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.

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.

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.

Epidemiological, clinical, diagnostic and economic features of an immigrant population of chronic schistosomiasis sufferers with long-term residence in a non-endemic country (North Metropolitan area of Barcelona, 2002-2016).

BACKGROUND: Schistosomiasis, one of the neglected tropical diseases (NTD) listed by the WHO, is an acute and chronic parasitic disease caused by blood flukes (trematode worms) of the genus Schistosoma. Complications of long-term infestation include liver cirrhosis, bladder tumors and kidney failure. The objective of this study was to carry out a clinical and epidemiological characterization of a schistosomiasis-diagnosed immigrant population with long-term residencein the EU as well as to evaluate the diagnostic methods available to date. METHODS AND RESULTS: A total of 61 individuals with Schistosoma infection who received medical attention between June 2002 and June 2016 at the North Metropolitan International Health Unit in Barcelona (Catalonia, Spain), were included in the study. All patients were sub-Saharan African immigrants. The majority were male (91.8%) with a median age of 34 years. Symptoms attributable to infection such as haematuria, abdominal pain and dysuria were recorded in up to 90% of patients. The percentage of eosinophils decreased amongst older patients (p = 0.002) and those with symptoms associated with urinary tract infections (p = 0.017). Serology was used for diagnosis in 80.3% of the cases, with microscopic examination showing the remaining 9.8% positive for parasite eggs. Direct microbiological diagnosis was more useful in patients with less than 5 years of residence in the EU (p = 0.05). Chronic complications were present in 22 (36%) of the patients, with renal failure affecting 20 (33%). Of these 20, 6(10%) developed terminal renal failure and required hemodialysis, while 3 (5%) received a renal transplantation. CONCLUSION: Morbidity associated with chronic long-term schistosomiasis is frequent among African immigrants in non-endemic countries. Better diagnostic tools and appropriate early treatment would prevent the development of visceral damage. Thorough screening in selected patients would also be useful to avoid chronic complications.

Chikungunya Pathogenesis: From the Clinics to the Bench.

Chikungunya alphavirus has caused large epidemics worldwide and leads to acute incapacitating polyarthralgia. The inflammatory reaction over several days will drive robust innate and humoral responses essential to control the infection. Critically, fatal cases and mother-to-child transmission have also been described. Chikungunya can give rise to chronic musculoskeletal diseases, which can last for months to years, particularly in elderly individuals, and occasionally leads to seronegative rheumatoid arthritis-like pathologies. Histopathological studies of patient biopsy specimens and animal models have revealed that chikungunya virus can hide in tissue sanctuaries, and ongoing research should help to decipher the inflammatory mechanisms of tissue injuries.

Infección grave por el virus del Chikungunya / Severe Chikungunya virus infection

Publicaciones recientes han desafiado la visión convencional sobre la naturaleza benigna de la infección por el virus de Chikungunya (VCHIK). Las manifestaciones clínicas son muy variables y pueden ser graves en algunos casos. Los estudios sugieren que la forma grave de la infección por el VCHIK puede ser asociada con disfunción orgánica múltiple, hepatitis, meningitis, nefritis, encefalitis, dermatitis ampollosa, miocarditis, arritmias cardiacas, entre otras. La fisiopatología subyacente para algunas de las complicaciones de la enfermedad por el VCHIK sigue siendo poco clara. Sin embargo, de acuerdo con las características clínicas de los casos graves o atípicos descritos a la fecha, el desarrollo de complicaciones podría agruparse principalmente en tres categorías: la exacerbación de condiciones médicas subyacentes, el deterioro de un trastorno no reconocido previamente y la respuesta inmunológica inadecuada a la infección. Se ha encontrado asociación entre las manifestaciones graves de la infección, niveles elevados de citoquinas y algunas secuencias genómicas específicas del VCHIK. La inmunoterapia pasiva puede constituir una estrategia eficaz en el tratamiento de individuos expuestos al VCHIK con riesgo de infección grave. Actualmente no existe evidencia clínica que soporte el uso de antivirales en la prevención o tratamiento de la infección por el VCHIK.

Recent publications have challenged the conventional view of the benign nature of the Chikungunya virus (CHIKV) infection. The clinical manifestations are highly variable and can be severe in some cases. Studies suggest that the severe form of CHIKV infection may be associated with multiple organ failure, hepatitis, meningitis, nephritis, encephalitis, bullous dermatitis, myocarditis, cardiac arrhythmias, among others. The underlying pathophysiology for some of these complications remains unclear. However, according to the clinical characteristics of severe or atypical cases reported to date, the development of complications could be grouped into three main categories, such as exacerbation of underlying medical conditions, deterioration of a previously unrecognized condition and inadequate immune response to infection. Some studies have found association between severe manifestations of infection and high levels of cytokines or some specific genomic sequences CHIKV. Experimental studies suggest that passive immunotherapy can be an effective strategy for the management of individuals at risk of severe CHIKV infection. Currently there is no clinical evidence to support antiviral drug use in the prevention or treatment of the disease.

Mortalidad asociada a infección por el virus de Chikungunya / Mortality case associated with Chikungunya virus infection

La infección por el virus de Chikungunya presenta manifestaciones clínicas típicas: fiebre, erupción cutánea y artralgia. La enfermedad es generalmente autolimitada y de evolución benigna. Las complicaciones graves y la muerte ocurren en raras ocasiones y en pacientes con factores de riesgo, principalmente en aquellos con comorbilidades o que se encuentran en edades extremas de la vida. En este artículo describimos un paciente, sin comorbilidades previas conocidas, con infección por el virus de Chickungunya que progresó rápidamente a disfunción orgánica múltiple y murió luego de 36 horas de su ingreso. Este caso ilustra la dificultad del diagnóstico y el tratamiento de la infección grave por el virus de Chikungunya.

Chikungunya virus infection has typical clinical manifestations such as fever, rash and arthralgia. The disease is usually self-limiting and has a benign course. Serious complications and death occur rarely in patients with Chikungunya virus infection and usually happen in patients with risk factors, particularly in those with comorbidities or at extreme ages of life. In the present article, we describe a patient without comorbidities that progressed rapidly to multiple organ failure and died 36 hours after admission associated to Chikungunya virus infection. This case exemplifies the challenges of diagnosis and management of severe Chikungunya virus infection.

Impact of an Educational Program to Reduce Healthcare Resources in Community-Acquired Pneumonia: The EDUCAP Randomized Controlled Trial.

BACKGROUND: Additional healthcare visits and rehospitalizations after discharge are frequent among patients with community-acquired pneumonia (CAP) and have a major impact on healthcare costs. We aimed to determine whether the implementation of an individualized educational program for hospitalized patients with CAP would decrease subsequent healthcare visits and readmissions within 30 days of hospital discharge. METHODS: A multicenter, randomized trial was conducted from January 1, 2011 to October 31, 2014 at three hospitals in Spain. We randomly allocated immunocompetent adults patients hospitalized for CAP to receive either an individualized educational program or conventional information before discharge. The educational program included recommendations regarding fluid intake, adherence to drug therapy and preventive vaccines, knowledge and management of the disease, progressive adaptive physical activity, and counseling for alcohol and smoking cessation. The primary trial endpoint was a composite of the frequency of additional healthcare visits and rehospitalizations within 30 days of hospital discharge. Intention-to-treat analysis was performed. RESULTS: We assigned 102 patients to receive the individualized educational program and 105 to receive conventional information. The frequency of the composite primary end point was 23.5% following the individualized program and 42.9% following the conventional information (difference, -19.4%; 95% confidence interval, -6.5% to -31.2%; P = 0.003). CONCLUSIONS: The implementation of an individualized educational program for hospitalized patients with CAP was effective in reducing subsequent healthcare visits and rehospitalizations within 30 days of discharge. Such a strategy may help optimize available healthcare resources and identify post-acute care needs in patients with CAP. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN39531840.

The effect of simvastatin on inflammatory cytokines in community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial.

OBJECTIVES: It has been suggested that statins have an effect on the modulation of the cytokine cascade and on the outcome of patients with community-acquired pneumonia (CAP). The aim of this prospective, randomised, double-blind, placebo-controlled trial was to determine whether statin therapy given to hospitalised patients with CAP improves clinical outcomes and reduces the concentration of inflammatory cytokines. SETTING: A tertiary teaching hospital in Barcelona, Spain. PARTICIPANTS: Thirty-four patients were randomly assigned and included in an intention-to-treat analysis (19 to the simvastatin group and 15 to the placebo group). INTERVENTION: Patients were randomly assigned to receive 20 mg of simvastatin or placebo administered in the first 24 h of hospital admission and once daily thereafter for 4 days. OUTCOME: Primary end point was the time from hospital admission to clinical stability. The secondary end points were serum concentrations of inflammatory cytokines and partial pressure of arterial oxygen/fractional inspired oxygen (PaO2/FiO2) at 48 h after treatment administration. RESULTS: The trial was stopped because enrolment was much slower than originally anticipated. The baseline characteristics of the patients and cytokine concentrations at the time of enrolment were similar in the two groups. No significant differences in the time from hospital admission to clinical stability were found between study groups (median 3 days, IQR 2-5 vs 3 days, IQR 2-5; p=0.47). No significant differences in PaO2/FiO2 (p=0.37), C reactive protein (p=0.23), tumour necrosis factor-α (p=0.58), interleukin 6 (IL-6; p=0.64), and IL-10 (p=0.61) levels at 48 h of hospitalisation were found between simvastatin and placebo groups. Similarly, transaminase and total creatine kinase levels were similar between study groups at 48 h of hospitalisation (p=0.19, 0.08 and 0.53, respectively). CONCLUSIONS: Our results suggest that the use of simvastatin, 20 mg once daily for 4 days, since hospital admission did not reduce the time to clinical stability and the levels of inflammatory cytokines in hospitalised patients with CAP. TRIAL REGISTRATION NUMBER: ISRCTN91327214.

Incidence, timing and risk factors associated with 1-year mortality after hospitalization for community-acquired pneumonia.

OBJECTIVE: To identify the incidence, causes, timing and risk factors associated with 1-year mortality in CAP patients after hospital discharge. METHODS: Adult patients with CAP who were admitted to a tertiary hospital from 2007 to 2011 were prospectively recruited and followed up for 1 year after hospital discharge. RESULTS: Of the 1284 patients discharged, 93 (7.2%) died within 1-year of leaving hospital. Sixty eight (73.1%) patients died in the first six months. The main reasons for 1-year mortality after hospital discharge were infectious diseases, mainly pneumonia, followed by acute cardiovascular events. Mortality from infectious diseases was higher during the first 6 months (86.1%), while the number of deaths from cardiovascular causes was stable throughout the months of follow-up. After adjustment for confounders, chronic obstructive pulmonary disease, diabetes mellitus, cancer, dementia, rehospitalization within 30 days of hospital discharge and nursing home were independently associated with 1-year mortality. The incidence of long-term mortality increased >50% when ≥4 risk factors were present (P < .001). CONCLUSIONS: Patients mainly died from infectious diseases and acute cardiovascular events in the first six months after leaving hospital for an acute CAP episode. Certain features may help to identify the risk of long-term mortality in CAP patients.

Historia del protozoo Entamoeba histolytica: [revisión] / History of the Entamoeba histolytica protozoan: [review]

This article presents a history of Entamoeba histolytica spanning since the remote times when it was not even recognized as a cause of human disease to the recent molecular advances. Feder Losch (1875) in Saint Petersburg, found amoebae in fecal samples but only regarded them as responsible for maintaining the inflammatory process, not as a cause of dysentery. Fritz Schaudinn (1903) established the differentiation between Entamoeba histolytica and Endamoeba coli, Schaudinn decided to call it E. histolytica because of its ability to cause tissue lysis. Emile Brumpt (1925) based on experimental studies, pointed out the existence ofE. Histolytica as a species complex, comprising two morphologically indistinguishable species, E. dysenteríae which is the cause of symptomatic infection, and Entamoeba dispar found only in asymptomatic carriers. Louis Diamond et al (1961) during the 1960s developed an axenic culture medium for E. histolytica which allowed in vivo and in vitro studies. Sargeaunt and Williams (1978) distinguished for the first time E. histolytica strains by isoenzyme electrophoresis, thus confirming thatE. hystolytica was indeed a species complex comprising both pathogenic and non-pathogenic species. William Petri et al (1987 demonstrated that the 170 kDa protein with greater antigenicity was the Gal/GalNac-specific lectin. Diamond and Clark (1993) described again Brumpt's original 1925hypothesis, concluding that there was enough evidence to support the existence of two morphologically indistinguishable species, a pathogenic and a nonpathogenic one, corresponding to E. histolytica and Entamoeba dispar respectively. The World Health Organization accepted this hypothesis in 1997.