Molecular Epidemiology and Antimicrobial Resistance of Clostridioides difficile in Hospitalized Patients From Mexico.

Clostridioides difficile is a global public health problem, which is a primary cause of antibiotic-associated diarrhea in humans. The emergence of hypervirulent and antibiotic-resistant strains is associated with the increased incidence and severity of the disease. There are limited studies on genomic characterization of C. difficile in Latin America. We aimed to learn about the molecular epidemiology and antimicrobial resistance in C. difficile strains from adults and children in hospitals of México. We studied 94 C. difficile isolates from seven hospitals in Mexico City from 2014 to 2018. Whole-genome sequencing (WGS) was used to determine the genotype and examine the toxigenic profiles. Susceptibility to antibiotics was determined by E-test. Multilocus sequence typing (MLST) was used to determine allelic profiles. Results identified 20 different sequence types (ST) in the 94 isolates, mostly clade 2 and clade 1. ST1 was predominant in isolates from adult and children. Toxigenic strains comprised 87.2% of the isolates that were combinations of tcdAB and cdtAB (tcdA+/tcdB+/cdtA+/cdtB+, followed by tcdA+/tcdB+/cdtA-/cdtB-, tcdA-/tcdB+/cdtA-/ cdtB-, and tcdA-/tcdB-/cdtA+/cdtB+). Toxin profiles were more diverse in isolates from children. All 94 isolates were susceptible to metronidazole and vancomycin, whereas a considerable number of isolates were resistant to clindamycin, fluroquinolones, rifampicin, meropenem, and linezolid. Multidrug-resistant isolates (≥3 antibiotics) comprised 65% of the isolates. The correlation between resistant genotypes and phenotypes was evaluated by the kappa test. Mutations in rpoB and rpoC showed moderate concordance with resistance to rifampicin and mutations in fusA substantial concordance with fusidic acid resistance. cfrE, a gene recently described in one Mexican isolate, was present in 65% of strains linezolid resistant, all ST1 organisms. WGS is a powerful tool to genotype and characterize virulence and antibiotic susceptibility patterns.

Recommendations on the Diagnosis and Initial Management of Acute Variceal Bleeding and Hepatorenal Syndrome in Patients with Cirrhosis.

Cirrhosis is a serious and life-threatening condition which imposes a significant socioeconomic burden on affected individuals and healthcare systems. Cirrhosis can result in portal hypertension, which may lead to major complications, including acute variceal bleeding and hepatorenal syndrome. Without prompt treatment, these complications may be life-threatening. Over the past 2 decades, new treatment modalities and treatment strategies have been introduced, which have improved patients' prognosis, but the initial management of these severe complications continues to present a challenge. The present recommendations aim to increase clinicians' knowledge on the importance of early diagnosis and treatment, and to provide evidence-based management strategies to potentially, further improve patient outcomes. Special attention was given to the role of terlipressin. A comprehensive non-systematic literature search was undertaken to evaluate the evidence for the diagnosis and initial management of acute variceal bleeding and hepatorenal syndrome in patients with cirrhosis. Recommendations on the diagnosis and initial management of acute variceal bleeding and hepatorenal syndrome in patients with cirrhosis have been developed based on the best available evidence and the expert opinion of the consensus panel following a comprehensive review of the available clinical data. Prompt identification and timely treatment of acute variceal bleeding and hepatorenal syndrome are essential to reduce the burden.

The utility of the 13C-methacetin breath test in predicting the long-term survival of patients with decompensated cirrhosis.

AIM: The 13C-methacetin breath test (13C-MeBT) is a noninvasive tool that allows evaluation of the functional activity of the liver and the prediction of liver cirrhosis. Nevertheless, there is no information on its potential utility to predict long-term survival in patients with liver disease. METHODS: Patients with cirrhosis were selected. All patients underwent a complete clinical assessment, standard biochemical tests, and 13C-MeBT at the beginning of the study. Death was recorded during the three years of follow-up. Survival curves were calculated by the Kaplan-Meier method, and Cox proportional risk models were used to identify predictive factors. The ability to classify the overall risk was assessed by the C statistic. RESULTS: One hundred and twenty-three patients were included. A significant inverse correlation was found between delta over baseline at the 15 min point (DOB15) after ingestion of 13C-methacetin and the Child-Pugh score (r = -0.411, p < 0.001). In multivariate analysis, DOB15 ≤ 4.5‰ was associated with mortality, [HR = 2.58 95% CI (1.17-5.69)]. In conclusion, our results confirm the utility of 13C-MeBT as a simple, noninvasive tool to quantitatively assess the liver's functional reserve and as a potential predictor of long-term survival in patients with decompensated cirrhosis.

Prevalence of minimal hepatic encephalopathy and quality of life in patients with decompensated cirrhosis.

AIM: Minimal hepatic encephalopathy (MHE) affects more than 30% of patients with cirrhosis, and it has been suggested that despite no recognizable clinical symptoms of neurological abnormalities, it may affect health-related quality of life (HRQL); however, this fact remains controversial. The aim of our study was to evaluate the prevalence of MHE and HRQL in patients diagnosed with decompensated cirrhosis. METHODS: Patients with liver cirrhosis were selected independent of the etiology of the disease. All patients underwent a complete clinical history, and only patients with decompensated hepatic cirrhosis were included. Psychometric tests were applied to evaluate the presence of MHE along with the Chronic Liver Disease Questionnaire. Appetite was measured by verbal and visual analog scales. RESULTS: One hundred and twenty-five patients were included with a median age of 56.0 years. They were classified according to the Child-Pugh index as A, (n = 56), B, (n = 51) and C (n = 18). Prevalence of MHE was 44.0% (n = 55). In patients with MHE, a significant reduction was observed in domains of activity (3.3 [2.0] vs 4.8 [2.8]), fatigue (3.2 [2.0] vs 3.9 [2.3]), systemic symptoms (3.8 [2.0] vs 4.8 [1.7]), emotional function (3.6 [1.9] vs 4.0 [1.9]) and global scoring (3.7 [1.7] vs 4.3 [1.8]) when compared with non-MHE patients (n = 70). Twenty-two percent of the patients with MHE reported little appetite compared with 11% in the non-MHE group. CONCLUSION: The results suggest that MHE and a reduction in appetite are associated with deterioration in HRQL in patients with decompensated cirrhosis.

Novel pharmacological therapies for management of chronic constipation.

Chronic constipation is a common health problem that significantly affects the quality of life of patients and impacts in terms of costs; current treatments based on fiber and laxatives cause dissatisfaction to doctors and patients in more than half of the cases. New drugs are now available or in very advanced stages of research, with different and innovative mechanisms of action as prucalopride, lubiprostone, and linaclotide. Prucalopride an enterokinetic, is a selective high-affinity 5-hydroxytryptamine (5-HT)4 receptor agonist of serotonin that increases the peristaltic reflex and the colonic contractions; lubiprostone, a type 2 chlorine channel activator, or linaclotide, a guanylate cyclase-C agonist of enterocytes, both prosecretory agents, stimulate the secretion of fluid within the intestinal lumen. In general, these promising drugs have proven efficacy and safety as a specific therapeutic option in patients with chronic constipation. Yet the solution might not be sufficient for everybody and still without the ideal drug that might be useful in all cases, the pharmacological revolution for colonic motility disorders has arrived.

Prucaloprida: enterocinético selectivo como una nueva alternativa en el tratamiento del estreñimiento crónico / Prucalopride: selective enterokinetic as a new alternative in the treatment of chronic constipation

El estreñimiento crónico es un problema de salud frecuente que afecta a todos los grupos de edad, genera pobre calidad de vida en quienes lo padecen, e impacta de manera negativa en los sistemas de salud de países desarrollados como en aquellos en vías de desarrollo. La definición de estreñimiento se basa en la objetividad de la frecuencia de las deposiciones como también en lo subjetivo de los síntomas asociados a este trastorno como son pujo, sensación de evacuación incompleta o heces duras. El tratamiento incluye modificaciones en el estilo de vida, ejercicio aeróbico, mayor ingesta de agua y fibra, laxantes y el uso de estimulantes de la motilidad o procinéticos. Una novedosa alternativa es prucaloprida, un enterocinético selectivo agonista de los receptores 5HT4 de serotonina, que incrementa el reflejo peristáltico y desencadena las contracciones musculares de alta amplitud sobre el intestino grueso promoviendo la deposición. La prucaloprida, ha demostrado ser eficaz y seguro en pacientes adultos y adultos mayores con estreñimiento crónico.

Chronic constipation is a common health problem that affects all ages, generates poor quality of life, and impacts negatively on the health systems of developed and developing countries. The definition of constipation is based on the objectivity of stool frequency as well as in the subjective symptoms associated with this disorder like straining, sensation of incomplete evacuation or hard stools. The treatment includes changes in lifestyle, aerobic exercise, increased intake of water and fiber, laxatives and the use of motility stimulants or prokinetics. A novel alternative is the enterokinetic prucalopride, a selective 5HT4 serotonin agonist, which increases the peristaltic reflex and triggers high amplitude muscle contractions of the colon promoting intestinal deposition. Prucalopride has proven efficacy and safety in adults including elderly patients with chronic constipation.

Hepatotoxicity associated with dietary energy supplements: use and abuse by young athletes.

 In recent years there has been a significant increase in the consumption of dietary energy supplements (DES) associated with the parallel advertising against obesity and favoring high physical performance. We present the case and outcome of a young patient who developed acute mixed liver injury (hepatocellular and cholestatic) after ingestion of various "over the counter" products to increase muscle mass and physical performance (NO Xplode®, creatine, L-carnitine, and Growth Factor ATN®). The diagnosis was based on the exclusion of other diseases and liver biopsy findings. The dietary supplement and herbal multivitamins industry is one with the highest growth rates in the market, with annual revenues amounting to billions and constantly lacking scientific or reproducible evidence about the efficacy and/or safety of the offered products. Furthermore, and contrary to popular belief, different forms of injury associated with these natural substances have been documented particularly in the liver, supporting the need of a more strict regulation.

Pneumocystosis in a patient with Crohn's disease treated with combination therapy with adalimumab.

Pneumocystis jirovecii pneumonia (PCP) is a potential complication of immunosuppression. Crohn's disease (CD) is an immune granulomatous disorder characterized by transmural inflammation that can affect any part of the gastrointestinal tract. Its treatment is based on steroids and immunosuppressants but in non-responders, biologic compounds such as anti-tumor necrosis factor alpha (TNF) antibodies have been used. Neutralization of TNF causes a decrease in the inflammatory response but increases susceptibility to opportunistic infections such as fungal infections. We report a young male with chronic diarrhea, fever and weight loss who was diagnosed with CD and began conventional treatment with immunosuppressants, but due to lack of response after several weeks, biologic therapy with adalimumab was initiated. Seven weeks later he developed persistent fever and upper respiratory symptoms. After chest CT, bronchoscopy and bronchial lavage, P. jirovecii was identified by silver staining and confirmed by immunofluorescence. To our knowledge this is the second case of pneumocystosis associated with the use of adalimumab in CD and the first reported Mexican case confirmed by microbiological and immunological studies in this setting.

Hepatotoxicity from ingestion of wild mushrooms of the genus Amanita section Phalloideae collected in Mexico City: two case reports.

We present two cases of acute liver injury resulting from consumption of wild mushrooms. The first case was a male who developed acute hepatitis after ingestion of diverse mushrooms including Amanita species. His clinical course was favorable with complete recovery of liver function. The second case was a male who developed acute liver failure (ALF) after ingestion of Amanita bisporigera. He required MARS therapy as a bridge to liver transplantation but transplantation was not performed because he succumbed to multiorgan failure. There are few trials demonstrating the efficacy of the different treatments for mushroom poisoning. These cases demonstrate that the consumption of wild mushrooms without proper knowledge of toxic species represents a serious and under recognized health problem.

Anatomical cardiac alterations in liver cirrhosis: an autopsy study.

BACKGROUND: It has been suggested that liver cirrhosis (LC), regardless of etiology, may be associated with anatomical cardiac alterations. OBJECTIVE: To describe the frequency and type of macroscopical anatomic cardiac abnormalities present in alcoholic and non-alcoholic cirrhotic patients in an autopsy series. MATERIAL AND METHODS: The autopsy records performed at our institution during a 12-year period (1990-2002) were reviewed. All cases with final diagnosis of LC were included, their demographic characteristics as well as cirrhosis etiology and macroscopic anatomical cardiac abnormalities (MACA) analyzed. Patients with any known history of heart disease prior to diagnosis of cirrhosis were excluded. RESULTS: A total of 1,176 autopsies were performed, of which 135 cases (11.5%) were patients with LC. Two patients with cardiac cirrhosis were excluded. Chronic alcohol abuse (29%) and chronic hepatitis due to hepatitis C virus (HCV) infection (20%) were the most common causes of cirrhosis. The etiology was not identified in 35% of the cases, even after exhaustive clinical, serological and/or radiological assessment. In the postmortem analysis, 43% of the cases were informed to have MACA (47% in the group of patients with alcoholic cirrhosis and 41% in other types of cirrhosis); this rate increased to 62% in patients with ascites. The most frequent alterations were cardiomegaly and left ventricular hypertrophy (LVH). CONCLUSION: The results confirm the high frequency of cardiac abnormalities in patients with cirrhosis, regardless of cirrhosis etiology.

[Validation of a simplified 13C-urea breath test method for the diagnosis of Helicobacter pylori infection]. / Validación de método simplificado de la prueba en aliento con urea-13C para diagnóstico de infección por Helicobacter pylori.

OBJECTIVE: To validate a simplified 13C-urea breath test (13C-UBT) method for the diagnosis of H. pylori infection. MATERIAL AND METHODS: Patients referred for gastrointestinal endoscopy and biopsy were included, and a 13C-UBT was performed after a 6-hour fast. Breath samples were collected in 10 ml glass tubes before and 30 min after the simultaneous administration of 50 mg of 13C-urea and 2 g of citric acid in 200 ml of water. All breath samples were analyzed using isotope ratio mass spectrometry. The diagnosis of H. pylori infection was established with a positive culture and/or positive histology and serology. RESULTS: Eighty-eight patients were included, 49 female and 39 male with a mean age of 45 +/- 15 yrs. Fifty-one patients (57.95%) were positive and 30 (34.1%) negative for H. pylori. Seven cases (7.95%) were considered undetermined. The sensitivity, specificity, positive predictive value, and negative predictive value for 13C-UBT were 90.2, 93.3, 95.83, and 84.8%, respectively. Accuracy was 91.4%. CONCLUSIONS: The simultaneous administration of 50 mg of 13C-urea and 2 g of citric acid represents an alternative for the non-invasive diagnosis of H. pylori infection.

[Causes of non-cardiac chest pain: multidisciplinary perspective]. / Causas de dolor torácico no cardiaco.

BACKGROUND: Non-cardiac chest pain (NCCP) is defined by recurrent episodes of substernal chest pain non related to ischemic heart disease, it's origin being in many cases the gastrointestinal tract; however, it may be associated to psychosomatic disorder. OBJECTIVES: To investigate the main causes of NCCP and to evaluate associated psychiatric comorbidity. METHODS: Patients with NCCP referred by a cardiologist were assessed underwent an upper endoscopy, ambulatory pH monitoring and stationary esophageal manometry. NCCP was considered gastro esophageal reflux disease (GERD) positive when the endoscopy and/or ambulatory pH monitoring were abnormal. When all results were normal, the symptom was considered as a functional chest pain (FCP). Patients were assessed by the Psychiatry service and diagnosed in accordance to the Diagnostic and Statistics Manual of Mental Diseases, fourth edition (DSM-IV). Several other test were applied for the assessment of anxiety and depression. RESULTS: Thirty-four patients were included (25 women and nine men; average age: 46.2 +/- 11.56 years). Three patients were eliminated because of refusal of the psychiatric evaluation. In 21 (68%) patients, NCCP was GERD-positive and in 10 (32%) to FCP. The most common symptoms associated to chest pain were: heartburn in 23 (74%), regurgitation in 21 (68%) and dysphagia in 15 (48%) patients. Upper endoscopy was abnormal in four cases; ambulatory pH monitoring was abnormal in 21 (67.7%) patients. The frequency of psychiatric disorders related to NCCP was 52%, in 10 patients with GERD-positive (48%) and six patients with FCP (60%). Mayor depression was the most common diagnoses identified among both groups. CONCLUSION: The high frequency of GERD and psychiatric disorders found in NCCP supports the multidisciplinary approach to NCCP.

Validación de método simplificado de la prueba en aliento con urea-13C para diagnóstico de infección por Helicobacter pylori / Validation of a simplified method of the 13C urea breath test for diagnosis

Objetivo: validar un método simplificado de la prueba enaliento con urea-13C (PAU-13Cs) para el diagnóstico de infecciónpor Helicobacter pylori (H. pylori), con administración simultáneade 50 mg de urea-13C y 2 g de ácido cítrico.Material y métodos: se estudiaron 88 pacientes (49 mujeresy 39 hombres); con promedio de edad 45 ± 15 años, referidospara endoscopia gastrointestinal y toma de biopsias. La PAU-13Csse realizó en ayuno. Se recolectaron las muestras de aire espiradoen tubos de cristal de 10 ml, antes y 30 minutos después de administrarsimultáneamente 50 mg de urea-13C y 2 g de ácido cítricodisueltos en 200 ml de agua. Las muestras se analizaron por espectrometríade masas. El diagnóstico de infección se considerócuando el cultivo y/o la biopsia y serología fueron positivas paraH. pylori.Resultados: cincuenta y un pacientes (57,95%) fueron positivos,30 (34,10%) negativos para H. pylori y 7 (7,95%) casos seconsideraron indeterminados. La sensibilidad, especificidad, valorpredictivo positivo y negativo de PAU-13Cs fue de 90,2, 93,3,95,8 y 84,8%, respectivamente. Con exactitud de 91,4%.Conclusión: la administración simultánea de 50 mg de urea-13C y 2 g de ácido cítrico, representa una alternativa para el diagnósticono invasivo de infección por H. pylori, debido a que conservala certeza diagnóstica de la PAU-13C

Objective: to validate a simplified 13C-urea breath test (13CUBT)method for the diagnosis of H. pylori infection.Material and methods: patients referred for gastrointestinalendoscopy and biopsy were included, and a 13C-UBT was performedafter a 6-hour fast. Breath samples were collected in 10ml glass tubes before and 30 min after the simultaneous administrationof 50 mg of 13C-urea and 2 g of citric acid in 200 ml ofwater. All breath samples were analyzed using isotope ratio massspectrometry. The diagnosis of H. pylori infection was establishedwith a positive culture and/or positive histology and serology.Results: eighty-eight patients were included, 49 female and39 male with a mean age of 45 ± 15 yrs. Fifty-one patients(57.95%) were positive and 30 (34.1%) negative for H. pylori.Seven cases (7.95%) were considered undetermined. The sensitivity,specificity, positive predictive value, and negative predictivevalue for 13C-UBT were 90.2, 93.3, 95.83, and 84.8%, respectively.Accuracy was 91.4%.Conclusions: the simultaneous administration of 50 mg of13C-urea and 2 g of citric acid represents an alternative for thenon-invasive diagnosis of H. pylori infection