A High-Dimensional Atlas of Human T Cell Diversity Reveals Tissue-Specific Trafficking and Cytokine Signatures.

Depending on the tissue microenvironment, T cells can differentiate into highly diverse subsets expressing unique trafficking receptors and cytokines. Studies of human lymphocytes have primarily focused on a limited number of parameters in blood, representing an incomplete view of the human immune system. Here, we have utilized mass cytometry to simultaneously analyze T cell trafficking and functional markers across eight different human tissues, including blood, lymphoid, and non-lymphoid tissues. These data have revealed that combinatorial expression of trafficking receptors and cytokines better defines tissue specificity. Notably, we identified numerous T helper cell subsets with overlapping cytokine expression, but only specific cytokine combinations are secreted regardless of tissue type. This indicates that T cell lineages defined in mouse models cannot be clearly distinguished in humans. Overall, our data uncover a plethora of tissue immune signatures and provide a systemic map of how T cell phenotypes are altered throughout the human body.

Ancestral SARS-CoV-2 and Omicron BA.5-specific neutralizing antibody and T-cell responses after Omicron bivalent booster vaccination in previously infected and infection-naive individuals.

Coronavirus disease-2019 (COVID-19) bivalent ancestral/Omicron messenger RNA (mRNA) booster vaccinations became available to boost and expand the immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron infections. In a prospective cohort study including 59 healthcare workers, we assessed SARS-CoV-2 ancestral and Omicron BA.5-specific neutralizing antibody and T-cell responses in previously infected and infection-naive individuals. Also, we assessed the effect of an ancestral/Omicron BA.1 bivalent mRNA booster vaccination on these immune responses. 10 months after previous monovalent mRNA vaccinations, ancestral SARS-CoV-2 S1-specific T-cell and anti-RBD IgG responses remained detectable in most individuals and a previous SARS-CoV-2 infection was associated with increased T-cell responses. T-cell responses, anti-RBD IgG, and Omicron BA.5 neutralization activity increased after receiving an ancestral/Omicron BA.1 bivalent booster mRNA vaccination. An Omicron BA.5 infection in addition to bivalent vaccination, led to a higher ratio of Omicron BA.5 to ancestral strain neutralization activity compared to no bivalent vaccination and no recent SARS-CoV-2 infection. In conclusion, SARS-CoV-2 T-cell and antibody responses persist for up to 10 months after a monovalent booster mRNA vaccination. An ancestral/Omicron BA.1 bivalent booster mRNA vaccination increases these immune responses and also induces Omicron BA.5 cross-neutralization antibody activity. Finally, our data indicate that hybrid immunity is associated with improved preservation of T-cell immunity.

Airborne virus shedding of the alpha, delta, omicron SARS-CoV-2 variants and influenza virus in hospitalized patients.

Airborne transmission is an important transmission route for the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological data indicate that certain SARS-CoV-2 variants, like the omicron variant, are associated with higher transmissibility. We compared virus detection in air samples between hospitalized patients infected with different SARS-CoV-2 variants or influenza virus. The study was performed during three separate time periods in which subsequently the alpha, delta, and omicron SARS-CoV-2 variants were predominant. In total, 79 patients with coronavirus disease 2019 (COVID-19) and 22 patients with influenza A virus infection were included. Collected air samples were positive in 55% of patients infected with the omicron variant in comparison to 15% of those infected with the delta variant (p < 0.01). In multivariable analysis, the SARS-CoV-2 omicron BA.1/BA.2 variant (as compared to the delta variant) and the viral load in nasopharynx were both independently associated with air sample positivity, but the alpha variant and COVID-19 vaccination were not. The proportion of positive air samples patients infected with the influenza A virus was 18%. In conclusion, the higher air sample positivity rate of the omicron variant compared to previous SARS-CoV-2 variants may partially explain the higher transmission rates seen in epidemiological trends.

Two vs One Forward View Examination of Right Colon on Adenoma Detection: An International Multicenter Randomized Trial.

BACKGROUND & AIMS: Second forward view (SFV) examination of the right colon (RC) in colonoscopy was suggested to improve the adenoma detection rate (ADR), but multicenter data to inform its routine use remain limited. We performed an international multicenter randomized trial comparing SFV vs a standard single forward view examination of the RC on adenoma detection. METHODS: Asymptomatic individuals undergoing screening or surveillance colonoscopies from 6 Asia Pacific regions were invited for study. A forward view examination of the RC was first performed in all patients, followed by randomization at the hepatic flexure to either SFV examination of the RC and standard withdrawal examination from the hepatic flexure to rectum, or a standard withdrawal colonoscopy (SWC) examination from the hepatic flexure to rectum. The primary outcome was RC ADR. RESULTS: Between 2016 and 2019, there were 1011 patients randomized (SFV group, 502 patients; SWC group, 509 patients). Forty-five endoscopists performed the colonoscopies. The RC ADR was significantly higher in the SFV group than in the SWC group (27.1% vs 21.6%; P = .042). The whole-colon ADR was high in both groups (49.0% vs 45.0%; P =.201). The SFV examination identified 58 additional adenomas in 49 patients (9.8%), leading to a change in surveillance recommendations in 15 patients (3.0%). The median overall withdrawal time was 1.5 minutes longer in the SFV group (12.0 vs 10.5 min; P < .001). Older age, male sex, ever smoking, and longer RC withdrawal time were independent predictors of right-sided adenoma detection. CONCLUSIONS: In this multicenter trial, SFV examination significantly increased the RC ADR in screening and surveillance colonoscopies. Routine RC SFV examination should be considered. ClinicalTrials.gov ID: NCT03121495.

Small bowel adenocarcinoma in Crohn's disease: a systematic review and meta-analysis of the prevalence, manifestation, histopathology, and outcomes.

BACKGROUND AND AIMS: Small bowel adenocarcinoma (SBA) is a rare neoplasm that is associated with Crohn's disease (CD). This study aims to quantify the prevalence of CD-SBA, review the current evidence of histopathology and molecular analysis findings, and identify the clinical presentation and outcomes of CD-SBA. METHODS: Electronic databases Medline and Embase were searched for articles describing SBA in inflammatory bowel disease patients. The histopathology, molecular analysis findings, clinical presentation, prevalence, and outcomes of CD-SBA were extracted, and results were pooled with random effects. RESULTS: In total, 33 articles were included in the analysis. Prevalence of SBA was 1.15 (CI: 0.31-2.33) per 1000 CD patients. Only 11% (CI: 0.04-0.21) of CD-SBA patients had observable radiological features. CD-SBA was most commonly found in the ileum (84%), diagnosed at stage 2 (36%), with main presenting complaints including obstruction, weight loss, and abdominal pain. Significant histopathological findings included adjacent epithelial dysplasia, and an equal distribution of well-differentiated (49%) and poorly differentiated subtypes (46%). Most prevalent genetic mutation was KRAS mutation (18%), followed by mismatch repair deficiency (9.7%). The 5-year overall survival for CD-SBA patients was 29% (CI: 0.18-0.41), and 33% (CI: 0.26-0.41) for de novo SBA. No statistically significant increase in risk for CD-SBA was noted for treatment with thiopurines, steroids, and 5-ASA. CONCLUSION: Our meta-analysis found the prevalence of CD-SBA to be 1.15 per 1000 CD patients. The 5-year overall survival for CD-SBA was poor. The presenting symptoms were non-specific, and therefore the diagnosis requires a high index of suspicion.

Biological Subphenotypes of Acute Respiratory Distress Syndrome Show Prognostic Enrichment in Mechanically Ventilated Patients without Acute Respiratory Distress Syndrome.

Rationale: Recent studies showed that biological subphenotypes in acute respiratory distress syndrome (ARDS) provide prognostic enrichment and show potential for predictive enrichment. Objectives: To determine whether these subphenotypes and their prognostic and potential for predictive enrichment could be extended to other patients in the ICU, irrespective of fulfilling the definition of ARDS. Methods: This is a secondary analysis of a prospective observational study of adult patients admitted to the ICU. We tested the prognostic enrichment of both cluster-derived and latent-class analysis (LCA)-derived biological ARDS subphenotypes by evaluating the association with clinical outcome (ICU-day, 30-day mortality, and ventilator-free days) using logistic regression and Cox regression analysis. We performed a principal component analysis to compare blood leukocyte gene expression profiles between subphenotypes and the presence of ARDS. Measurements and Main Results: We included 2,499 mechanically ventilated patients (674 with and 1,825 without ARDS). The cluster-derived "reactive" subphenotype was, independently of ARDS, significantly associated with a higher probability of ICU mortality, higher 30-day mortality, and a lower probability of successful extubation while alive compared with the "uninflamed" subphenotype. The blood leukocyte gene expression profiles of individual subphenotypes were similar for patients with and without ARDS. LCA-derived subphenotypes also showed similar profiles. Conclusions: The prognostic and potential for predictive enrichment of biological ARDS subphenotypes may be extended to mechanically ventilated critically ill patients without ARDS. Using the concept of biological subphenotypes for splitting cohorts of critically ill patients could add to improving future precision-based trial strategies and lead to identifying treatable traits for all critically ill patients.

Clinical evaluation of rapid point-of-care antigen tests for diagnosis of SARS-CoV-2 infection.

The RT-qPCR in respiratory specimens is the gold standard for diagnosing acute COVID-19 infections. However, this test takes considerable time before test results become available, thereby delaying patients from being diagnosed, treated, and isolated immediately. Rapid antigen tests could overcome this problem. In the first study, clinical performances of five rapid antigen tests were compared to RT-qPCR in upper respiratory specimens from 40 patients with positive and 40 with negative RTq-PCR results. In the second study, the rapid antigen test with one of the best test characteristics (Romed) was evaluated in a large prospective collection of upper respiratory specimens from 900 different COVID-19-suspected patients (300 emergency room patients, 300 nursing home patients, and 300 health care workers). Test specificities ranged from 87.5 to 100.0%, and test sensitivities from 55.0 to 80.0%. The clinical specificity of the Romed test was 99.8% (95% CI 98.9-100). Overall clinical sensitivity in the study population was 73.3% (95% CI 67.9-78.2), whereas sensitivity in the different patient groups varied from 65.3 to 86.7%. Sensitivity was 83.0 to 86.7% in patients with short duration of symptoms. In a population with a COVID-19 prevalence of 1%, the negative predictive value in all patients was 99.7%. There is a large variability in diagnostic performance between rapid antigen tests. The Romed rapid antigen test showed a good clinical performance in patients with high viral loads (RT-qPCR cycle threshold ≤30), which makes this antigen test suitable for rapid identification of COVID-19-infected health care workers and patients.

The impact of the coronavirus disease 2019 pandemic on gastroenterologists in Southeast Asia: A mixed-methods study.

BACKGROUND AND AIM: The coronavirus disease 2019 pandemic has impacted gastroenterology practices worldwide; however, its protracted effects within Southeast Asia were unknown. The primary aim of the study was to determine the impact of the pandemic on clinical demands including burnout among gastroenterologists within the region. The secondary aim was to identify risk factors for burnout and determine regional stressors. METHODS: This was a mixed-methods study. Gastroenterologists were surveyed electronically between September 1 and December 7, 2020, via gastroenterology and endoscopy societies of Brunei, Indonesia, Malaysia, Philippines, Singapore, and Thailand. Quantitative and qualitative data were collected. The 22-item Maslach Burnout Inventory-Human Services Survey (MBI-HSS) was used to detect burnout. Quantitative data were non-parametric; non-parametric methods were used for statistical comparisons. Logistic regression was used to determine risk factors for burnout. Content analysis method was used to analyze qualitative data. Ethical approval was obtained. RESULTS: A total of 73.0% reported that they were still significantly affected by the pandemic. Of these, 40.5% reported increased workload and 59.5% decreased workload. Statistically significant differences in weekly working hours, endoscopy, and inpatient volumes were present. No differences were observed in outpatient volumes, likely because of telemedicine. Burnout was common; however, 50.1% of gastroenterologists were unaware of or did not have access to mental health support. This, as well as depression, being a trainee, and public sector work, increased burnout risk significantly. CONCLUSION: The effects of the pandemic are multifaceted, and burnout is common among Southeast Asian gastroenterologists. Safeguards for mental health are suboptimal, and improvements are urgently needed.

Understanding Heterogeneity in Biologic Phenotypes of Acute Respiratory Distress Syndrome by Leukocyte Expression Profiles.

Rationale: Two biologic phenotypes of acute respiratory distress syndrome (ARDS) have been identified based on plasma protein markers in four previous studies. Objectives: To determine if blood leukocyte gene expression is different between the "reactive" and "uninflamed" phenotype. Methods: This is a new study adding blood leukocyte transcriptomics and bioinformatics analysis to an existing patient cohort of ARDS in patients with sepsis admitted to two ICUs during a 1.5-year period. Canonical pathway analysis was performed. Measurements and Main Results: A total of 210 patients with sepsis and ARDS were included, of whom 128 had a reactive and 82 an uninflamed phenotype. A total of 3,332/11,443 (29%) transcripts were significantly different between the phenotypes. Canonical pathway analysis showed upregulation of oxidative phosphorylation genes indicative of mitochondrial dysfunction (52% of genes in pathway). The uninflamed phenotype was characterized by upregulation of mitogen-activated protein kinase pathways. Conclusions: A third of genes are differentially expressed between biologic phenotypes of ARDS supporting the observation that the subgroups of ARDS are incomparable in terms of pathophysiology. These data provide additional support for biologic heterogeneity in patients with ARDS and suggests that a personalized approach to intervention focusing on oxidative phosphorylation is pivotal in this condition.

Chest CT for triage during COVID-19 on the emergency department: myth or truth?

PURPOSE: We aimed to investigate the diagnostic performance of chest CT compared with first RT-PCR results in adult patients suspected of COVID-19 infection in an ED setting. We also constructed a predictive machine learning model based on chest CT and additional data to improve the diagnostic accuracy of chest CT. METHODS: This study's cohort consisted of 319 patients who underwent chest CT and RT-PCR testing at the ED. Patient characteristics, demographics, symptoms, vital signs, laboratory tests, and chest CT results (CO-RADS) were collected. With first RT-PCR as reference standard, the diagnostic performance of chest CT using the CO-RADS score was assessed. Additionally, a predictive machine learning model was constructed using logistic regression. RESULTS: Chest CT, with first RT-PCR as a reference, had a sensitivity, specificity, PPV, and NPV of 90.2%, 88.2%, 84.5%, and 92.7%, respectively. The prediction model with CO-RADS, ferritin, leucocyte count, CK, days of complaints, and diarrhea as predictors had a sensitivity, specificity, PPV, and NPV of 89.3%, 93.4%, 90.8%, and 92.3%, respectively. CONCLUSION: Chest CT, using the CO-RADS scoring system, is a sensitive and specific method that can aid in the diagnosis of COVID-19, especially if RT-PCR tests are scarce during an outbreak. Combining a predictive machine learning model could further improve the accuracy of diagnostic chest CT for COVID-19. Further candidate predictors should be analyzed to improve our model. However, RT-PCR should remain the primary standard of testing as up to 9% of RT-PCR positive patients are not diagnosed by chest CT or our machine learning model.

Population Density and Risk of Inflammatory Bowel Disease: A Prospective Population-Based Study in 13 Countries or Regions in Asia-Pacific.

INTRODUCTION: Living in an urban environment may increase the risk of developing inflammatory bowel disease (IBD). It is unclear if this observation is seen globally. We conducted a population-based study to assess the relationship between urbanization and incidence of IBD in the Asia-Pacific region. METHODS: Newly diagnosed IBD cases between 2011 and 2013 from 13 countries or regions in Asia-Pacific were included. Incidence was calculated with 95% confidence interval (CI) and pooled using random-effects model. Meta-regression analysis was used to assess incidence rates and their association with population density, latitude, and longitude. RESULTS: We identified 1175 ulcerative colitis (UC), 656 Crohn's disease (CD), and 37 IBD undetermined (IBD-U). Mean annual IBD incidence per 100 000 was 1.50 (95% CI: 1.43-1.57). India (9.31; 95% CI: 8.38-10.31) and China (3.64; 95% CI, 2.97-4.42) had the highest IBD incidence in Asia. Incidence of overall IBD (incidence rate ratio [IRR]: 2.19; 95% CI: 1.01-4.76]) and CD (IRR: 3.28; 95% CI: 1.83-9.12) was higher across 19 areas of Asia with a higher population density. In China, incidence of IBD (IRR: 2.37; 95% CI: 1.10-5.16) and UC (IRR: 2.63; 95% CI: 1.2-5.8) was positively associated with gross domestic product. A south-to-north disease gradient (IRR: 0.94; 95% CI: 0.91-0.98) was observed for IBD incidence and a west-to-east gradient (IRR: 1.14; 95% CI: 1.05-1.24) was observed for CD incidence in China. This study received IRB approval. CONCLUSIONS: Regions in Asia with a high population density had a higher CD and UC incidence. Coastal areas within China had higher IBD incidence. With increasing urbanization and a shift from rural areas to cities, disease incidence may continue to climb in Asia.

Adenoma detection rates in colonoscopies for positive fecal immunochemical tests versus direct screening colonoscopies.

BACKGROUND AND AIMS: Recent guidelines propose higher adenoma detection rate (ADR) benchmarks for colonoscopies performed for positive results for fecal immunochemical tests (FIT), but this is based on low-quality evidence. We aimed to compare ADR, advanced ADR (AADR), and number of adenomas per colonoscopy (APC) in direct screening colonoscopy (DSC) versus FIT-positive colonoscopy (FITC) in a multicenter Asia-Pacific cohort to justify differential targets. METHODS: Asymptomatic average-risk patients ≥50 years of age who underwent screening colonoscopy directly or as follow-up for positive OC-Sensor FIT results were identified from 8 sites across the Asia-Pacific region. Overall, sex-specific ADR, overall AADR, and overall APC were compared between the 2 screening methods. Multivariable logistic regression was performed to adjust for confounding by differences in patient characteristics. Linear regression was used to correlate ADR with APC and to propose APC benchmarks. RESULTS: A total of 2901 (mean age, 60.1 years; 57% men) individuals had DSC, and 2485 (mean age, 62.8 years; 57% men) underwent FITC. Overall ADR (53.6% vs 37.5%; odds ratio [OR], 1.93; P < .001), male-specific ADR (61.6% vs 44.6%; OR, 2; P < .001), female-specific ADR (43.2% vs 28.2%; OR, 1.94; P < .001) and overall AADR (29.9% vs 4.9%; OR, 8.2; P < .001) in FITC were significantly higher than the corresponding values for DSC. Differences remained significant after adjustment for patient characteristics. ADR was strongly and positively correlated to APC, with an ADR of 45% and 35% correlating to an APC of ∼1 and ∼0.65. CONCLUSIONS: Results from this international multicenter cohort study provide early evidence that newly proposed higher ADR targets are justified as quality indicators for FITC.

Organization and training at national level of antimicrobial stewardship and infection control activities in Europe: an ESCMID cross-sectional survey.

Antimicrobial stewardship (AMS) and Infection prevention and control (IPC) are two key complementary strategies that combat development and spread of antimicrobial resistance. The ESGAP (ESCMID Study Group for AMS), EUCIC (European Committee on Infection Control) and TAE (Trainee Association of ESCMID) investigated how AMS and IPC activities and training are organized, if present, at national level in Europe. From February 2018 to May 2018, an internet-based cross-sectional survey was conducted through a 36-item questionnaire, involving up to three selected respondents per country, from 38 European countries in total (including Israel), belonging to the ESGAP/EUCIC/TAE networks. All 38 countries participated with at least one respondent, and a total of 81 respondents. Education and involvement in AMS programmes were mandatory during the postgraduate training of clinical microbiology and infectious diseases specialists in up to one-third of countries. IPC was acknowledged as a specialty in 32% of countries. Only 32% of countries had both guidance and national requirements regarding AMS programmes, in contrast to 61% for IPC. Formal national staffing standards for AMS and IPC hospital-based activities were present in 24% and 63% of countries, respectively. The backgrounds of professionals responsible for AMS and IPC programmes varied tremendously between countries. The organization and training of AMS and IPC in Europe are heterogeneous and national requirements for activities are frequently lacking.

Current mentorship practices in the training of the next generation of clinical microbiology and infectious disease specialists: an international cross-sectional survey.

The purpose of this study was to describe the current practice of mentorship in clinical microbiology (CM) and infectious diseases (ID) training, to identify possible areas for improvement and to assess the factors that are associated with satisfactory mentorship. An international cross-sectional survey containing 35 questions was answered by 317 trainees or specialists who recently completed clinical training. Overall, 179/317 (56%) trainees were satisfied with their mentors, ranging from 7/9 (78%) in non-European countries, 39/53 (74%) in Northern Europe, 13/22 (59%) in Eastern Europe, 61/110 (56%) in Western Europe, 37/76 (49%) in South-Western Europe to 22/47 (47%) in South-Eastern Europe. However, only 115/317 (36%) respondents stated that they were assigned an official mentor during their training. In multivariable logistic regression analysis, the satisfaction of trainees was significantly associated with having a mentor who was a career model (OR 6.4, 95%CI 3.5-11.7), gave constructive feedback on work performance (OR 3.3, 95%CI 1.8-6.2), and knew the family structure of the mentee (OR 5.5, 95%CI 3.0-10.1). If trainees felt overburdened, 70/317 (22%) felt that they could not talk to their mentors. Moreover, 67/317 (21%) stated that they could not talk to their mentor when unfairly treated and 59/317 (19%) felt uncertain. Training boards and authorities responsible for developing and monitoring CM&ID training programmes should invest in the development of high-quality mentorship programmes for trainees in order to contribute to the careers of the next generation of professionals.

Moderate positive predictive value of a multiplex real-time PCR on whole blood for pathogen detection in critically ill patients with sepsis.

A novel multiplex real-time PCR for bloodstream infections (BSI-PCR) detects pathogens directly in blood. This study aimed at determining the positive predictive value (PPV) of BSI-PCR in critically ill patients with sepsis. We included consecutive patients with presumed sepsis upon admission to the intensive care unit (ICU). The multiplexed BSI-PCR included 17 individual PCRs for a broad panel of species- and genus-specific DNA targets. BSI-PCR results were compared with a reference diagnosis for which plausibility of infection and causative pathogen(s) had been prospectively assessed by trained observers, based on available clinical and microbiological evidence. PPV and false positive proportion (FPP) were calculated. Clinical plausibility of discordant positive results was adjudicated by an expert panel. Among 325 patients, infection likelihood was categorized as confirmed, uncertain, and ruled out in 210 (65%), 88 (27%), and 27 (8%) subjects, respectively. BSI-PCR identified one or more microorganisms in 169 (52%) patients, of whom 104 (61%) had at least one detection in accordance with the reference diagnosis. Discordant positive PCR results were observed in 95 patients, including 30 subjects categorized as having an "unknown" pathogen. Based on 5525 individual PCRs yielding 295 positive results, PPV was 167/295 (57%) and FPP was 128/5525 (2%). Expert adjudication of the 128 discordant PCR findings resulted in an adjusted PPV of 68% and FPP of 2%. BSI-PCR was all-negative in 156 patients, including 79 (51%) patients in whom infection was considered ruled out. BSI-PCR may complement conventional cultures and expedite the microbiological diagnosis of sepsis in ICU patients, but improvements in positive predictive value of the test are warranted before its implementation in clinical practice can be considered.

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia.

The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.

Clinical Utility of Routine Chest X-Rays During the Initial Stabilization of Trauma Patients.

OBJECTIVES: The Advanced Trauma Life Support (ATLS) course encourages the use of chest x-ray (CXR) to identify injuries that may change clinical management during the initial stage of trauma resuscitations. Several studies have failed to show benefit for the routine use of CXR without a clinical indication, however. We sought to validate these findings by determining the incidence of clinically significant findings discovered on a portable single-view CXR during the initial stabilization of trauma patients at a Level 1 trauma center. METHODS: Using our electronic medical record system, we searched for all of the patients who were brought in as a trauma activation that had a portable single-view CXR performed in the emergency department. We used a selected sampling of available subjects for inclusion into the study. We reviewed the staff radiologist reports for positive findings and reviewed the physician and nursing flow sheets for procedural interventions occurring after the CXR was performed but before leaving the resuscitation area. Subjects who were transferred from another facility, had a thoracic procedure performed before CXR or underwent computed tomography before CXRs were excluded. RESULTS: From 2011 through 2012, we found 2101 subjects who had a portable CXR performed in the emergency department. We reviewed the first 400 subjects' records, with 33 (8.3%) subjects having positive findings on CXR. Of those 33, 8 met inclusion criteria and the remainder met exclusion criteria. The most common findings were pneumothorax (n = 4), clavicle fracture (n = 3), and rib fracture (n = 2). No subjects received a procedural intervention before leaving the resuscitation bay to be transported to the operating room or the computed tomography suite. CONCLUSIONS: We observed a low incidence of abnormal findings on portable CXR during the initial stabilization of trauma patients, none of whom received an immediate procedural intervention. This dataset supports previously published reports that suggest that a more targeted approach to CXR use may reduce resource utilization.

Respiratory Viruses in Invasively Ventilated Critically Ill Patients-A Prospective Multicenter Observational Study.

OBJECTIVES: The presence of respiratory viruses and the association with outcomes were assessed in invasively ventilated ICU patients, stratified by admission diagnosis. DESIGN: Prospective observational study. SETTING: Five ICUs in the Netherlands. PATIENTS: Between September 1, 2013, and April 30, 2014, 1,407 acutely admitted and invasively ventilated patients were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nasopharyngeal swabs and tracheobronchial aspirates were collected upon intubation and tested for 14 respiratory viruses. Out of 1,407 patients, 156 were admitted because of a severe acute respiratory infection and 1,251 for other reasons (non-severe acute respiratory infection). Respiratory viruses were detected in 28.8% of severe acute respiratory infection patients and 17.0% in non-severe acute respiratory infection (p < 0.001). In one third, viruses were exclusively detected in tracheobronchial aspirates. Rhinovirus and human metapneumovirus were more prevalent in severe acute respiratory infection patients (9.6% and 2.6% vs 4.5 and 0.2%; p = 0.006 and p < 0.001). In both groups, there were no associations between the presence of viruses and the number of ICU-free days at day 28, crude mortality, and mortality in multivariate regression analyses. CONCLUSIONS: Respiratory viruses are frequently detected in acutely admitted and invasively ventilated patients. Rhinovirus and human metapneumovirus are more frequently found in severe acute respiratory infection patients. Detection of respiratory viruses is not associated with worse clinically relevant outcomes in the studied cohort of patients.

Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients.

Preclinical studies have suggested that platelets influence the host response during sepsis. We sought to assess the association of admission thrombocytopenia with the presentation, outcome, and host response in patients with sepsis. Nine hundred thirty-one consecutive sepsis patients were stratified according to platelet counts (very low <50 × 10(9)/L, intermediate-low 50 × 10(9) to 99 × 10(9)/L, low 100 × 10(9) to 149 × 10(9)/L, or normal 150 × 10(9) to 399 × 10(9)/L) on admission to the intensive care unit. Sepsis patients with platelet counts <50 × 10(9)/L and 50 × 10(9) to 99 × 10(9)/L presented with higher Acute Physiology and Chronic Health Evaluation scores and more shock. Both levels of thrombocytopenia were independently associated with increased 30-day mortality (hazard ratios with 95% confidence intervals 2.00 [1.32-3.05] and 1.72 [1.22-2.44], respectively). To account for baseline differences besides platelet counts, propensity matching was performed, after which the association between thrombocytopenia and the host response was tested, as evaluated by measuring 17 plasma biomarkers indicative of activation and/or dysregulation of pathways implicated in sepsis pathogenesis and by whole genome blood leukocyte expression profiling. In the propensity matched cohort, platelet counts < 50 × 10(9)/L were associated with increased cytokine levels and enhanced endothelial cell activation. All thrombocytopenic groups showed evidence of impaired vascular integrity, whereas coagulation activation was similar between groups. Blood microarray analysis revealed a distinct gene expression pattern in sepsis patients with <50 × 10(9)/L platelets, showing reduced signaling in leukocyte adhesion and diapedesis and increased complement signaling. These data show that admission thrombocytopenia is associated with enhanced mortality and a more disturbed host response during sepsis independent of disease severity, thereby providing clinical validity to animal studies on the role of platelets in severe infection.

How are trainees in clinical microbiology and infectious diseases supervised in Europe? An international cross-sectional questionnaire survey by the Trainee Association of ESCMID.

The purpose of this study was to map the supervision of European trainees in clinical microbiology and infectious diseases during their training. An international cross-sectional questionnaire survey of 38 questions was distributed among trainees and recently graduated medical specialists from European countries. Descriptive analyses were performed on both the total group of respondents and regionally. In total, 393 respondents from 37 different countries were included. The median of overall satisfaction with the supervisor was 4 (interquartile range 3-4) on a Likert scale (range 1, not satisfied at all-5, completely satisfied). Overall, merely 34% of respondents received constructive feedback from their supervisor on a regularly basis, 36% could evaluate their own supervisor, and just 63% were evaluated on their skills using a written plan. Fifty-two percent did not receive the opportunity to do a part of the specialty training abroad and 63% received support from their supervisors to be involved in research projects or publishing papers. A considerable proportion of trainees, mainly in Southern and Eastern European regions, felt that they did not receive sufficient supervision. This information may be useful in the pursuit of harmonizing the quality of training, achieving a common curriculum, and identifying robust and objective criteria to coach and evaluate trainees in a proper way.