Outcome of patients hospitalized for COVID‐19 and exposure to angiotensin‐converting enzyme inhibitors and angiotensin‐receptor blockers in France: results of the ACE‐CoV study

Data are lacking on the impact of ACEI/ARB exposure on unfavorable outcome in the population of patients hospitalized for COVID‐19 with hypertension/cardiovascular disease, particularly in Europe. The ACE‐CoV study was designed to assess this question. The study was conducted in the Covid‐Clinic‐Toul cohort, which contains data about all patients hospitalized at Toulouse University hospital, France with a SARS‐CoV‐2 infection since March, 2020. We selected the patients with a history of cardiovascular disease (heart failure or coronary disease) and/or arterial hypertension. We conducted a subgroup analysis in patients with arterial hypertension. ACEI/ARB exposures at admission were assessed. The outcome was composite: admission to intensive care unit, need of mechanical ventilation or death during the 14 days after admission to hospital. We used logistic regression models with propensity scores (PS) weighted by overlap weighting (OW) and inverse probability of treatment weighting (IPTW). Between March 2020 and April 20, 2020, the Covid‐Clinic‐Toul included 263 patients. Among them, 111 were included in the ACE‐CoV study population. In OW‐PS‐adjusted analyses, the association of exposure to ACEIs or ARBs with outcome occurrence was OR: 1.56 (95% CI: 0.73–3.33). It was 0.99 (95% CI: 0.68–1.45) for ACEIs and 1.64 (95% CI: 0.77–3.50) for ARBs. Analyses with weighting by the IPTW‐PS method gave similar results. Results were similar when considering the subgroup of patients with arterial hypertension. The ACE‐CoV study found no association between exposure to ACEIs or ARBs and unfavorable outcome in hospitalized patients for COVID‐19 with a history of cardiovascular disease/arterial hypertension.     

Prostatic abscess: clinical features,management, and outcomes of a “Stealth” infection: retrospective case series and review of the literature

Prostatic abscess (PA) is uncommon and may be difficult to distinguish from acute prostatitis which often leads to delayed or missed diagnoses. Although gram-negative bacilli are the traditional etiology of PA, Staphylococcus aureus is an emerging cause. The goals of this study were to characterize the current clinical features, microbiology, management, and outcomes of PA at a US academic center.A retrospective review of adult patients hospitalized with an ICD-9/10 diagnosis of PA between January 2013 and July 2018 was conducted. Inclusion criteria included age ≥18 years, a compatible genitourinary (GU) infection syndrome, and imaging consistent with PA. Relevant data were extracted and analyzed by univariate analysis as appropriate.Twenty-two patients with PA were identified with median age 57 years. Five patients (23%) were immunosuppressed and 11 (50%) had diabetes. No patient had prior PA but 3 had past prostatitis. Only 1 patient had recent GU instrumentation and none had indwelling urinary catheters. The most common presenting symptoms were fever (59%), dysuria (45%), and urinary retention (32%). Only 7 out of 18 (39%) patients had prostate tenderness on exam and none had fluctuance. As demonstrated by computed tomography, PAs were multifocal in 8 (36%) patients and 16 (73%) had PAs >2 cm in diameter. The median abscess size was 3.2 cm. S. aureus was isolated in 60% of positive urine cultures and 78% of positive blood cultures; 46% were methicillin-resistant. Nine patients (41%) received antibiotics alone whereas 13 (59%) required antibiotics plus drainage. The median duration of antimicrobial therapy was 34.5 days. Four week mortality was 9%. When comparing S. aureus PA to other causes, S. aureus patients tended to have higher fevers, more often had diabetes, and received longer durations of antibiotic therapy (median 35 days vs 31 days, P = 0.04) but age, abscess size, and mortality did not differ.PA is relatively uncommon and often clinically unsuspected. Imaging may be critical to accurate diagnosis. Optimal management usually requires antibiotics and sometimes drainage depending on abscess size. We found a significant proportion of cases due to S. aureus which might be relevant when deciding empiric antimicrobial therapy     

A study of 589 consecutive implants supporting complete fixed prostheses. Part I: Periodontal aspects.

Ninety-one consecutive edentulous patients who had been treated by means of fixed prostheses (n = 103) supported by Br?nemark implants (n = 589) were examined. Eighteen fixtures (3%) failed to integrate. After a mean loading time of 32 (range 6 to 80) and 38 months (range 5 to 83) for fixtures in the maxilla and mandible, respectively, an additional 12 fixtures lost integration. The cumulative failure rate for individual fixtures after 6 years was 8.4% and 5% for maxillae and mandibles, respectively. Only one patient had to revert to complete dentures. For fixtures in the maxillae, the mean marginal bone loss was 0.7, 0.1, and 0.2 mm for each of the first 3 years of loading, respectively; for fixtures in mandibles, the corresponding values were 0.7, 0.2, and 0.1 mm. The loss in marginal bone height was equal in both jaws and was not related to bleeding on probing or to the preoperative resorption anatomy.     

A methodological validation of an easy one-step swimout semen preparation procedure for selecting DNA fragmentation-free spermatozoa for ICSI

The main purpose of this methodological paper was to describe a recently designed one-step ICSI semen preparation swim-out method (called swim-ICSI) and to compare its efficacy with our conventional two-step swim-out method for the selection of motile spermatozoa for ICSI with minimal DNA damage. In this observational cohort study, 42 fresh ejaculate sperm samples for ICSI were included to compare the new swim-ICSI with the conventional swim-out. In a sub-analysis (n = 20), both in-house designed ICSI preparation methods were compared with a commercial magnetic-activated cell sorting test (MACS^®). Sperm DNA fragmentation (SDF), using Halosperm^®, was determined at different time points during sperm preparation: on the native sample (a), after density gradient centrifugation (DG) (b), on the motile (A + B) spermatozoa selected with conventional swim-out post-DG (c) and selected with swim-ICSI method post-DG (d). For a subgroup (n = 20), SDF was also calculated after MACS (e). The mean SDF significantly reduced after EACH preparation step and reduced to almost zero in the recovered A + B spermatozoa when the semen prepared with DG was further processed for ICSI (swim-ICSI vs. swim-out, p = .001). In conclusion, the optimised one-step and fine-tuned swim-ICSI technique shows the possibility to select a population of spermatozoa with almost zero SDF to be used in ICSI treatments.     

Tolerance and Efficacy of Regorafenib according to UGT Pharmacogenetical Status in the Treatment of Metastatic Refractory Colorectal Cancer

Introduction: Regorafenib is a multi tyrosin-kinase inhibitor prescribed in metastatic refractory colorectal cancer treatment. Its toxicity is significant but inconstant. The metabolism of regorafenib includes oxydation via cytochrome P3A4, then glucuroconjugation. A pharmacogenetical approach of mutational status of Uridine-Diphospho-Glucuronosyltransfersase (UDP-glucuronosyl-transferase, UGT) could be a strategy to optimise the use of regorafenib. Patients and Method: This is a restrospective, unicentric study. All adult patients treated with regorafenib for a metastatic colorectal cancer in our center between 2013 and 2017 were analysed. UGT1A1 polypmorphism was previously researched in the laboratory after written informed consent. Results: Thirty-five patients received regorafenib during the study period. A TA repetition in UGT1A1 gene was present for 16 patients including two Gilbert syndrome. There were no more adverse events on patients with a heterozygous TA repetition or with a Gilbert syndrome compared with patients without UGT polymorphism, whatever the dosage at initiation of regorafenib. Adverse events grade 2 or superior, and grade 3 or superior tended to be more noticeable when the starting dose was 120 or 160 mg per day compared to 80 mg per day, but not statistically significant. No difference was observed on progression-free survival neither depending on UGT status nor depending on initating dose of regorafenib. Conclusion: This is a preliminary study evaluating safety of regorafenib according to UGT1A1 polymorphism. Larger and prospective studies are needed to evaluate dose-escalation strategy in patients with variable activity of glucuroconidation, especially Gilbert syndrome, or with abnormalities in other UGT enzymes such as UGT1A9.     

Association between inflammatory mediators and response to inhaled nitric oxide in a model of endotoxin-induced lung injury

Introduction  

Inhaled nitric oxide (INO) allows selective pulmonary vasodilation in acute respiratory distress syndrome and improves PaO₂ by redistribution of pulmonary blood flow towards better ventilated parenchyma. One-third of patients are nonresponders to INO, however, and it is difficult to predict who will respond. The aim of the present study was to identify, within a panel of inflammatory mediators released during endotoxin-induced lung injury, specific mediators that are associated with a PaO₂ response to INO.     

Intensive care unit acquired infection and organ failure

Objective To assess the temporal relationship between ICU-acquired infection (IAI) and the prevalence and severity of organ dysfunction or failure (OD/F). Design and setting Observational, single center study in a mixed intensive care unit of a university hospital. Patients We analyzed 1,191 patients hospitalized for more than 2 days during a 2-year observation period: 845 did not acquire IAI, 306 of whom had infection on admission (IOA); 346 did acquire IAI, 125 of whom had IOA. Measurements and results The SOFA score was calculated daily, both SOFAmax, the sum of the worst OD/F during the ICU stay, and SOFApreinf, the sum of the worst OD/F existing before the occurrence of the first IAI. The SAPS II and SOFA score of the first 24 h were significantly higher in patients with than in those without IAI. SOFApreinf of IAI patients was also higher than the SOFAmax of patients without IAI both in patients with (12.1 ± 4.6 vs. 8.9 ± 4.7) and those without IOA (9.2 ± 4.0 vs. 6.7 ± 3.5). SOFApreinf represented 85.7% of the value of SOFAmax in patients with IAI. SOFApreinf increased significantly with the occurrence of sepsis, severe sepsis, or septic shock during ICU stay. Severe sepsis and septic shock during ICU stay as well as SOFApreinf were part of the factors associated with hospital mortality. Conclusions IAI is significantly associated with hospital mortality; however, its contribution to OD/F is minor. Moreover, severity of IAI seems to be related to previous health status. This article is discussed in the editorial available at: .     

Link Between Carbapenemase-Producing Enterobacteria Carriage and Cross-Border Exchanges: Eight-Year Surveillance in a Large French Multihospitals Institution

Assistance Publique-H?pitaux de Paris launched a specific strategy to survey and control the spread of emerging multidrug-resistant bacteria such as carbapenemase-producing Enterobacteria (CPE). Among the 63 CPE events that occurred between 2004 and 2011, 87% involved patients with a link with cross-border exchanges, justifying the recommendation to screen and isolate such patients.