Efficacy and Safety of Meropenem\u2013Vaborbactam Versus Best Available Therapy for the Treatment of Carbapenem-Resistant Enterobacteriaceae Infections in Patients Without Prior Antimicrobial Failure: A Post Hoc Analysis

open5siIntroduction: Infections due to Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacteriaceae are associated with increased morbidity and high mortality. Meropenem–vaborbactam (MV) is a novel β-lactam/β-lactamase inhibitor combination active against KPC-producing Enterobacteriaceae. The aim of this post hoc analysis of the TANGO-II randomized controlled trial was to assess the efficacy of MV versus best available therapy (BAT) in the subgroup of patients without prior antimicrobial failure. Methods: The primary outcome measure was clinical cure at the test of cure (TOC). Secondary outcome measures included (1) clinical cure at the end of therapy (EOT), (2) microbiological cure at TOC, (3) microbiological cure at EOT, and (4) 28-day all-cause mortality. Results: First-line MV was associated with a 42.9% absolute increase in clinical cure rate at TOC (95% confidence intervals [CI] 13.7–72.1) in comparison with first-line BAT. A 49.3% absolute increase in clinical cure rate at EOT (95% CI 20.8–77.7), a 42.6% absolute increase in microbiological cure rate at EOT (95% CI 13.4–71.8), and a 36.2% absolute increase in microbiologic cure rate at TOC (95% CI 5.9–66.6) were also observed, in addition to a 29.0% absolute reduction in mortality (95% CI − 54.3 to − 3.7). Overall, fewer adverse events were observed in the MV group than in the BAT group. Conclusion: MV was superior to BAT in the subgroup of patients with serious carbapenem-resistant Enterobacteriaceae (CRE) infections and no prior antimicrobial failure, with very high rates of clinical success, and was well tolerated. Post approval and real-world studies remain essential to clearly define the most appropriate population for early, empirical MV coverage, in accordance with antimicrobial stewardship principles. Funding: The Medicines Company.openBassetti M.; Giacobbe D.R.; Patel N.; Tillotson G.; Massey J.Bassetti, M.; Giacobbe, D. R.; Patel, N.; Tillotson, G.; Massey, J

A NLP Pipeline for the Automatic Extraction of a Complete Microorganism’s Picture from Microbiological Notes

The Italian “Istituto Superiore di Sanità” (ISS) identifies hospital-acquired infections (HAIs) as the most frequent and serious complications in healthcare. HAIs constitute a real health emergency and, therefore, require decisive action from both local and national health organizations. Information about the causative microorganisms of HAIs is obtained from the results of microbiological cultures of specimens collected from infected body sites, but microorganisms’ names are sometimes reported only in the notes field of the culture reports. The objective of our work was to build a NLP-based pipeline for the automatic information extraction from the notes of microbiological culture reports. We analyzed a sample composed of 499 texts of notes extracted from 1 month of anonymized laboratory referral. First, our system filtered texts in order to remove nonmeaningful sentences. Thereafter, it correctly extracted all the microorganisms’ names according to the expert’s labels and linked them to a set of very important metadata such as the translations into national/international vocabularies and standard definitions. As the major result of our pipeline, the system extracts a complete picture of the microorganism

Measles: An overview of a re-emerging disease in children and immunocompromised patients

Despite the availability of a safe and effective vaccine, in 2018, around 350,000 measles cases were reported worldwide, which resulted in an estimate of 142,300 deaths from measles. Additionally, in 2017, global measles cases spiked, causing the death of 110,000 people, mostly children under the age of 5 years and immunocompromised adults. The increase in measles incidence is caused by the ongoing reduction of vaccination coverage. This event has triggered public and scientific interest. For this reason, we reviewed the pathophysiology of measles infection, focusing on mechanisms by which the virus spreads systemically through the host organism. By reaching the lymphocytes from the airways through a \u201ctrojan horse\u201d strategy, measles induces an immunosuppression status. H and F glycoproteins, both expressed in the envelope, ensure attachment of the virus to host cells and spreading from one cell to another by binding to several receptors, as described in detail. The severity of the disease depends both on the age and underlying conditions of patients as well as the social and health context in which epidemics spread, and is often burdened by sequelae and complications that may occur several years after infection. Particular attention was paid to special groups that are more susceptible to severe or atypical measles. An overview of microbiology, symptoms, diagnosis, prevention, and treatment completes and enriches the review

A Wide Database for a Multicenter Study on Pneumocystis jirovecii Pneumonia in Intensive Care Units

Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection that may affect patients with immunosuppression. In order to improve the diagnosis accuracy for PJP, facilitating the collection of data across Europe to reliably assess the performance of diagnostic tests for PJP is essential to improve the care of critically ill patients developing this severe condition. Such large data can be collected thanks to the contribution of several European hospitals in the compilation of a dedicated electronic Case Report Form (eCRF). The main focus of this work is to create an interface with high ergonomics both in the compilation and in the subsequent validation of the records

Mycobacterium tuberculosis Surgical Site Infection after Cardiac Surgery in the COVID-19 Era: A Case Report

Infection of surgical wounds with acid-fast bacilli, including tubercle bacilli, is rare, and is poorly described in the literature. We present the case of a 74-year-old male who developed a sternal wound infection after cardiac surgery due to Mycobacterium tuberculosis complex, diagnosed post-mortem. SARS-CoV-2 infection contributed to worsened clinical conditions and surgical site infection. A high degree of suspicion to avoid unnecessary treatments and progression to severe disease with dismal prognosis is necessary in these types of infections

The GAPS Programme with HARPS-N@TNG IX. The multi-planet system KELT-6: detection of the planet KELT-6 c and measurement of the Rossiter-McLaughlin effect for KELT-6 b

Aims. For more than 1.5 years we monitored spectroscopically the star KELT-6 (BD+312447), known to host the transiting hot Saturn KELT-6b, because a previously observed long-term trend in radial velocity time series suggested the existence of an outer companion. Methods. We collected a total of 93 new spectra with the HARPS-N and TRES spectrographs. A spectroscopic transit of KELT-6b was observed with HARPS-N, and simultaneous photometry was obtained with the IAC-80 telescope. Results. We proved the existence of an outer planet with a mininum mass M$_{\rm p}$sini=3.71$\pm$0.21 M$_{\rm Jup}$ and a moderately eccentric orbit ($e=0.21_{-0.036}^{+0.039}$) of period P$\sim$3.5 years. We improved the orbital solution of KELT-6b and obtained the first measurement of the Rossiter-McLaughlin effect, showing that the planet has a likely circular, prograde, and slightly misaligned orbit, with a projected spin-orbit angle $\lambda$=$-$36$\pm$11 degrees. We improved the KELT-6b transit ephemeris from photometry, and we provided new measurements of the stellar parameters. KELT-6 appears as an interesting case to study the formation and evolution of multi-planet systems.Comment: Letter, 4 figures, accepted for publication in A&A. Some language editing and numbering of the paper series changed (from X to IX

Exploring the realm of scaled Solar System analogs with HARPS

The assessment of the frequency of planetary systems reproducing the Solar System's architecture is still an open problem. Detailed study of multiplicity and architecture is generally hampered by limitations in quality, temporal extension and observing strategy, causing difficulties in detecting low-mass inner planets in the presence of outer giant planetary bodies. We present the results of high-cadence and high-precision HARPS observations on 20 solar-type stars known to host a single long-period giant planet in order to search for additional inner companions and estimate the occurence rate $f_p$ of scaled Solar System analogs, i.e. systems featuring lower-mass inner planets in the presence of long-period giant planets. We carry out combined fits of our HARPS data with literature radial velocities using differential evolution MCMC to refine the literature orbital solutions and search for additional inner planets. We then derive the survey detection limits to provide preliminary estimates of $f_p$. We generally find better constrained orbital parameters for the known planets than those found in the literature. While no additional inner planet is detected, we find evidence for previously unreported long-period massive companions in systems HD 50499 and HD 73267. We finally estimate the frequency of inner low mass (10-30 M$_\oplus$) planets in the presence of outer giant planets as $f_p<9.84\%$ for P<150 days. Our preliminary estimate of $f_p$ is significantly lower than the values found in the literature; the lack of inner candidate planets found in our sample can also be seen as evidence corroborating the inward migration formation model for super-Earths and mini-Neptunes. Our results also underline the need for high-cadence and high-precision follow-up observations as the key to precisely determine the occurence of Solar System analogs.Comment: 32 pages, 27 figures, accepted for publication in A&

Accuracy of elastic fusion biopsy in daily practice: results of a multicenter study of 2115 patients

OBJECTIVES: To assess the accuracy of Koelis fusion biopsy for the detection of prostate cancer and clinically significant prostate cancer in the everyday practice. METHODS: We retrospectively enrolled 2115 patients from 15 institutions in four European countries undergoing transrectal Koelis fusion biopsy from 2010 to 2017. A variable number of target (usually 2-4) and random cores (usually 10-14) were carried out, depending on the clinical case and institution habits. The overall and clinically significant prostate cancer detection rates were assessed, evaluating the diagnostic role of additional random biopsies. The cancer detection rate was correlated to multiparametric magnetic resonance imaging features and clinical variables. RESULTS: The mean number of targeted and random cores taken were 3.9 (standard deviation 2.1) and 10.5 (standard deviation 5.0), respectively. The cancer detection rate of Koelis biopsies was 58% for all cancers and 43% for clinically significant prostate cancer. The performance of additional, random cores improved the cancer detection rate of 13% for all cancers (P < 0.001) and 9% for clinically significant prostate cancer (P < 0.001). Prostate cancer was detected in 31%, 66% and 89% of patients with lesions scored as Prostate Imaging Reporting and Data System 3, 4 and 5, respectively. Clinical stage and Prostate Imaging Reporting and Data System score were predictors of prostate cancer detection in multivariate analyses. Prostate-specific antigen was associated with prostate cancer detection only for clinically significant prostate cancer. CONCLUSIONS: Koelis fusion biopsy offers a good cancer detection rate, which is increased in patients with a high Prostate Imaging Reporting and Data System score and clinical stage. The performance of additional, random cores seems unavoidable for correct sampling. In our experience, the Prostate Imaging Reporting and Data System score and clinical stage are predictors of prostate cancer and clinically significant prostate cancer detection; prostate-specific antigen is associated only with clinically significant prostate cancer detection, and a higher number of biopsy cores are not associated with a higher cancer detection rate

The APACHE survey hardware and software design: Tools for an automatic search of small-size transiting exoplanets

Small-size ground-based telescopes can effectively be used to look for transiting rocky planets around nearby low-mass M stars using the photometric transit method, as recently demonstrated for example by the MEarth project. Since 2008 at the Astronomical Observatory of the Autonomous Region of Aosta Valley (OAVdA), we have been preparing for the long-term photometric survey APACHE, aimed at finding transiting small-size planets around thousands of nearby early and mid-M dwarfs. APACHE (A PAthway toward the Characterization of Habitable Earths) is designed to use an array of five dedicated and identical 40-cm Ritchey-Chretien telescopes and its observations started at the beginning of summer 2012. The main characteristics of the survey final set up and the preliminary results from the first weeks of observations will be discussed