Prognostic bioindicators in severe COVID-19 patients.

BACKGROUND: Severe acute respiratory syndrome caused by novel coronavirus 2 (SARS-CoV-2) emerged in Wuhan (China) in December 2019. Here we evaluated a panel of biomarkers to phenotype patients and to define the role of immuno-inflammatory mediators as biomarkers of severity. MATERIALS AND METHODS: Serum samples were obtained from 24 COVID-19 patients on admission to hospital, before any treatment or infusion of intravenous steroids or invasive ventilation. KL-6 IL-6 and C-peptide were measured by chemiluminescent enzyme immunoassay. IL-6 assay was validated for accuracy and precision. The validity of variables used to distinguish severe from mild-to-moderate patients was assessed by areas under curves (AUC) of the receiver operating characteristic (ROC) and logistic regression was performed to combine parameters of the two groups. RESULTS: In the severe group, IL-6, CRP and KL-6 concentrations were significantly higher than in mild-to-moderate patients. KL-6, IL-6 and CRP concentrations were directly correlated with each other. ROC curve analysis of the logistic regression model including IL-6, KL-6 and CRP showed the best performance with an AUC of 0.95. CONCLUSIONS: Besides corroborating previous reports of over-expression of IL-6 in severe COVID-19 patients requiring mechanical ventilation, analytical determination of other mediators showed that IL-6 concentrations were correlated with those of KL-6 and CRP. The combination of these three prognostic bioindicators made it possible to distinguish severe COVID-19 patients with poor prognosis from mild-to-moderate patients.

Incidence and risk factors for respiratory tract bacterial colonization and infection in lung transplant recipients.

To evaluate incidence of and risk factors for respiratory bacterial colonization and infections within 30 days from lung transplantation (LT). We retrospectively analyzed microbiological and clinical data from 94 patients transplanted for indications other than cystic fibrosis, focusing on the occurrence of bacterial respiratory colonization or infection during 1 month of follow-up after LT. Thirty-three percent of patients developed lower respiratory bacterial colonization. Bilateral LT and chronic heart diseases were independently associated to a higher risk of overall bacterial colonization. Peptic diseases conferred a higher risk of multi-drug resistant (MDR) colonization, while longer duration of aerosol prophylaxis was associated with a lower risk. Overall, 35% of lung recipients developed bacterial pneumonia. COPD (when compared to idiopathic pulmonary fibrosis, IPF) and higher BMI were associated to a lower risk of bacterial infection. A higher risk of MDR infection was observed in IPF and in patients with pre-transplant colonization and infections. The risk of post-LT respiratory infections could be stratified by considering several factors (indication for LT, type of LT, presence of certain comorbidities, and microbiologic assessment before LT). A wider use of early nebulized therapies could be useful to prevent MDR colonization, thus potentially lowering infectious risk.

The S-Finger: A Synergetic Externally Powered Digit With Tactile Sensing and Feedback.

Partial hand amputation is by far the most common type of amputation worldwide. Nevertheless, regardless of their potential clinical and socioeconomic impact, battery-powered partial hand prostheses, namely, powered digits, have modestly progressed so far, and very few clinical solutions are available today. Here, we present a mechanical architecture, an alternative to state-of-the-art solutions, which exploits a high efficiency, non-back drivable mechanical transmission based on a face-gear pair and a miniaturized clutch. We took inspiration from the synergetic prehension approach proposed by Childress for whole hand amputation. The finger was equipped with a myoelectric controller and a tactile sensor able to provide users with discrete event sensory feedback. Measured speed (90°/s) and force (6.5 N) of the newly dubbed S-Finger proved comparable with those of clinically available prostheses. The design demonstrated to be compact and rugged enough to undergo a clinical viability test with two partial hand amputees, fitted with custom three-fingered research prostheses using the S-Finger. The subjects successfully completed several dexterity tests and gave relevant feedback for the development of a second-generation device. These results contribute to the increasing research endeavors in the field of partial hand amputation.

A systematic review of FOLFOXIRI chemotherapy for the first-line treatment of metastatic colorectal cancer: improved efficacy at the cost of increased toxicity.

AIM: The simultaneous administration of irinotecan, 5-fluorouracil, folinic acid and oxaliplatin (FOLFOXIRI) has been compared with standard 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) in randomized trials in metastatic colorectal cancer patients. A superior efficacy of FOLFOXIRI has been reported by some authors, but others have failed to show any differences and do not recommend its use because of greater cost and toxicity. We performed a systematic review of the literature to analyse efficacy and toxicity of FOLFOXIRI. METHOD: Odds ratios (OR) with 95% confidence intervals (CI) were used to analyse dichotomous variables. Hazard ratios (HR) for progression and death were combined with an inverse variance method based on logarithmic conversion. A fixed-effect model and Mantel-Haenszel's method were used. Heterogeneity was tested with Cochrane's Q test and I(2) test. RESULTS: A significant increase in response rate (OR 2.04; P < 0.01) was associated with treatment by FOLFOXIRI and a benefit was also shown by the HR for progression (HR 0.72; P < 0.01) and death (HR 0.71; P < 0.01). Analysis for toxicity found a significant increase associated with FOLFOXIRI except for anaemia, fatigue and febrile neutropenia. CONCLUSION: FOLFOXIRI confers significant benefit in progression-free survival, survival, response and R0 resection rates but is more toxic compared with FOLFIRI.

Use of recombinant chimeric antigens for the serodiagnosis of Mycoplasma pneumoniae infection.

In this paper, we have evaluated the diagnostic utility of three antigenic regions of the Mycoplasma pneumoniae P1, P30, and MPN456 gene products in order to replace the soluble, whole-cell bacterial extract in serological assays. Antigenic regions, being previously identified as B-cell epitopes, were used individually or assembled in a recombinant chimeric antigen by genetic engineering. Paired serum samples from 47 patients with M. pneumoniae infection and from 39 subjects with a clinical picture of atypical pneumonia but without a defined diagnosis of M. pneumoniae infection were included. Immunoglobulin G (IgG) antibodies against epitopes carried by recombinant antigens were measured by performing recombinant enzyme-linked immunosorbent assays (Rec-ELISAs). Rec-ELISA results were compared to those obtained by a commercial assay using the whole-cell Mycoplasma antigen. Our study demonstrates that all IgG Rec-ELISAs using recombinant antigens have better sensitivity with respect to the commercial assay. Furthermore, we show that the use of chimeric antigens improve the performance of the assays. The use of recombinant antigens is effective in distinguishing M. pneumoniae-infected patients from uninfected individuals and shows that immunoassays based on recombinant antigens could provide the basis for standardized commercial tests for the serodiagnosis of M. pneumoniae diseases.

Erythromycin resistance in Streptococcus pyogenes and macrolide consumption in a central Italian region.

BACKGROUND: The study investigated macrolide resistance in Streptococcus pyogenes in a central Italian area from 2001 to 2006 and the possible correlation between antibiotic consumption and fluctuations of resistance percentages. MATERIALS AND METHODS: Macrolide and lincosamide susceptibility of 1,419 S. pyogenes isolates was tested by Kirby Bauer method. Macrolide consumption was evaluated as defined daily dose/1,000 inhabitants per day (DID), according to the World Health Organization anatomic therapeutic chemical classification. Spearman's correlation coefficient was used to assess the association between resistance and use of (1) all macrolides pooled, (2) once daily, (3) twice daily, and (4) three times daily dosage regimens. RESULTS: : In total, 320 strains (22.6%) were erythromycin-resistant, 11.4% with the M phenotype and 11.2% with the MLS phenotype. There was a significant decrease in erythromycin resistance during the study period-from 28.1% in 2001 to 15.6% in 2006 (p < 0.01). No significant correlation was found between erythromycin resistance and local overall macrolide consumption, neither during the same year nor during the previous year. In contrast, a significant correlation was found between resistance rates and once-daily macrolide use during the preceding 6 months in Siena r = 0.747, p = 0.008). CONCLUSION: The known greater selective effect of long-acting agents could establish a pressure outcome, resulting in a specific local epidemiology during a relatively short time gap.

Occurrence of autoimmunity in a long-term survivor with metastatic colon carcinoma treated with a new chemo-immunotherapy regimen.

GOLFIG-1 chemo-immunotherapy is a new translational anticancer regimen based on the combined use of gemcitabine, oxalipatin, levofolinic acid and infusional 5-fluorouracil together with the subcutaneous administration immunoadjuvant cytokines (GM-CSF and ultra low dose IL-2). This regimen, tested in a phase II trial, was safe and very active in patients with metastatic colorectal carcinoma and it has been shown to have powerful immunobiological activity. Treatment with the GOLFIG regimen resulted in the induction of a colon cancer specific cell mediated immune response associated with a significant reduction in the percentage of peripheral regulatory T (T(reg)) cells, a very immunosuppressive lymphocyte subset which is commonly over-represented in cancer patients. These cells are able to prevent the occurrence of autoimmunity in response to immunological stimuli, thus their malfunctioning has been associated with the occurrence of auto-immune diseases but may also be responsible for more efficient anticancer immune reaction. In this manuscript we describe a clinical case concerning a patient with metastatic colon carcinoma who responded to the GOLFIG regimen, showed symptoms of autoimmunity [Discoid Lupus Erythematosus (DLE)] and had a very long survival.

Biweekly triple combination chemotherapy with gemcitabine, oxaliplatin, levofolinic acid and 5-fluorouracil (GOLF) is a safe and active treatment for patients with inoperable pancreatic cancer.

GOLF is a triple translational combination chemotherapy regimen with gemcitabine, oxaliplatin, and 5-fluorouracil (5-FU) (plus levofolinic acid), cytotoxic drugs currently used in the treatment of pancreatic carcinoma. Considering its promising anti-tumor effects in patients with gastroenteric malignancies, we carried out the present study to investigate its toxicity and anti-tumor activity in patients with advanced pancreatic carcinoma. Twenty-seven patients were enrolled in the study, 15 males and 12 females with an average age of 61 years and a performance status (ECOG)

Antimicrobial susceptibility of Streptococcus pyogenes and Streptococcus pneumoniae: surveillance from 1993 to 2004 in Central Italy.

The susceptibility of 1870 Streptococcus pyogenes and 1595 Streptococcus pneumoniae to macrolides and lincosamides has been monitored from 1993 to 2004 in Central Italy. Among S. pyogenes, 30.2% were erythromycin resistant; 18.5% were also resistant to josamycin and clindamycin (MLS phenotype). After an increasing erythromycin resistance rate in 1993-1997 (maximum 53.16%), a definite decrease was observed since 2001 with resistance rates always less than 30%. Thirty six percent of pneumococcal isolates were erythromycin-resistant, with minor temporal fluctuations; the MLS phenotype was the most prevalent overall (32.6%) and in individual years. S. pneumoniae strains were also tested for susceptibility to beta-lactams and other antimicrobial agents: 11.2% were penicillin non-susceptible, with a gradually increasing prevalence after 2001 (maximum rate 17.3% in 2004), 31.15% were resistant to tetracycline, 4.9% to chloramphenicol, 0.74% to rifampin. All pneumococcal isolates were susceptible to teicoplanin and 99.9% to ceftriaxone and ofloxacin.

Patterns of macrolide resistance determinants among community-acquired Streptococcus pneumoniae isolates over a 5-year period of decreased macrolide susceptibility rates.

Erythromycin resistance rates were found to be increased, from 7.1 in 1993 to 32.8% in 1997, among community-acquired Streptococcus pneumoniae isolates from the Siena area of central Italy. Most of the erythromycin-resistant isolates carried ermAM determinants and were also resistant to josamycin and clindamycin, whereas a minority (5.8%) carried mefA determinants and remained susceptible to the latter drugs.