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Background Patients with SARS-CoV-2 infection are at higher risk for ventilator-associated pneumonia (VAP). No study has evaluated the relationship between VAP and mortality in this population, or compared this relationship between SARS-CoV-2 patients and other populations. The main objective of our study was to determine the relationship between VAP and mortality in SARS-CoV-2 patients. Methods Planned ancillary analysis of a multicenter retrospective European cohort. VAP was diagnosed using clinical, radiological and quantitative microbiological criteria. Univariable and multivariable marginal Cox’s regression models, with cause-specific hazard for duration of mechanical ventilation and ICU stay, were used to compare outcomes between study groups. Extubation, and ICU discharge alive were considered as events of interest, and mortality as competing event. Findings Of 1576 included patients, 568 were SARS-CoV-2 pneumonia, 482 influenza pneumonia, and 526 no evidence of viral infection at ICU admission. VAP was associated with significantly higher risk for 28-day mortality in SARS-CoV-2 group (adjusted HR 1.65 (95% CI 1.11–2.46), p  = 0.013), but not in influenza (1.74 (0.99–3.06), p  = 0.052), or no viral infection groups (1.13 (0.68–1.86), p  = 0.63). VAP was associated with significantly longer duration of mechanical ventilation in the SARS-CoV-2 group, but not in the influenza or no viral infection groups. VAP was associated with significantly longer duration of ICU stay in the 3 study groups. No significant difference was found in heterogeneity of outcomes related to VAP between the 3 groups, suggesting that the impact of VAP on mortality was not different between study groups. Interpretation VAP was associated with significantly increased 28-day mortality rate in SARS-CoV-2 patients. However, SARS-CoV-2 pneumonia, as compared to influenza pneumonia or no viral infection, did not significantly modify the relationship between VAP and 28-day mortality. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693.

PurposeThrombocytopenia is a frequent and serious adverse event in patients treated with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock. Similarly to postcardiac surgery patients, heparin-induced thrombocytopenia (HIT) could represent the causative underlying mechanism. However, the epidemiology as well as related mortality regarding HIT and VA-ECMO remains largely unknown. We aimed to define the prevalence and associated 90-day mortality of HIT diagnosed under VA-ECMO.MethodsThis retrospective study included patients under VA-ECMO from 20 French centers between 2012 and 2016. Selected patients were hospitalized for more than 3 days with high clinical suspicion of HIT and positive anti-PF4/heparin antibodies. Patients were classified according to results of functional tests as having either Confirmed or Excluded HIT.ResultsA total of 5797 patients under VA-ECMO were screened; 39/5797 met the inclusion criteria, with HIT confirmed in 21/5797 patients (0.36% [95% CI] [0.21–0.52]). Fourteen of 39 patients (35.9% [20.8–50.9]) with suspected HIT were ultimately excluded because of negative functional assays. Drug-induced thrombocytopenia tended to be more frequent in Excluded HIT at the time of HIT suspicion (p = 0.073). The platelet course was similar between Confirmed and Excluded HIT (p = 0.65). Mortality rate was 33.3% [13.2–53.5] in Confirmed and 50% [23.8–76.2] in Excluded HIT (p = 0.48).ConclusionsPrevalence of HIT among patients under VA-ECMO is extremely low at 0.36% with an associated mortality rate of 33.3%, which appears to be in the same range as that observed in patients treated with VA-ECMO without HIT. In addition, HIT was ultimately ruled out in one-third of patients with clinical suspicion of HIT and positive anti-PF4/heparin antibodies.

Objectives: Large studies are needed to update risk factors of bronchiolitis hospitalization. We performed a nationwide analysis of hospitalization rates for bronchiolitis over four consecutive bronchiolitis seasons to identify underlying medical disorders at risk of bronchiolitis hospitalization and assess their frequency.Methods: Data were retrieved from the French National Hospital Discharge database. Of all infants discharged alive from maternity wards from January 2008 to December 2013 in France (N = 3,884,791), we identified four consecutive cohorts at risk of bronchiolitis during the seasons of 2009–2010 to 2012–2013. The main outcome was bronchiolitis hospitalization during a season. Individual risk factors were collected.Results: Among infants, 6.0% were preterm and 2.0% had ≥1 chronic condition including 0.2% bronchopulmonary dysplasia (BPD) and 0.2% hemodynamically significant congenital heart disease (HS-CHD). Bronchiolitis hospitalization rates varied between seasons (min: 1.26% in 2010–2011; max: 1.48% in 2012–2013; p<0.001). Except omphalocele, the following conditions were associated with an increased risk for bronchiolitis hospitalization: solid organ (9.052; 95% CI, 4.664–17.567) and stem cell transplants (6.012; 95% CI, 3.441–10.503), muscular dystrophy (4.002; 95% CI, 3.1095–5.152), cardiomyopathy (3.407; 95% CI, 2.613–4.442), HS-CHD (3.404; 95% CI, 3.153–3.675), congenital lung disease and/or bronchial abnormalities, Down syndrome, congenital tracheoesophageal fistula, diaphragmatic hernia, pulmonary hypertension, chromosomal abnormalities other than Down syndrome, hemodynamically non-significant CHD, congenital abnormalities of nervous system, cystic fibrosis, cleft palate, cardiovascular disease occurring during perinatal period, and BPD.Conclusion: Besides prematurity, BPD, and HS–CHD, eighteen underlying conditions were associated with a significant increased risk for bronchiolitis hospitalization in a nationwide population.

ObjectiveThe primary objective was to assess the characteristics and prognosis of pyogenic spondylodiscitis (PS) in patients with infective endocarditis (IE). The secondary objectives were to assess the factors associated with occurrence of PS.MethodsProspective case–control bi-centre study of 1755 patients with definite IE with (n=150) or without (n=1605) PS. Clinical, microbiological and prognostic variables were recorded.ResultsPatients with PS were older (mean age 69.7±18 vs 66.2±14; p=0.004) and had more arterial hypertension (48% vs 34.5%; p<0.001) and autoimmune disease (5% vs 2%; p=0.03) than patients without PS. The lumbar vertebrae were the most frequently involved (84 patients, 66%), especially L4–L5. Neurological symptoms were observed in 59% of patients. Enterococci and Streptococcus gallolyticus were more frequent (24% vs 12% and 24% vs 11%; p<0001, respectively) in the PS group. The diagnosis of PS was based on contrast-enhanced MRI in 92 patients, bone CT in 88 patients and 18F-FDG PET/CT in 56 patients. In-hospital (16% vs 13.5%, p=0.38) and 1-year (21% vs 22%, p=0.82) mortalities did not differ between patients with or without PS.ConclusionsPS is a frequent complication of IE (8.5% of IE), is observed in older hypertensive patients with enterococcal or S. gallolyticus IE, and has a similar prognosis than other forms of IE. Since PS is associated with specific management, multimodality imaging including MRI, CT and PET/CT should be used for early diagnosis of this complication of endocarditis.

Viral infections are known to hijack the transcription and translation of the host cell. However, the extent to which viral proteins coordinate these perturbations remains unclear. Here we used a model system, the human T-cell leukemia virus type 1 (HTLV-1), and systematically analyzed the transcriptome and interactome of key effectors oncoviral proteins Tax and HBZ. We showed that Tax and HBZ target distinct but also common transcription factors. Unexpectedly, we also uncovered a large set of interactions with RNA-binding proteins, including the U2 auxiliary factor large subunit (U2AF2), a key cellular regulator of pre-mRNA splicing. We discovered that Tax and HBZ perturb the splicing landscape by altering cassette exons in opposing manners, with Tax inducing exon inclusion while HBZ induces exon exclusion. Among Tax- and HBZ-dependent splicing changes, we identify events that are also altered in Adult T cell leukemia/lymphoma (ATLL) samples from two independent patient cohorts, and in well-known cancer census genes. Our interactome mapping approach, applicable to other viral oncogenes, has identified spliceosome perturbation as a novel mechanism coordinated by Tax and HBZ to reprogram the transcriptome.

Early diagnosis of neuroendocrine cell hyperplasia of infancy (NEHI) is crucial as, conversely to the other causes of intersititial lung disease, corticosteroids are not recommended. Diagnosis is historically based on lung biopsy (NEHI), but in current practice, a clinical and radiological approach is more and more preferred (NEHI syndrome). This national study aimed to address diagnosis and initial management of patients followed up for a NEHI pattern in pediatric centers for rare lung diseases (RespiRare, France). Data on neonatal and familial events, symptoms at diagnosis, explorations performed and results, and therapeutic management were collected by questionnaire. Fifty-four children were included (boys 63%). The mean onset of symptoms was 3.8 ± 2.6 months. The most frequent symptoms at diagnosis were tachypnea (100%), retraction (79.6%), crackles (66.7%), and hypoxemia (59.3%). The mean NEHI clinical score, evocative when ≥ 7/10, was 7.9 ± 1.4 (76% with a score ≥ 7). All chest CT-scans showed ground glass opacities evolving at least the middle lobe and the lingula. Lung biopsy was performed in 38.9% of the cases and was typical of NEHI in only 52.4%, even when the clinical presentation was typical. Initial treatments were oxygen (83.6%) and more curiously intravenous pulses of steroids (83.3%) and azithromycin (70.2%).Conclusion: This national cohort of patients underlines diagnosis difficulties of NEHI. A composite clinical and radiological score should help clinicians for limiting the use of anti-inflammatory drugs.What is Known:•Neuroendocrine cell hyperplasia of infancy (NEHI) is an interstitial lung disease whose diagnosis is essential to limit corticosteroids therapy.What is New:•In this national cohort of 54 patients with a NEHI pattern, diagnosis is mainly based on clinical symptoms and chest CT-scan results. The newly proposed clinical score and, when performed, the lung biopsies are faulted in 25 and 50% of the cases, respectively.•Corticosteroids are widely used. Such results plead for a new composite score to formally diagnose NEHI.

The Pacific region, also referred to as Oceania, is a geographically widespread region populated by people of diverse cultures and ethnicities. Indigenous people in the region (Melanesians, Polynesians, Micronesians, Papuans, and Indigenous Australians) are over-represented on national, regional, and global scales for the burden of infectious and non-communicable diseases. Although social and environmental factors such as poverty, education, and access to health-care are assumed to be major drivers of this disease burden, there is also developing evidence that genetic and microbiotic factors should also be considered. To date, studies investigating genetic and/or microbiotic links with vulnerabilities to infectious and non-communicable diseases have mostly focused on populations in Europe, Asia, and USA, with uncertain associations for other populations such as indigenous communities in Oceania. Recent developments in personalized medicine have shown that identifying ethnicity-linked genetic vulnerabilities can be important for medical management. Although our understanding of the impacts of the gut microbiome on health is still in the early stages, it is likely that equivalent vulnerabilities will also be identified through the interaction between gut microbiome composition and function with pathogens and the host immune system. As rapid economic, dietary, and cultural changes occur throughout Oceania it becomes increasingly important that further research is conducted within indigenous populations to address the double burden of high rates of infectious diseases and rapidly rising non-communicable diseases so that comprehensive development goals can be planned. In this article, we review the current knowledge on the impact of nutrition, genetics, and the gut microbiome on infectious diseases in indigenous people of the Pacific region.

Acute Respiratory Infections (ARIs) are responsible for considerable morbidity and mortality worldwide. Documentation of respiratory specimens can help for an appropriate clinical management with a significant effect on the disease progress in patient, the antimicrobial therapy used and the risk of secondary spread of infection. Here, we compared the performances of four commercial multiplex kits used in French University Hospital diagnostic microbiology laboratories for the detection of ARI pathogens (i.e., the xTAG Respiratory Viral Panel Fast, RespiFinder SMART 22, CLART PneumoVir and Fast Track Diagnostics Respiratory Pathogen 33 kits). We used a standardised nucleic acids extraction protocol and a comprehensive comparative approach that mixed reference to well established real-time PCR detection techniques and analysis of convergent positive results. We tested 166 respiratory clinical samples and identified a global high degree of correlation for at least three of the techniques (xTAG, RespiFinder and FTD33). For these techniques, the highest Youden's index (YI), positive predictive (PPV) and specificity (Sp) values were observed for Core tests (e.g., influenza A [YI:0.86-1.00; PPV:78.95-100.00; Sp:97.32-100.00] & B [YI:0.44-1.00; PPV:100.00; Sp:100.00], hRSV [YI:0.50-0.99; PPV:85.71-100.00; Sp:99.38-100.00], hMPV [YI:0.71-1.00; PPV:83.33-100.00; Sp:99.37-100.00], EV/hRV [YI:0.62-0.82; PPV:93.33-100.00; Sp:94.48-100.00], AdV [YI:1.00; PPV:100.00; Sp:100.00] and hBoV [YI:0.20-0.80; PPV:57.14-100.00; Sp:98.14-100.00]). The present study completed an overview of the multiplex techniques available for the diagnosis of acute respiratory infections.

Background Ingestion of cranberry ( Vaccinium macrocarpon Ait.) has traditionally been utilized for prevention of urinary tract infections. The proanthocyanidins (PACs) in cranberry, in particular the A-type linkages have been implicated as important inhibitors of primarily P-fimbriated E. coli adhesion to uroepithelial cells. Additional experiments were required to investigate the persistence in urine samples over a broader time period, to determine the most effective dose per day and to determine if the urinary anti-adhesion effect following cranberry is detected within volunteers of different origins. Methods Two separate bioassays (a mannose-resistant hemagglutination assay and an original new human T24 epithelial cell-line assay) have assessed the ex-vivo urinary bacterial anti-adhesion activity on urines samples collected from 32 volunteers from Japan, Hungary, Spain and France in a randomized, double-blind versus placebo study. An in vivo Caenorhabditis elegans model was used to evaluate the influence of cranberry regimen on the virulence of E. coli strain. Results The results indicated a significant bacterial anti-adhesion activity in urine samples collected from volunteers that consumed cranberry powder compared to placebo (p < 0.001). This inhibition was clearly dose-dependent, prolonged (until 24 h with 72 mg of PAC) and increasing with the amount of PAC equivalents consumed in each cranberry powder regimen. An in vivo Caenorhabditis elegans model showed that cranberry acted against bacterial virulence: E. coli strain presented a reduced ability to kill worms after a growth in urines samples of patients who took cranberry capsules. This effect is particularly important with the regimen of 72 mg of PAC. Conclusions Administration of PAC-standardized cranberry powder at dosages containing 72 mg of PAC per day may offer some protection against bacterial adhesion and virulence in the urinary tract. This effect may offer a nyctohemeral protection.

Background Mycobacterium abscessus infections remain difficult to manage in both cystic fibrosis (CF) and non-CF patients and reported clinical outcomes are largely unsatisfactory. Clinical trial data are limited and no approved therapies are currently available for the management of M abscessus lung diseases. As an alternative, cohort studies may provide insightful information into the management of M abscessus pulmonary disease.Methods Based on a retrospective observational cohort study, we investigated the safety and efficacy of amikacin liposome inhaled suspension (ALIS) as an adjunct to a standard antibiotic regimen for M abscessus lung infection in both CF and non-CF patients. We also assessed the association of patient drug compliance with culture conversion and clinical outcomes.Results Twenty-six patients had long-term follow-up data available. Culture conversion was achieved in 54% (14/26) of the patients with no difference between CF and non-CF patients after an average treatment duration of 10 months. Patient treatment compliance was significantly better in the converter group compared to nonconverters with an odds ratio of 44.78 associated with good compared to poor patient compliance. Overall, 9 patients (35%) experienced an adverse event that led to treatment discontinuation.Conclusions ALIS appears beneficial in both CF and non-CF populations with M abscessus lung disease.