BACKGROUND:Recent studies supported the association between occupational exposure to asbestos and risk of cholangiocarcinoma (CC). Aim of the present study is to investigate this association using an update of mortality data from the Italian pooled asbestos cohort study and to test record linkage to Cancer Registries to distinguish between hepatocellular carcinoma (HCC) and intrahepatic/extrahepatic forms of CC. METHODS:The update of a large cohort study pooling 52 Italian industrial cohorts of workers formerly exposed to asbestos was carried out. Causes of death were coded according to ICD. Linkage was carried out for those subjects who died for liver or bile duct cancer with data on histological subtype provided by Cancer Registries. RESULTS:47 cohorts took part in the study (57,227 subjects). We identified 639 causes of death for liver and bile duct cancer in the 44 cohorts covered by Cancer Registry. Of these 639, 240 cases were linked to Cancer Registry, namely 14 CC, 83 HCC, 117 cases with unspecified histology, 25 other carcinomas, and one case of cirrhosis (likely precancerous condition). Of the 14 CC, 12 occurred in 2010-2019, two in 2000-2009, and none before 2000. CONCLUSION:Further studies are needed to explore the association between occupational exposure to asbestos and CC. Record linkage was hampered due to incomplete coverage of the study areas and periods by Cancer Registries. The identification of CC among unspecific histology cases is fundamental to establish more effective and targeted liver cancer screening strategies.

The standardization of Gram-negative bloodstream infection (GN-BSI) management is challenging ( 1 Thaden J.T. Tamma P.D. Pan Q. Doi Y. Daneman N. Survey of infectious diseases providers reveals variability in duration of antibiotic therapy for the treatment of Gram-negative bloodstream infections. JAC Antimicrob Resist. Marzo 2022; 4dlac005 Crossref Scopus (2) Google Scholar , 2 Gatti M. Bonazzetti C. Tazza B. Pascale R. Miani B. Malosso M. et al. Impact on clinical outcome of follow-up blood cultures and risk factors for persistent bacteraemia in patients with gram-negative bloodstream infections: a systematic review with meta-analysis. Clin Microbiol Infect. Settembre 2023; 29: 1150-1158 Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar ). Heil and colleagues proposed a definition of uncomplicated GN-BSI (uGN-BSI) based on the host immune system status, the source of GN-BSI, the quality of source control and the clinical response ( 3 Heil E.L. Bork J.T. Abbo L.M. Barlam T.F. Cosgrove S.E. Davis A. et al. Optimizing the Management of Uncomplicated Gram-Negative Bloodstream Infections: Consensus Guidance Using a Modified Delphi Process. Open Forum Infect Dis. Ottobre 2021; 8ofab434 Crossref Scopus (33) Google Scholar ). The authors proposed that patients with uGN-BSI may not need follow-up blood cultures (FU-BCs) and can receive a short treatment duration. A real-life evaluation of this new definition is necessary before introducing it into clinical practice. We retrospectively analysed the prognostic utility of uGN-BSI definition in a cohort of adult patients with GN-BSI hospitalized at the IRCCS Azienda Ospedaliero-Universitaria of Bologna during 5-year period (see Supplementary Material). The study was approved by the local Ethics Committee (n° 894/2021/Oss/AOUBo).

BACKGROUND:Management of infections due to carbapenemase-resistant Enterobacterales (CRE) in solid organ transplant (SOT) recipients remains a difficult challenge. The INCREMENT-SOT-CPE score has been specifically developed from SOT recipients to stratify mortality risk, but an external validation is lacking.METHODS:Multicenter retrospective cohort study of liver transplant (LT) recipients colonized with CRE infection who developed infection after transplant over 7-year period. Primary endpoint was all-cause 30-day mortality from infection onset. A comparison between INCREMENT-SOT-CPE and other selected scores was performed. A two-level mixed effects logistic regression model with random effects for the center was fitted. Performance characteristics at optimal cut-point were calculated. Multivariable Cox regression analysis of risk factors for all-cause 30-day mortality was carried out.RESULTS:Overall, 250 CRE carriers developed infection after LT and were analyzed. The median age was 55 years (interquartile range [IQR]: 46-62) and 157 were males (62.8%). All-cause 30-day mortality was 35.6%. A sequential organ failure assessment (SOFA) score ≥ 11 showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 69.7%, 76.4%, 62.0%, 82.0%, and 74.0%, respectively. An INCREMENT-SOT-CPE ≥ 11 reported a sensitivity, specificity, PPV, NPV, and accuracy of 73.0%, 62.1%, 51.6%, 80.6% and 66.0%, respectively. At multivariable analysis acute renal failure, prolonged mechanical ventilation, INCREMENT-SOT-CPE score ≥ 11 and SOFA score ≥ 11 were independently associated with all-cause 30-day mortality, while a tigecycline-based targeted regimen was found to be protective.CONCLUSIONS:Both INCREMENT-SOT-CPE ≥ 11 and SOFA ≥ 11 were identified as strong predictors of all-cause 30-day mortality in a large cohort of CRE carriers developing infection after LT.

Abstract Purpose To investigate the clinical impact of three available antivirals for early COVID-19 treatment in a large real-life cohort. Methods Between January and October 2022 all outpatients tested positive for SARS-CoV-2 referring to IRCCS S. Orsola hospital treated with an early antiviral therapy were enrolled. A comparison between patients treated with nirmatrelvir/ritonavir (NTV/r), molnupiravir (MPV) and remdesivir (RDV) was conducted in term of indications and outcome. To account for differences between treatment groups a propensity score analysis was performed. After estimating the weights, we fitted a survey-weighted Cox regression model with inverse-probability weighting with hospital admission/death versus clinical recovery as the primary outcome. Results Overall 1342 patients were enrolled, 775 (57.8%), 360 (26.8%) and 207 (15.4%) in MPV, NTV/r and RDV group, respectively. Median age was 73 (59–82) years, male sex was 53.4%. Primary indication was immunosuppression (438, 32.6%), the median time from symptom onset to drug administration was 3 [2–4] days. Overall, clinical recovery was reached in 96.9% of patients, with hospital admission rate of 2.6%. No significant differences were found in clinical recovery nor hospitalization. Cox regression showed a decreased probability of hospital admission/ death among prior vaccinated patients compared with unvaccinated (HR 0.31 [95%CI 0.14–0.70], p = 0.005]). No difference in hospitalization rates in early treatment compared to late treatment were found. Conclusions No differences among MPV, NTV/r and RDV in terms of clinical recovery or hospitalization were found. Patients not vaccinated had a significant increased risk of hospitalization.

Background and aim. Cholangiocarcinoma (CC) is the second most common primary liver malignancy. Anatomically, CC is divided into intrahepatic (ICC) and extrahepatic (ECC) forms. A possible causal association between ICC and exposure to asbestos has been hypothesized. To support this, we compared age-standardized incidence rates (ASR) of CC and malignant pleural mesothelioma (MPM) in Italy considering that asbestos is thought one of the major risk factors for MPM. Materials and Methods. We extracted ASR of ICC, ECC and MPM reported by 36 Italian cancer registries and listed in the last report on Cancer Incidence in Five Continents of the IARC. Data referred to 2008-2012 and covered 29 million population. We used linear regression analysis to evaluate the possible association between ASR of ICC, ECC and MPM. Analyses were stratified by sex. Results. From 2008 to 2012 ASR per 100,000/years in men ranged: 0.4-2.2 for ICC, 0.5-1.8 for ECC, and 0.0-0.7 for MPM. In women, ASR per 100,000/years ranged: 0.2-1.0 for ICC, 0.1-1.3 for ECC, and 0.0-0.6 for MPM. At regression analysis ICC did not report an association with MPM in men (beta coefficient -0.044, 95%CI -0.980–0.892) and women (beta coefficient -0.093, 95%CI -0.670–0.485). No association was detected for ECC as well. Conclusions. This crude analysis does not appear to support the hypothesis that CC could be associated to exposure to asbestos. This could be related to the large amount of known and suspected risk factors for CC that include common liver diseases due to genes, viruses and personal habits. Analyses adjusted for aggregated data might help disentangle this issue. Keywords: Asbestos, Cholangiocarcinoma, age-standardized incidence rates.

The aim of our study was to build a predictive model able to stratify the risk of bacterial co-infection at hospitalization in patients with COVID-19. Multicenter observational study of adult patients hospitalized from February to December 2020 with confirmed COVID-19 diagnosis. Endpoint was microbiologically documented bacterial co-infection diagnosed within 72 h from hospitalization. The cohort was randomly split into derivation and validation cohort. To investigate risk factors for co-infection univariable and multivariable logistic regression analyses were performed. Predictive risk score was obtained assigning a point value corresponding to β-coefficients to the variables in the multivariable model. ROC analysis in the validation cohort was used to estimate prediction accuracy. Overall, 1733 patients were analyzed: 61.4% males, median age 69 years (IQR 57–80), median Charlson 3 (IQR 2–6). Co-infection was diagnosed in 110 (6.3%) patients. Empirical antibiotics were started in 64.2 and 59.5% of patients with and without co-infection (p = 0.35). At multivariable analysis in the derivation cohort: WBC ≥ 7.7/mm3, PCT ≥ 0.2 ng/mL, and Charlson index ≥ 5 were risk factors for bacterial co-infection. A point was assigned to each variable obtaining a predictive score ranging from 0 to 5. In the validation cohort, ROC analysis showed AUC of 0.83 (95%CI 0.75–0.90). The optimal cut-point was ≥2 with sensitivity 70.0%, specificity 75.9%, positive predictive value 16.0% and negative predictive value 97.5%. According to individual risk score, patients were classified at low (point 0), intermediate (point 1), and high risk (point ≥ 2). CURB-65 ≥ 2 was further proposed to identify patients at intermediate risk who would benefit from early antibiotic coverage. Our score may be useful in stratifying bacterial co-infection risk in COVID-19 hospitalized patients, optimizing diagnostic testing and antibiotic use.