Prognostic Value of Mid-Region Proadrenomedullin and In Vitro Interferon Gamma Production for In-Hospital Mortality in Patients with COVID-19 Pneumonia and Respiratory Failure: An Observational Prospective Study.

Coagulopathy and immune dysregulation have been identified as important causes of adverse outcomes in coronavirus disease (COVID-19). Mid-region proadrenomedullin (MR-proADM) is associated with endothelial damage and has recently been proposed as a prognostic factor in COVID-19. In non-COVID-19 immunocompromised patients, low in vitro interferon gamma (IFNγ) production correlates with infection risk and mortality. This prospective, monocentric, observational study included adult patients consecutively admitted with radiologic evidence of COVID-19 pneumonia and respiratory failure. MR-proADM and in vitro IFNγ production were measured at T0 (day 1 from admission) and T1 (day 7 from enrollment). One hundred patients were enrolled. Thirty-six percent were females, median age 65 (Q1−Q3 54.5−75) years, and 58% had ≥1 comorbidity. Only 16 patients had received COVID-19 vaccination before hospitalization. At admission, the median PaO2:FiO2 ratio was 241 (157−309) mmHg. In-hospital mortality was 13%. MR-proADM levels differed significantly between deceased and survivors both at T0 (1.41 (1.12−1.77) nmol/L vs. 0.79 (0.63−1.03) nmol/L, p < 0.001) and T1 (1.67 (1.08−1.96) nmol/L vs. 0.66 (0.53−0.95) nmol/L, p < 0.001). In vitro IFNγ production at T0 and T1 did not vary between groups. When only the subset of non-vaccinated patients was considered, both biomarkers at T1 resulted significantly associated with in-hospital mortality. AUROC for MR-proADM at T0 to predict in-hospital mortality was 0.87 (95%CI 0.79−0.94), with the best cut-off point at 1.04 nmol/L (92% sensitivity, 75% specificity and 98% negative predictive value). In patients with COVID-19 pneumonia and different degrees of respiratory failure, MR-proADM at admission and during hospitalization resulted strongly associated with in-hospital mortality. Low in vitro IFNγ production after the first week of hospitalization was associated with mortality in non-vaccinated patients possibly identifying the subgroup characterized by a higher degree of immune suppression.

Risk Factors and Predictive Score for Bacteremic Biliary Tract Infections Due to Enterococcus faecalis and Enterococcus faecium: a Multicenter Cohort Study from the PROBAC Project.

Biliary-tract bloodstream infections (BT-BSI) caused by Enterococcus faecalis and E. faecium are associated with inappropriate empirical treatment and worse outcomes compared to other etiologies. The objective of this study was to investigate the risk factors for enterococcal BT-BSI. Patients with BT-BSI from the PROBAC cohort, including consecutive patients with BSI in 26 Spanish hospitals between October 2016 and March 2017, were selected; episodes caused by E. faecalis or E. faecium and other causes were compared. Independent predictors for enterococci were identified by logistic regression, and a predictive score was developed. Eight hundred fifty episodes of BT-BSI were included; 73 (8.5%) were due to target Enterococcus spp. (48 [66%] were E. faecium and 25 [34%] E. faecalis). By multivariate analysis, the variables independently associated with Enterococcus spp. were (OR; 95% confidence interval): cholangiocarcinoma (4.48;1.32 to 15.25), hospital acquisition (3.58;2.11 to 6.07), use of carbapenems in the previous month (3.35;1.45 to 7.78), biliary prosthesis (2.19;1.24 to 3.90), and moderate or severe chronic kidney disease (1.55;1.07 to 2.26). The AUC of the model was 0.74 [95% CI0.67 to 0.80]. A score was developed, with 7, 6, 5, 4, and 2 points for these variables, respectively, with a negative predictive value of 95% for a score ≤ 6. A model, including cholangiocarcinoma, biliary prosthesis, hospital acquisition, previous carbapenems, and chronic kidney disease showed moderate prediction ability for enterococcal BT-BSI. Although the score will need to be validated, this information may be useful for deciding empirical therapy in biliary tract infections when bacteremia is suspected. IMPORTANCE Biliary tract infections are frequent, and a significant cause of morbidity and mortality. Bacteremia is common in these infections, particularly in the elderly and patients with cancer. Inappropriate empirical treatment has been associated with increased risk of mortality in bacteremic cholangitis, and the probability of receiving inactive empirical treatment is higher in episodes caused by enterococci. This is because many of the antimicrobial agents recommended in guidelines for biliary tract infections lack activity against these organisms. To the best of our knowledge, this is the first study analyzing the predictive factors for enterococcal BT-BSI and deriving a predictive score.

Risk Factors for Mortality in COVID-19 Hospitalized Patients in Piedmont, Italy: Results from the Multicenter, Regional, CORACLE Registry.

BACKGROUND: CORACLE is a retrospective and prospective, regional multicenter registry, developed to evaluate risk factors for mortality in a cohort of patients admitted with SARS-CoV-2 infection within non-intensive wards. METHODS: The primary objective was to estimate the role of several prognostic factors on hospital mortality in terms of adjusted Odds Ratios (aOR) with multivariable logistic regression models. RESULTS: A total of 1538 patients were enrolled; 42% were female, and 58% were >70 years old. Deceased patients were 422 (27%), with a median age of 83 years (IQR (Inter Quartile Range) 76-87). Older age at admission (aOR 1.07 per year, 95%CI 1.06-1.09), diabetes (1.41, 1.02-1.94), cardiovascular disease (1.79, 1.31-2.44), immunosuppression (1.65, 1.04-2.62), estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (3.53, 2.26-5.51), higher C-reactive protein values and a decreased PaO2/FiO2 ratio at admission were associated with a higher risk of hospital mortality. Amongst patients still alive on day 7, only hydroxychloroquine (HCQ) treatment was associated with reduced mortality (0.57, 0.36-0.90). CONCLUSIONS: Several risk factors were associated with mortality in SARS-CoV-2 positive patients. Although HCQ seems to be the only factor significantly associated with reduced mortality, this result is in contrast with evidence from randomized studies. These results should be interpreted in light of the study limitations.

Baseline clinical characteristics and prognostic factors in hospitalized COVID-19 patients aged ≤ 65 years: A retrospective observational study.

BACKGROUND: Individual differences in susceptibility to SARS-CoV-2 infection, symptomatology and clinical manifestation of COVID-19 have thus far been observed but little is known about the prognostic factors of young patients. METHODS: A retrospective observational study was conducted on 171 patients aged ≤ 65 years hospitalized in Alessandria's Hospital from 1st March to 30th April 2020 with laboratory confirmed COVID-19. Epidemiological data, symptoms at onset, clinical manifestations, Charlson Comorbidity Index, laboratory parameters, radiological findings and complications were considered. Patients were divided into two groups on the basis of COVID-19 severity. Multivariable logistic regression analysis was used to establish factors associated with the development of a moderate or severe disease. FINDINGS: A total of 171 patients (89 with mild/moderate disease, 82 with severe/critical disease), of which 61% males and a mean age (± SD) of 53.6 (± 9.7) were included. The multivariable logistic model identified age (50-65 vs 18-49; OR = 3.23 CI95% 1.42-7.37), platelet count (per 100 units of increase OR = 0.61 CI95% 0.42-0.89), c-reactive protein (CPR) (per unit of increase OR = 1.12 CI95% 1.06-1.20) as risk factors for severe or critical disease. The multivariable logistic model showed a good discriminating capacity with a C-index value of 0.76. INTERPRETATION: Patients aged ≥ 50 years with low platelet count and high CRP are more likely to develop severe or critical illness. These findings might contribute to improved clinical management.

Cryptococcosis in an HIV-negative, HCV positive, immunosenescent patient: a case report.

Cryptococcus species is still a very common opportunistic infection in AIDS patients. However, it is increasingly responsible for disease in otherwise immunocompromised individuals, such as transplant recipients and the heterogeneous group of patients with underlying immunologic diseases, hematologic disorders and organ failure syndromes. Clinical presentation, prognosis, and outcomes are difficult to define given these varied host groups, and tailoring treatments to fit the necessities of each patient is likewise challenging. Our patient was on treatment with steroids and direct-acting antiviral agents (DAAs) for a chronic HCV-related hepatitis, worsened by cryoglobulinemia, membranoproliferative glomerulonephritis and a lowgrade B cells lymphoma. We report a case of systemic cryptococcal infection in an immunosenescent, HIV-negative patient.

Primary Spinal Epidural Abscesses Not Associated With Pyogenic Infectious Spondylodiscitis: A New Pathogenetic Hypothesis.

Introduction: Spinal epidural abscess (SEA) incidence is rising. However, most series do not differentiate between SEAs associated with pyogenic infectious spondylodiscitis (PS) and SEAs limited to the epidural space. Methods: We retrospectively reviewed the records and radiological images of all patients admitted to our institutions with a diagnosis of SEA not associated with PS between January 2013 and December 2018. Results: We found three males and four females; five of the seven were intravenous drug users. All patients presented with pain: in six, it was associated with acute motor and sensory deficits, while one had only pain and paresthesias. Staphylococcus aureus was cultured from abscesses and/or from multiple blood cultures in four patients. Abscesses were localized to the cervical spine in one patient, thoracic in three, lumbar in one, and in two, the SEAs involved multiple segments. All patients but one underwent urgent open surgery. This patient had a multisegmental abscess and was successfully treated by percutaneous aspiration when pain became intractable. After abscess evacuation, the neurological deficits improved in all patients except one. The patients that were treated without spine instrumentation did not develop delayed kyphosis or instability at follow-up. Conclusion: Patients with SEAs not associated with PS are likely to present with pain and motor deficits, appear to benefit from urgent abscess evacuation, and seem to be less dependent on spine instrumentation to avoid delayed spinal deformities compared to SEA associated with PS. Finally, the lack of initial involvement of bone and intervertebral disks may suggest that at least some of the SEAs without PS originate from infection of epidural lymphatic vessels that are not present inside those structures.

Cryptococcosis in an HIV-negative, HCV positive, immunosenescent patient: a case report.

Cryptococcus species is still a very common opportunistic infection in AIDS patients. However, it is increasingly responsible for disease in otherwise immunocompromised individuals, such as transplant recipients and the heterogeneous group of patients with underlying immunologic diseases, hematologic disorders and organ failure syndromes. Clinical presentation, prognosis, and outcomes are difficult to define given these varied host groups, and tailoring treatments to fit the necessities of each patient is likewise challenging. Our patient was on treatment with steroids and direct-acting antiviral agents (DAAs) for a chronic HCV-related hepatitis, worsened by cryoglobulinemia, membranoproliferative glomerulonephritis and a low-grade B cells lymphoma. We report a case of systemic cryptococcal infection in an immunosenescent, HIV-negative patient.

Necrotizing Fasciitis by Two Anaerobic Bacteria in an Immunocompetent Patient after Minor Trauma: A Case Report.

Necrotizing fasciitis (NF) is a soft tissue infection affecting subcutaneous tissue and the muscular fascia without involvement of the muscle and can be either monomicrobial or polymicrobial. Monomicrobial infections are usually caused by group A streptococci, while infections caused by anaerobic germs usually affect immunodepressed patients. We report a rare case of NF caused by two anaerobic bacteria in an immunocompetent patient.

Emerging biological agents for hepatitis C.

INTRODUCTION: New direct-acting antiviral agents have changed the landscape of treatment of chronic HCV infection. Despite current treatments are well tolerated with a high rate of sustained virological response (SVR), some medical needs remain. Nowadays there are a large number of approved medications for the treatment of HCV infection; nevertheless, new studies are conducted to find new agents and new combinations. AREAS COVERED: A literature research of new antiviral compounds indicated for the treatment of HCV infection was achieved by an online search of medication undergoing development on Pubmed and clinicalTrials.gov clinical trials registry. We considered phase I/II studies and some randomized Phase III trials. EXPERT OPINION: More knowledge about impact of HCV eradication on disease progression and more confidence regarding drug-drug interaction are needed. Furthermore, each treatment should be individualized targeting the patients needs with the aim not only to obtain viral suppression but also to stop progression of liver disease and HCV related conditions, and to improve patient health status.