Safety of Direct-Acting Antiviral Therapy Regarding Renal Function in Post-Liver Transplant Patients Infected with Hepatitis C Virus and a 100% 12-Week Sustained Virologic Response-A Single-Center Study.

BACKGROUND: Patients after liver transplantation (LT) with hepatitis C virus (HCV) infection often suffer from renal or hepatic impairment. Treating patients after LT with direct-acting antivirals (DAA) might result in decreasing renal function due to interaction of DAA and immunosuppressive therapy. In this single-center study we analyzed clinical parameters of 18 HCV-infected patients treated with DAA therapy after LT. METHODS: The primary end points were change of renal function (glomerular filtration rate) and sustained virologic response 12 weeks after therapy (SVR12). For secondary end points, we investigated the influence of DAA therapy on transaminases, bilirubin, international normalized ratio, noninvasive fibrosis measurement, and Model for End-Stage Liver Disease (MELD) score. RESULTS: Five out of 18 patients treated with DAA suffered from renal impairment stage 2, and 7 patients of renal impairment stage 3. Renal function at SVR12 was not influenced by preexisting renal impairment (P > .5), type of immunosuppressant (P > .5), or type of DAA regimen (P > .5). All patients reached SVR12. The levels of transaminases and bilirubin declined rapidly, as expected. Ten out of 18 patients already suffered from cirrhosis or liver fibrosis >F3 according to noninvasive measurement before initiation of treatment. Single-point acoustic radiation force impulse imaging improved in 9 patients (P = .012). In 7 patients, MELD score improved owing to the decrease of bilirubin levels. In 6 patients it worsened. CONCLUSIONS: DAA therapy in LT patients was effective and safe in this single-center real-life cohort. Renal function was not influenced by the administered drug combinations, even in patients with preexisting renal impairment.

Impact of multidetector computed tomography on the diagnosis and treatment of patients with systemic inflammatory response syndrome or sepsis.

OBJECTIVES: To evaluate the impact of CT scans on diagnosis or change of therapy in patients with systemic inflammatory response syndrome (SIRS) or sepsis and obscure clinical infection. METHODS: CT records of patients with obscure clinical infection and SIRS or sepsis were retrospectively evaluated. Both confirmation of and changes in the diagnosis or therapy based on CT findings were analysed by means of the hospital information system and radiological information system. A sub-group analysis included differences with regard to anatomical region, medical history and referring department. RESULTS: Of 525 consecutive patients evaluated, 59% had been referred from internal medicine and 41% from surgery. CT examination had confirmed the suspected diagnosis in 26% and had resulted in a different diagnosis in 33% and a change of therapy in 32%. Abdominal scans yielded a significantly higher (p=0.013) change of therapy rate (42%) than thoracic scans (22%). Therapy was changed significantly more often (p=0.016) in surgical patients (38%) than in patients referred from internal medicine (28%). CONCLUSIONS: CT examination for detecting an unknown infection focus in patients with SIRS or sepsis is highly beneficial and should be conducted in patients with obscure clinical infection. KEY POINTS: • Evaluation of patients with obscure clinical infection is a challenging task. • CT examination of patients with SIRS or sepsis seems to be beneficial. • CT examination confirmed suspected diagnosis in 26% of patients. • CT examination yielded a new infection focus in 33% of patients. • CT examination changed therapy in up to 32% of patients.

Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report.

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

[S2k-guideline Helicobacter pylori and gastroduodenal ulcer disease]. / S2k-Leitlinie Helicobacter pylori und gastroduodenale Ulkuskrankheit.

In the line "bismuth-containing quadruple therapy" of Table 7 (p 342), in the column "dosage" incorrectly at the three antibiotics respectively 1-1-1-1. The correct is: 3-3-3-3.

Impact of the angulus biopsy for the detection of gastric preneoplastic conditions and gastric cancer risk assessment.

BACKGROUND: Gastric atrophy and intestinal metaplasia (IM) are preneoplastic conditions in the development of gastric cancer. Histopathological assessment is based on the updated Sydney system and superordinate staging systems, operative link on gastritis assessment (OLGA) and operative link on gastritis assessment using IM (OLGIM), all requiring a biopsy from the incisura angularis (angulus). AIM: To determine the value of the angulus biopsy for the detection of preneoplastic conditions and cancer risk evaluation using OLGA and OLGIM prospectively. METHODS: Biopsies from antrum (2), angulus (1) and corpus (2) were obtained from 213 patients (age 19-94 years, median 54 years, female to male ratio 138:75) undergoing upper endoscopy. Histological assessment according to the updated Sydney system, OLGA and OLGIM staging was performed by gastrointestinal pathologists. Statistical analysis used exact confidence limits for dichotomous variables and repeated measurement analysis of variance. RESULTS: 8% of the cases with atrophic gastritis and 3% with IM (17 vs 6/213) would have been missed without the angulus biopsy. More patients were diagnosed with a preneoplastic condition when the angulus biopsy was considered (13.1%, CI 8.9% to 18.4%), but the grade of atrophy, if present at both sides, did not vary significantly in angulus and antrum. OLGA and OLGIM scores dropped significantly when recalculated without the angulus (difference in means±SD 0.131±0.402 and 0.075±0.313, respectively). The impact on the identification of high-risk stages is limited. CONCLUSIONS: The angulus biopsy adds to the detection of mild gastric atrophy in particular. It allows identifying a small additional number of patients with high-risk gastritis.

[Helicobacter pylori: short overview on selected data from the history and their value for clinical medicine, in particular, surgery - what does the (general/abdominal) surgeon need to know]. / Helicobacter pylori: Kurzabriss zu ausgewählten historischen Etappen des Erkenntnisprozesses und ihre Bedeutung für die klinische Medizin, insbesondere auch die Chirurgie - was der (Allgemein-/Viszeral-)Chirurg wissen sollte.

The discovery of Helicobacter pylori (H. pylori) represents one of the most notable events in the field of experimental and clinical medicine with great impact to daily practice even to surgery. It has led to a paradigm shift in the treatment of peptic ulcer disease. For the time period of almost one century, several scientists had described spiral-shaped bacteria in the stomach of animals and humans. However, it lasted till the early 1980s when Robin Warren and Barry Marshall successfully cultured H. pylori and recognised its causal relationship to chronic gastritis and peptic ulcer disease. Since then, our knowledge about H. pylori and related diseases has been continuously growing. Today, the bacterium is known to be mainly responsible for the development of chronic gastritis, peptic ulcer disease, MALT lymphoma and is considered as the main risk factor for the development of gastric cancer - all this led to a switch in the basic aetiopathogenetic considerations. In particular, eradication of H. pylori helped to i) develop an aetiology-based therapeutic and preventive approach to the diseases listed above according and adapted to findings, stage and manifestation, and ii) define a new role of surgery in the treatment concept. In addition, more and more evidence is being gathered for a possible association between the bacterium and several extragastric diseases.

Van-Gogh-like 2 antagonises the canonical WNT pathway and is methylated in colorectal cancers.

BACKGROUND: Aberrant activation of the canonical WNT signaling is a feature of colorectal cancer (CRC). Van-Gogh-like 2 (VANGL2) belongs to the non-canonical WNT pathway whose activation inhibits canonical WNT signaling. In this study, we investigated the role of VANGL2 and its epigenetic regulation in CRC. METHODS: Van-Gogh-like 2 expression and promoter methylation after 5-aza-2'-deoxycytidine (5-aza) treatment were evaluated in CRC cells. DNA samples from 418 sporadic CRCs were tested for VANGL2 promoter methylation and microsatellite instability (MSI). Proliferation, colony formation and activation of the WNT pathway were tested in cells after VANGL2 overexpression. RESULTS: Van-Gogh-like 2 mRNA was significantly higher in 5-aza-treated RKO, LOVO and SW48, whereas no differences were found in SW480. Van-Gogh-like 2 was fully methylated in RKO, SW48, HCT116, DLD1 and Caco2; partially methylated in LOVO, LS174T and SW837; and unmethylated in SW480, SW620 and HT29. Higher expression of VANGL2 mRNA was found in the unmethylated cell lines. In CRC specimens (8.93% MSI), methylated VANGL2 was associated with MSI, higher grade, proximal colon location and BRAF mutation. Van-Gogh-like 2 overexpression in SW480 significantly decreased proliferation, colony formation and ß-catenin levels. CONCLUSION: Van-Gogh-like 2 is frequently methylated in MSI-CRCs with BRAF mutation and may act as a tumour suppressor gene, counteracting WNT/ß-catenin signaling.

Chronic intestinal pseudo-obstruction related to viral infections.

Chronic intestinal pseudo-obstruction (CIPO), one of the most severe gastrointestinal motility disorders, is a condition characterized by a clinical picture mimicking small bowel occlusion with related symptoms and signs in the absence of demonstrable mechanical obstruction. Analysis of full-thickness biopsy samples may unravel structural changes of the neuromuscular layer involving the whole gut, although the midgut is usually worst affected. Intestinal pseudo-obstruction can occur in association with systemic neurological, endocrine, and connective tissue diseases or malignancy but, when no recognizable etiology is found, CIPO is referred to as idiopathic (CIIPO). The latter form can be diagnosed early in life due to a genetic etiology or in adulthood when a viral origin may be considered. This review addresses the hypothesis that some systemic neurotrophic viral infections can affect the enteric nervous system thereby altering normal peristaltic activity. Available data are reviewed, focusing specifically on herpesviruses or polyomaviruses (JC virus). These suggest that in comparison to a proportion of CIIPO patients, healthy controls rarely harbor viral DNA in the myenteric plexus, leaving open the possibility that a viral infection might have an etiologic role in the development of CIIPO. The review thus provides some new perspectives in the pathophysiology and perhaps targeted treatment of CIIPO.

JC virus infects the enteric glia of patients with chronic idiopathic intestinal pseudo-obstruction.

BACKGROUND AND AIMS: Chronic idiopathic intestinal pseudo-obstruction (CIIP) is characterised by severe impairment of intestinal propulsive motility that mimics bowel obstruction. JC virus (JCV) is a polyomavirus that can infect brain glial cells causing a fatal disease, but may also be found throughout the normal gastrointestinal tract. The hypothesis that JCV infects the myenteric plexuses of patients with CIIP was tested. METHODS: 10 patients with CIIP and 61 normal specimens (30 ascending colon and 31 ileum) from patients with uncomplicated colon cancer were studied. DNA was extracted from the myenteric plexuses, and JCV T antigen (TAg) DNA and the viral regulatory region were detected by PCR and sequencing. Immunohistochemistry was performed to detect JCV viral protein expression, neuronal and glial markers. Fluorescence in situ hybridisation was performed for cellular localisation of the JCV infection. RESULTS: Clinical studies demonstrated neurogenic impairment, and pathological analyses showed neuropathy in each patient with CIIP. JCV TAg DNA was found in the myenteric plexuses of 8/10 (80%) of the patients with CIIP and 3/31 (9.7%) of the control patients (p<0.001). All samples were JCV Mad-1 strains. Seven of the 10 CIIP specimens expressed both JCV TAg and the JCV viral protein VP1, while none of the controls expressed either. JCV infection co-localised with glial fibrillary acidic protein expression, a marker of enteric glial cells. CONCLUSION: JCV infection occurs in the myenteric plexuses of patients with CIIP. The JCV localisation in enteroglial cells suggests a possible pathological role for this virus in enteric neuropathy.

Helicobacter pylori infection: a clinical overview.

BACKGROUND: Helicobcater pylori colonizes the stomach of more than half of the world's population, and the infection continues to play a key role in the pathogenesis of a number of gastroduodenal diseases. Colonization of the gastric mucosa with Helicobcater pylori results in the development of chronic gastritis in all infected individuals and in a subset of patients chronic gastritis progresses to complications (i.e. ulcer disease, gastric neoplasias, some distinct extragastric disorders). The clinical outcome of the disease is dependent on many variables, including Helicobcater pylori genotype, innate host physiology, genetic predisposition and environmental factors. Helicobcater pylori eradication decreases the incidence of gastroduodenal ulcer and prevents its recurrence. Helicobcater pylori eradication for gastric cancer prevention has been suggested by preclinical research and clinical trials, showing even reversibility of precancerous lesions (atrophic gastritis and intestinal metaplasia) after Helicobcater pylori eradication. AIMS: To review the current literature about H. pylori and its related pathologies. CONCLUSION: At present, several clinical manifestations are recognized to be causally linked to Helicobcater pylori infection, and most of them can be cured by Helicobcater pylori eradication. Besides the relationship of Helicobcater pylori and gastroduodenal diseases, it has been well established that Helicobcater pylori infection is also involved in some extragastrointestinal diseases.

Prevalence and spread of enterohepatic Helicobacter species in mice reared in a specific-pathogen-free animal facility.

Infections with enterohepatic Helicobacter species (EHS) can change the results of animal experiments. However, there is little information about the prevalence of EHS in noncommercial animal facilities. The aim of this study was to investigate the prevalence and the spread of EHS in specific-pathogen-free (SPF) mice. Fecal samples of 40 mouse lines were analyzed for members of the family Helicobacteraceae using a group-specific PCR targeting the 16S rRNA gene. Additional experiments were carried out to evaluate the spread of EHS among mice harbored in different caging systems. Helicobacter species were detected in 87.5% of the mouse lines tested. Five different Helicobacter species were identified: H. ganmani, H. hepaticus, H. typhlonicus, and the putative Helicobacter species represented by the isolates hamster B and MIT 98-5357. Helicobacter infection did not spread between animals in neighboring cages when individually ventilated cages were used; in contrast, when the mice were reared in open-air cages, EHS were found to spread from cage to cage. However, the spread was prevented by adding polycarbonate filter tops to the cages. When Helicobacter-negative and infected mice shared the same cage, transmission of the infection occurred in 100% within 2 weeks. Furthermore, we found that mice from commercial breeding facilities may carry undetected Helicobacter infections. Taken together, we show that infection with EHS may frequently occur and spread easily in mice reared under SPF conditions despite extensive safety precautions. Moreover, there is a high prevalence of rather uncommon Helicobacter species that may be a consequence of the current routine procedures used for health screening of SPF mice.

Calidad microbiológica de los quesos blancos venezolanos analizados en el Instituto Nacional de Higiene "Rafael Rangel": período enero 1988 a junio 1998 / Microbiological quality of the white cheese venezuelan analyzed in the Instituto Nacional de Higiene \"Rafael Rangel\": period january 1988 a june 1998

Este trabajo tiene como objetivo evaluar la calidad microbiológica de los quesos blancos venezolanos analizados en el Instituto Nacional de Higiene "Rafael Rangel" en un período de 10 años: enero 1988 a Junio 1998. Se estudiaron 512 muestras recibidas para análisis de registro, control sanitario y como sospechosas de ocasionar enfermedades transmitidas por alimentos (ETA). Los quesos blancos evaluados incluyeron las sigientes denominaciones : duro, semi-duro, blando, criollo, llanero, de cincho y pasteurizado. Se determinó: coliformes; coliformes fecales; salmonella sp; Staphylococcus aureus ; mohos y levaduras; según las normas COVENIN. Además se investigó presencia de enterotoxinas de S. aureus (Tipos A-B-C-D) en las muestras implicadas con casos o brotes de ETA. Se encontró respectivamente, que el 80,6 por ciento y 73,8 por ciento de las muestras analizadas contenían coliformes y coliformes fecales en valores superiores de 3,0 log Nmp/g. El recuento de mohos para las muestras analizadas de registro y control fue menor o igual a 3,0 log ufc/g en el 73,7 por ciento de las mismas; mientras que el recuento de levaduras fue mayor de 3,0 log ufc/g en el 88,4 por ciento de las muestras. La incidencia de Salmonella sp en las muestras analizadas fue de 2,1 y la de S aureus expresada como log ufc/g, indicó que el 73,8 por ciento de las muestras de registro tenían valores menores o iguales a 3,0; mientras que el 72,3 por ciento y el 82,9 por ciento de las muestras de control y las sospechosas de ETA respectivamente, se ubicaron en valores superiores de 44,2 por ciento de las muestras, resultando el tipo A como la más frecuente. El 98,8 por ciento del total de las muestras analizadas presentaron resultados no satisfactorios para los parámetros evaluados. Estos resultados revelan una calidad microbiológica deficiente e indican que este alimento representa un riesgo directo para la salud de los consumidores, por tanto es necesario establecer controles permanentes durante el proceso de elaboración y distribución, así como promover cambios tecnológicos en la fabricación y la comercialización para garantizar la obtención de un producto de adecuada calidad higiénica