Fecal Fungal Microbiota (Mycobiome) Study as a Potential Tool for Precision Medicine in Inflammatory Bowel Disease.

There is growing evidence of the role of fungal microbiota in the pathogenesis of inflammatory bowel disease (IBD). Fungi can exert direct pro-inflammatory effects or modify the bacterial composition via interkingdom interactions. Although several studies have demonstrated alterations in the fecal fungal microbiota composition in IBD, there is a wide variation in the mycobiome in different populations, with no definite pattern that can define the mycobiome in IBD having yet been identified. Recent work has suggested that characterizing the fecal fungal composition may influence therapeutic decisions and help to predict outcomes in a subset of IBD patients. In this study, we review the current literature on the emerging role of the fecal mycobiome as a potential tool for precision medicine in IBD.

Next-Generation Biomarkers for Cholangiocarcinoma.

The increasing mortality rates of cholangiocarcinoma (CCA) registered during the last decades are, at least in part, a result of the lack of accurate non-invasive biomarkers for early disease diagnosis, making the identification of patients who might benefit from potentially curative approaches (i.e., surgery) extremely challenging. The obscure CCA pathogenesis and associated etiological factors, as well as the lack of symptoms in patients with early tumor stages, highly compromises CCA identification and to predict tumor development in at-risk populations. Currently, CCA diagnosis is accomplished by the combination of clinical/biochemical features, radiological imaging and non-specific serum tumor biomarkers, although a tumor biopsy is still needed to confirm disease diagnosis. Furthermore, prognostic and predictive biomarkers are still lacking and urgently needed. During the recent years, high-throughput omics-based approaches have identified novel circulating biomarkers (diagnostic and prognostic) that might be included in large, international validation studies in the near future. In this review, we summarize and discuss the most recent advances in the field of biomarker discovery in CCA, providing new insights and future research directions.

Current impact of viral hepatitis on liver cancer development: The challenge remains.

Chronic infections due to hepatitis B and hepatitis C viruses are responsible for most cases of hepatocellular carcinoma (HCC) worldwide, and this association is likely to remain during the next decade. Moreover, viral hepatitis-related HCC imposes an important burden on public health in terms of disability-adjusted life years. In order to reduce such a burden, some major challenges must be faced. Universal vaccination against hepatitis B virus, especially in the neonatal period, is probably the most relevant primary preventive measure against the development of HCC. Moreover, considering the large adult population already infected with hepatitis B and C viruses, it is also imperative to identify these individuals to ensure their access to treatment. Both hepatitis B and C currently have highly effective therapies, which are able to diminish the risk of development of liver cancer. Finally, it is essential for individuals at high-risk of HCC to be included in surveillance programs, so that tumors are detected at an early stage. Patients with hepatitis B or C and advanced liver fibrosis or cirrhosis benefit from being followed in a surveillance program. As hepatitis B virus is oncogenic and capable of leading to liver cancer even in individuals with early stages of liver fibrosis, other high-risk groups of patients with hepatitis B are also candidates for surveillance. Considerable effort is required concerning these strategies in order to decrease the incidence and the mortality of viral hepatitis-related HCC.

Hepatitis E virus infection in pregnant women, Argentina.

BACKGROUND: Hepatitis E virus (HEV) infection is an important cause of acute hepatitis worldwide. In pregnant women, HEV can cause more severe symptoms, with high rates of fatal hepatic failure in endemic countries. However, HEV prevalence and circulation among pregnant women from South America is almost unknown. We aimed to investigate HEV infection in pregnant women for the first time in Argentina. METHODS: IgG and IgM anti-HEV antibodies and RNA-HEV were investigated (by ELISA assays and RT-Nested-PCR, respectively) in 202 serum samples from pregnant women collected in the central region of Argentina between 2015 and 2017. A control group of 155 non-pregnant women was included (year 2018). RESULTS: The IgG anti-HEV positivity rate was 8.4% (17/202), higher than the 2.6% (4/155) obtained for the non-pregnant women control group, and showing association between pregnancy and HEV infection (p = 0.023, OR = 3.5, CI95% = 1.1-10.5). Women younger than 25 years old presented higher levels of antibodies, and there were no differences in the prevalences between trimesters of pregnancy. Two samples were reactive for IgM anti-HEV, showing recent infections, although no symptoms were registered in these patients. All samples were negative for RNA-HEV amplification. CONCLUSIONS: HEV produces infections in pregnant women from Argentina, alerting health teams to consider it as a possible cause of liver disease.

Unexpected high seroprevalence of hepatitis E virus in patients with alcohol-related cirrhosis.

INTRODUCTION: Little is known about hepatitis E virus (HEV) infection in patients with cirrhosis. The aim of the present study was to describe the frequency of HEV infection and associated risk factors in patients with cirrhosis from Argentina. MATERIALS AND METHODS: We evaluated HEV seroprevalence (IgG anti-HEV) and acute infections (IgM and RNA) in patients with cirrhosis (n = 140) vs. healthy controls (n = 300). Additionally, we compared the same outcomes in individuals with alcohol-related cirrhosis (n = 43) vs. patients with alcohol use disorder (without cirrhosis, n = 72). RESULTS: The overall HEV seroprevalence in the cohort of subjects with cirrhosis was 25% (35/140), compared to 4% in the healthy control group [12/300; OR = 8; (95% CI = 4-15.99); p<0.05]. HEV seropositivity was significantly higher in alcohol-related cirrhosis compared to other causes of cirrhosis [39.5% vs. 12.4%; OR = 4.71; (95% CI = 1.9-11.6); p<0.05] and to healthy controls [OR = 15.7; (95% CI = 6.8-36.4); p = 0.0001]. The HEV seroprevalence in alcoholic-related cirrhosis vs. with alcohol use disorder was 39.5% vs. 12.5% [OR = 4.58; (95% CI = 1.81-11.58); p<0.001]. CONCLUSION: We found a high seroprevalence of HEV in patients with cirrhosis and in individuals with alcohol use disorder. The simultaneous presence of both factors (cirrhosis + alcohol) showed more association to HEV infection. Larger studies with prospective follow up are needed to further clarify this interaction.

Streptococcus agalactiae bacteremia in non-pregnant adult patients at two teaching hospitals / Bacteriemia por Streptococcus agalactiae en pacientes adultos y mujeres no embarazadas de dos hospitales universitarios

Streptococcus agalactiae or group B streptococcus (GBS) is a frequent pathogen in immunocompromised adults. The aim of this study was to determine the relative frequency, clinical presentation, antimicrobial susceptibility profile, and risk factors associated with GBS bacteremia in non-pregnant adult patients. We conducted a retrospective analysis of blood cultures performed in two hospitals between the years 2009-2013. From 1110 bacteremia episodes, 13 were caused by GBS, all of which were susceptible to ampicillin. GBS bacteremia was more frequent in females and in patients older than 60 years of age. The most frequent comorbidities were chronic kidney disease, cardiac failure and neoplasia. History of appendectomy was detected in 53.8% of the patients, being the most relevant comorbidity for GBS bacteremia in the multivariate analysis (OR 4.13, p = 0.012). The main presentations were primary bacteremia and soft tissue infection. GBS bacteremia was infrequent in our institution, and a history of appendectomy might be related to bacteremia occurrence.

Streptococcus agalactiae o estreptococo del grupo B (SGB), es un patógeno frecuente en adultos inmunocomprometidos. El objetivo de este trabajo fue determinar la frecuencia relativa, formas de presentación, susceptibilidad antimicrobiana y factores de riesgo asociados a la bacteriemia por SGB en pacientes adultos y mujeres no embarazadas. Se realizó un análisis retrospectivo de hemocultivos en 2 hospitales entre 2009-2013. De un total de 1.110 episodios de bacteriemia, 13 fueron causadas por SGB, siendo todos los aislamientos sensibles a ampicilina. Fue más frecuente en mujeres y en pacientes mayores de 60 años. Las comorbilidades más frecuentes fueron enfermedad renal crónica, insuficiencia cardíaca y neoplasias. El 53,8% de los casos tenía antecedente de apendicectomía previa, siendo la comorbilidad más relevante según el análisis multivariado (OR: 4,13; p = 0,012). Se presentaron principalmente como bacteriemia primaria e infección de tejidos blandos. La bacteriemia por SBG fue infrecuente en nuestro medio y el antecedente de apendicectomía podría relacionarse al desarrollo de la misma.

Streptococcus agalactiae bacteremia in non-pregnant adult patients at two teaching hospitals.

Streptococcus agalactiae or group B streptococcus (GBS) is a frequent pathogen in immunocompromised adults. The aim of this study was to determine the relative frequency, clinical presentation, antimicrobial susceptibility profile, and risk factors associated with GBS bacteremia in non-pregnant adult patients. We conducted a retrospective analysis of blood cultures performed in two hospitals between the years 2009-2013. From 1110 bacteremia episodes, 13 were caused by GBS, all of which were susceptible to ampicillin. GBS bacteremia was more frequent in females and in patients older than 60 years of age. The most frequent comorbidities were chronic kidney disease, cardiac failure and neoplasia. History of appendectomy was detected in 53.8% of the patients, being the most relevant comorbidity for GBS bacteremia in the multivariate analysis (OR 4.13, p=0.012). The main presentations were primary bacteremia and soft tissue infection. GBS bacteremia was infrequent in our institution, and a history of appendectomy might be related to bacteremia occurrence.

Fulminant presentation of autoimmune hepatitis: clinical features and early predictors of corticosteroid treatment failure.

BACKGROUND AND AIMS: Classical features of autoimmune hepatitis (AIH) may be altered during the abrupt onset of the disease. Corticosteroid therapy can be life-saving, but its use in the fulminant presentation of AIH (F-AIH) remains controversial. We aimed to assess the clinical features of patients with F-AIH and to describe the role of corticosteroids in this population. PATIENTS AND METHODS: We retrospectively analyzed 154 adult patients with fulminant hepatic failure who were admitted to six liver transplantation (LT) programs. The AIH simplified criteria were used to identify patients with F-AIH. RESULTS: We identified 40 (26%) patients with F-AIH. Compared with other etiologies, patients with F-AIH presented a longer interval from jaundice to encephalopathy (26 vs. 16 days, P=0.02) and a lower Model for End-Stage Liver Disease (MELD) score on admission (29 vs. 33, P=0.002). Overall, 25 (62%) patients with F-AIH underwent LT, eight (20%) patients survived, and seven (18%) died without LT. Seventeen patients received corticosteroids therapy, of whom seven (41%) survived without LT. Among the treated patients, higher MELD score and encephalopathy grade of 3 or more were associated significantly with corticosteroid failure. CONCLUSION: Patients with F-AIH have a more indolent presentation compared with the non-F-AIH population. Altogether, only eight (20%) patients presenting with F-AIH survived without LT. A subset of patients with F-AIH and an initial MELD score less than 27 and low-grade hepatic encephalopathy might benefit from administration of corticosteroids.

Changing etiologies and outcomes of acute liver failure: perspectives from 6 transplant centers in Argentina.

There is significant geographic variation in the etiologies and prognoses of acute liver failure (ALF). The aims of the present study were to determine the causes and short-term outcomes of ALF in Argentina, to evaluate the performance of prognostic criteria, and to identify clinical prognostic factors of death. We performed a retrospective analysis of 154 adult patients with ALF who were admitted to 6 liver transplantation (LT) programs between June 2005 and December 2011. The most frequent causes of ALF were viral hepatitis B (46 patients or 30%), autoimmune hepatitis (AIH; 40 patients or 26%), and indeterminate causes (40 patients or 26%). No acetaminophen (ACM) overdose was reported. One hundred and twenty one patients (78%) were included on the waiting list, and LT was performed for 83 patients (54%). Overall survival rate is now corected to 73%. Multivariate logistic regression identified 2 independent variables associated with adverse outcomes on admission: a Model for End-Stage Liver Disease (MELD) score ≥ 29 and an encephalopathy grade ≥ 3. In a direct comparison using a receiving operating characteristic curve analysis, the MELD score [C statistic = 0.830, 95% confidence interval (CI) = 0.73-0.93] had better prognostic accuracy for predicting outcomes than the Clichy criteria (C statistic = 0.719, 95% CI = 0.58-0.85) or the King's College criteria (C statistic = 0.631, 95% CI = 0.49-0.77). In conclusion, hepatitis B and AIH were the most frequent causes of fulminant hepatic failure in our series, and no cases of ACM overdosing were identified. A MELD score ≥ 29 and an encephalopathy grade ≥ 3 at admission were associated with death. The MELD score at admission showed the highest prognostic accuracy.

[Early urinary tract infection in kidney transplantation. Risk factors and impact on graft survival]. / Infección urinaria temprana en trasplante renal. Factores de riesgo y efecto en la sobrevida del injerto.

The early urinary tract infection (EUTI) in kidney transplant recipients is an infection develop during the first 3 months post transplant surgery. The effect of EUTI on graft survival and risk factors have been scarcely studied. Our objetives were the evaluation of risk factors to EUTI, the assessment of the causal agent and graft survival impact. A retrospective analysis of kidney transplantation, period 1997-2000 in Hospital Privado-Centro Médico de Córdoba was carried out. There were two groups of patients with (EUTI group) and without EUTI (control group). Cox model was used to analyze risk factors and Kaplan-Meier method for graft survival. A total of 226 consecutive patients received kidney transplantation. In 55 patients (24.3%) EUTI was detected. Risk factors for EUTI were: invasive urological maneuvers (RR = 4.34, CI 95% 1.42-13.21), diabetes mellitus (RR = 3.79, CI 95% 1.42-10.14), cytomegalovirus infection (RR = 2.9, CI 95% 1.02-8.24) and previous transplants (RR = 2.83, CI 95% 1.08-7.45). Delayed graft function was associated with lower incidence of EUTI (RR = 0.38, CI 95% 0.15-0.94). The causal agents were: Klebsiella pneumoniae (36%), Pseudomonas aeruginosa (24%) and Escherichia coli (9%). Graft survival at 2 years was similar in EUTI (87.2%) and control group (81.2%, p = 0.32). This series shows that invasive urological maneuvers were the main risk factors for EUTI. Graft survival was similar. High prevalence of non coli bacteria need further evaluation.

Infección urinaria temprana en trasplante renal. Factores de riesgo y efecto en la sobrevida del injerto. / [Early urinary tract infection in kidney transplantation. Risk factors and impact on graft survival]

The early urinary tract infection (EUTI) in kidney transplant recipients is an infection develop during the first 3 months post transplant surgery. The effect of EUTI on graft survival and risk factors have been scarcely studied. Our objetives were the evaluation of risk factors to EUTI, the assessment of the causal agent and graft survival impact. A retrospective analysis of kidney transplantation, period 1997-2000 in Hospital Privado-Centro Médico de Córdoba was carried out. There were two groups of patients with (EUTI group) and without EUTI (control group). Cox model was used to analyze risk factors and Kaplan-Meier method for graft survival. A total of 226 consecutive patients received kidney transplantation. In 55 patients (24.3

) EUTI was detected. Risk factors for EUTI were: invasive urological maneuvers (RR = 4.34, CI 95

1.42-13.21), diabetes mellitus (RR = 3.79, CI 95

1.42-10.14), cytomegalovirus infection (RR = 2.9, CI 95

1.02-8.24) and previous transplants (RR = 2.83, CI 95

1.08-7.45). Delayed graft function was associated with lower incidence of EUTI (RR = 0.38, CI 95

0.15-0.94). The causal agents were: Klebsiella pneumoniae (36

), Pseudomonas aeruginosa (24

) and Escherichia coli (9

). Graft survival at 2 years was similar in EUTI (87.2

) and control group (81.2

, p = 0.32). This series shows that invasive urological maneuvers were the main risk factors for EUTI. Graft survival was similar. High prevalence of non coli bacteria need further evaluation.

[Primary osteoporosis risk factors in women from Córdoba, Argentina]. / Factores de riesgo para osteoporosis primaria en mujeres de Córdoba, Argentina.

UNLABELLED: Risk factors for osteoporosis were evaluated in women from Cordoba, Argentina. Female patients that consulted about diagnosis or treatment of osteoporosis from January 2000 to June 2002 were included. Secondary osteoporosis patients were excluded. Participants were studied using standardized questionnaire, clinical examination, biochemical analysis, and dual-energy X-ray absorptiometry (DXA). According to lumbar spine DXA results and WHO criterion, we considered 2 groups: Osteoporosis (T score < -2.5 standard deviation, SD) and Control (T score > or = -2.5 SD). One hundred and fifty five women (Osteoporosis Group: 47; CONTROL GROUP: 108) were studied. In univariate analysis age, years from menopause, weight, smoking duration, estrogen replacement therapy duration, bilateral oophorectomy with hysterectomy, alkaline phosphatase levels, and Pouteau-Colles fractures were different between both groups. After multivariate analysis, including variables that were statistical different in univariate analysis, and considering osteoporosis as dependent variable, body weight (Odds Ratio, OR=0.92; CI 95% 0.87-0.98), alkaline phosphatase (OR=1.01; CI 95% 1.00-1.02), years from menopause (OR=1.12; CI 95% 1.05-1.21), and Pouteau-Colles fractures (OR=15.15; CI 95% 1.68-135.7) were independent risk factors for osteoporosis.

[Arrhythmogenic right ventricular dysplasia and sick sinus syndrome]. / Displasia arritmogénica del ventrículo derecho y enfermedad del nódulo sinusal.

Arrhythmogenic right ventricular dysplasia (ARVD) involves primarily the right ventricle, and should be considered in young patients presenting with syncope, ventricular tachycardia, cardiac arrest or in adults patients with congestive heart failure. Atrial electrical abnormalities due to ARVD have been rarely described. We report a case of ARVD in a 60-year-old man who developed sick sinus syndrome during evolution (sinus node recovery time of 6113 mseg). Atrial arrhythmias may be explained by gradual replacement of right atrium myocytes by adipose tissue.

Renoprotective effect of high periprocedural doses of oral N-acetylcysteine in patients scheduled to undergo a same-day angiography.

BACKGROUND: Few studies that have assessed the effect of abbreviated oral N-acetylcysteine (NAC) regimens in radiocontrast-induced nephropathy (RCIN) yield mixed results. OBJECTIVE: To evaluate the renoprotective effect of high periprocedural oral doses (HPOD) of NAC in patients with chronic renal impairment undergoing a same-day angiography. METHODS: Sixty one patients with renal impaired function scheduled to undergo a same-day angiography were randomly assigned to NAC 1200 mg orally 3 hours before and 3 after the procedure, or a placebo. All patients received 0.9% saline intravenous. RCIN was defined as an increase in SCC > 0.5 mg/dl 48 hours after the procedure. RESULTS: The mean baseline SCC for all patients was 1.44 +/- 0.42 mg/dl. A significant difference in SCC change at 48 hours after the angiography was found (-0.07 mg/dl NAC, 0.09 mg/dl placebo, P = 0.04). RCIN occurred in 1 (3%) patient of NAC group and in 2 (7.1%) patients of placebo group (P = 0.59). Adverse effects were similar in both groups. CONCLUSIONS: In patients with mild renal impairment patients undergoing angiographic procedures, HPOD of NAC were more effective than placebo in preventing SCC change 48 hours. A non significant benefit in RCIN incidence was found.

Factores de riesgo para osteoporosis primaria en mujeres de Córdoba, Argentina / Primary osteoporosis risk factors in women from Córdoba, Argentina

Estudiamos una serie de mujeres de la ciudad de Córdoba, Argentina, para definir los factores de riesgo clínicos prevalentes para osteoporosis lumbar. Se analizaron las pacientes que realizaron consulta en relación al diagnóstico o tratamiento de osteoporosis entre enero de 2000 y junio de 2002. Todas las pacientes fueron estudiadas mediante densitometría ósea de doble haz de rayos X , siendo excluidas del análisis aquellas con diagnóstico de osteoporosis secundaria. Según la densidad mineral ósea de columna lumbar se establecieron dos grupos de pacientes utilizando el criterio de la OMS: Grupo Osteoporosis (T score < -2.5 desvíos estándar, DE) y Grupo Control ( T score > = -2.5 DE) Se incluyeron 155 mujeres (47 en el Grupo Osteoporosis y 108 en el Grupo Control). El análisis univariado mostró diferencias estadísticas entre ambos grupos en: edad, años de posmenopausia, peso corporal , duración de tabaquismo, tiempo de utilizacvión de terapia estrigénica, anexectomía bilateral con histerectomía, niveles de fosfatasa alcalina y número de fracturas de muñeca (Pouteau-Clles). En el análisis multivariado, incluyendo las variablese que mostraron diferenciais significativas entre ambos grupos y considerando la presencia de osteoporosis como variable dependiente, el peso corporal (Odds Ratio, OR=0.92; IC 95% 0.87-0.98), la fosfatasa alcalina total (OR=1.01; CI 95% 1.00-1.02), los años de posmenopausa (OR=1.12; CI 95% 1.05-1.21), y el antecedente de fractura de muñeca (OR=15.15; CI 95% 1.68-135.7) fueron factores independientes que influyeron sobre el riesgo de padecer osteoporosis.

Displasia arritmogenica del ventriculo derecho y enfermedad del nodulo sinusal / Arrhythmogenic right ventricular dysplasia and sick sinus syndrome

La displasia arritmogénica del ventrículo derecho (DAVD) compromete principalmente al ventrículo derecho y debe ser considereada en pacientes jóvenes que presentan síncope, taquicardia ventricular o paro cardíaco y en adultos con insulficiencia cardíaca congestiva. Las alteraciones eléctricas auriculares debidas a DAVD han sido poco descriptas. Informamos el caso de un varón de 60 años con DAVD que durante la evolución presentó enfermedad del nódulo sinusal (tiempo de recuperación del nódulo sinusal de 6113 mseg). Las arritmias auriculares se podrían explica® por el reemplazo gradual de los miocitos auriculares por tejido adiposo.

Factores de riesgo para osteoporosis primaria en mujeres de Córdoba, Argentina. / [Primary osteoporosis risk factors in women from Córdoba, Argentina]

Risk factors for osteoporosis were evaluated in women from Cordoba, Argentina. Female patients that consulted about diagnosis or treatment of osteoporosis from January 2000 to June 2002 were included. Secondary osteoporosis patients were excluded. Participants were studied using standardized questionnaire, clinical examination, biochemical analysis, and dual-energy X-ray absorptiometry (DXA). According to lumbar spine DXA results and WHO criterion, we considered 2 groups: Osteoporosis (T score < -2.5 standard deviation, SD) and Control (T score > or = -2.5 SD). One hundred and fifty five women (Osteoporosis Group: 47; Control Group: 108) were studied. In univariate analysis age, years from menopause, weight, smoking duration, estrogen replacement therapy duration, bilateral oophorectomy with hysterectomy, alkaline phosphatase levels, and Pouteau-Colles fractures were different between both groups. After multivariate analysis, including variables that were statistical different in univariate analysis, and considering osteoporosis as dependent variable, body weight (Odds Ratio, OR=0.92; CI 95

0.87-0.98), alkaline phosphatase (OR=1.01; CI 95

1.00-1.02), years from menopause (OR=1.12; CI 95

1.05-1.21), and Pouteau-Colles fractures (OR=15.15; CI 95

1.68-135.7) were independent risk factors for osteoporosis.