics, representing a leading research sector nowadays. This is demonstrated by a long list of studies describing multiple applications of nanoalloys in photonics, photocatalysis, sensing and magneto-optics, where plasmons are combined with other physical and chemical phenomena. In some remarkable cases, the amplification of the conventional properties and even new effects emerged. However, this field is still in its infancy and several challenges must be overcome, starting with the synthesis (control of composition, crystalline order, size, processability, achievement of metastable phases and disordered compounds) as well as the modelling of the structure and properties (accuracy of results, reliability of structural predictions, description of disordered phases, evolution over time) of nanoalloys. To foster the research on plasmonic nanoalloys, here we provide an overview of the most recent results and developments in the field, organized according to synthetic strategies, modelling approaches, dominant properties and reported applications. Considering the several plasmonic nanoalloys under development as well as the large number of those still awaiting synthesis, modelling, properties assessment and technological exploitation, we expect a great impact on the forthcoming solutions for sustainability, ultrasensitive and accurate detection, information processing and many other fields