A large multicenter Ralstonia pickettii outbreak in critically ill patients during the COVID-19 pandemic: Epidemiological and clinical characteristics of 66 cases.

Objective: To describe a multicenter outbreak of R. pickettii that occurred in a large number of critically ill patients in a city in Colombia, during the COVID-19 pandemic. Methods: In April 2021, the National Institute for Food and Drug Surveillance (INVIMA) reported an outbreak of R. pickettii infection associated with contaminated intravenous medications. The Municipal Health Department began collecting data for all cases identified by the hospitals and the results of microbiological studies. Medical records and death certificates of included cases were reviewed. Results: Between March and May 2021, 66 cases of R. pickettii bloodstream infections from nine hospitals were documented. The median age of the patients was 60 years (IQR 51-72), and most of them had comorbidities (78.8%), mainly arterial hypertension and diabetes mellitus. At the time of the R. pickettii bloodstream infection, 89.4% had COVID-19, 86.4% were on mechanical ventilation, and 98.5% were receiving corticosteroids. The overall mortality was 81.8%. Nearly 60% of the deaths were related to R. pickettii bloodstream infections. R. pickettii was identified in the cultures from intravenous medications. Conclusions: This large multicenter outbreak caused by intravenous medications contaminated with R. pickettii mainly affected critically ill COVID-19 patients. Mortality was high and largely related to R. pickettii bloodstream infection.

A Systematic Review of Gene Expression Studies in Critically Ill Patients with Sepsis and Community-Acquired Pneumonia.

(1) Background: Sepsis is present in nearly 90% of critically ill patients with community-acquired pneumonia (CAP). This systematic review updates the information on studies that have assessed gene expression profiles in critically ill septic patients with CAP. (2) Methods: We searched for studies that satisfied the following criteria: (a) expression profile in critically ill patients with sepsis due to CAP, (b) presence of a control group, and (c) adult patients. Over-representation analysis was performed with clusterProfiler using the Hallmark and Reactome collections. (3) Results: A total of 4312 differentially expressed genes (DEGs) and sRNAs were included in the enrichment analysis. In the Hallmark collection, genes regulated by nuclear factor kappa B in response to tumor necrosis factor, genes upregulated by signal transducer and activator of transcription 5 in response to interleukin 2 stimulation, genes upregulated in response to interferon-gamma, genes defining the inflammatory response, a subgroup of genes regulated by MYC-version 1 (v1), and genes upregulated during transplant rejection were significantly enriched in critically ill septic patients with CAP. Moreover, 88 pathways were identified in the Reactome database. (4) Conclusions: This study summarizes the reported DEGs in critically ill septic patients with CAP and investigates their functional implications. The results highlight the complexity of immune responses during CAP.

Intrahepatic cholestasis due to Treponema pallidum in an immunocompetent patient / Colestasis intrahepática por Treponema pallidum en paciente inmunocompetente

Hepatitis due to Treponema pallidum is a rare entity and its diagnosis represents a clinical challenge. Treponema pallidum should be considered as a presumptive etiology in all patients with acute liver disease, when other frequent causes have been ruled out. We present the case of a young, immunocompetent patient with elevated values in his liver tests, a cholestatic pattern, and maculopapular lesions on his palms and soles. Given his clinical picture, diagnostic tests, and response to the antimicrobial therapy, a diagnosis of cholestasis due to secondary syphilis has been established. It is important to include secondary syphilis within the possible causes of acute liver disease.

La hepatitis por Treponema pallidum es una entidad poco frecuente y su diagnóstico representa un reto clínico. Treponema pallidum debe considerarse como etiología presuntiva en todo paciente con enfermedad hepática aguda, en el cual se hayan descartado otras causas más frecuentes. Se presenta el caso de un paciente joven,  inmunocompetente, quien presentó elevación de los valores de las pruebas hepáticas con patrón colestásico y lesiones maculopapulares en palmas y plantas. Dado su cuadro clínico, las pruebas diagnósticas y la respuesta a la terapia antimicrobiana instaurada, se estableció el diagnóstico de colestasis por una sífilis secundario sifilítiao. Es importante incluir la sífilis secundaria entre las posibles causas de enfermedad hepática aguda.

Colestasis intrahepática por Treponema pallidum en paciente inmunocompetente / Intrahepatic cholestasis due to Treponema pallidum in an immunocompetent patient

La hepatitis por Treponema pallidum es una entidad poco frecuente y su diagnóstico representa un reto clínico. Treponema pallidum debe considerarse como etiología presuntiva en todo paciente con enfermedad hepática aguda, en el cual se hayan descartado otras causas más frecuentes. Se presenta el caso de un paciente joven, inmunocompetente, quien presentó elevación de los valores de las pruebas hepáticas con patrón colestásico y lesiones maculopapulares en palmas y plantas. Dado su cuadro clínico, las pruebas diagnósticas y la respuesta a la terapia antimicrobiana instaurada, se estableció el diagnóstico de colestasis por una sífilis secundario sifilítiao. Es importante incluir la sífilis secundaria entre las posibles causas de enfermedad hepática aguda.

Hepatitis due to Treponema pallidum is a rare entity and its diagnosis represents a clinical challenge. Treponema pallidum should be considered as a presumptive etiology in all patients with acute liver disease, when other frequent causes have been ruled out. We present the case of a young, immunocompetent patient with elevated values in his liver tests, a cholestatic pattern, and maculopapular lesions on his palms and soles. Given his clinical picture, diagnostic tests, and response to the antimicrobial therapy, a diagnosis of cholestasis due to secondary syphilis has been established. It is important to include secondary syphilis within the possible causes of acute liver disease.

Executive summary - Diagnosis, treatment and prophylaxis of influenza virus infection - Consensus statement of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Pediatric Infectious Diseases (SEIP), the Spanish Association of Vaccinology (AEV), the Spanish Society of Family and Community Medicine (SEMFYC) and the Spanish Society of Preventive Medicine, Public Health and Health Management (SEMPSPGS).

The influenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasional pandemics. It is a respiratory infection with multiple repercussions on people's lives at an individual and social level, as well as representing a significant burden on the health system. This Consensus Document arises from the collaboration of various Spanish scientific societies involved in influenza virus infection. The conclusions drawn are based on the highest quality evidence available in the scientific literature and, failing that, on the opinion of the experts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventive aspects (with respect to the prevention of transmission and in relation to vaccination) of influenza, for both adult and pediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventive approach to influenza virus infection and, consequently, to reduce its important consequences on the morbidity and mortality of the population.

Executive summary. Diagnosis, treatment and prophylaxis of influenza virus infection. Consensus statement of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Pediatric Infectious Diseases (SEIP), the Spanish Association of Vaccinology (AEV), the Spanish Society of Family and Community Medicine (SEMFYC) and the Spanish Society of Preventive Medicine, Public Health and Health Management (SEMPSPGS).

The influenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasional pandemics. It is a respiratory infection with multiple repercussions on people's lives at an individual and social level, as well as representing a significant burden on the health system. This Consensus Document arises from the collaboration of various Spanish scientific societies involved in influenza virus infection. The conclusions drawn are based on the highest quality evidence available in the scientific literature and, failing that, on the opinion of the experts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventive aspects (with respect to the prevention of transmission and in relation to vaccination) of influenza, for both adult and pediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventive approach to influenza virus infection and, consequently, to reduce its important consequences on the morbidity and mortality of the population.

Whole-Blood Gene Expression Profiles Associated with Mortality in Community-Acquired Pneumonia.

(1) Background: Information regarding gene expression profiles and the prognosis of community-acquired pneumonia (CAP) is scarce. We aimed to examine the differences in the gene expression profiles in peripheral blood at hospital admission between patients with CAP who died during hospitalization and those who survived. (2) Methods: This is a multicenter study of nonimmunosuppressed adult patients who required hospitalization for CAP. Whole blood samples were obtained within 24 h of admission for genome-expression-profile analysis. Gene expression profiling identified both differentially expressed genes and enriched gene sets. (3) Results: A total of 198 samples from adult patients who required hospitalization for CAP were processed, of which 13 were from patients who died. Comparison of gene expression between patients who died and those who survived yielded 49 differentially expressed genes, 36 of which were upregulated and 13 downregulated. Gene set enrichment analysis (GSEA) identified four positively enriched gene sets in survivors, mainly associated with the interferon-alpha response, apoptosis, and sex hormone pathways. Similarly, GSEA identified seven positively enriched gene sets, associated with the oxidative stress, endoplasmic reticulum stress, oxidative phosphorylation, and angiogenesis pathways, in the patients who died. Protein-protein-interaction-network analysis identified FOS, CDC42, SLC26A10, EIF4G2, CCND3, ASXL1, UBE2S, and AURKA as the main gene hubs. (4) Conclusions: We found differences in gene expression profiles at hospital admission between CAP patients who died and those who survived. Our findings may help to identify novel candidate pathways and targets for potential intervention and biomarkers for risk stratification.

Executive summary. Diagnosis, treatment and prophylaxis of influenza virus infection. Consensus statement of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC), the Spanish Society of Pediatric Infectious Diseases (SEIP), the Spanish Association of Vaccinology (AEV), the Spanish Society of Family and Community Medicine (SEMFYC) and the Spanish Society of Preventive Medicine, Public Health and Health Management (SEMPSPGS).

The influenza virus has accompanied humans since time immemorial, in the form of annual epidemics and occasional pandemics. It is a respiratory infection with multiple repercussions on people's lives at an individual and social level, as well as representing a significant burden on the health system. This Consensus Document arises from the collaboration of various Spanish scientific societies involved in influenza virus infection. The conclusions drawn are based on the highest quality evidence available in the scientific literature and, failing that, on the opinion of the experts convened. The Consensus Document addresses the clinical, microbiological, therapeutic, and preventive aspects (with respect to the prevention of transmission and in relation to vaccination) of influenza, for both adult and pediatric populations. This Consensus Document aims to help facilitate the clinical, microbiological, and preventive approach to influenza virus infection and, consequently, to reduce its important consequences on the morbidity and mortality of the population.

High levels of cardiovascular biomarkers in fatal Chikungunya virus infection.

Chikungunya virus (CHIKV) infection is an emerging arboviral disease that has spread geographically to many previously unaffected areas. Although severe cases of acute CHIKV infection have been documented, little is known about its pathogenesis. We aimed to determine the levels of cardiovascular biomarkers in fatal and non-fatal patients with acute CHIKV infection. This study included fatal and non-fatal patients with CHIKV reported to National System for Public Health Surveillance and laboratory-confirmed by the Colombian National Institute of Health. Each fatal patient was matched to 2 non-fatal patients for age (± 10 years). Blood samples were processed for cardiovascular biomarkers by multiplex immunoassays. Twenty-five cases of fatal CHIKV infection and 50 patients of non-fatal CHIKV infection were included. Nearly 20% of the population were under 10 years old and 52% were over 60. The median serum levels of endocan-1 (p = 0.000), creatine kinase MB isoenzyme (p = 0.000), oncostatin (p = 0.000), fatty-acid-binding protein 3 (p = 0.000) and fatty-acid-binding protein 4 (p = 0.000) were significantly higher in fatal CHIKV infection cases than in non-fatal patients. Troponin I tended to be higher in fatal CHIKV infection cases than in non-fatal CHIKV infection patients (p = 0.063). Among fatal patients, no significant differences were found in serum levels of cardiovascular biomarkers among younger (< 50 years-old) and older (≥ 50 years-old) patients. We found high serum levels of cardiovascular biomarkers in fatal CHIKV infection. These results promote the fact that endothelial and cardiac damage can occurs and may be significant factors related organ failure and death in these patients.

Effect of Undernutrition and Obesity on Clinical Outcomes in Adults with Community-Acquired Pneumonia.

Malnutrition comprises two groups of conditions: undernutrition and overweight or obesity. It has been associated with a high risk of contracting infectious diseases and with elevated mortality rates. Community-acquired pneumonia (CAP) is one of the most common infectious diseases worldwide and its prognosis is affected by a large number of recognizable risk factors. This narrative review updates the information on the impact of malnutrition, including both undernutrition and obesity, on the risk and prognosis of adults with CAP. Studies of CAP that have evaluated undernutrition have applied a variety of definitions when assessing the nutritional status of patients. Undernutrition has been associated with unfavorable clinical outcomes, such as prolonged hospital stay, need for intensive care unit admission, and mortality; in contrast, most published studies have found that increased body mass index is significantly associated with higher survival in patients with CAP. However, some authors have presented divergent results, mainly in relation to the etiology of CAP (bacterial versus viral). Influenza infection, caused by influenza A (H1N1) pdm09, has been associated with worse prognosis in obese patients. The current data underscore the need for larger studies to examine the physiological mechanisms that explain the differential impact of malnutrition on outcomes. Achieving a better understanding may help to guide the design of new interventions to improve prognosis.

Causative Agents of Ventilator-Associated Pneumonia and Resistance to Antibiotics in COVID-19 Patients: A Systematic Review.

Patients with coronavirus disease 2019 (COVID-19) have an increased risk of ventilator-associated pneumonia (VAP). This systematic review updates information on the causative agents of VAP and resistance to antibiotics in COVID-19 patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed/MEDLINE, and LILACS databases from December 2019 to December 2021. Studies that described the frequency of causative pathogens associated with VAP and their antibiotic resistance patterns in critically ill COVID-19 adult patients were included. The Newcastle-Ottawa Quality Assessment Scale was used for critical appraisal. The data are presented according to the number or proportions reported in the studies. A total of 25 articles were included, involving 2766 VAP cases in COVID-19 patients (range 5-550 VAP cases). Most of the studies included were carried out in France (32%), Italy (20%), Spain (12%) and the United States (8%). Gram-negative bacteria were the most frequent causative pathogens of VAP (range of incidences in studies: P. aeruginosa 7.5-72.5%, K. pneumoniae 6.9-43.7%, E. cloacae 1.6-20% and A. baumannii 1.2-20%). S. aureus was the most frequent Gram-positive pathogen, with a range of incidence of 3.3-57.9%. The median incidence of Aspergillus spp. was 6.4%. Few studies have recorded susceptibility patterns among Gram-negative causative pathogens and have mainly reported extended-spectrum beta-lactamase (ESBL), AmpC, and carbapenem resistance. The median frequency of methicillin resistance among S. aureus isolates was 44.4%. Our study provides the first comprehensive description of the causative agents and antibiotic resistance in COVID-19 patients with VAP. Gram-negative bacteria were the most common pathogens causing VAP. Data on antibiotic resistance patterns in the published medical literature are limited, as well as information about VAP from low- and middle-income countries.

Legionnaires' Disease: Update on Diagnosis and Treatment.

Legionellosis is the infection caused by bacteria of the genus Legionella, including a non-pneumonic influenza-like syndrome, and Legionnaires' disease is a more serious illness characterized by pneumonia. Legionellosis is becoming increasingly important as a public health problem throughout the world; although it is an underreported disease, studies have consistently documented a high incidence. In addition, health costs associated with the disease are high. Diagnosis of Legionnaires' disease is based mainly on the detection of Legionella pneumophila serogroup 1 antigen in urine. However, there have been advances in detection tests for patients with legionellosis. New methodologies show greater sensitivity and specificity, detect more species and serogroups of Legionella spp., and have the potential for use in epidemiological studies. Testing for Legionella spp. is recommended at hospital admission for severe community-acquired pneumonia, and antibiotics directed against Legionella spp. should be included early as empirical therapy. Inadequate or delayed antibiotic treatment in Legionella pneumonia has been associated with a worse prognosis. Either a fluoroquinolone (levofloxacin or moxifloxacin) or a macrolide (azithromycin preferred) is the recommended first-line therapy for Legionnaires' disease; however, little information is available regarding adverse events or complications, or about the duration of antibiotic therapy and its association with clinical outcomes. Most published studies evaluating antibiotic treatment for Legionnaires' disease are observational and consequently susceptible to bias and confounding. Well-designed studies are needed to assess the usefulness of diagnostic tests regarding clinical outcomes, as well as randomized trials comparing fluoroquinolones and macrolides or combination therapy that evaluate outcomes and adverse events.

Epidemiology of 4963 deaths associated with COVID-19 during three pandemic waves in a Latin American city with a high mortality rate, 2020-2021.

OBJECTIVE: To describe the characteristics of COVID-19-associated deaths in Barranquilla, Colombia, a city with a high mortality rate, and their changes between pandemic waves. METHODS: The local Health Department obtained information on all laboratory-confirmed COVID-19 deaths reported from March 2020 to May 2021. Data were collected using national surveillance reports and death certificates. RESULTS: Four thousand nine hundred and sixty-three COVID-19-associated deaths were documented for a mortality rate of 389.4 deaths per 100,000 population. Sixty-two percent of all deaths occurred in people aged ≥65 years and 58% in males. Only 7 COVID-19-associated deaths in children were reported. Comorbidities were found in 47.9% of cases. The number of deaths among people aged 50-64 years increased significantly during the pandemic waves (from 25% to 29%). Conversely, the frequency of male sex (from 64.6% to 53.9%) and deaths with comorbidities (from 60.9% to 39.6%) decreased significantly between the waves of pandemic. Early mortality, defined as death within 48 h after hospital admission, was higher during the first pandemic wave than in the others (29.5%, 9.7% and 10.5%), and time from hospital admission to death increased during waves (from 9 to 14 days). CONCLUSIONS: The COVID-19-associated mortality rate was high and mainly affects older people, with comorbidities and male sex. Early mortality was higher during the first wave. Women and healthy people without comorbidities died more frequently after the first pandemic wave.

Burden of invasive pneumococcal disease (IPD) over a 10-year period in Bogotá, Colombia.

BACKGROUND: Invasive pneumococcal disease (IPD) is the leading cause of infectious death worldwide. This study aimed to describe the epidemiology of IPD and the impact of pneumococcal conjugate vaccine-10 (PCV-10) over a 10-year period in Bogotá, Colombia. METHODS: This was a laboratory-based surveillance study of Streptococcus pneumoniae isolated from patients with IPD from 82 hospitals over 10 years in Bogotá, Colombia. Data were compared between two periods: 2007-2011 (before the introduction of PCV-10) and 2012-2017 (after the introduction of PCV-10). RESULTS: In total, 1670 patients with IPD were included in the study between 2007 and 2017. Between 2007 and 2011, the most common serotypes were 14, 1, 6B, 6A and 3. Between 2012 and 2017, the most common serotypes were 19A, 3, 14 and 1. A decrease in the incidence of IPD, particularly in children aged 0-4 years, was noted after the introduction of PCV-10. Importantly, this reduction in incidence was not observed in patients aged ≥50 years. CONCLUSIONS: The IPD burden in Bogotá remained stable between 2007 and 2017. The incidence of IPD decreased in children but not in older adults. The introduction of PCV-10 led to a change in the most prevalent serotypes to serotypes that are not included in PCV-10.

Unexpected high frequency of early mortality in COVID-19: a single-centre experience during the first wave of the pandemic.

We report the high frequency of early mortality in COVID-19 patients (48.6% of 72 deaths). Early deaths were not explained by differences in age, sex and comorbidities, but they had a more severe disease at hospital admission compared with late deaths. These data highlight the importance of outpatient monitoring for the early identification of COVID-19 patients who require hospital admission.

Human Proteinase 3, an important autoantigen of c-ANCA associated vasculitis, shares cross-reactive epitopes with serine protease allergens from mites: an in silico analysis.

Background: In autoimmune vasculitis, autoantibodies to Human Proteinase 3 (PR3), a human serine protease, seems to have a role on the inception of c-ANCA associated vasculitis. The origin of this autoreactive response remains unclear. However, for several autoreactive responses, molecular mimicry between environmental antigens and human proteins is key to trigger autoantibodies and finally autoimmunity manifestations. Considering that PR3 is a serine protease and house dust mite (HDM) group 3 allergens share this biochemical activity, the aim of this study was to identify cross-reactive epitopes between serine proteases from human and mites using an in silico approach. Methods: Multi alignment among amino acid sequences of PR3 and HDM group 3 allergens was performed to explore identity and structural homology. ElliPro and BepiPred  in silico tools were used to predict B and T cell epitopes. Consurf tool was used to conduct identification of conserved regions in serine proteases family. Results: PR3 and HDM group 3 allergens shared moderate identity and structural homology (root mean square deviation < 1). One B cell cross reactive epitope among serine proteases was identified (29I, 30V, 31G, 32G, 34E, 36K, 37A, 38L, 39A and 54C) and two T cell epitopes. Conclusions: PR3 have structural homology and share cross reactive epitopes with HDM group 3 allergens.

Effects of age and comorbidities on serum levels of inflammatory markers in community-acquired pneumonia.

INTRODUCTION: Studies have suggested that an inappropriate inflammatory response is a major cause of treatment failure and mortality in patients with community-acquired pneumonia (CAP). We aimed to determine the effect of age and comorbidities on serum inflammatory markers in CAP. METHODS: We performed a prospective cohort study of adults hospitalized with CAP. For the purposes of this study, we compared patients according to comorbidities and age. Inflammatory markers were measured at hospital admission, focusing on acute phase proteins, cytokines and monocyte human leucocyte antigen DR (mHLA-DR) expression. RESULTS: In patients with chronic pulmonary disease (COPD), serum cytokines had significantly decreased levels of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and mHLA-DR expression, as well as the C-reactive protein (CRP), compared with patients who had no comorbidities. Similarly, patients with chronic heart disease had a significantly reduced CRP levels and mHLA-DR expression, whereas patients with chronic kidney disease had significantly higher serum levels of procalcitonin and TNF-α. Lower procalcitonin, IL-6 and IL-10 levels, as well as mHLA-DR expression, were documented in older patients, but with no significant differences compared to younger patients. Multimorbidity in older patients was associated with significant lower levels of CRP and mHLA-DR expression. CONCLUSIONS: The circulating inflammatory markers to CAP have profiles that differ with age and underlying comorbidities. Multimorbidity in the elderly is also associated with lower serum levels of some inflammatory markers. Our findings suggest that inflammatory markers in CAP should be interpreted after considering age and comorbid conditions.

Diabetic Ketoacidosis Precipitated by COVID-19 in Patients Without Respiratory Symptoms: Case Reports.

Worse outcomes of coronavirus disease 2019 (COVID-19) have been documented in older patients with comorbidities, especially in those with diabetes mellitus (DM). However, the clinical picture and risk factors of COVID-19 in DM is still emerging. Here, we report four cases of severe COVID-19 patients with acute diabetic ketoacidosis (DKA) without respiratory symptoms, with viral and bacterial coinfection, and poor clinical outcomes. Higher monitoring of patients with DM and COVID-19 is advised, as well as rapid and accurate diagnostic tests and treatment.

Chikungunya outbreak (2015) in the Colombian Caribbean: Latent classes and gender differences in virus infection.

Chikungunya virus (CHIKV), a mosquito-borne alphavirus of the Togaviridae family, is part of a group of emergent diseases, including arbovirus, constituting an increasing public health problem in tropical areas worldwide. CHIKV causes a severe and debilitating disease with high morbidity. The first Colombian autochthonous case was reported in the Colombian Caribbean region in September 2014. Within the next two to three months, the CHIKV outbreak reached its peak. Although the CHIKV pattern of clinical symptomatology has been documented in different epidemiological studies, understanding of the relationship between clinical symptomatology and variation in phenotypic response to CHIKV infection in humans remains limited. We performed a cross sectional study following 1160 individuals clinically diagnosed with CHIKV at the peak of the Chikungunya outbreak in the Colombian Caribbean region. We examined the relationship between symptomatology and diverse phenotypic responses. Latent Class Cluster Analysis (LCCA) models were used to characterize patients' symptomatology and further identify subgroups of individuals with differential phenotypic response. We found that most individuals presented fever (94.4%), headache (73.28%) and general discomfort (59.4%), which are distinct clinical symptoms of a viral infection. Furthermore, 11/26 (43.2%) of the categorized symptoms were more frequent in women than in men. LCCA disclosed seven distinctive phenotypic response profiles in this population of CHIKV infected individuals. Interestingly, 282 (24.3%) individuals exhibited a lower symptomatic "extreme" phenotype and 74 (6.4%) patients were within the severe complex "extreme" phenotype. Although clinical symptomatology may be diverse, there are distinct symptoms or group of symptoms that can be correlated with differential phenotypic response and perhaps susceptibility to CHIKV infection, especially in the female population. This suggests that, comparatively to men, women are a CHIKV at-risk population. Further study is needed to validate these results and determine whether the distinct LCCA profiles are a result of the immune response or a mixture of genetic, lifestyle and environmental factors. Our findings could contribute to the development of machine learning approaches to characterizing CHIKV infection in other populations. Preliminary results have shown prediction models achieving up to 92% accuracy overall, with substantial sensitivity, specificity and accuracy values per LCCA-derived cluster.

Usefulness of sputum gram stain for etiologic diagnosis in community-acquired pneumonia: a systematic review and meta-analysis.

BACKGROUND: Implementation of sputum Gram stain in the initial assessment of community-acquired pneumonia (CAP) patients is still controversial. We performed a systematic review and meta-analysis to investigate the usefulness of sputum Gram stain for defining the etiologic diagnosis of CAP in adult patients. METHODS: We systematically searched the Medline, Embase, Science Direct, Scopus and LILACS databases for full-text articles. Relevant studies were reviewed by at least three investigators who extracted the data, pooled them using a random effects model, and carried out quality assessment. For each bacterium (Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and Gram-negative bacilli), pooled sensitivity, specificity, positive and negative likelihood ratios were reported. RESULTS: After a review of 3539 abstracts, 20 articles were included in the present meta-analysis. The studies included yielded 5619 patients with CAP. Pooled sensitivity and pooled specificity of sputum Gram stain were 0.59 (95% CI, 0.56-0.62) and 0.87 (95% CI, 0.86-0.89) respectively for S. pneumoniae, 0.78 (95% CI, 0.72-0.84) and 0.96 (95% CI, 0.94-0.97) for H. influenzae, 0.72 (95% CI, 0.53-0.87) and 0.97 (95% CI, 0.95-0.99) for S. aureus, and 0.64 (95% CI, 0.49-0.77) and 0.99 (95% CI, 0.97-0.99) for Gram-negative bacilli. CONCLUSION: Sputum Gram stain test is sensitive and highly specific for identifying the main causative pathogens in adult patients with CAP. TRIAL REGISTRATION: This study has been registered at PROSPERO International prospective register of systematic reviews under registration no. CRD42015015337 .