Achromobacter spp. adaptation in cystic fibrosis infection and candidate biomarkers of antimicrobial resistance

Achromobacter spp. can establish occasional or chronic lung infections in patients with cystic fibrosis (CF). Chronic colonization has been associated with worse prognosis highlighting the need to identify markers of bacterial persistence. To this purpose, we analyzed phenotypic features of 95 Achromobacter spp. isolates from 38 patients presenting chronic or occasional infection. Virulence was tested in Galleria mellonella larvae, cytotoxicity was tested in human bronchial epithelial cells, biofilm production in static conditions was measured by crystal violet staining and susceptibility to selected antibiotics was tested by the disk diffusion method. The presence of genetic loci associated to the analyzed phenotypic features was evaluated by a genome-wide association study. Isolates from occasional infection induced significantly higher mortality of G. mellonella larvae and showed a trend for lower cytotoxicity than chronic infection isolates. No significant difference was observed in biofilm production among the two groups. Additionally, antibiotic susceptibility testing showed that isolates from chronically-infected patients were significantly more resistant to sulfonamides and meropenem than occasional isolates. Candidate genetic biomarkers associated with antibiotic resistance or sensitivity were identified. Achromobacter spp. strains isolated from people with chronic and occasional lung infection exhibit different virulence and antibiotic susceptibility features, which could be linked to persistence in CF lungs. This underlines the possibility of identifying predictive biomarkers of persistence that could be useful for clinical purposes

Antimeningococcal and antipneumococcal vaccination determinants: A European systematic literature review

EACKGROUND: ESCULAPIO is a multicenter project, funded by the Italian Centre for Disease Prevention and Control, aimed at implementing communication strategies to improve vaccination knowledge and attitudes among different target populations. OBJECTIVE: The objective of the Sicilian research unit was, in the first phase, to identify, through systematic literature revision, which vaccination determinants play a role in the uptake of recommended vaccines included in the Italian Vaccination Plan. DESIGN: A systematic literature review was carried out on studies describing the determinants underlying pneumococcal and meningococcal vaccination uptake. The analysis was limited to papers published in English from 2000 to date. RESULTS: A total of 188 (meningococcal) and 731 (pneumococcal) papers were found. After selection by publication data, country (Europe), article type (original article), target population (healthy subjects), 7 (meningococcal) and 4 ( pneumococcal) manuscripts were finally included in the analysis. For meningococcal vaccination a better socioeconomic status is related to vaccination acceptance, whereas distance from immunization service is a negative determinant. For pneumococcal vaccination the determinants related to vaccination uptake are older parental age and a strong vaccine recommendation. Conversely, when the vaccine needs to be paid for, a refusal is more likely. CONCLUSIONS: Our results show that payment for vaccination is a major barrier and communication about meningococcal and pneumococcal vaccination should be targeted towards specific population groups, especially through the counseling activities by health professionals

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 < 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

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Virulence and antibiotic resistance of Achromobacter spp. isolates from chronic and occasional lung infection in cystic fibrosis patients

Background: Achromobacter spp. are opportunistic pathogens that can establish both chronic or occasional infections in the lungs of cystic fibrosis (CF) patients. Chronic infections caused by these bacterial species have been associated with decline in respiratory function and lung inflammation, highlighting the need to identify markers of persistence. To this purpose, in this study virulence and antibiotic resistance of isolates from CF chronic and occasional infection were analyzed. Methods: Ninety-five Achromobacter spp. clinical isolates were collected from 38 patients followed at the CF centers of Verona and Rome (Italy): 24 patients presented a chronic colonization and 14 an occasional infection. A number of features were evaluated in vitro: virulence potential through inoculation of bacteria in Galleria mellonella larvae; susceptibility to selected antibiotics by Kirby-Bauer disk diffusion test; cytotoxicity by quantitative measurement of lactate dehydrogenase; biofilm formation by crystal violet staining of surface‐attached bacteria cultured in static conditions. Statistical analysis was performed to compare chronic and occasional isolates and ascertain the significance of results. Results: Virulence testing showed that isolates from occasionally infected patients induced significantly higher mortality of G. mellonella larvae than chronic infection isolates (Kaplan-Meier survival estimate p-value=0.02; Cox hazard ratio=1.32; 95% confidence interval (CI)=1.04-1.66). As concerns antibiotic susceptibility, isolates from chronically infected patients were significantly more resistant to sulfonamide and meropenem (respectively: Fisher’s exact test p-value=0.04 and 0.01 after 10000 permutations; CI=0.04-0.62 and 0-0.34; odds ratio=0.17 and 0) than occasional isolates. Cytotoxicity was tested in human bronchial epithelial cells: although no statistically significant difference was found, we observed that chronic infection isolates induced greater cytotoxicity than occasional isolates (Wilcoxon Mann Whitney p-value=0.05). Finally, no significant difference was observed in biofilm production among the two groups. Conclusion: Our results show that Achromobacter spp. isolates from chronic and occasional lung infection exhibit different virulence and antibiotic resistance characteristics, some of which might be linked to persistence in CF lungs. This highlights the potential to identify predictive markers of persistence that could be translated into the clinical setting. Acknowledgements: This study was supported by the Italian Cystic Fibrosis Research Foundation (project FFC#18/2019)

Analysis of RBFOX1 gene expression in lymphoblastoid cell lines of Italian discordant autism spectrum disorders sib-pairs

Several lines of evidence suggest that RBFOX1 is a key regulator of transcriptional and splicing programs in neural cells during development, and that it is expressed in a neuronal module enriched for known autism susceptibility genes. We have investigated its expression by semiquantitative RT-PCR in accessible nonbrain resources in eighteen autism spectrum disorder sib-pairs belonging to the Italian Autism Network cohort. RBFOX1 gene expression was detected in lymphoblastoid cell lines but not in lymphocytes. No significant differences between autism spectrum disorders and non-affected brothers were found. We were not able to replicate in lymphoblastoid cell lines the previously reported RBFOX1 gene downregulation in autism, even if a trend was observed. This might be due to less pronounced transcription level differences in RBFOX1 gene expression in lymphoblastoid cell lines than in brain samples. \ua9 2014 Elsevier Ltd

Riluzole and other prognostic factors in ALS: a population-based registry study in Italy

In this prospective population-based registry study on ALS survival, we investigated the role of riluzole treatment, together with other clinical factors, on the prognosis in incident ALS cases in Emilia Romagna Region (ERR), Italy

Riluzole and other prognostic factors in ALS: a population-based registry study in Italy

Objective: In this prospective population-based registry study on ALS survival, we investigated the role of riluzole treatment, together with other clinical factors, on the prognosis in incident ALS cases in Emilia Romagna Region (ERR), Italy. Methods: A registry for ALS has been collecting all incident cases in ERR since 2009. Detailed clinical data from all patients diagnosed with ALS between 1.1.2009 and 31.12.2014 have been analyzed for this study, with last follow up date set at 31.12.2015. Results: During the 6 years of the study, there were 681 incident cases with a median tracheostomy-free survival of 40 months (95% CI 36â\u80\u9344) from onset and of 26 months (95% CI 24â\u80\u9330) from diagnosis; 573 patients (84.14%) were treated with riluzole, 207 (30.39%) patients underwent gastrostomy, 246 (36.12%) non invasive ventilation, and 103 (15.15%) invasive ventilation. Patients who took treatment for â\u89¥Â 75% of disease duration from diagnosis had a median survival of 29 months compared to 18 months in patients with < 75% treatment duration. In multivariable analysis, factors independently influencing survival were age at onset (HR 1.04, 95% CI 1.02â\u80\u931.05, p < 0.001), dementia (HR 1.56, 95% CI 1.05â\u80\u932.32, p = 0.027), degree of diagnostic certainty (HR 0.88, 95% CI 0.78â\u80\u930.98, p = 0.021), gastrostomy (HR 1.46, 95% CI 1.14â\u80\u931.88, p = 0.003), NIV (HR 1.43, 95% CI 1.12â\u80\u931.82, p = 0.004), and weight loss at diagnosis (HR 1.05, 95% CI 1.03â\u80\u931.07, p < 0.001), diagnostic delay (HR 0.98, 95% CI 0.97â\u80\u930.99, p = 0.004), and % treatment duration (HR 0.98, 95% CI 0.98â\u80\u930.99, p < 0.001). Conclusions: Independently from other prognostic factors, patients who received riluzole for a longer period of time survived longer, but further population based studies are needed to verify if long-tem use of riluzole prolongs survival