Increased in-hospital mortality from COVID-19 in patients with schizophrenia.

BACKGROUND: There is limited information describing the presenting characteristics and outcomes of patients with schizophrenia (SCZ) requiring hospitalization for coronavirus disease 2019 (COVID-19). AIMS: We aimed to compare the clinical characteristics and outcomes of COVID-19 SCZ patients with those of non-SCZ patients. METHOD: This was a case-control study of COVID-19 patients admitted to 4 AP-HM/AMU acute care hospitals in Marseille, southern France. COVID-19 infection was confirmed by a positive result on polymerase chain reaction testing of a nasopharyngeal sample and/or on chest computed scan among patients requiring hospital admission. The primary outcome was in-hospital mortality. The secondary outcome was intensive care unit (ICU) admission. RESULTS: A total of 1092 patients were included. The overall in-hospital mortality rate was 9.0%. The SCZ patients had an increased mortality compared to the non-SCZ patients (26.7% vs. 8.7%, P=0.039), which was confirmed by the multivariable analysis after adjustment for age, sex, smoking status, obesity and comorbidity (adjusted odds ratio 4.36 [95% CI: 1.09-17.44]; P=0.038). In contrast, the SCZ patients were not more frequently admitted to the ICU than the non-SCZ patients. Importantly, the SCZ patients were mostly institutionalized (63.6%, 100% of those who died), and they were more likely to have cancers and respiratory comorbidities. CONCLUSIONS: This study suggests that SCZ is not overrepresented among COVID-19 hospitalized patients, but SCZ is associated with excess COVID-19 mortality, confirming the existence of health disparities described in other somatic diseases.

Human Tregs at the materno-fetal interface show site-specific adaptation reminiscent of tumor Tregs.

Tregs are crucial for maintaining maternal immunotolerance against the semiallogeneic fetus. We investigated the elusive transcriptional profile and functional adaptation of human uterine Tregs (uTregs) during pregnancy. Uterine biopsies, from placental bed (materno-fetal interface) and incision site (control) and blood were obtained from women with uncomplicated pregnancies undergoing cesarean section. Tregs and CD4+ non-Tregs were isolated for transcriptomic profiling by Cel-Seq2. Results were validated on protein and single cell levels by flow cytometry. Placental bed uTregs showed elevated expression of Treg signature markers, including FOXP3, CTLA-4, and TIGIT. Their transcriptional profile was indicative of late-stage effector Treg differentiation and chronic activation, with increased expression of immune checkpoints GITR, TNFR2, OX-40, and 4-1BB; genes associated with suppressive capacity (HAVCR2, IL10, LAYN, and PDCD1); and transcription factors MAF, PRDM1, BATF, and VDR. uTregs mirrored non-Treg Th1 polarization and tissue residency. The particular transcriptional signature of placental bed uTregs overlapped strongly with that of tumor-infiltrating Tregs and was remarkably pronounced at the placental bed compared with uterine control site. In conclusion, human uTregs acquire a differentiated effector Treg profile similar to tumor-infiltrating Tregs, specifically at the materno-fetal interface. This introduces the concept of site-specific transcriptional adaptation of Tregs within 1 organ.

Reliability of gastric suctioning compared with ultrasound assessment of residual gastric volume: a prospective multicentre cohort study.

We aimed to compare the reliability of aspiration via a nasogastric tube with ultrasound for assessment of residual gastric volume. Sixty-one adult patients who were mechanically ventilated and received continuous enteral feeding through a nasogastric tube for > 48 h were included. A first qualitative and quantitative ultrasound examination of the gastric antrum was followed by gastric suctioning, performed by an operator blinded to the result of the ultrasound examination. A second ultrasound examination was performed thereafter, followed by re-injection of the aspirated gastric contents (≤ 250 ml) into the stomach. A third ultrasound assessment was then immediately performed. If the suctioned volume was ≥ 250 ml, 250 mg erythromycin was infused over 30 min. A fourth ultrasound was performed 90 min after the third. Sixty (98%) patients had a qualitatively assessed full stomach at first ultrasound examination vs. 52 (85%) after gastric suctioning (p = 0.016). The calculated gastric volume significantly decreased after gastric suctioning, without a significant decrease in the number of patients with volume ≥ 250 ml. Four of the nine patients with calculated gastric volume ≥ 250 ml had vomiting within the last 24 h (p = 0.013). The antral cross-sectional area significantly decreased between the third and the fourth ultrasound examination (p = 0.015). Erythromycin infusion did not make a significant difference to gastric volume (n = 10). Our results demonstrate that gastric suctioning is not a reliable tool for monitoring residual gastric volume. Gastric ultrasound is a feasible and promising tool for gastric volume monitoring in clinical practice.

Mediastinitis in the intensive care unit patient: a narrative review.

BACKGROUND: Mediastinitis is a rare but severe infection, defined as an inflammation of the connective tissues and structures within the mediastinum. Due to its proximity to vital structures, mediastinitis represents a highly morbid pathological process associated with a high risk of mortality. In most cases mediastinitis requires treatment in the intensive care unit. OBJECTIVES: To highlight to the reader the clinical features of mediastinitis, to attempt to define each clinical scenario, to describe the responsible pathogens and finally to depict both the medical and surgical treatments. SOURCES: We performed a literature search of the PubMed and Cochrane libraries, limited for articles published between January 2003 and December 2018, reporting on acute mediastinitis. CONTENT: The term covers different entities of different aetiologies including deep sternal wound infection related to sternotomy; oesophageal perforation or anastomosis leakage; and finally descending necrotizing mediastinitis, often secondary to oropharyngeal abscess. The responsible pathogens and therefore subsequent management depends on the underlying aetiology. Empirical antimicrobial therapy should cover the suspected microorganisms while surgery and supportive measures should aim to reduce the inoculum of pathogens by providing adequate drainage and debridement. IMPLICATIONS: Literature concerning mediastinitis in the intensive care unit is relatively scarce. We have collated the evidence and reviewed the different causes and treatment options of acute mediastinitis with a particular focus on microbiological epidemiology. Future research in larger cohorts is needed to better understand the treatment of this difficult disease.

Implementation of antibiotic stewardship programmes in French ICUs in 2018: a nationwide cross-sectional survey.

BACKGROUND: Antibiotic stewardship programmes have a pivotal role in ICUs, but the level of implementation of these programmes at the regional or national level is not well known. OBJECTIVES: The aim of our study was to assess the level of implementation of antibiotic stewardship programmes in French ICUs. METHODS: We conducted a nationwide cross-sectional survey from January to March 2018 using an online questionnaire sent as an E-mail link to ICU specialists (one questionnaire per ICU). RESULTS: Overall, 113 out of 206 (55%) ICUs participated. Access to local epidemiology regarding bacterial resistance and antibiotic consumption data was reported in 84% and 65% of ICUs, respectively. Local guidelines for antibiotic use were available in 54% of ICUs. The duration of empirical antibiotic therapy was limited in 46% of cases, following the recommendation of an external expert in 33%. An antibiotic stewardship programme leader was reported at the hospital level by 94% of respondents, being an infectious disease physician in 80%. His/her role in the ICU was mostly to discuss specific cases (50%) and to provide advice on antibiotic prescriptions (26%). Regarding microbiological diagnosis, blood cultures were not processed at night or during weekends in 57%. Molecular biology and MS techniques were available in 62% and 59% of cases, respectively. Therapeutic drug monitoring of ß-lactams was available in 46% of cases. Forty-three percent of respondents knew the expression 'antimicrobial/antibiotic stewardship'. CONCLUSIONS: Antibiotic stewardship programmes are not optimally implemented in French ICUs. Improvement efforts and regular monitoring of the level of implementation are needed.

Antibioprophylaxis in surgery and interventional medicine (adult patients). Update 2017.

Infection is a risk for any intervention. In surgery, for example, pathogenic bacteria are found in more than 90% of operative wounds during closure. This exists whatever the surgical technique and whatever the environment (the laminar flow does not entirely eliminate this risk). These bacteria are few in number but can proliferate. They find in the operative wound a favourable environment (haematoma, ischaemia, modification of oxido-reduction potential...) and the intervention induces anomalies of the immune defences. In the case of the installation of foreign material, the risk is increased. The objective of antibiotic prophylaxis (ABP) is to prevent bacterial growth in order to reduce the risk of infection at the site of the intervention. The preoperative consultation represents a privileged moment to decide on the prescription of a ABP. It is possible to define the type of intervention planned, the associated risk of infection (and therefore the necessity or not of ABP), the time of prescription before surgery and any allergic antecedents which may modify the choice of the selected antibiotic molecule.

Pelvic fracture in multiple trauma: A 67-case series.

INTRODUCTION: Severe pelvic trauma remains associated with elevated mortality, largely due to hemorrhagic shock. OBJECTIVE: The main study objective was to test for correlation between fracture type and mortality. The secondary objective was to assess the efficacy in terms of mortality of multidisciplinary management following a decision-tree in multiple trauma victims admitted to a level 1 trauma center. MATERIAL AND METHODS: Between July 2011 and July 2013, 534 severe trauma patients were included in a single-center continuous prospective observational study. All patients with hemorrhagic shock received early treatment by pelvic binder. Patients with active bleeding on full-body CT or persisting hemorrhagic shock underwent arteriography with or without embolization. Pelvic trauma was graded on the Tile classification. The principle end-point was mortality. RESULTS: Median age was 40 years (range, 26-48 years), with a 79% male/female sex ratio. Thirty-two of the 67 patients with pelvic trauma (48%) were in hemorrhagic shock at admission. Median injury severity score (ISS) was 36 (range, 24-43). On the Tile classification, 22 patients (33%) were grade A, 33 (49%) grade B and 12 (18%) grade C. Overall mortality was 19%, and 42% in case of hemorrhagic shock. Mortality was significantly higher with Tile C than A or B (58% vs. 9.1% and 12.1%, respectively; P=0.001). CONCLUSION: Vertical shear fracture (Tile C) was associated with greater mortality from hemorrhagic shock. LEVEL OF EVIDENCE: IV, case series.

Efficacy of adalimumab in sarcoidosis patients who developed intolerance to infliximab.

BACKGROUND: Tumor necrosis factor-alpha (TNF-α) inhibitors are regarded as the third-line therapy in sarcoidosis, the first choice generally being infliximab. To date, data regarding response to adalimumab in sarcoidosis patients intolerant to infliximab are lacking. The objective of this retrospective observational study was to establish if adalimumab could achieve stabilization or improvement of the disease in refractory sarcoidosis patients who developed intolerance to infliximab. MATERIAL AND METHODS: Sarcoidosis patients referred to St Antonius Interstitial Lung Diseases Center of Excellence, Nieuwegein, The Netherlands, between January 2008 and April 2015 who switched from infliximab to adalimumab were included. Changes in organ function, inflammatory biomarker levels, and adverse events were retrieved from medical records. RESULTS: Out of 142 infliximab treated patients, 18 (13%) had to discontinue treatment due to antibody formation or severe adverse events and switched to adalimumab therapy. Organ function improved in 7 patients (39%), was stable in 6 patients (33%), and worsened in 5 patients (28%) after 12 months of treatment or after 6 months if evaluation after 12 months was not available (n = 4). In none of the patients biomarker levels of soluble interleukin-2 receptor (sIL-2R) deteriorated. Median decrease in sIL-2R was 3614 pg/mL. Most reported adverse event was infection (n = 10). CONCLUSIONS: Adalimumab is an effective alternative for patients intolerant to infliximab. The switch to adalimumab achieved clinical improvement in 39% and stabilization in 33% of patients intolerant to infliximab. Further research is needed to develop guidelines on how to use adalimumab for sarcoidosis in terms of dosing regimen.

Efficacy of the endoscopic management of postoperative fistulas of leakages after esophageal surgery for cancer: a retrospective series.

BACKGROUND AND AIMS: Anastomotic leakages are severe and often lethal adverse events of surgery for esophageal cancer. The endoscopic treatment is growing up in such indications. The aim was to evaluate the efficacy and describe the strategy of the endoscopic management of anastomotic leakages/fistulas after esophageal oncologic surgery. METHODS: Single-center retrospective study on 126 patients operated for esophageal carcinomas between 2010 and 2014. Thirty-five patients with postoperative fistulas/leakages (27 %) were endoscopically managed and included. The primary endpoint was the efficacy of the endoscopic treatment. The secondary endpoints were: delays between surgery, diagnosis, endoscopy and recovery; number of procedures; material used; and adverse events rate. Uni- and multivariate analyses were carried out to determine predictive factors of success. RESULTS: There were mostly men, with a median age of 61.7 years ± 8.9 [43-85]. 48.6 % underwent Lewis-Santy surgery and 45.7 % Akiyama's. 71.4 % patients received neo-adjuvant chemo-radiation therapy. The primary and secondary efficacy was 48.6 and 68.6 %, respectively. The delay between surgery and endoscopy was 8.5 days [6.00-18.25]. Eighty-eight percentages of the patients were treated using double-type metallic stents, with removability and migration rates of 100 and 18 %, respectively. In the other cases, we used over-the-scope clips, naso-cystic drain or combined approach. The mean number of endoscopy was 2.6 ± 1.57 [1-10]. The mortality rate was 17 %, none being related to procedures. No predictive factor of efficacy could be identified. CONCLUSIONS: The endoscopic management of leakages or fistulas after esophageal surgery reached an efficacy rate of 68.8 %, mostly using stents, without significant adverse events. The mortality rate could be decreased from 40-100 to 17 %.

High prevalence of gluten sensitivity in a cohort of patients with undifferentiated connective tissue disease.

OBJECTIVES: The aim of this study was to investigate if co-morbid conditions as hepatitis C virus infection and celiac disease may be associated to undifferentiated connective tissue disease. METHODS: We studied retrospectively and prospectively 52 patients with diagnosis of undifferentiated connective tissue disease, subdivided, according to Vaz criteria, in systemic lupus erythematosus, systemic sclerosis and Sjögren's syndrome-like subgroups. Serological markers of celiac disease as anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies were investigated. An esophagogastroduodenoscopy with duodenal biopsy and histological examination was proposed to patients with positive celiac disease serology. In addition antibodies directed to hepatitis C virus and total IgA-antibodies were investigated. RESULTS: Six patients (11,5%) were positive for celiac disease serological tests although two of them were asymptomatic. Four patients underwent an esophagogastroduodenoscopy, showing total or subtotal villous atrophy at duodenal biopsies. Hepatitis C virus serology was negative in all patients and none had IgA deficiency. 83% of celiac patients showed a scleroderma-like phenotype. We observed a statistically higher incidence of autoimmune symptoms in patients with gluten sensitivity. Fatigue and myalgia regressed early after the beginning of gluten-free diet. CONCLUSIONS: In our cohort of patients the prevalence of celiac disease was higher than that reported in the general population. We believe that all patients with diagnosis of undifferentiated connective tissue disease, especially those with a systemic sclerosis-like presentation, should be investigated for celiac disease, even in absence of gastrointestinal symptoms. Gluten-free diet should be early recommended to all patients having undifferentiated connective tissue disease and gluten sensitivity.

The boson peak of amyloid fibrils: probing the softness of protein aggregates by inelastic neutron scattering.

Proteins and polypeptides are characterized by low-frequency vibrations in the terahertz regime responsible for the so-called "boson peak". The shape and position of this peak are related to the mechanical properties of peptide chains. Amyloid fibrils are ordered macromolecular assemblies, spontaneously formed in nature, characterized by unique biological and nanomechanical properties. In this work, we investigate the effects of the amyloid state and its polymorphism on the boson peak. We used inelastic neutron scattering to probe low-frequency vibrations of the glucagon polypeptide in the native state and in two different amyloid morphologies in both dry and hydrated sample states. The data show that amyloid fibril formation and hydration state affect the softness of the polypeptide not only by changing the distribution of vibrational modes but also, and most significantly, the dissipative mechanisms of collective low-frequency vibrations provided by water-protein and protein-protein interactions. We show how the morphology of the fibril is able to tune these effects. Atomic fluctuations were also measured by elastic neutron scattering. The data confirm that any effect of protein aggregation on fluctuation amplitudes is essentially due to changes in surface exposure to hydration water. The results demonstrate the importance of protein-protein and protein-water interactions in the dynamics and mechanics of amyloid fibrils.

Impact of a goal-directed therapy protocol on postoperative fluid balance in patients undergoing liver transplantation: a retrospective study.

OBJECTIVE: Liver transplantation carries major risks during the perioperative period. Few studies focused on the hemodynamics of patients undergoing liver transplantation. The present study was aimed to evaluate the impact of the implementation of a protocol including goal-directed therapy in patients undergoing liver transplantation. Our first goal was to determine its impact on the fluid balance. Secondarily, we evaluated possible improvements in the patient outcomes. STUDY DESIGN: A before and after study. PATIENTS AND METHODS: Fifty patients undergoing liver transplantation were included during two successive six-month periods. During the first period, the management of the patients was left at the discretion of the senior physicians (control group, n=25). During the second period, the patients were treated according to a predetermined protocol including a specific hemodynamic monitoring (protocol group, n=25). RESULTS: The fluid balance was negative in the protocol group and positive in the control group at 24h (-606mL vs. +3445mL, P<0.01) and 48h (-2315mL vs. +1170mL, P<0.01) after liver transplantation. The volume of the crystalloid administration was lower in the protocol group than in the control group (5000mL vs. 8000mL, P<0.01, and 1500mL vs. 6000mL, P<0.01, during surgery and 48h after liver transplantation, respectively). The duration of mechanical ventilation and postoperative ileus were significantly reduced in the protocol group, as compared with the control group, 20h vs. 94h (P<0.01) and 4days vs. 6days (P<0.01), respectively. CONCLUSION: For patients undergoing liver transplantation, the implementation of a protocol aiming to optimize hemodynamics was associated with reduced fluid balance and decreased requirement for mechanical ventilation and postoperative ileus duration.

Blunt bowel and mesenteric injuries detected on CT scan: who is really eligible for surgery?

BACKGROUND: There is no consensually accepted approach to the management of blunt bowel and mesenteric injuries. Surgery is required urgently in the case of bowel perforation or haemodynamic instability, but several patients can be treated non-operatively. This study aimed to identify the risk factors for surgery in an initial assessment. METHODS: We retrospectively reviewed the medical charts and computed tomography (CT) scans of adult patients presenting with a blunt abdominal trauma to our centre between the years 2004 and 2011. We included only patients with a CT scan showing suspected injury to the mesentery or bowel. RESULTS: There were 43 patients (33 males and 10 females), with a mean Injury Severity Score (ISS) of 22. The most frequently suspected injuries based on a CT scan were mesenteric infiltrations in 40 (93 %) patients and bowel wall thickening in 22 (51 %) patients. Surgical therapy was required for 23 (54 %) patients. Four factors were independently associated with surgical treatment: a free-fluid peritoneal effusion without solid organ injury [adjusted odds ratio (OR) = 14.4, 95 % confidence interval (CI) [1.9-111]; p = 0.015], a beaded appearance of the mesenteric vessels (OR = 9 [1.3-63]; p = 0.027), female gender (OR = 14.2 [1.3-159]; p = 0.031) and ISS >15 (OR = 6.9 [1.1-44]; p = 0.041). Surgery was prescribed immediately for 11 (26 %) patients and with delay, after the failure of initially conservative treatment, for 12 (28 %) patients. The presence of a free-fluid peritoneal effusion without solid organ injury was also an independent risk factor for delayed surgery (OR = 9.8 [1-95]; p = 0.048). CONCLUSIONS: In blunt abdominal trauma, the association of a bowel and/or mesenteric injury with a peritoneal effusion without solid organ injury on an initial CT scan should raise the suspicion of an injury requiring surgical treatment. Additionally, this finding should lead to a clinical discussion of the benefit of explorative laparotomy to prevent delayed surgery. However, these findings need validation by larger studies.

[Lung ultrasound: clinical applications and perspectives in intensive care unit]. / Échographie pleuropulmonaire: applications cliniques et perspectives en réanimation.

OBJECTIVE: To describe the use of lung ultrasound in clinical practice and the new opportunities offered by this technology in intensive care unit (ICU) patients. METHOD: Review of signs identified by lung ultrasound and systematic analysis of data published within the last 5 years on its use in ICU. The literature has been extracted from the database Pubmed™. Specific keywords were used to select relevant publications. Clinical studies published in French and English languages were assessed. RESULTS: Lung ultrasound serves to diagnose, quantify, drain and monitor pleural effusions. In patients with acute respiratory failure, lung ultrasound participates to the diagnosis, the implementation of treatments and their follow-up. It helps to manage patients with pneumonia and acute lung injury. Finally, the investigation of the interstitial edema brings information about hemodynamics that can serve to manage our patients. CONCLUSION: Lung ultrasound is an easy, non-invasive, and non-irradiant technology. It brings lot of useful information at the patient's bedside.

Role of proinflammatory cytokines on lipopolysaccharide-induced phase shifts in locomotor activity circadian rhythm.

We previously reported that early night peripheral bacterial lipopolysaccharide (LPS) injection produces phase delays in the circadian rhythm of locomotor activity in mice. We now assess the effects of proinflammatory cytokines on circadian physiology, including their role in LPS-induced phase shifts. First, we investigated whether differential systemic induction of classic proinflammatory cytokines could explain the time-specific behavioral effects of peripheral LPS. Induction levels for plasma interleukin (IL)-1α, IL-1ß, IL-6, or tumor necrosis factor (TNF)-α did not differ between animals receiving a LPS challenge in the early day or early night. We next tested the in vivo effects of central proinflammatory cytokines on circadian physiology. We found that intracerebroventricular (i.c.v.) delivery of TNF-α or interleukin IL-1ß induced phase delays on wheel-running activity rhythms. Furthermore, we analyzed if these cytokines mediate the LPS-induced phase shifts and found that i.c.v. administration of soluble TNF-α receptor (but not an IL-1ß antagonistic) prior to LPS stimulation inhibited the phase delays. Our work suggests that the suprachiasmatic nucleus (SCN) responds to central proinflammatory cytokines in vivo, producing phase shifts in locomotor activity rhythms. Moreover, we show that the LPS-induced phase delays are mediated through the action of TNF-α at the central level, and that systemic induction of proinflammatory cytokines might be necessary, but not sufficient, for this behavioral outcome.

[French clinical guidelines for prevention of perianaesthetic dental injuries: long text]. / Bris dentaires périanesthésiques: texte long.

INTRODUCTION: Dental injuries represent the most common claims against the anaesthesiologists. Dental lesions are frequent complications of orotracheal intubation and major causal factors are, firstly, preexisting poor dentition, and, secondly, difficult laryngoscopy and tracheal intubation. The aim of this work was to prioritize propositions for prevention in perianaesthetic dental injury and for care in case of dental trauma. METHOD: A GRADE consensus procedure consisting of three rounds was conducted. A purposively selected heterogeneous panel (n=15) of experts, comprising 10 practitioners in anesthesiology, one practitioner who is jurist and anaesthesiologist, two practitioners in maxillofacial surgery, and two practitioners in dentist surgery. In cases where the data did not appear conclusive, recommendations were based on the consensus opinion of the board members. The guidelines represent the best current evidence based on literature search and professional opinion. RESULTS: The entire panel completed all three rounds and 31 plus six propositions were written for adult and paediatric clinical practice in anaesthesiology, respectively. The experts highlight the interest of preoperative visit for minimizing dental injuries: the practitioner must identify risk factors for difficult intubation and ventilation, describe precisely patient's preoperative dental condition, including upper incisor most commonly involved teeth in dental trauma. Patients have to be informed by practitioner for risk dental injury and anaesthesiology staff must choose his anesthesia protocol before the induction of intubation narcosis, avoiding insufficient anaesthesia and lack of experience by the anaesthesiologist. The choice of accurate proceeding during laryngoscopy, tracheal intubation and extubation for example, can aid in the prevention of dental injury, reduce the number of claims and the cost of litigation process. DISCUSSION: These guidelines delineate an approach for the prevention of perianaesthetic dental trauma and for the immediate or urgent care in case of perianaesthetic dental injury.