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People deprived of liberty (PDL) are at high risk of acquiring Mycobacterium tuberculosis infection (latent tuberculosis infection [LTBI]) and progressing to active tuberculosis (TB). We sought to determine the incidence rates and factors associated with LTBI and active TB in Colombian prisons. Using information of four cohort studies, we included 240 PDL with two-step tuberculin skin test (TST) negative and followed them to evaluate TST conversion, as well as, 2,134 PDL that were investigated to rule out active TB (1,305 among people with lower respiratory symptoms of any duration, and 829 among people without respiratory symptoms and screened for LTBI). Latent tuberculosis infection incidence rate was 2,402.88 cases per 100,000 person-months (95% CI 1,364.62–4,231.10) in PDL with short incarceration at baseline, and 419.66 cases per 100,000 person-months (95% CI 225.80–779.95) in individuals with long incarceration at baseline (who were enrolled for the follow after at least 1 year of incarceration). The TB incidence rate among PDL with lower respiratory symptoms was 146.53 cases/100,000 person-months, and among PDL without respiratory symptoms screened for LTBI the incidence rate was 19.49 cases/100,000 person-months. History of Bacillus Calmette-Guerin vaccination decreased the risk of acquiring LTBI among PDL who were recently incarcerated. Female sex, smoked drugs, and current cigarette smoking were associated with an increased risk of developing active TB. This study shows that PDL have high risk for LTBI and active TB. It is important to perform LTBI testing at admission to prison, as well as regular follow-up to control TB in prisons.

Background: Tuberculosis (TB) and human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) infections are leading causes of morbidity and mortality worldwide. People living with HIV/AIDS (PLWHA) are highly susceptible to TB infection and progression to active TB disease. This study aims to determine the proportion and risk factors of TB among PLWHA in Jazan Region, southwestern Saudi Arabia. Methods: A cross-sectional study was conducted among HIV-infected individuals attending the main referral hospital in Jazan Region during the period 2017–2019. The participants’ TB status, CD4+ lymphocyte count, and viral load were assessed. In addition, their demographic and clinical information was collected using a structured questionnaire. Results: A total of 316 HIV-positive individuals aged between 13 and 81 years (75% male and 25% female) were enrolled in this study. Of them, 30 (9.5%; 95% confidence interval [CI]: 5.2, 10.6%) were diagnosed with TB: 46.7% (14/30) had pulmonary TB and 53.3% (16/30) had extrapulmonary TB. The highest proportion of TB-positive PLWHA was found among participants aged 18–30 years (11.6%) and among non-Saudis (14.0%) when compared to other age groups and Saudi participants (7.4%). Multivariate analysis showed that male gender (adjusted odds ratio [AOR] = 4.79; 95% CI = 1.22, 18.74), past medical history (PMH) of TB (AOR = 29.67; 95% CI = 5.31, 164.32), PMH of other RTIs (AOR = 5.86; 95 % CI = 2.14, 16.06), CD4+ lymphocyte count of

International audience; Background - Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD). Objectives - This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients. Methods - Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression. Results - A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non-HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p

This retrospective study included allDuring the study period, 1014

A retrospective study of medically treated isolated left-sided infective endocarditis (LSIE) patients identifying predictors of outcomes with nonoperative management was undertaken.Medical records of 135 Manitoban medically managed LSIE patients from January 2004 to December 2016 were reviewed. Five-year survival for 135 patients and hospitalization data till March 2016 for 65 patients were collected from the Manitoba Centre for Health Policy.In-hospital mortality was 44%. Patients with surgical indications were more likely to die in-hospital than those without (53% vs 24%; P = 0.002). Survival at 1 and 5 years was 43% and 23%, respectively. All-cause readmission at 1 and 5 years was 64% and 84%, respectively. At 1 and 5 years, readmission from major adverse events (heart failure, stroke, endocarditis) was 25% and 47%, and from recurrent endocarditis was 17% and 26%, respectively. Severe valvular regurgitation was a risk factor for in-hospital mortality (odds ratio, 3.52; P = 0.022), poor long-term survival (hazard ratio [HR], 2.57; P0.001), and recurrent endocarditis (HR, 5.93; P 0.001). Prosthetic valve endocarditis was a risk factor for poor long-term survival (HR, 2.11; P = 0.002). Streptococcus viridans group was associated with better rates of in-hospital mortality (odds ratio, 0.28; P = 0.018) and long-term survival (HR, 0.34; P0.001).Nonoperative management of LSIE carries a poor prognosis but may have a role in select cases. Surgical management remains the mainstay for patients with clear surgical indications, including severe regurgitation and prosthetic valve endocarditis. Further prospective analyses are required to better delineate appropriate patient selection for nonsurgical management.

Prior studies have shown that HIV patients develop permanent pulmonary dysfunction following an episode of community-acquired pneumonia (CAP). However, the mechanism causing pulmonary dysfunction remains an enigma. HIV patients experience chronic inflammation. We hypothesized that CAP exacerbates inflammation in HIV patients resulting in an accelerated decline in lung function. A prospective cohort pilot study enrolled HIV patients hospitalized in Medellin, Colombia, with a diagnosis of CAP. Sixteen patients were eligible for the study; they were split into 2 groups: HIV and HIV+CAP. Plasma, sputum, and pulmonary function test (PFT) measurements were retrieved within 48 h of hospital admission and at 1 month follow-up. The concentrations of 13 molecules and PFT values were compared between the 2 cohorts. The HIV+CAP group had lower lung function compared to the HIV group; forced vital capacity (FVC)% predicted and forced expiratory volume in 1 s (FEV

The role of remdesivir in the treatment of patients in hospital with COVID-19 remains ill defined in a global context. The World Health Organization Solidarity randomized controlled trial (RCT) evaluated remdesivir in patients across many countries, with Canada enrolling patients using an expanded data collection format in the Canadian Treatments for COVID-19 (CATCO) trial. We report on the Canadian findings, with additional demographics, characteristics and clinical outcomes, to explore the potential for differential effects across different health care systems.We performed an open-label, pragmatic RCT in Canadian hospitals, in conjunction with the Solidarity trial. We randomized patients to 10 days of remdesivir (200 mg intravenously [IV] on day 0, followed by 100 mg IV daily), plus standard care, or standard care alone. The primary outcome was in-hospital mortality. Secondary outcomes included changes in clinical severity, oxygen- and ventilator-free days (at 28 d), incidence of new oxygen or mechanical ventilation use, duration of hospital stay, and adverse event rates. We performed a priori subgroup analyses according to duration of symptoms before enrolment, age, sex and severity of symptoms on presentation.Across 52 Canadian hospitals, we randomized 1282 patients between Aug. 14, 2020, and Apr. 1, 2021, to remdesivir (Remdesivir, when compared with standard of care, has a modest but significant effect on outcomes important to patients and health systems, such as the need for mechanical ventilation.

Objective: To determine factors associated with mortality in tuberculosis/HIV co-infected patients in Cali, Colombia Methods: This retrospective cohort design included tuberculosis/HIV co-infected persons. Kaplan-Meier and Cox regression were used to estimate survival and risk factors associated with mortality. Results: Of the 279 tuberculosis/HIV co-infected participants, 27.2% died during the study. Participants mainly were adults and males. CD4 count information was available for 41.6% (the median count was 83 cells/mm3), and half were subject to tuberculosis susceptibility testing. The median time between HIV diagnosis and antiretroviral therapy initiation was 372 days. HIV was identified prior to tuberculosis in 53% and concurrent HIV-tuberculosis were diagnosed in 37% of patients. 44.8% had tuberculosis treatment success. Body mass index above 18 kg/m2, initiation of tuberculosis treatment within two weeks, having any health insurance coverage and CD4 count information conferred a survival advantage. Conclusions: Delays in treatment initiation and factors associated with limited health care access or utilization were associated with mortality. As HIV and tuberculosis are both reportable conditions in Colombia, strategies should be focused on optimizing treatment outcomes within both tuberculosis and HIV programs, particularly improving early HIV diagnosis, early antiretroviral therapy treatment initiation, and adherence to tuberculosis treatment. Resumen Objetivo: Determinar factores asociados con mortalidad en personas con co-infeccion Tuberculosis/VIH en Cali, Colombia. Métodos: Este diseño de cohorte retrospectiva incluyó personas co-infectadas con tuberculosis /VIH. Se utilizó Kaplan Meier y regresion de Cox para estimar supervivencia y factores de riesgo asociados con mortalidad. Resultados: De los 279 participantes coinfectados con tuberculosis/VIH, el 27.2% falleció durante el estudio. Los participantes fueron principalmente adultos y hombres. Se dispuso de información de recuento de CD4 en el 41.6% (la mediana del recuento fue 83 células/mm3), y en la mitad se realizaron pruebas de susceptibilidad para tuberculosis. La mediana de tiempo entre el diagnóstico de VIH e inicio de terapia antirretroviral fue 372 días. Se identificó VIH previo a tuberculosis en un 53%, e infección concurrente tuberculosis-VIH en el 37% de los pacientes. El 44.8% presentó éxito en el tratamiento para tuberculosis. Un índice de masa corporal superior a 18 kg/m2, inicio del tratamiento para TB dentro de las primeras dos semanas, contar con aseguramiento en salud y con recuento de CD4 se asociaron con mayor supervivencia. Conclusiones: Retraso en el inicio de tratamiento y factores relacionados con brechas en el acceso a atención en salud se asociaron con mortalidad. Dado que VIH y tuberculosis son enfermedades de notificación obligatoria en Colombia, las estrategias deben centrarse en optimizar los desenlaces del tratamiento dentro de ambos programas, en particular mejorar el diagnóstico temprano de VIH, el inicio temprano de la terapia antirretroviral y fomentar la adherencia al tratamiento para tuberculosis.

Objective To determine the gene expression profile in individuals with new latent tuberculosis infection (LTBI), and to compare them with people with active tuberculosis (TB) and those exposed to TB but not infected. Design A prospective cohort study. Recruitment and follow-up were conducted between September 2016 to December 2018. Gene expression and data processing and analysis from April 2019 to April 2021. Setting Two male Colombian prisons. Participants 15 new tuberculin skin test (TST) converters (negative TST at baseline that became positive during follow-up), 11 people that continued with a negative TST after two years of follow-up, and 10 people with pulmonary ATB. Main outcome measures Gene expression profile using RNA sequencing from PBMC samples. The differential expression was assessed using the DESeq2 package in Bioconductor. Genes with |logFC| >1.0 and an adjusted p-value < 0.1 were differentially expressed. We analyzed the differences in the enrichment of KEGG pathways in each group using InterMiner. Results The gene expression was affected by the time of incarceration. We identified group-specific differentially expressed genes between the groups: 289 genes in people with a new LTBI and short incarceration (less than three months of incarceration), 117 in those with LTBI and long incarceration (one or more years of incarceration), 26 in ATB, and 276 in the exposed but non-infected individuals. Four pathways encompassed the largest number of down and up-regulated genes among individuals with LTBI and short incarceration: cytokine signaling, signal transduction, neutrophil degranulation, and innate immune system. In individuals with LTBI and long incarceration, the only enriched pathway within up-regulated genes was Emi1 phosphorylation. Conclusions Recent infection with MTB is associated with an identifiable RNA pattern related to innate immune system pathways that can be used to prioritize LTBI treatment for those at greatest risk for developing active TB.

Due to poor diagnostics and increased co-infections, HIV-associated Legionella infections are underreported. We aimed to retrospectively determine the frequency of Legionella infections in bronchoalveolar lavage (BAL) from HIV-associated pneumonia patients hospitalized in Medellin, Colombia, between February 2007 and April 2014. Although culture was negative, 17 BAL (36%) were positive for Legionella by quantitative polymerase chain reaction, most of which were in the Mycobacterium tuberculosis or Pneumocystis jirovecii co-infected patients, and included L. anisa (n = 6), L. bozemanae (n = 4), L. pneumophila (n = 3), and L. micdadei (n = 2). All L. bozemanae and L. micdadei associated with Pneumocystis, while all L. pneumophila associated with M. tuberculosis. Legionella probable cases had more complications and higher mortality rates (P = 0.02) and were rarely administered empirical anti-Legionella therapy while in hospital. Clinicians should be aware of the possible presence of Legionella in HIV and M. tuberculosis or P. jirovecii co-infected patients.

Severe influenza infection has no effective treatment available. One of the key barriers to developing host-directed therapy is a lack of reliable prognostic factors needed to guide such therapy. Here, we use a network analysis approach to identify host factors associated with severe influenza and fatal outcome. In influenza patients with moderate-to-severe diseases, we uncover a complex landscape of immunological pathways, with the main changes occurring in pathways related to circulating neutrophils. Patients with severe disease display excessive neutrophil extracellular traps formation, neutrophil-inflammation and delayed apoptosis, all of which have been associated with fatal outcome in animal models. Excessive neutrophil activation correlates with worsening oxygenation impairment and predicted fatal outcome (AUROC 0.817–0.898). These findings provide new evidence that neutrophil-dominated host response is associated with poor outcomes. Measuring neutrophil-related changes may improve risk stratification and patient selection, a critical first step in developing host-directed immune therapy., Identification of host factors associated with severe influenza infection could provide insights into treatment options. Here, the authors provide transcriptomic analyses of blood from >100 influenza infected patients and show that changes in circulating neutrophils are associated with severe influenza infection.

Antioquia Department is the state with the highest burden of tuberculosis (TB) in Colombia. Our aim was to determine the risk factors associated with unsuccessful TB treatment in HIV-seropositive and homeless persons, compared with non-HIV-infected and non-homeless persons with TB. We conducted a retrospective cohort study using observational, routinely collected health data from all drug-susceptible TB cases in homeless and/or HIV-seropositive individuals in Antioquia from 2014 to 2016. Unsuccessful TB treatment was defined as individuals having been lost to follow-up, having died, or treatment failure occurrence during the study period. Successful treatment was defined as cure of TB or treatment completion according to the WHO definitions. We identified 544 homeless persons with TB (432 HIV- and 112 HIV+), 835 HIV+ persons with TB and non-homeless, and 5,086 HIV-/non-homeless people with TB. Unsuccessful treatment rates were 19.3% in HIV-/non-homeless persons, 37.4% in non-homeless HIV+ patients, 61.5% in homeless HIV- patients, and 70.3% in homeless HIV+ patients; all rates fall below End TB strategy targets. More than 50% of homeless patients were lost to follow-up. Risk factors associated with unsuccessful treatment were HIV seropositivity, homelessness, male gender, age ≥ 25 years, noncontributory-type health insurance, TB diagnosis made during hospitalization, and previous treatment for TB. These results highlight the challenge of treating TB in the homeless population. These findings should put an onus on TB programs, governments, clinicians, and others involved in the collaborative care of TB patients to pursue innovative strategies to improve treatment success in this population.

[See related article at [www.cmaj.ca/lookup/doi/10.1503/cmaj.191075][2]][2] A 37-year-old man with HIV infection (CD4+ cell count 706 cells/μL, viral load undetectable) presented with a 3-month history of cough, pharyngitis, low-grade fevers and dark black hemoptysis. A rash had also developed

PurposeThe LHIV-Manitoba cohort was developed as a way to provide a comprehensive source of HIV-related health information in the central Canadian Prairie province of Manitoba. The cohort will provide important information as we aim to better understand local HIV epidemiology and address key knowledge and practice gaps in HIV prevention, treatment and care programming in the province.ParticipantsIn total, 890 individuals, aged 18 or older and living or receiving HIV care in Manitoba are enrolled in the cohort. A complete clinical dataset exists for 725 participants, which includes variables on sociodemographic characteristics, comorbidities and co-infections, self-reported HIV exposure categories and HIV clinical indicators. A limited clinical dataset exists for an additional 165 individuals who were enrolled posthumously. 97.5% of cohort participants’ clinical records are linked to provincial administrative health datasets.Findings to dateThe average age of cohort participants is 49.7 years. Approximately three-quarters of participants are male, 42% self-identified as white and 42% as Indigenous. The majority of participants (64%) reported condomless vaginal sex as a risk exposure for HIV. Nearly one-fifth (18%) of participants have an active hepatitis C virus infection and the cohort’s median CD4 count increased from 316 cells/mm3 to 518 cells/mm3 between time of entry into care and end of the first quarter in 2019.Future plansThe LHIV-Manitoba cohort is an open cohort, and as such, participant enrolment, data collection and analyses will be continually ongoing. Future analyses will focus on the impact of provincial drug plans on clinical outcomes, determinants of mortality among cohort participants and deriving estimates for a local HIV care cascade.

Background Influenza infections produce a spectrum of disease severity, ranging from a mild respiratory illness to respiratory failure and death. The host-response pathways associated with the progression to severe influenza disease are not well understood. Methods To gain insight into the disease mechanisms associated with progression to severe infection, we analyzed the leukocyte transcriptome in severe and moderate influenza patients and healthy control subjects. Pathway analysis on differentially expressed genes was performed using a topology-based pathway analysis tool that takes into account the interaction between multiple cellular pathways. The pathway profiles between moderate and severe influenza were then compared to delineate the biological mechanisms underpinning the progression from moderate to severe influenza. Results 107 patients (44 severe and 63 moderate influenza patients) and 52 healthy control subjects were included in the study. Severe influenza was associated with upregulation in several neutrophil-related pathways, including pathways involved in neutrophil differentiation, migration, degranulation and neutrophil extracellular trap (NET) formation. The degree of upregulation in neutrophil-related pathways were significantly higher in severely infected patients compared to moderately infected patients. Severe influenza was also associated with downregulation in immune response pathways, including pathways involved in antigen presentation such as CD4+ T-cell co-stimulation, CD8+ T cell and Natural Killer (NK) cells effector functions. Apoptosis pathways were also downregulated in severe influenza patients compare to moderate and healthy controls. Conclusions These findings showed that there are changes in gene expression profile that may highlight distinct pathogenic mechanisms associated with progression from moderate to severe influenza infection.

Coxiella burnetii causes Q fever in humans and coxiellosis in animals. In humans, it causes acute febrile illnesses like influenza, pneumonia, hepatitis, and chronic illnesses such as endocarditis, vascular infection, and post-infectious fatigue syndrome. It is widely distributed worldwide, and its main reservoirs are sheep, goats, and cattle. This study aimed to determine the frequency of C. burnetii infection using molecular detection and to identify the associated factors in livestock farmers and cattle from the Magdalena Medio region of Antioquia, Colombia. Using real-time polymerase chain reaction (PCR), molecular detection was performed for the IS1111 insertion sequence of C. burnetii using genomic DNA collected from the peripheral blood of 143 livestock farmers and 192 cattle from 24 farms located in Puerto Berrío, Puerto Nare, and Puerto Triunfo. To confirm the results, bidirectional amplicon sequencing of 16S rRNA was performed in four of the positive samples. Additionally, factors associated with C. burnetii were identified using a Poisson regression with cluster effect adjustment. Real-time PCR showed positive results in 25.9% and 19.5% of livestock farmer samples and cattle samples, respectively. For livestock farmers, factors associated with C. burnetii were the area where the farm was located [Puerto Berrío, adjusted prevalence ratio (aPR): 2.13, 95% confidence interval (CI): 1.10-4.11], presence of hens (aPR: 1.47, 95% CI: 1.21-1.79), horses (aPR: 1.61, 95% CI: 1.54-1.67), and ticks (aPR: 2.36, 95% CI: 1.03-5.42) in the residence, and consumption of raw milk (aPR: 1.47, 95% CI: 1.26-1.72). For cattle, the factors associated with Coxiella genus were municipality (Puerto Nare; aPR: 0.39, 95% CI: 0.37-0.41) and time of residence on the farm (≥49 months; aPR: 2.28, 95% CI: 1.03-5.20). By analyzing sequences of the 16S rRNA molecular marker, C. burnetii infection was confirmed in livestock farmers. However, in cattle, only the presence of Coxiella-type bacteria was identified. Further research is necessary to determine the potential role that these types of bacteria have as etiological agents for disease in livestock farmers and cattle from the study area.

To determine the prevalence and incidence of LTBI among prison guards and to the risk factors associated with infection. Two male prisons in Medellín and Itaguí, Colombia. A cohort study was conducted in adult prison guards that consented to participate. Exclusion criteria included: previous or current active TB, or conditions that preclude TST administration. We screened 194 guards and completed 155 TST administrations. The prevalence of LTBI was 55.8% in prison one, and 39.1% in prison two. The risk factors associated with LTBI diagnosis included drug use at least once in a lifetime (PR: 1.75; 95% CI 1.42-2.15) and male sex (PR: 2.16; 95% CI 1.01-4.62). The cumulative incidence of TST conversion over 6 months was 3.2%. All conversions occurred in prison 1. Our findings suggest an occupational risk for LTBI prevalence and incidence among guards (different prevalence and incidence according to the prison they work).

HIV-1 infection is characterized by loss of CD4 T cells, leading to immunodeficiency. Initiation of antiretroviral therapy (ART) results in suppression of the viral load and increased CD4 counts. Both viral and host factors determine CD4 cell responses to ART with approximately 15–30% of individuals having suboptimal increase of CD4 T cell count, most commonly due to lack of compliance to ART. A smaller fraction of patients will have immune reconstitution failure and suboptimal CD4 increase despite suppression of HIV replication, and these individuals are at risk for adverse health outcomes. We sought to characterize the factors associated with decreased immunological response among Manitoba’s HIV patient population.This retrospective case-control study included HIV patients with immune reconstitution failure despite suppression of HIV replication by ART. The immune reconstitution failure was defined by CD4 cell count increase from baseline of less than 100 CD4 cells/mm3 or lack of increase to above 200 CD4 cells/mm3 within one year of viral load suppression. Age and nadir CD4 cell counts are known risk factors associated with immune reconstitution failure. We chose controls (Patients with immune reconstitution success) of similar age and CD4 nadir cell with cases (Patients with immune reconstitution failure). We explored the potential effects of gender, HLA type, presence of co-infection, ethnicity, ART type, and rate of pre-treatment CD4 decline among cases and controls. Of more than 550 patients followed by our HIV clinic, 42 individuals met our definition of immune reconstitution failure and they were assigned to the cases group. 31 patients, comprising a range of ages and CD4 nadirs similar to those of the cases, were assigned to the control group. Our primary analysis was a regression model, predicting post-ART change in CD4 over time.After controlling for age and nadir CD4 cell counts, the only potential predictor that appears consistently associated with the rate of post-ART rise in CD4 over time in our cohort, regardless of the other variables that we have controlled for, is the rate of decline in CD4 pre-ART initiation.Several factors have been variably correlated with immune reconstitution failure of CD4 T cell count. Age and low CD4 nadir are factors previously shown to correlate with immune reconstitution failure; and we have controlled for them in our study. Another possible predictor is the rate of decline in CD4 pre-ART, which can serve as an additional marker of reconstitution failure and necessitate prioritizing individuals to ART initiation or identification of a subset of individuals that may be targeted for future adjunct strategies to improve immune recovery. Keywords: HIV, CD4, Immune reconstitution, Virologic suppression

Objectives: The aim of this study was to determine the incidence of infective endocarditis (IE) in patients with bacteremia caused by group C and group G streptococci (GCGS) and to characterize the burden of disease, clinical characteristics, and outcomes through a case series of patients with GCGS IE. Methods: Individuals with blood cultures growing GCGS in Manitoba, Canada, between January 2012 and December 2015 were included. Clinical and echocardiographic parameters were collected retrospectively. IE was suspected or confirmed according to the modified Duke criteria. Results: Two hundred and nine bacteremic events occurred in 198 patients. Transthoracic echocardiography (TTE) was performed in 33%. Suspected or confirmed IE occurred in 6% of all patients and in 18% of those with TTE. Native valve infection was more common than prosthetic valve and device-related infections (75%, 17%, and 8%, respectively). Metastatic infection was observed in 64%, primarily to the lungs (57%), skin (43%), osteoarticular system (29%), and central nervous system (29%). Sepsis occurred in 58% and streptococcal toxic shock syndrome in 50% of those with IE, with overall mortality of 17%. Conclusions: IE from GCGS bacteremia is common and is frequently associated with severe disease, embolic events, and mortality. In the appropriate clinical context, GCGS bacteremic events should prompt investigation for IE. Keywords: Streptococcus dysgalactiae, Group C streptococci, Group G streptococci, Bacteremia, Infective endocarditis

Lung infection in human immunodeficiency virus (HIV)-positive individuals remains an important cause of morbidity and mortality, even in the current antiretroviral therapy era. Pneumonia is the most common cause of admission in HIV-positive individuals in our centre as reported in a previously published study. The objective of this retrospective observational study was to further characterize these admissions, with respect to index of disease severity at presentation, organisms identified, and investigations pursued including bronchoalveolar lavage (BAL). There were 123 unique patients accounting for a total of 209 admissions from 2005 to 2015. An organism was isolated in only 33% of all admissions (68/209). The most common organism was Pneumocystis jirovecii with a frequency of 29% of all admissions. Eighty-seven percent of presentations were mild, and 13% were moderate by CURB-65 criteria. A total of 39 BALs were performed, of which 27 yielded an organism (69%). Considering the burden of disease, low diagnostic yield of the current diagnostic strategy and increased morbidity and mortality caused by pneumonia in HIV-positive individuals, further methods are needed to more accurately target therapy. The preponderance of mild disease in this study suggests that better diagnostic tests may identify individuals that can be candidates for outpatient therapy.

Introduction Despite the life-prolonging effects of Highly Active Antiretroviral Therapy (HAART), persons with HIV are still prone to higher rates of non-AIDS related morbidity (such as heart, kidney, and liver disease) than the general public. This is likely due to chronic immune activation and inflammation that persists in HIV-positive persons despite virological suppression. What remains undetermined, however, is whether a link exists between chronic inflammation/immune activation and suboptimal immune recovery on HAART. The hypothesis of the present study is that higher levels of systemic subclinical inflammation and immune activation are linked with suboptimal immune recovery on HAART. Methods Fifteen eligible patients from the Manitoba HIV program were enrolled and followed for up to two years; blood samples were drawn at 4 timepoints each, and concentrations of 21 proinflammatory markers were measured. Patients were grouped according to CD4:CD8 recovery at viral suppression, and the inflammatory profiles of the two groups were compared. Results and conclusions APRIL and BAFF are higher in those with poor recovery at the point of viral suppression, but were also higher in this group at the onset of therapy and through the three additional follow-up visits. TNF-R1, CD163, and Osteopontin, were also in higher concentrations at the outset of therapy and beyond. These five molecules could thus see potential use in the future as biomarkers of likely poor immune recovery. Future work should focus on replicating these findings with larger cohorts.

This study aims to analyze survival, repeat hospitalization, and risk factors for surgically treated left-sided endocarditis. Retrospective review of all 166 (114 native and 52 prosthetic) patients operated between January 2004 and March 2015 was performed. Long-term survival and repeat hospitalization data for 134 of 166 patients were obtained via linked clinical databases with the Manitoba Centre for Health Policy. Kaplan-Meier estimates of survival and hospital readmission and Cox multivariable regression analysis of factors influencing outcomes were performed. Survival at 1 and 5 years was 91% and 80%, respectively, and major adverse prosthesis-related event repeat hospitalization rates were 12% and 21%, respectively. Repeat hospitalization because of endocarditis was 7% and 11% at 1 and 5 years, respectively. Survival and repeat hospitalization were similar for aortic and mitral valves. Survival after surgically treated endocarditis was similar to survival for age-, sex-, and valve-matched surgical valve replacements for noninfectious indications (P = 0.53). Viridans Streptococci was the most common organism in native valve endocarditis, and culture negative endocarditis was most common in prosthetic valves. Prosthetic valve endocarditis (P 0.01) and preoperative renal dysfunction (P 0.01) were risk factors for in-hospital mortality and major postoperative adverse events. Diabetes and renal dysfunction were associated with poor long-term survival, functional survival, and repeat hospitalization. This analysis suggests that surgery remains a very effective tool in management of these complex patients in terms of survival and major adverse prosthesis-related event repeat hospitalization.

Blastomyces dermatitidis is a thermally dimorphic fungus that is capable of causing pulmonary and extra-pulmonary disease, including infections of the central nervous system (CNS). Diagnosis of CNS blastomycosis with non-invasive testing can be difficult, and a surgical biopsy may ultimately be required for microbiological and/or histopathological confirmation. A case of B. dermatitidis meningitis is presented where the diagnosis was made by testing cerebrospinal fluid (CSF) using the MVista® Blastomyces Quantitative Antigen Enzyme Immunoassay test. The utility of performing this test on CSF for diagnosis of CNS mass lesions/abscesses caused by B. dermatitidis in the absence of associated meningitis remains unclear. Cross reaction of the Blastomyces antigen test with other dimorphic fungi is a concern, necessitating that positive test results are interpreted in the context of the patient's exposure and travel history.

Background The incidence of Staphylococcus aureus infective endocarditis (IE) is steadily rising due to advances in health care delivery. Routine echocardiography is essential in the management of Staphylococcus aureus bacteremia (SAB). The aim of this retrospective cohort study was to characterize the real-world use of echocardiography in adult patients with SAB and native valve S aureus IE. Methods Using an academic hospital microbiological database, all cases of SAB in adults between 2010 and 2016 were identified. Demographic, echocardiographic, and clinical features were recorded. Results A total of 738 episodes of SAB were identified, of which 504 (68%) patients underwent transthoracic echocardiography (TTE) within 30 days. Of 73 patients with definite IE, 46 (63%) patients had definite IE diagnosed on the initial TTE. An additional 14 (19%) patients had definite IE diagnosed on repeat TTE, 6 (8%) on transesophageal echocardiography (TEE), and 7 (10%) were diagnosed without fulfilling Duke echocardiographic criteria. The yield of repeat TTE was comparable to that of TEE for identifying new vegetations not identified on the initial TTE (17% vs 21%, P = .78). Conclusions Most cases of IE in SAB were identified using TTE alone, with repeat TTE improving the diagnostic yield in the setting of clinical decompensation.

Understanding patterns of serological testing for hepatitis B & C, and syphilis among HIV-positive individuals, prior to HIV diagnosis, can inform HIV diagnosis, engagement and prevention strategies. This was a population-based, retrospective analysis of prior serological testing among HIV-positive individuals in Manitoba, Canada. HIV cases were age-, sex- and region-matched to HIV-negative controls at a 1:5 ratio. Conditional logistic regression was used to examine previous serological tests and HIV status. Odds ratios (ORs) and their 95% confidence intervals (95% CI) were reported. A total of 193 cases and 965 controls were included. In the 5 years prior to diagnosis, 50% of cases had at least one test, compared to 26% of controls. Compared to those who did not have serological testing in the 5 years prior to HIV infection, those who had one serological test were at twice the odds of being HIV positive (OR: 1.9, 95% CI: 1.2-2.9), while those with 2 or more tests were at even higher odds (OR: 5.5, 95%CI: 3.7-8.4). HIV cases had higher serological testing rates. Interactions between public health and other healthcare providers should be strengthened.

Introduction Determining vaccine responsiveness is challenging in immune compromised individuals. The microbead array (MBA) assay is a rapid, inexpensive test for evaluating influenza vaccine immunogenicity. MBA performance was compared to hemagglutination inhibition assay (HAI) utilizing HIV seropositive vaccine recipient specimens. Methods CTN 253 evaluated standard dose, single antigen, inactivated split adjuvanted (AS03(A)) H1N1 influenza vaccine (Arepanrix) vs standard dose plus booster. CTN237 evaluated three doses of a seasonal, trivalent killed split non-adjuvanted influenza vaccine (Fluviral). Samples of convenience from 75 CTN 253 and 58 CTN 237 participants were evaluated by MBA and HAI. MBA seroreactivity cut-offs of 500 and 1000 mean fluorescent intensity were used to compare those derived by HAI [titer ≥40 (seroprotection) and 4-fold titer increase from baseline (seroconversion)]. Results CTN253: Using a MBA cut-off of 500, 75% and 59% had seroreactive titers at visit 2 and 78% and 61% at visit 3 for the single versus double dose study arms. Many participants were categorized differently by the HAI and MBA tests, with raw agreement of 59% at visit 2 and 57% at visit 3. CTN 237: Baseline MBA medians (IQR) were 803 (12-2626) for the A/Brisbane strain and 460 (14-1758) for the B/Florida strain. Using a cut-off of 500 yielded for the A/Brisbane strain seroreactivity rates of 44%, 58%, and 63% were observed for the three doses of vaccine tested. The raw agreement was 47%. B/Florida strain analyses yielded similar results. For all strains assessed in both studies, no relationship between MBA values and baseline variables was identified. Conclusion The concordance of results between the MBA assay and the HAI assay is very low. MBA assay may be more sensitive than the HAI assay suggesting that it was either detecting more false-positive results and/or that the HAI assay had more false negative.

Tetanus is a life-threatening clinical syndrome that commonly presents with muscular spasms, rigidity, and autonomic instability. It is considered rare in industrialized countries, and tetanus occurring secondary to dental abscesses, procedures, or infections has been infrequently reported. We describe the case of a patient inadequately immunized for tetanus, who presented to the emergency department with muscular spasms, rigidity, and autonomic instability in the setting of an odontogenic infection. A clinical diagnosis of tetanus was made and subsequently managed successfully.

The high prevalence of substance use among HIV-infected individuals creates numerous challenges to patient care. This study was undertaken in order to understand the impact of substance use on care outcomes for HIV-infected individuals in Manitoba. Clinical records of 564 HIV-infected individuals in care at Health Sciences Centre in Winnipeg, Manitoba were reviewed. Clinical data were extracted from patient charts for substance users (illicit substance users, alcohol abusers and chronic users of opioids or benzodiazepines) and non-users. Substance users and non-users were analysed using chi-square analysis and logistic regression models to compare basic socio-demographic and clinic variables. Chi-square and analysis of variance were used to compare a subset of substance users based on similar socio-demographic and clinical characteristics. Among HIV-infected individuals in Manitoba, 38% were substance users with over-representation by Aboriginals, females, young adults and residents of Winnipeg's core areas. Opioids and benzodiazepines were the most commonly used substances with the majority of substance users having used multiple classes of substances in their lifetime. Substance users were more likely than non-users to have missed clinic appointments. Among substance users, missed appointments were more common among those who self-identified as Aboriginal, female, young adults, residents of Winnipeg's core areas, heterosexuals and those who had abused alcohol or cocaine/crack. Aboriginal substance users were also less likely to achieve viral load suppression compared to non-Aboriginal substance users. With the high prevalence of substance use among HIV-infected individuals in Manitoba, it is important to identify at-risk individuals in order to implement appropriate care strategies and improve treatment adherence and health outcomes.

SUMMARYThe main aim was to measure the incidence of latent tuberculosis infection (LTBI) and identify risk factors associated with infection. In addition, we determined the number needed to screen (NNS) to identify LTBI and active tuberculosis. We followed 129 prisoners for 2 years following a negative two-step tuberculin skin test (TST). The cumulative incidence of TST conversion over 2 years was 29·5% (38/129), among the new TST converters, nine developed active TB. Among persons with no evidence of LTBI, the NNS to identify a LTBI case was 3·4 and an active TB case was 14·3. The adjusted risk factors for LTBI conversion were incarceration in prison number 1, being formerly incarcerated, and overweight. In conclusion, prisoners have higher risk of LTBI acquisition compared with high-risk groups, such as HIV-infected individuals and children for whom LTBI testing should be performed according to World Health Organization guidance. The high conversion rate is associated with high incidence of active TB disease, and therefore we recommend mandatory LTBI screening at the time of prison entry. Individuals with a negative TST at the time of entry to prison are at high risk of acquiring infection, and should therefore be followed in order to detect convertors and offer LTBI treatment. This approach has a very low NNS for each identified case, and it can be utilized to decrease development of active TB disease and transmission.

These strains are more likely to cause invasive infection, which is an emerging public health concern as incidence and disease severity are on the rise., The incidence of group C and G Streptococcus (GCGS) bacteremia, which is associated with severe disease and death, is increasing. We characterized clinical features, outcomes, and genetic determinants of GCGS bacteremia for 89 patients in Winnipeg, Manitoba, Canada, who had GCGS bacteremia during 2012–2014. Of the 89 patients, 51% had bacteremia from skin and soft tissue, 70% had severe disease features, and 20% died. Whole-genome sequencing analysis was performed on isolates derived from 89 blood samples and 33 respiratory sample controls: 5 closely related genetic lineages were identified as being more likely to cause invasive disease than non-clade isolates (83% vs. 57%, p = 0.002). Virulence factors cbp, fbp, speG, sicG, gfbA, and bca clustered clonally into these clades. A clonal distribution of virulence factors may account for severe and fatal cases of bacteremia caused by invasive GCGS.

Echocardiography is an important diagnostic tool in evaluating a patient with Staphylococcus aureus bacteremia (SAB) for diagnosing infective endocarditis (IE). We sought to compare the utility of transthoracic echocardiography (TTE) with transesophageal echocardiography (TEE) in screening for IE in patients with SAB. We performed a retrospective chart review of 285 adult patients from two tertiary care hospitals with at least one positive blood culture for S. aureus between 2010 and 2012. Patients who underwent echocardiography were divided into two groups: TTE (screened with TTE only) and TEE (screened with both TTE and TEE). The demographic factors and clinical outcomes were compared between the groups. Of the 285 charts reviewed, 213 (74.7 %) patients were screened with echocardiography: 183 (85.9 %) were screened with TTE alone and 30 (14.1 %) were screened with both TTE and TEE. TEE disclosed more cases of definite IE than TTE (8 [26.7 %] vs. 22 [12.0 %], p = 0.046). The TEE group had higher mortality than the TTE group (15 [50.0 %] vs. 43 [23.5 %], p = 0.004). In patients with definite IE, mortality was higher in the TEE group than in the TTE group (6 [75.0 %] vs. 6 [27.3 %], p = 0.034). TEE discovered additional findings that were missed by TTE in 36.7 % of cases and refuted the findings of TTE in 13.3 % of cases. We do not support the routine use of TEE in patients with uncomplicated SAB. High-risk patients in which IE is a serious consideration should undergo investigation with TEE.

Background Host factors and complications have been associated with higher mortality in infective endocarditis ( IE ). We sought to develop and validate a model of clinical characteristics to predict 6‐month mortality in IE . Methods and Results Using a large multinational prospective registry of definite IE (International Collaboration on Endocarditis [ ICE ]–Prospective Cohort Study [ PCS ], 2000–2006, n=4049), a model to predict 6‐month survival was developed by Cox proportional hazards modeling with inverse probability weighting for surgery treatment and was internally validated by the bootstrapping method. This model was externally validated in an independent prospective registry ( ICE ‐ PLUS , 2008–2012, n=1197). The 6‐month mortality was 971 of 4049 (24.0%) in the ICE ‐ PCS cohort and 342 of 1197 (28.6%) in the ICE ‐ PLUS cohort. Surgery during the index hospitalization was performed in 48.1% and 54.0% of the cohorts, respectively. In the derivation model, variables related to host factors (age, dialysis), IE characteristics (prosthetic or nosocomial IE , causative organism, left‐sided valve vegetation), and IE complications (severe heart failure, stroke, paravalvular complication, and persistent bacteremia) were independently associated with 6‐month mortality, and surgery was associated with a lower risk of mortality (Harrell's C statistic 0.715). In the validation model, these variables had similar hazard ratios (Harrell's C statistic 0.682), with a similar, independent benefit of surgery (hazard ratio 0.74, 95% CI 0.62–0.89). A simplified risk model was developed by weight adjustment of these variables. Conclusions Six‐month mortality after IE is ≈25% and is predicted by host factors, IE characteristics, and IE complications. Surgery during the index hospitalization is associated with lower mortality but is performed less frequently in the highest risk patients. A simplified risk model may be used to identify specific risk subgroups in IE .

Summary: Immune Reconstitution Syndrome (IRIS) has been associated with a variety of infections in patients with human immunodeficiency virus (HIV). However, we are reporting the first case of IRIS secondary to Rhodococcus equi (R. equi) in a patient with HIV.We report the case of a 48-year-old male found to have HIV infection in the setting of Burkitt's lymphoma. While on anti-retroviral therapy and chemotherapy, he had developed IRIS secondary to R. equi that manifested as a cavitating pneumonia. This report outlines the successful management of the R. equi infection with the use of a combination of antibiotics, radiographic follow up and suppressive antibiotic while on chemotherapy. Keywords: Human immunodeficiency virus, Rhodococcus equi, Burkitt's lymphoma, Cavitating pneumonia

BACKGROUND: HIV controllers demonstrate a natural ability to control HIV replication in the absence of antiretroviral therapy. We performed a comprehensive evaluation of inflammation and T-cell activation in a demographically unique cohort of HIV controllers and noncontrollers. METHODS: Plasma concentrations of 22 cytokines and chemokines were evaluated using a multiplex bead array approach. Multicolor flow cytometry was used to measure baseline levels of T-cell activation and regulatory T cells (Tregs) and HIV-specific T-cell cytokine (interferon γ, interleukin 2) and proliferation responses. RESULTS: HIV controllers were characterized by elevated macrophage inflammatory protein 1α and low levels of interferon γ-induced protein 10, monocyte chemotactic protein 1, and Transforming growth factor beta. Activated (CD38(+) HLA DR(+)) CD4(+) and CD8(+) T cells were reduced in HIV controllers relative to noncontrollers. HIV controllers and noncontrollers had comparable proportions of Tregs within the CD4(+) T-cell compartment, but absolute Treg counts were depleted in noncontrollers. Absolute Treg counts correlated inversely with T-cell activation. Proliferative CD4(+) and CD8(+) T-cell responses directed against HIV gag epitopes were found most frequently among HIV controllers with the lowest viral loads (elite controllers) and were rarely detected among noncontrollers, supporting a relationship between HIV-specific T-cell proliferation and viral control. CONCLUSIONS: Collectively, these data suggest a model in which HIV controllers maintain low levels of viral replication through robust HIV-specific T-cell responses in an environment of low inflammation and reduced availability of activated target cells.

The purpose of this study was to increase awareness, gain insight into acquisition, and assess the virulence of the hypervirulent (hypermucoviscous) clinical variant (hvKP) that is entrenched in the Pacific Rim but emerging in Western countries. A case of community-acquired liver abscess with metastatic spread to the spleen is described. Comparative in vitro and in vivo virulence studies on this isolate (hvKP1) and four randomly chosen blood isolates of "classic" K. pneumonia strains (cKP1-4) were performed. Cases of hvKP infection are occurring in Western countries and are under-recognized. A hypermucoviscous phenotype is a surrogate laboratory marker for this variant. The propensity of hvKP strains for metastatic spread in non-compromised hosts is both a defining and unusual trait. The mode of acquisition in the described case was unclear but potential means are discussed. hvKP1 was more resistant to complement and neutrophil-mediated bactericidal activity and was more virulent in a rat subcutaneous abscess model than cKP1-4. Recognition of the hypermucoviscous phenotype, defined by a positive "string-test", will alert the microbiologist or clinician that the infecting strain may be a hvKP, which is hypervirulent compared to cKP. This will improve our understanding of the epidemiology and clinical spectrum of infection, which may be more extensive than appreciated.

Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers.In this study, we combined an integrated genomic analysis of 1071 individuals with

Human leucocyte antigen (HLA) alleles influence the rate of CD4 decline among HIV-infected individuals. We investigated the association between HLA B35 and HLA B51 and the rate of CD4 decline and/or opportunistic infections, among 294 HIV-positive individuals from Manitoba, Canada. All individuals presenting with a CD4 count >200 cells μL(-1) , who had at least two CD4 counts, and no evidence of co-infection were included. Individuals bearing HLA B35 or HLA B51 were compared to controls. A multivariate model demonstrated that HLA B35 allele was associated with a hazard ratio of 2.05 (95% CI 1.31-3.18) for reaching AIDS and HLA B51 allele with HR of 2.03 (95% CI 1.18-3.49) for reaching the same end-point. High prevalence of HLA B35 was seen in the patient population receiving care in Manitoba. Our observations confirm the association of HLA B35 with rapid disease progression. We report, for the first time, faster CD4 decline among individuals with HLA B51 allele.

Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different antifungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high, with 36% mortality in the hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A subgroup analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this subgroup, 11 patients received amphotericin B-based therapy and 14 received echinocandin-based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality rates were similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B-based therapy in the small subgroup analysis.

International audience; Background : Nearly half of patients require cardiac surgery during the acute phase of infective endocarditis (IE). We describe the characteristics of patients according to the type of valve replacement (mechanical or biological), and examine whether the type of prosthesis was associated with in-hospital and 1-year mortality.Methods and results : Among 5591 patients included in the International Collaboration on Endocarditis Prospective Cohort Study, 1467 patients with definite IE were operated on during the active phase and had a biological (37%) or mechanical (63%) valve replacement.Patients who received bioprostheses were older (62 vs 54 years), more often had a history of cancer (9% vs 6%), and had moderate or severe renal disease (9% vs 4%); proportion of health care-associated IE was higher (26% vs 17%); intracardiac abscesses were more frequent (30% vs 23%). In-hospital and 1-year death rates were higher in the bioprosthesis group, 20.5% vs 14.0% (p = 0.0009) and 25.3% vs 16.6% (p < .0001), respectively.In multivariable analysis, mechanical prostheses were less commonly implanted in older patients (odds ratio: 0.64 for every 10 years), and in patients with a history of cancer (0.72), but were more commonly implanted in mitral position (1.60).Bioprosthesis was independently associated with 1-year mortality (hazard ratio: 1.298).Conclusions :Patients with IE who receive a biological valve replacement have significant differences in clinical characteristics compared to patients who receive a mechanical prosthesis. Biological valve replacement is independently associated with a higher in-hospital and 1-year mortality, a result which is possibly related to patient characteristics rather than valve dysfunction.

International audience; Background - The impact of early valve surgery (EVS) on the outcome of Staphylococcus aureus (SA) prosthetic valve infective endocarditis (PVIE) is unresolved. The objective of this study was to evaluate the association between EVS, performed within the first 60 days of hospitalization, and outcome of SA PVIE within the International Collaboration on Endocarditis-Prospective Cohort Study. Methods - Participants were enrolled between June 2000 and December 2006. Cox proportional hazards modeling that included surgery as a time-dependent covariate and propensity adjustment for likelihood to receive cardiac surgery was used to evaluate the impact of EVS and 1-year all-cause mortality on patients with definite left-sided S. aureus PVIE and no history of injection drug use. Results - EVS was performed in 74 of the 168 (44.3%) patients. One-year mortality was significantly higher among patients with S. aureus PVIE than in patients with non-S. aureus PVIE (48.2% vs 32.9%; P = .003). Staphylococcus aureus PVIE patients who underwent EVS had a significantly lower 1-year mortality rate (33.8% vs 59.1%; P = .001). In multivariate, propensity-adjusted models, EVS was not associated with 1-year mortality (risk ratio, 0.67 [95% confidence interval, .39-1.15]; P = .15). Conclusions - In this prospective, multinational cohort of patients with S. aureus PVIE, EVS was not associated with reduced 1-year mortality. The decision to pursue EVS should be individualized for each patient, based upon infection-specific characteristics rather than solely upon the microbiology of the infection causing PVIE.

RESUMEN: Queríamos investigar el perfil de citoquinas pro-inflamatorias / quimiocinas asociados con los agentes etiológicos identificados en pacientes con VIH. Los pacientes inmunodeprimidos ingresados ​​en dos hospitales en Medellín, Colombia, con diagnóstico clínico y radiográfico de la neumonía se inscribieron en el estudio. Después de la autorización, se recogió el lavado broncoalveolar (BAL) para bacterias, micobacterias y hongos diagnóstico. Todos los pacientes fueron seguidos durante un año. Una muestra de BAL almacenada se utiliza para la detección de citoquinas / quimioquinas y citoquinas medida usando ensayos comerciales humana, basados ​​en perlas magnéticas 19-plex. El análisis estadístico se realizó mediante la asignación de niveles de concentraciones de citoquinas / quimioquinas en 75 percentil (superior). Se llevaron a cabo análisis de componentes principales (PCA) y el análisis de Kruskal-Wallis para identificar la agrupación de citoquinas con las diversas etiologías infecciosas (hongos, Mycobacterium tuberculosis - BTT, y bacterias). La edad promedio de los pacientes era de 35 años, de los cuales el 77% eran hombres, y la mediana del recuento de CD4 de 33cells / l. De los 57 pacientes infectados por el VIH, la mortalidad hospitalaria fue del 12,3% y el 33% murió dentro de un año de seguimiento. El PCA reveló aumento de IL-10, IL-12, IL-13, IL-17, eotaxina, GCSF, MIP-1α, y las concentraciones de MIP-1 beta que se asocia con la infección MTB. En los pacientes con infección fúngica probada, bajas concentraciones de IL-1RA, IL-8, se identificaron TNF-α y VEGF. Las infecciones bacterianas muestran un patrón de citoquinas distintas y no fueron mal clasificados utilizando los patrones de citoquinas MTB u hongos (valor de p 75 percentile (higher). Principal component analysis (PCA) and Kruskal-Wallis analysis were conducted to identify the clustering of cytokines with the various infectious etiologies (fungi, Mycobacterium tuberculosis - MTB, and bacteria). Average age of patients was 35, of whom 77% were male, and the median CD4 count of 33cells/μl. Of the 57 HIV infected patients, in-hospital mortality was 12.3% and 33% died within a year of follow up. The PCA revealed increased IL-10, IL-12, IL-13, IL-17, Eotaxin, GCSF, MIP-1α, and MIP-1β concentrations to be associated with MTB infection. In patients with proven fungal infection, low concentrations of IL-1RA, IL-8, TNF-α and VEGF were identified. Bacterial infections displayed a distinct cytokine pattern and were not misclassified using the MTB or fungi cytokine patterns (p-value

Background— Use of surgery for the treatment of infective endocarditis (IE) as related to surgical indications and operative risk for mortality has not been well defined. Methods and Results— The International Collaboration on Endocarditis–PLUS (ICE-PLUS) is a prospective cohort of consecutively enrolled patients with definite IE from 29 centers in 16 countries. We included patients from ICE-PLUS with definite left-sided, non–cardiac device–related IE who were enrolled between September 1, 2008, and December 31, 2012. A total of 1296 patients with left-sided IE were included. Surgical treatment was performed in 57% of the overall cohort and in 76% of patients with a surgical indication. Reasons for nonsurgical treatment included poor prognosis (33.7%), hemodynamic instability (19.8%), death before surgery (23.3%), stroke (22.7%), and sepsis (21%). Among patients with a surgical indication, surgical treatment was independently associated with the presence of severe aortic regurgitation, abscess, embolization before surgical treatment, and transfer from an outside hospital. Variables associated with nonsurgical treatment were a history of moderate/severe liver disease, stroke before surgical decision, and Staphyloccus aureus etiology. The integration of surgical indication, Society of Thoracic Surgeons IE score, and use of surgery was associated with 6-month survival in IE. Conclusions— Surgical decision making in IE is largely consistent with established guidelines, although nearly one quarter of patients with surgical indications do not undergo surgery. Operative risk assessment by Society of Thoracic Surgeons IE score provides prognostic information for survival beyond the operative period. S aureus IE was significantly associated with nonsurgical management.

Underwater hearing acuity and sound localization are improved by the presence of an air interface around the pinnae and inside the external ear canals.Hearing threshold and the ability to localize sound sources are reduced underwater. The resonance frequency of the external ear is lowered when the external ear canal is filled with water, and the impedance-matching ability of the middle ear is significantly reduced due to elevation of the ambient pressure, the water-mass load on the tympanic membrane, and the addition of a fluid-air interface during submersion. Sound lateralization on land is largely explained by the mechanisms of interaural intensity differences and interaural temporal or phase differences. During submersion, these differences are largely lost due to the increase in underwater sound velocity and cancellation of the head's acoustic shadow effect because of the similarity between the impedance of the skull and the surrounding water.Ten scuba divers wearing a regular opaque face mask or an opaque ProEar 2000 (Safe Dive, Ltd., Hofit, Israel) mask that enables the presence of air at ambient pressure in and around the ear made a dive to a depth of 3 m in the open sea. Four underwater speakers arranged on the horizontal plane at 90-degree intervals and at a distance of 5 m from the diver were used for testing pure-tone hearing thresholds (PTHT), the reception threshold for the recorded sound of a rubber-boat engine, and sound localization. For sound localization, the sound of the rubber boat's engine was randomly delivered by one speaker at a time at 40 dB HL above the recorded sound of a rubber-boat engine, and the diver was asked to point to the sound source. The azimuth was measured by the diver's companion using a navigation board.Underwater PTHT with both masks were significantly higher for frequencies of 250 to 6000 Hz when compared with the thresholds on land (p0.0001). No differences were found in the PTHT or the reception threshold for the recorded sound of a rubber-boat engine for dry or wet ear conditions. There was no difference in the sound localization error between the regular mask and the ProEar 2000 mask.The presence of air around the pinna and inside the external ear canal did not improve underwater hearing sensitivity or sound localization. These results support the argument that bone conduction plays the main role in underwater hearing.

Setting: Two prisons in Medellín and Itagüí, Colombia. Objective: To determine the prevalence of tuberculin skin test (TST) positivity in prisoners and the annual risk of tuberculous infection (ARTI), to identify risk factors associated with a positive result, and to describe progression to active disease. Design: Cross-sectional study. Inmates were included if time of incarceration was ⩾1 year and excluded if subjects had had previous or active tuberculosis (TB), or conditions that could hamper TST administration or interpretation. Results: We screened 1014 inmates. The overall prevalence of TST positivity was 77.6%. The first TST administration resulted in 66% positivity, and the second TST an additional 11.6%. In Prison One, the ARTI was 5.09% in high TB incidence cell blocks and 2.72% in low TB incidence blocks. In Prison Two, the ARTI was 2.77%. Risk factors associated with TST positivity were history of previous incarceration and length of incarceration. Among all those included in the study, four individuals developed active pulmonary TB. Conclusion: Prevalence of TST positivity in prisoners and the ARTI were higher than in the general population, but differed between prisons; it is important to apply a second TST to avoid an overestimation of converters during follow-up. COL0003249 COL0004362 COL0126131

Currently, the treatment of sudden deafness (SD) is based mainly on complete bed rest and the administration of corticosteroids. Hyperbaric oxygen therapy (HBOT) has previously been suggested as adjunctive treatment. We describe two cases of successful HBOT for SD. The first patient presented with moderate mid-frequency hearing loss without accompanying symptoms, whereas the second patient had moderate low-frequency hearing loss with persistent tinnitus and a single episode of vertigo. HBOT in addition to conventional treatment soon after diagnosis resulted in full recovery of hearing in both patients. The pathogenesis of SD may involve a reduction in cochlear blood flow and perilymph oxygenation, making early HBOT a reasonable treatment modality for this condition.

Community-acquired primary pyogenic liver abscess (PLA) caused by Klebsiella pneumoniae is an emerging infectious entity, with cases reported in the scientific literature over the past 15 y mainly from Taiwan and Asia, but also from Europe and North America. We describe a case of PLA caused by the hypermucoviscous, K1 capsular serotype of Klebsiella pneumoniae in a Canadian man and highlight the unique features of this increasingly common cause of liver abscess.

Bilateral vision loss during hemodialysis is a rare but devastating entity, with grim prognosis for sight. The etiologies are diverse but share ischemia as a common mechanism. This is a report of a patient with bilateral sight loss during hemodialysis, with early hyperbaric treatment and return of visual acuity to baseline. Hyperbaric treatment should be considered, where early administration is possible, for bilateral blindness during hemodialysis.

Staphylococcus aureus and methicillin-resistant S aureus have emerged as the most important nosocomial pathogens. Traditional therapy may be sufficient in most but not all patients, in whom alternatives should be sought. The infection is often complicated with several sites of metastatic foci and is nosocomial frequently. New antibiotics to fight MRSA have been introduced and are equivalent or better than vancomycin.