A 43-Year-Old Brazilian Man with Acute Impairment of Lung Function and Pulmonary Nodules with Features of Electronic Cigarette or Vaping Product Use-Associated Lung Injury (EVALI).

BACKGROUND Electronic smoking devices were created, and their production industrialized, recently. Since their creation, their use has spread widely. This increase in users led to the appearance of a new lung condition. In 2019, the CDC established the criteria for the diagnosis of electronic cigarette or vaping product use-associated lung injury (EVALI) and the eponym EVALI is now widely recognized. The condition results from the inhalation of heated vapor, which damages the large and small airways and alveoli. CASE REPORT This report presents the case of a 43-year-old Brazilian man with acute impairment of lung function, pulmonary nodules on chest computed tomography (CT) and features of EVALI. He was hospitalized after 9 days of respiratory symptoms due to worsening dyspnea, and underwent a bronchoscopy on the same day. His condition evolved into severe hypercapnic respiratory failure that took 3 weeks to improve, and he underwent a surgical lung biopsy that showed an organizing pneumonia pattern. He was discharged after 50 days of hospitalization. Infectious diseases and other lung conditions were ruled out on clinical, laboratory, radiological, epidemiological, and histopathological grounds. CONCLUSIONS In conclusion, we report the unusual presentation of EVALI on chest CT showing nodules instead of a ground-glass pattern, as stated in the CDC definitions of a confirmed case. We also report the progression to a critical clinical state and, after treatment, the evolution to complete recovery. We also draw attention to the difficulties in diagnosing and managing the disease, especially at a time when COVID-19 has emerged.

Long-term respiratory outcomes after COVID-19: a Brazilian cohort study.

Objective: To investigate the prevalence and risk factors for persistent symptoms up to 12 months after hospital discharge in COVID-19 survivors. Methods: This prospective cohort study included patients with COVID-19 discharged from a university hospital in Brazil. Follow-up was performed 2, 6, and 12 months after discharge. Lung function tests and chest computed tomography (CT) were performed 2 months after discharge and were repeated if abnormal. The primary outcomes were the symptoms present, work status, and limitations in daily activities. Results: Eighty-eight patients were included. Dyspnea (54.5%), fatigue (50.0%), myalgia, and muscle weakness (46.6%) were the most common symptoms, which decreased over time. Anxiety was frequent (46.6%) and remained unchanged. One year after discharge, 43.2% of the patients reported limitations in daily activities, and 17.6% had not returned to work. Corticosteroid use was significantly associated with dyspnea and limitations in daily activities. Females had an increased risk of fatigue at the 12-month assessment, with marginal significance after multivariable adjustment. Young age and bronchial wall thickening on admission CT were also risk factors for dyspnea at follow-up. The most common lung function abnormalities were reduced diffusion capacity and small airway disease, which partially improved over time. Conclusions: One year after hospital discharge, more than one-third of patients still had persistent COVID-19-related symptoms, remarkable dyspnea, fatigue, and limitations in daily activities, regardless of acute disease severity. Age, female sex, corticosteroid use during hospitalization, and bronchial thickening on admission CT were associated with an increased risk of sequelae.

Long-term respiratory outcomes after COVID-19: a Brazilian cohort study

[ABSTRACT]. Objective. To investigate the prevalence and risk factors for persistent symptoms up to 12 months after hospi- tal discharge in COVID-19 survivors. Methods. This prospective cohort study included patients with COVID-19 discharged from a university hos- pital in Brazil. Follow-up was performed 2, 6, and 12 months after discharge. Lung function tests and chest computed tomography (CT) were performed 2 months after discharge and were repeated if abnormal. The primary outcomes were the symptoms present, work status, and limitations in daily activities. Results. Eighty-eight patients were included. Dyspnea (54.5%), fatigue (50.0%), myalgia, and muscle weak- ness (46.6%) were the most common symptoms, which decreased over time. Anxiety was frequent (46.6%) and remained unchanged. One year after discharge, 43.2% of the patients reported limitations in daily activ- ities, and 17.6% had not returned to work. Corticosteroid use was significantly associated with dyspnea and limitations in daily activities. Females had an increased risk of fatigue at the 12-month assessment, with mar- ginal significance after multivariable adjustment. Young age and bronchial wall thickening on admission CT were also risk factors for dyspnea at follow-up. The most common lung function abnormalities were reduced diffusion capacity and small airway disease, which partially improved over time. Conclusions. One year after hospital discharge, more than one-third of patients still had persistent COVID-19- related symptoms, remarkable dyspnea, fatigue, and limitations in daily activities, regardless of acute disease severity. Age, female sex, corticosteroid use during hospitalization, and bronchial thickening on admission CT were associated with an increased risk of sequelae.

[RESUMEN]. Objetivo. Investigar la prevalencia y los factores de riesgo de los síntomas persistentes de la COVID-19 hasta 12 meses después del alta hospitalaria en pacientes sobrevivientes de esta enfermedad. Métodos. Este estudio prospectivo de cohorte incluyó pacientes con COVID-19 que recibieron el alta de un hospital universitario en Brasil. El seguimiento se hizo a los 2, 6 y 12 meses del alta. Se realizaron pruebas de función pulmonar y tomografía computarizada de tórax dos meses después del alta y se repitieron si los resul- tados eran anormales. Los resultados primarios investigados fueron síntomas presentes, situación laboral y limitaciones en las actividades diarias. Resultados. Se incluyeron 88 pacientes. Los síntomas más comunes fueron disnea (54,5%), fatiga (50,0%), mialgia y debilidad muscular (46,6%), que disminuyeron con el tiempo. La ansiedad fue frecuente (46,6%) y se mantuvo sin cambios. Un año después del alta, 43,2% de los pacientes notificaron limitaciones en las actividades diarias, y 17,6% no se había reincorporado al trabajo. El consumo de corticosteroides se asoció significativamente con disnea y limitaciones en las actividades diarias. Las mujeres tuvieron un mayor riesgo de fatiga en la evaluación a los 12 meses, con una importancia marginal después del ajuste multivariable. También fueron factores de riesgo de disnea en el seguimiento: edad temprana y engrosamiento de las pare- des bronquiales en la tomografía computarizada al momento del ingreso hospitalario. Las anomalías más comunes de la función pulmonar fueron la reducción de la capacidad de difusión y la enfermedad de las vías respiratorias pequeñas, que mejoraron parcialmente con el tiempo. Conclusiones. Un año después del alta hospitalaria, más de un tercio de los pacientes todavía tenían sín- tomas persistentes relacionados con la COVID-19, disnea notable, fatiga y limitaciones en las actividades diarias, independientemente de la gravedad aguda de la enfermedad. La edad, el sexo femenino, el uso de corticosteroides durante la hospitalización y el engrosamiento bronquial en la tomografía computarizada al momento del ingreso hospitalario se asociaron con un mayor riesgo de secuelas.

[RESUMO]. Objetivo. Investigar a prevalência e os fatores de risco para sintomas persistentes por até 12 meses após a alta hospitalar entre sobreviventes da COVID-19. Métodos. Este estudo de coorte prospectivo incluiu pacientes com COVID-19 que receberam alta de um hos- pital universitário do Brasil. O acompanhamento foi realizado 2, 6 e 12 meses após a alta. Testes de função pulmonar e tomografia computadorizada (TC) do tórax foram realizados 2 meses após a alta hospitalar e repetidos em caso de resultados alterados. Os desfechos primários foram os sintomas presentes, a situação de trabalho e as limitações nas atividades diárias. Resultados. Foram incluídos 88 pacientes. Dispneia (54,5%), fadiga (50,0%), mialgia e fraqueza muscular (46,6%) foram os sintomas mais comuns, que diminuíram com o tempo. A ansiedade era frequente (46,6%) e permaneceu inalterada. Um ano após a alta, 43,2% dos pacientes relatavam limitações nas atividades diárias e 17,6% não haviam retornado ao trabalho. O uso de corticosteroides estava significativamente asso- ciado à dispneia e a limitações nas atividades diárias. Pacientes do sexo feminino tinham um risco maior de fadiga na avaliação de 12 meses, com significância marginal após ajuste multivariado. A idade jovem e o espessamento da parede brônquica na TC de admissão também eram fatores de risco para dispneia no acompanhamento. As alterações mais comuns da função pulmonar foram capacidade de difusão reduzida e doença das pequenas vias aéreas, que melhoraram parcialmente com o tempo. Conclusões. Um ano após a alta hospitalar, mais de um terço dos pacientes ainda apresentava sintomas persistentes relacionados à COVID-19, dispneia marcante, fadiga e limitações nas atividades diárias, inde- pendentemente da gravidade da doença aguda. A idade, o sexo feminino, o uso de corticosteroides durante a internação e o espessamento brônquico na TC de admissão estavam associados a um maior risco de sequelas.

Long-term respiratory outcomes after COVID-19: a Brazilian cohort study / Resultados respiratorios a largo plazo tras la COVID-19: estudio de cohorte en Brasil / Desfechos respiratórios de longo prazo pós-COVID-19: estudo de coorte brasileiro

ABSTRACT Objective. To investigate the prevalence and risk factors for persistent symptoms up to 12 months after hospital discharge in COVID-19 survivors. Methods. This prospective cohort study included patients with COVID-19 discharged from a university hospital in Brazil. Follow-up was performed 2, 6, and 12 months after discharge. Lung function tests and chest computed tomography (CT) were performed 2 months after discharge and were repeated if abnormal. The primary outcomes were the symptoms present, work status, and limitations in daily activities. Results. Eighty-eight patients were included. Dyspnea (54.5%), fatigue (50.0%), myalgia, and muscle weakness (46.6%) were the most common symptoms, which decreased over time. Anxiety was frequent (46.6%) and remained unchanged. One year after discharge, 43.2% of the patients reported limitations in daily activities, and 17.6% had not returned to work. Corticosteroid use was significantly associated with dyspnea and limitations in daily activities. Females had an increased risk of fatigue at the 12-month assessment, with marginal significance after multivariable adjustment. Young age and bronchial wall thickening on admission CT were also risk factors for dyspnea at follow-up. The most common lung function abnormalities were reduced diffusion capacity and small airway disease, which partially improved over time. Conclusions. One year after hospital discharge, more than one-third of patients still had persistent COVID-19-related symptoms, remarkable dyspnea, fatigue, and limitations in daily activities, regardless of acute disease severity. Age, female sex, corticosteroid use during hospitalization, and bronchial thickening on admission CT were associated with an increased risk of sequelae.

RESUMEN Objetivo. Investigar la prevalencia y los factores de riesgo de los síntomas persistentes de la COVID-19 hasta 12 meses después del alta hospitalaria en pacientes sobrevivientes de esta enfermedad. Métodos. Este estudio prospectivo de cohorte incluyó pacientes con COVID-19 que recibieron el alta de un hospital universitario en Brasil. El seguimiento se hizo a los 2, 6 y 12 meses del alta. Se realizaron pruebas de función pulmonar y tomografía computarizada de tórax dos meses después del alta y se repitieron si los resultados eran anormales. Los resultados primarios investigados fueron síntomas presentes, situación laboral y limitaciones en las actividades diarias. Resultados. Se incluyeron 88 pacientes. Los síntomas más comunes fueron disnea (54,5%), fatiga (50,0%), mialgia y debilidad muscular (46,6%), que disminuyeron con el tiempo. La ansiedad fue frecuente (46,6%) y se mantuvo sin cambios. Un año después del alta, 43,2% de los pacientes notificaron limitaciones en las actividades diarias, y 17,6% no se había reincorporado al trabajo. El consumo de corticosteroides se asoció significativamente con disnea y limitaciones en las actividades diarias. Las mujeres tuvieron un mayor riesgo de fatiga en la evaluación a los 12 meses, con una importancia marginal después del ajuste multivariable. También fueron factores de riesgo de disnea en el seguimiento: edad temprana y engrosamiento de las paredes bronquiales en la tomografía computarizada al momento del ingreso hospitalario. Las anomalías más comunes de la función pulmonar fueron la reducción de la capacidad de difusión y la enfermedad de las vías respiratorias pequeñas, que mejoraron parcialmente con el tiempo. Conclusiones. Un año después del alta hospitalaria, más de un tercio de los pacientes todavía tenían síntomas persistentes relacionados con la COVID-19, disnea notable, fatiga y limitaciones en las actividades diarias, independientemente de la gravedad aguda de la enfermedad. La edad, el sexo femenino, el uso de corticosteroides durante la hospitalización y el engrosamiento bronquial en la tomografía computarizada al momento del ingreso hospitalario se asociaron con un mayor riesgo de secuelas.

RESUMO Objetivo. Investigar a prevalência e os fatores de risco para sintomas persistentes por até 12 meses após a alta hospitalar entre sobreviventes da COVID-19. Métodos. Este estudo de coorte prospectivo incluiu pacientes com COVID-19 que receberam alta de um hospital universitário do Brasil. O acompanhamento foi realizado 2, 6 e 12 meses após a alta. Testes de função pulmonar e tomografia computadorizada (TC) do tórax foram realizados 2 meses após a alta hospitalar e repetidos em caso de resultados alterados. Os desfechos primários foram os sintomas presentes, a situação de trabalho e as limitações nas atividades diárias. Resultados. Foram incluídos 88 pacientes. Dispneia (54,5%), fadiga (50,0%), mialgia e fraqueza muscular (46,6%) foram os sintomas mais comuns, que diminuíram com o tempo. A ansiedade era frequente (46,6%) e permaneceu inalterada. Um ano após a alta, 43,2% dos pacientes relatavam limitações nas atividades diárias e 17,6% não haviam retornado ao trabalho. O uso de corticosteroides estava significativamente associado à dispneia e a limitações nas atividades diárias. Pacientes do sexo feminino tinham um risco maior de fadiga na avaliação de 12 meses, com significância marginal após ajuste multivariado. A idade jovem e o espessamento da parede brônquica na TC de admissão também eram fatores de risco para dispneia no acompanhamento. As alterações mais comuns da função pulmonar foram capacidade de difusão reduzida e doença das pequenas vias aéreas, que melhoraram parcialmente com o tempo. Conclusões. Um ano após a alta hospitalar, mais de um terço dos pacientes ainda apresentava sintomas persistentes relacionados à COVID-19, dispneia marcante, fadiga e limitações nas atividades diárias, independentemente da gravidade da doença aguda. A idade, o sexo feminino, o uso de corticosteroides durante a internação e o espessamento brônquico na TC de admissão estavam associados a um maior risco de sequelas.

Age and Interleukin-15 Levels Are Independently Associated With Intima-Media Thickness in Obesity-Related NAFLD Patients.

Common carotid intima-media thickness (IMT) represents a functional and structural marker of early, precocious, and subclinical atherosclerosis, independently from the carotid plaque. Macrophage cells, which have been detected in adipose tissue and atherosclerotic plaques, are regulated by interleukin-15 (IL-15). At the light of the conflicting results concerning the role of IL-15 in atherosclerosis, the aim of the study was to retrospectively evaluate in a population of 80 obese patients, with median age of 46 years (IQR 34-53 years), with a low rate of comorbidities but with non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis (HS), the relationship between IMT and serum concentrations of IL-15. Anthropometric measures, metabolic profile, and serum inflammatory markers, as well as the levels of IL-15, MCP-1, b FGF, and GM-CSF, were analyzed by a bead-based assay. IMT, HS, subcutaneous, and visceral adipose tissues were detected by ultrasonography. The IL-15 levels of the obese patients were increased with respect to those of 44 young healthy subjects, i.e., 2.77 (1.21-4.8) vs. 1.55 (1-2.4) pg/mL (P = 0.002). In the univariate analysis, IL-15 levels were associated to IMT and to those of MCP-1, b FGF, and GM-CSF, without any relation to other inflammatory markers such as CRP and ferritin, except fibrinogen. In the multivariate analysis, after adjusting the HS severity for the extent of visceral adiposity, a dramatic change in prediction of IMT by HS was shown (ß from 0.29 to 0.10, P from 0.008 to 0.37). When the visceral adipose tissue was combined with IL-15, on the one hand, and the well-known coronary artery disease (CAD) risk factors-i.e., age, gender, smoking status, HDL-cholesterol concentrations, triglycerides levels, and HOMA-on the other, only age and IL-15 remained the predictors of IMT (ß = 0.60, P = 0.0001 and ß = 0.25, P = 0.024, respectively). There was no association of IL-15 with various anthropometric parameters nor with body fat distribution and severity of HS, also after adjusting for age. Age is resulted to be the main factor in the prediction of IMT and thus of early atherosclerosis. The prediction of IMT by IL-15 coupled with the lack of prediction by the well-known CAD risks is in agreement with recent data, which emphasizes the main role of the immune system in the onset/worsening of atherosclerosis, even though the role of visceral adiposity should be further deepened. Age and IL-15 levels were both predictors of early atherosclerosis in this population of obese patients with NAFLD, suggesting a possible role of this cytokine in the atherosclerosis process.

Copper concentrations are prevalently associated with antithrombin III, but also with prothrombin time and fibrinogen in patients with liver cirrhosis: A cross-sectional retrospective study.

BACKGROUND: Concerning the link between copper excess and the pathogenesis of chronic liver diseases, its retention is reckoned to develop as a complication of cholestasis. Recently, it has been found that cholestatic liver injury involves largely inflammatory cell-mediated liver cell necrosis, with consequent reduced hepatic mass, more than occurring through direct bile acid-induced apoptosis. On the other hand, interference with protein synthesis could be expected to result, ending in an altered ability of the liver to retain copper. Little is known about the association between serum copper and clotting factors in cirrhotics. We aimed at studying a possible relationship between increased levels of copper and an aspect of the haemostatic process in liver cirrhosis patients, assessing an index of protein synthesis (albumin) and parameters of protein synthesis/coagulation/fibrinolysis, such as prothrombin time (PT), antithrombin (AT) III and fibrinogen. METHODS: Records from 85 patients suffering from liver cirrhosis of various aetiology and different severity were retrospectively examined. Serum concentrations of copper were determined by atomic absorption spectrophotometer. An index of protein synthesis, such as albumin and parameters of both synthesis and coagulation/hypercoagulation such as PT %, AT III%, levels of fibrinogen were taken into account to study possible correlations to serum copper. The severity of cirrhosis was evaluated by the Child-Pugh (C-P) classification. The relationship among variables were studied by linear regression. RESULTS: Copper levels of patients suffering from liver cirrhosis were increased respect to those of controls, 102.7+/-28.7 versus 80.4+/-19.5 mcg/dL, (P = .0009), independently from disease severity, and were positively predicted by PT% (P = 0. 017), fibrinogen (P = 0.007) and AT III% (P = 0.000), at linear regression. Among the previous parameters, to which serum albumin was added, the unique predictor of copper levels was AT III%, at multiple regression (P = 0. 010); AT III% was negatively predicted by the C-P classification (P = 0.000); copper levels, adjusted for C-P classification, were predicted by AT III% (P = 0.020) and fibrinogen concentrations, but not by PT% (P = 0.09). CONCLUSION: The copper concentration is reckoned as responsible for production of the hydroxyl radicals. On the basis that oxidants may enhance the activity of the extrinsic coagulation cascade, ultimately leading to thrombin formation, via their combined effects on stimulation of tissue factor activity and inhibition of fibrinolytic pathways, the positive relationship of copper to coagulation/hypercoagulation parameters (mainly AT III) in our research could find a plausible interpretation.

Diagnosis of tuberculosis: a consensus statement from the Brazilian Thoracic Association.

Early, accurate diagnosis of tuberculosis is one of the major pillars of the control of the disease. The purpose of this consensus statement is to provide health professionals with the most current, useful evidence for the diagnosis of tuberculosis in Brazil. To that end, the Tuberculosis Committee of the Brazilian Thoracic Association brought together 14 members of the Association with recognized expertise in tuberculosis in Brazil to compose the statement. A nonsystematic review of the following topics was carried out: clinical diagnosis, bacteriological diagnosis, radiological diagnosis, histopathological diagnosis, diagnosis of tuberculosis in children, and diagnosis of latent tuberculosis infection.

Association of NAFLD and Insulin Resistance with Non Metastatic Bladder Cancer Patients: A Cross-Sectional Retrospective Study.

Among risk factors (apart from smoking) likely involved in bladder cancer (BCa), metabolic syndrome (MS), obesity and type 2 diabetes mellitus (T2DM) have been explored with contrasting results. In spite of these studies, there is little data on the association between nonalcoholic fatty liver disease (NAFLD), its main driver, i.e., insulin resistance (IR), and BCa. Implanting a cross-sectional retrospective study we tried to investigate both NAFLD and IR prevalence in a hospital based population of BCa patients. We studied laboratory data from 204 patients with histologically confirmed non metastatic BCa and 50 subjects with no BCa, but with bladder diseases (no Ca BD). We evaluated the presence of NAFLD by the triglycerides/glucose Index (TyG Index), using a cut-off of 0.59 and by the Aspartate Aminotransferase/Alanine Aminotransferase AST/ALT ratio. IR was assessed by the same TyG Index (cut-off 4.68) and the triglycerides/High-Density Lipoprotein HDL ratio (cut-off 2.197). The diagnosis of impaired fasting glucose (IFG), condition of prediabetes, as well as that of T2DM was assessed according to canonical guidelines. The TyG Index predicted NAFLD presence in both groups (p = 0.000), but the BCa group showed a major percentage of NAFLD cases with respect to no Ca BD group (59% versus 40%). A greater proportion of IR (47%) in BCa group than in no Ca BD one (37%) was evidenced by the TyG Index with its median value significantly different (p = 0.0092). This high rate of IR in the BCa group was confirmed by the triglycerides/HDL ratio (p = 0.02). Prediabetes and T2DM were more prevalent in the BCa group than no Ca BD group (p = 0.024). In this study a consistent NAFLD presence was found in BCa patients. This is an important comorbidity factor that deserves further consideration in prospective studies. The higher prevalence of NAFLD, IR, prediabetes and T2DM in the BCa group evidences the need that these disorders should be reckoned as adjunct factors that could impact on this cancerous disease.

Diagnosis of tuberculosis: a consensus statement from the Brazilian Thoracic Association / Consenso sobre o diagnóstico da tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia

ABSTRACT Early, accurate diagnosis of tuberculosis is one of the major pillars of the control of the disease. The purpose of this consensus statement is to provide health professionals with the most current, useful evidence for the diagnosis of tuberculosis in Brazil. To that end, the Tuberculosis Committee of the Brazilian Thoracic Association brought together 14 members of the Association with recognized expertise in tuberculosis in Brazil to compose the statement. A nonsystematic review of the following topics was carried out: clinical diagnosis, bacteriological diagnosis, radiological diagnosis, histopathological diagnosis, diagnosis of tuberculosis in children, and diagnosis of latent tuberculosis infection.

RESUMO O diagnóstico precoce e adequado da tuberculose é um dos pilares mais importantes no controle da doença. A proposta deste consenso brasileiro é apresentar aos profissionais da área de saúde um documento com as evidências mais atuais e úteis para o diagnóstico da tuberculose. Para tanto, a Comissão de Tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia reuniu 14 membros da Sociedade com reconhecida experiência em tuberculose no Brasil. Foi realizada uma revisão não sistemática dos seguintes tópicos: diagnóstico clínico, diagnóstico bacteriológico, diagnóstico radiológico, diagnóstico histopatológico, diagnóstico da tuberculose na criança e diagnóstico da tuberculose latente.

Could SCGF-Beta Levels Be Associated with Inflammation Markers and Insulin Resistance in Male Patients Suffering from Obesity-Related NAFLD?

One of the pathologic hallmarks of obesity is macrophage infiltration of adipose tissue that has been confirmed as source of multipotent adult stem cells. Stem cell growth factor-beta (SCGF-ß) shows activity on granulocyte/macrophage progenitor cells in combination with granulocyte macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). Obesity-associated inflammation induces insulin resistance (IR), which is central to nonalcoholic fatty liver disease (NAFLD) or hepatic steatosis (HS). We searched for relationship between levels of SCGF-ß and those of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-ß (TNF-ß), interleukin-12p40 (IL-12p40), interleukin-10 (IL-10), ferritin, GM-CSF and M-CSF and between SCGF-ß concentrations and IR in obese patients with HS. Eighty obese patients were retrospectively studied. Serum cytokines levels were appreciated by magnetic bead-based multiplex immunoassays. IR was evaluated by homeostatic model assessment (HOMA), HOMA-derived ß-cell function (HOMA-B%), quantitative insulin sensitivity check Index (QUICKI) and single point insulin sensitivity estimator (SPISE). HS and spleen volume were assessed by ultrasonography (US). SCGF-ß and IL-6 levels predicted HOMA values (p = 0.032 and 0.041, respectively) only in males. In male patients, CRP and IL-6 levels (p = 0.007) predicted SCGF-ß concentrations (p = 0.03 and 0.007, respectively), which in turn predicted HS at US, p = 0.037. SCGF-ß levels were linked to IR and HS severity with the mediation role of CRP. IL-10 levels negatively predicted SCGF-ß concentrations (p = 0.033). M-CSF levels predicted serum concentration of both TNF-ß and IL-12p40 (p = 0.00), but did not predict serum IL-10 (p = 0.30). Prediction of HOMA values by SCGF-ß levels, likely mediated by markers of inflammation, characterizes this study, shedding some light on mechanisms inducing/worsening IR of male patients with obesity-related NAFLD.

Troponin Levels Relate to CRP Concentrations in Patients With NAFLD on Maintenance Haemodialysis: A Retrospective Study.

INTRODUCTION: Several studies have shown that high sensitivity cardiac troponin (hs-cTnT) levels are elevated in patients suffering from end-stage renal disease (ESRD), even in the absence of clinical signs and instrumental features of symptomatic acute coronary syndrome (ACS). In patients undergoing haemodialysis because of ESRD, nephrologists bear witness to this increase, whose origin and clinical impact are not yet well defined. METHODS: By a retrospective study, we evaluated data from records of 70 patients with ESRD on haemodialysis, all of them with a history of NAFLD, not suffering for at least 3 months from symptomatic angina and without a history of ischemic heart disease in the same period. RESULTS: Hs-cTnT and C-reactive protein (CRP) levels both increased and were correlated, rho = 0.34, P = 0.004. The correlation coefficient between troponin and age was significant, rho = 0.47, P = 0.0001. Serum concentrations of hs-cTnT for the whole population were positively predicted by CRP levels, P = 0.004. On separation of the population by gender, significant correlation between hs-cTnT and CRP was not found in women and was only present in men, P = 0.66 and P = 0.000, respectively. DISCUSSION: The assessment of hs-cTnT levels could represent a biological marker in particular subgroups of haemodialysis patients, especially for male patients with higher CRP, those at greater risk of silent myocardial ischemia and future major adverse cardiac events. CONCLUSIONS: The evaluation of hs-cTnT in haemodialysed patients with NAFLD could indicate that men with higher CRP should undergo close monitoring in order to adopt specific therapy.

Nonalcoholic Fatty Liver Disease: A Challenge from Mechanisms to Therapy.

Focusing on previously published mechanisms of non-alcoholic fatty liver disease (NAFLD), their uncertainty does not always permit a clear elucidation of the grassroot alterations that are at the basis of the wide-spread illness, and thus curing it is still a challenge. There is somehow exceptional progress, but many controversies persist in NAFLD research and clinical investigation. It is likely that hidden mechanisms will be brought to light in the near future. Hereby, the authors present, with some criticism, classical mechanisms that stand at the basis of NAFLD, and consider contextually different emerging processes. Without ascertaining these complex interactions, investigators have a long way left ahead before finding an effective therapy for NAFLD beyond diet and exercise.

Is There a Link between Basal Metabolic Rate, Spleen Volume and Hepatic Growth Factor Levels in Patients with Obesity-Related NAFLD?

BACKGROUND: Recent pieces of research point to a link between basal metabolic rate (BMR) and non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis (HS). The spleen in obese patients is associated with the cardiovascular system. Enlargement of the spleen is suggestive of nonalcoholic steatohepatitis (NASH). Patients with NASH present an increase in growth factor (HGF) as well as those with advanced heart failure. Interleukin-16 and interleukin-12p40 levels were found to correlate significantly with BMI, and waist circumference. AIM: We tried to find a relationship between BMR, spleen length and HGF. METHODS: We analysed retrospective data from 80 obese patients with NAFLD. We evaluated indices of indirect calorimetry by the bioimpendance analysis; carotid intima-media thickness (IMT), spleen length (SLD) and HS by ultrasonography; serum HGF, IL-16, IL-12p40 and IL-6 concentrations by a magnetic bead-based multiplex immunoassays and the severity of NAFLD by BARD score > 2. RESULTS: HGF levels of the obese were higher than those of controls, p < 0.001. At linear regression, BMR was foreseen by spleen length (p < 0.001), which was predicted by HGF (p = 0.04). BMR was predicted by IL-16 (p = 0.005), which predicted HGF, p = 0.034. Only fat mass, among other factors, predicted early atherosclerosis, p = 0.017; IL-12p40 did not predict IMT, HGF and BMR (p = 0.57, 0.09 and 0.59, respectively). The BARD score > 2 was negatively predicted by BMR and FFM (p =0.032 and 0.031, respectively), at the logistic regression. Interesting findings at the extended regression (mediation effect) were: IL-16 was likely causal in predicting BMR by HGF levels; HGF was influential in predicting BMR by SLD level. HS was predicted by SLD in males (p = 0.014), of advanced age (p < 0.001) and by BMR (p < 0.001). IL-6 concentrations, but not BMR were influential in the prediction of HS by SLD. CONCLUSION: These data reinforce the concept that the immune system is a sensor of the metabolic state, showing a link between HGF levels and BMR, which is mediated by IL-16 (cytokine inducing a cascade of inflammatory factors), and ascertaining the influential effect of the spleen, as main immune organ.

Do Transferrin Levels Predict Haemodialysis Adequacy in Patients with End-Stage Renal Disease?

BACKGROUND: Since haemodialysis is a lifesaving therapy, adequate control measures are necessary to evaluate its adequacy and to constantly adjust the dose to reduce hospitalisation and prolong patient survival. Malnutrition is common in haemodialysis patients and closely related to morbidity and mortality. Patients undergoing haemodialysis have a high prevalence of protein-energy malnutrition and inflammation, along with abnormal iron status. The haemodialysis dose delivered is an important predictor of patient outcome. AIM: To evaluate through haemodialysis adequacy, which parameter(s), if any, better predict Kt/V, among those used to assess nutritional status, inflammation response, and iron status. METHODS: We retrospectively studied 78 patients undergoing haemodialysis due to end-stage renal disease. As parameters of nutritional status, geriatric nutritional risk index (GNRI), transferrin levels, lymphocyte count, and albumin concentration were analysed. As signs of inflammation, C reactive protein (CRP) levels and ferritin concentrations were studied as well. Iron status was evaluated by both transferrin and ferritin levels, as well as by haemoglobin (Hb) concentration. RESULTS: The core finding of our retrospective study is that transferrin levels predict the adequacy of haemodialysis expressed as Kt/V; the latter is the only predictor (P = 0.001) when adjusting for CRP concentrations, a solid marker of inflammation, and for ferritin levels considered an iron-storage protein, but also a parameter of inflammatory response. DISCUSSION AND CONCLUSION: In keeping with the results of this study, we underline that the use of transferrin levels to assess haemodialysis quality combine into a single test the evaluation of the three most important factors of protein-energy wasting.

Neutrophil CD64 expression levels in IGRA-positive individuals distinguish latent tuberculosis from active disease.

BACKGROUND: CD64 (FcγR1) is a high-affinity receptor for monomeric IgG1 and IgG3. Circulating neutrophils express very low amounts of CD64 on their surface. OBJECTIVES: Our primary aim was to investigate the utility of neutrophil CD64 surface expression as a biomarker of active pulmonary tuberculosis (TB). We hypothesised that elevated neutrophil CD64 expression in TB infection would be associated with interferon gamma (IFN-γ) as an inducer of CD64 expression. METHODS: The expression level of CD64 per neutrophil (PMN CD64 index) was quantitatively measured with flow cytometry using a Leuko64 kit in samples from patients with TB and latent TB infection (LTBI) as well as healthy controls, as part of a prospective cohort study in Brazil. FINDINGS: The PMN CD64 index in patients with TB was higher than that in healthy controls and LTBI. Receiver operating characteristic curve analyses determined that the PMN CD64 index could discriminate patients with TB from those with LTBI and healthy individuals. PMN CD64 index levels returned to baseline levels after treatment. CONCLUSIONS: The positive regulation of CD64 expression in circulating neutrophils of patients with active TB could represent an additional biomarker for diagnosis of active TB and could be used for monitoring individuals with LTBI before progression of TB disease.

Interferon-alpha 2 but not Interferon-gamma serum levels are associated with intramuscular fat in obese patients with nonalcoholic fatty liver disease.

BACKGROUND: Intramuscular triglycerides (IMTGs) represent an important energy supply and a dynamic fat-storage depot that can expand during periods of elevated lipid availability and a fatty acid source. Ultrasonography (US) of human skeletal muscles is a practical and reproducible method to assess both IMTG presence and entity. Although a crosstalk between cytokines in skeletal muscle and adipose tissue has been suggested in obesity, condition leading to hepatic steatosis (HS) or better defined as nonalcoholic fatty liver disease and cancer, there are still questions to be answered about the role of interferons (IFNs), alpha as well as gamma, and IMTG in obesity. We aimed at discovering any correlation between IFNs and IMTG. METHODS: We analysed anthropometric data, metabolic parameters and imaging features of a population of 80 obese subjects with low-prevalence of co-morbidities but HS in relation to IFNs serum levels. A population of 38 healthy subjects (21 males) served as controls. The levels of serum IFNs were detected by a magnetic bead-based multiplex immunoassays. RESULTS: Serum concentrations of IFN-alpha 2 were increased, while serum levels of IFN-gamma were decreased confronted with those of controls; the severity of IMTG, revealed at US as Heckmatt scores, was inversely predicted by IFN-alpha 2 serum concentrations; IMTG scores were not predicted by serum levels of IFN-gamma; IMTG scores were predicted by HS severity, ascertained at US; HS severity was predicted by visceral adipose tissue, assessed by US, but the latter was not instrumental to IMTG. DISCUSSION AND CONCLUSION: This study has added some pieces of observation about the cytokine network regulating the interplay between IMTG and obesity in obese patients with HS.

Neutrophil CD64 expression levels in IGRA-positive individuals distinguish latent tuberculosis from active disease

BACKGROUND CD64 (FcγR1) is a high-affinity receptor for monomeric IgG1 and IgG3. Circulating neutrophils express very low amounts of CD64 on their surface. OBJECTIVES Our primary aim was to investigate the utility of neutrophil CD64 surface expression as a biomarker of active pulmonary tuberculosis (TB). We hypothesised that elevated neutrophil CD64 expression in TB infection would be associated with interferon gamma (IFN-γ) as an inducer of CD64 expression. METHODS The expression level of CD64 per neutrophil (PMN CD64 index) was quantitatively measured with flow cytometry using a Leuko64 kit in samples from patients with TB and latent TB infection (LTBI) as well as healthy controls, as part of a prospective cohort study in Brazil. FINDINGS The PMN CD64 index in patients with TB was higher than that in healthy controls and LTBI. Receiver operating characteristic curve analyses determined that the PMN CD64 index could discriminate patients with TB from those with LTBI and healthy individuals. PMN CD64 index levels returned to baseline levels after treatment. CONCLUSIONS The positive regulation of CD64 expression in circulating neutrophils of patients with active TB could represent an additional biomarker for diagnosis of active TB and could be used for monitoring individuals with LTBI before progression of TB disease.

Corrigendum to "Circulating Levels of Sirtuin 4, a Potential Marker of Oxidative Metabolism, Related to Coronary Artery Disease in Obese Patients Suffering from NAFLD, with Normal or Slightly Increased Liver Enzymes".

[This corrects the article DOI: 10.1155/2014/920676.].

Diagnosis and Management of Systemic Endemic Mycoses Causing Pulmonary Disease.

Systemic endemic mycoses cause high rates of morbidity and mortality in certain regions of the world and the real impact on global health is not well understood. Diagnosis and management remain challenging, especially in low-prevalence settings, where disease awareness is lacking. The main challenges include the variability of clinical presentation, the fastidious and slow-growing nature of the fungal pathogens, the paucity of diagnostic tests, and the lack of options and toxicity of antifungal drugs. Coccidioidomycosis and paracoccidioidomycosis are restricted to the Americas only, and while histoplasmosis and blastomycosis also occur predominantly in the Americas, these mycoses have also been reported on other continents, especially in sub-Saharan Africa. Talaromycosis is endemic in tropical and subtropical regions in South-East Asia and southern China. Systemic endemic mycoses causing pulmonary disease are usually acquired via the airborne route by inhalation of fungal spores. Infections can range from asymptomatic or mild with flu-like illnesses to severe pulmonary or disseminated diseases. Skin involvement is frequent in patients with paracoccidioidomycosis, blastomycosis, sporotrichosis, and talaromycosis and manifests as localized lesions or diffuse nodules in disseminated disease, but can also occur with other endemic mycoses. Culture and/or characteristic histopathology from clinical samples is the diagnostic standard for endemic mycoses. Immunological assays are often not available for the diagnosis of most endemic mycoses and molecular amplification methods for the detection of fungal nucleic acids are not standardized at present. The first-line treatment for mild to moderate histoplasmosis, paracoccidioidomycosis, blastomycosis, sporotrichosis, and talaromycosis is itraconazole. Severe illness is treated with amphotericin B. Patients with severe coccidioidomycosis should receive fluconazole. Treatment duration depends on the specific endemic mycosis, the severity of disease, and the immune status of the patient, ranging between 6 weeks and lifelong treatment.