Insertions and deletions in the hypervariable region of the hepatitis E virus genome in individuals with acute and chronic infection.

BACKGROUND AND AIMS: Hepatitis E virus is a major cause of acute hepatitis worldwide and can progress to chronicity in immunocompromised individuals. Various virus-host recombination events have been reported in the hypervariable region of the hepatitis E virus genome, but the patterns of assembly and selection remain unclear. METHODS: To gain further insight into viral evolution, we assessed the presence of low abundance variants in 16 samples from individuals with acute or chronic infection using a targeted next-generation sequencing approach. RESULTS: In seven samples, different variants with insertions and/or deletions were identified. Among them, eight insertions originating either from human genes or from the hepatitis E virus genome. Five different deletions could be identified. The amino acid composition of sequences with insertions showed a higher frequency of lysine and a lower abundance of proline, and additionally acetylation and ubiquitination sites were more frequent than in hepatitis E virus wild-type sequences. CONCLUSIONS: These findings suggest that the nucleotide composition of insertions and sites for post-translational modification may contribute to recombination events. Although the impact of low-level hepatitis E virus variants is uncertain, our results highlight the importance of a highly sensitive next-generation sequencing approach to capture the full diversity of hypervariable region.

Diversity of human astroviruses in Germany 2018 and 2019.

Aim of this study was to investigate the molecular diversity of human astroviruses (HAstV) in Germany. A follow-up study was performed with human stool samples collected in 2018-2019, which were genotyped retrospectively. A total of 2645 stool samples, collected between January 2018 and December 2019 from sporadic cases and outbreaks of acute gastroenteritis were analyzed. An algorithm of PCR systems was used to characterize human astrovirus. Human astroviruses were found in 40 samples (positive rate: 1.6%). During the study period, children aged 1-2 years (48%) were most affected by HAstV. Genotyping revealed a number of nine circulating genotypes representing four human Mamastrovirus species. Strain MLB1 was predominant in the study population with a detection rate of 25% followed by HAstV1 with a positive rate of 20%. The diversity of astrovirus genotypes seems to be rather stable in Germany in the last years. A clustering of regionally and/or temporally linked human astroviruses in Germany was not detectable.

Hepatitis E: An update on One Health and clinical medicine.

The hepatitis E virus (HEV) is one of the main causes of acute hepatitis and the de facto global burden is underestimated. HEV-related clinical complications are often undetected and are not considered in the differential diagnosis. Convincing findings from studies suggest that HEV is clinically relevant not only in developing countries but also in industrialized countries. Eight HEV genotypes (HEV-1 to HEV-8) with different human and animal hosts and other HEV-related viruses are in circulation. Transmission routes vary by genotype and location, with large waterborne outbreaks in developing countries and zoonotic food-borne infections in developed countries. An acute infection can be aggravated in pregnant women, organ transplant recipients, patients with pre-existing liver disease and immunosuppressed patients. HEV during pregnancy affects the fetus and newborn with an increased risk of vertical transmission, preterm and stillbirth, neonatal jaundice and miscarriage. Hepatitis E is associated with extrahepatic manifestations that include neurological disorders such as neuralgic amyotrophy, Guillain-Barré syndrome and encephalitis, renal injury and haematological disorders. The risk of transfusion-transmitted HEV is increasingly recognized in Western countries where the risk may be because of a zoonosis. RNA testing of blood components is essential to determine the risk of transfusion-transmitted HEV. There are currently no approved drugs or vaccines for HEV infections. This review focuses on updating the latest developments in zoonoses, screening and diagnostics, drugs in use and under development, and vaccines.

Patient Satisfaction and Clinical Complications after Endoscopic or Surgical Saphenous Vein Harvesting.

BACKGROUND: Endoscopic saphenous vein harvesting (EVH) for coronary artery bypass grafting (CABG) has been developed to reduce leg wound problems. This study was undertaken to evaluate postoperative complications and patient's subjective satisfaction comparing EVH and surgical vein harvesting (SVH). METHODS: From January to December 2017, patients undergoing elective cardiac surgery (CABG, CABG + Valve repair or replacement) underwent saphenous vein graft harvesting either by EVH (n = 136) or SVH (n = 104). Clinical follow-up was scheduled for day 7 and > 45 days after surgery. Primary end points were divided into two subgroups. The first one included postoperative extent of subjective pain and satisfaction with the cosmetic results described by the patients themselves, while the second subgroup included objective postoperative complications including wound healing disturbances, hematoma, and neuropathy. Secondary end point was length of hospital stay. RESULTS: At 7 days follow-up, EVH patients were more satisfied with the cosmetic results than those of the SVH group (p < 0.001) and expressed a significant tendency toward lower subjective pain compared with the SVH patients (p < 0.001), exhibited significantly lower cellulitis (p-0.002), neuropathy (p-0.005), and superficial wound healing disturbance (p-0.007). During further follow-up at > 45 days, patients with EVH were still more satisfied with the cosmetic results (p < 0.001) and expressed lower subjective pain (p < 0.001), while the other objective wound parameters did not show significant differences between both groups. Mean length of hospital stay of EVH patients was 0.7 days less compared with SVH patients. CONCLUSIONS: Our findings demonstrate the noninferiority of EVH in the short term and in the early medium term.

Wrapping in Ascending Aortic Aneurysms as an Alternative for Replacement: Is It Beneficial?

BACKGROUND: Prosthetic replacement of aneurysms of the ascending aorta is the gold standard in terms of long-term stability. Wrapping seems to be a less invasive procedure. It has not yet been shown if it is as safe in terms of long-term outcome. METHODS: We present a single-center analysis of our experience over 13 years. We retrospectively analyzed data from patients who received either aortic prosthetic wrapping (AW) or aortic prosthetic replacement (AR) with or without aortic valve replacement and assessed them through phone calls. We used propensity score matching to adjust the baseline of the groups. RESULTS: Before propensity matching, 144 patients received AW and 91 patients underwent AR. Mean age was 64 ± 11.8 years. After propensity score matching and adjusting for significant differences in age, gender, body mass index, logistic EuroSCORE I, and left ventricular function, 69 patients in each group remained for further analysis. Rate of early reoperation due to tamponade, inhospital mortality, and survival rates did not differ. In both groups, the surgically treated aortic segment did not show enlargement, whereas the nontreated aortic arch showed comparable aneurysmatical progression. CONCLUSIONS: AW is safe and feasible and can be used in elderly or frail patients in order to avoid an AR. Progression of the remaining native aortic segments occurs, thus requiring strict life-long follow-up to ensure an elective and thus safe approach for appropriate consecutive surgical measures, if required.

Adverse events of exercise therapy in randomised controlled trials: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the relative risk (RR) of serious and non-serious adverse events in patients treated with exercise therapy compared with those in a non-exercising control group. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Primary studies were identified based on The Cochrane Database of Systematic Reviews investigating the effect of exercise therapy. ELIGIBILITY CRITERIA: At least two of the authors independently evaluated all identified reviews and primary studies. Randomised controlled trials were included if they compared any exercise therapy intervention with a non-exercising control. Two authors independently extracted data. The RR of serious and non-serious adverse events was estimated separately. RESULTS: 180 Cochrane reviews were included and from these, 773 primary studies were identified. Of these, 378 studies (n=38 368 participants) reported serious adverse events and 375 studies (n=38 517 participants) reported non-serious adverse events. We found no increase in risk of serious adverse events (RR=0.96 (95%CI 0.90 to 1.02, I2: 0.0%) due to exercise therapy. There was, however, an increase in non-serious adverse events (RR=1.19 (95%CI 1.09 to 1.30, I2: 0.0%). The number needed to treat for an additional harmful outcome for non-serious adverse events was 6 [95%CI 4 to 11). CONCLUSION: Participating in an exercise intervention increased the relative risk of non-serious adverse events, but not of serious adverse events. Exercise therapy may therefore be recommended as a relatively safe intervention.PROSPERO registration numberCRD42014014819.

How Do Transcatheter Heart Valves Fit in Mitral Annuloplasty Rings and Which Combination Can be Recommended?

BACKGROUND: Transcatheter heart valve (THV) as valve-in-ring is increasingly used in the mitral position. Semi-rigid rings may serve as a more appropriate scaffold for proper anchoring of a THV as they may change from their oval to a round shape thereby fitting to the implanted THV. METHODS: One rigid and five semi-rigid rings of four manufacturers, Edwards Physio I and II, Sorin 3D Memo, Medtronic Simulus, and St. Jude Medical (SJM) Saddle and SJM Sequin, with sizes 28 to 36 mm and Edwards Sapien III THV 23, 26, and 29 mm were used. Preevaluation comprised insertion/inflation of the THV into the ring and visual inspection for the paravalvular gap ≥ 4 mm2. Only valves not showing paravalvular gap were then submitted to hemodynamic evaluation with a pulse duplicator. Cusp movement was assessed with a high-speed-camera. Mean transvalvular gradients (TVGs) were measured. RESULTS: SJM Saddle ring of all sizes and SJM Sequin ring 34 showed marked gaps combined with all THV sizes, thus not undergoing hemodynamic testing. It was further shown that ring sizes ≥ 36 mm did not allow for a proper fit of even the largest THV into the ring of all the manufacturers and were consequently not hemodynamically evaluated. The 23 mm THV was too small for any ring size. The lowest gradients were achieved with the 26 mm THV in 30 and 32 mm and the 29 mm THV in 32 and 34 mm rings. CONCLUSION: Not all currently available annuloplasty rings are ideal scaffolds for THV placement. It appears that a more proper fit can be achieved with semi-rigid rings than with rigid ones. Note that 23 mm THV appeared to be too small for an adequate anchoring in even the smallest available ring. Thus, 26 mm as well as 29 mm THV fit properly in ring sizes between 28 and 34 mm. Surgeons may consider to choose from those ring brands and sizes which allow for good placement of a THV in view of possible valve degeneration in the later course.

Endocarditis: An Ever Increasing Problem in Cardiac Surgery.

BACKGROUND: Endocarditis remains one of the most threatening diagnoses in cardiac surgery and is still increasing. Particularly, device-related as well as prosthetic endocarditis appears to be on the rise. Early mortality and periprocedural complications are high jeopardizing the success of surgical efforts. We looked at the development of the numbers and the distribution of endocarditis in an all-comer analysis. METHODS: From 2003 to 2017, 752 patients with endocarditis were transferred to our cardiosurgical institution (mean age 65 ± 13 years; mean logistic EuroSCORE 28.01%; males 74.33%). A total of 89.49% of them were surgically treated; 30.01% redo cases thereof; and 9.17% had been operated previously for acute endocarditis. RESULTS: While the total number of cardiosurgical procedures remained relatively stable throughout the years, 20 patients were admitted in 2003 and 79 in 2017 yielding more than fourfold increase (p < 0.001). Early mortality of all patients was 25.1%. Septic emboli occurred in 23.7% and 43.8% cerebral emboli thereof. A significant increase of aortic, mitral, and tricuspid valves involvement was observed (p < 0.001). An increase of device-related endocarditis was also noted (p < 0.001). CONCLUSION: Endocarditis remains a serious problem with high early mortality and morbidity. The vast increase of electrophysiological device implantations has resulted in an increase of tricuspid valve involvement. Liberalization of endocarditis prophylaxis, that is, more restrictive use of antibiotics in 2007 may have at least partially contributed to an increase of the individual risk to suffer from acute endocarditis. A renaissance of a stricter endocarditis-prophylaxis may thus be considered.

MitraClip for High-Risk Patients with Significant Mitral Insufficiency: Shall We Unreservedly Recommend It?

BACKGROUND: MitraClip (Abbott Inc.) is propagated as a palliative option for high-risk patients with mitral insufficiency considered not qualifying for surgical repair. A proportion of patients requires consecutive surgery because of technical failure or inappropriate clinical improvement. Furthermore, surgical reconstruction is impossible in almost all patients after MitraClip implantation. Consequently, these patients receive replacement although primary repair may have been possible. The outcome of those patients compared with patients receiving primary mitral valve replacement (MVR) or mitral valve repair (MVP) was analyzed. METHODS: A total of 23 patients were retrospectively analyzed after MVR following MitraClip. Overall, 46 patients with corresponding demographic data and risk profile receiving primary MVR (23 patients) or MVP (23 patients) were retrieved for matched pair analysis. RESULTS: Mean age was 70 years in all groups, log European system for cardiac operative risk evaluation (EuroSCORE) was 22.47% ± 16.30 in MVR after MitraClip (MC), 22.34% ± 16.23 in MVP, and 22.33% ± 16.14 in MVR group. Preoperative left ventricular ejection fraction (LVEF) was 44%, and postoperative LVEF was 48% in all groups. The 30-day mortality was 21.7% in the MitraClip group whereas it was 4.3% in the MVR and 13.0% in the MVP group. The 1-year survival was 56.5% in the MitraClip group while it was 95.6% in the MVR group and 82.6% in the MVP group (Wilcoxon test: p = 0.007; chi-square test: p = 0.001 MitraClip vs. MVR; p = 0.054 MitraClip vs. MVP). CONCLUSIONS: Patients requiring surgical MVR after the previous MitraClip fared worse than matched cohorts receiving primary MVR or MVP. Indication for MitraClip should, therefore, be made very cautiously given the excellent results gained with primary surgery.

Detection and genome characterization of four novel bat hepadnaviruses and a hepevirus in China.

BACKGROUND: In recent years, novel hepadnaviruses, hepeviruses, hepatoviruses, and hepaciviruses have been discovered in various species of bat around the world, indicating that bats may act as natural reservoirs for these hepatitis viruses. In order to further assess the distribution of hepatitis viruses in bat populations in China, we tested the presence of these hepatitis viruses in our archived bat liver samples that originated from several bat species and various geographical regions in China. METHODS: A total of 78 bat liver samples (involving two families, five genera, and 17 species of bat) were examined using nested or heminested reverse transcription PCR (RT-PCR) with degenerate primers. Full-length genomic sequences of two virus strains were sequenced followed by phylogenetic analyses. RESULTS: Four samples were positive for hepadnavirus, only one was positive for hepevirus, and none of the samples were positive for hepatovirus or hepacivirus. The hepadnaviruses were discovered in the horseshoe bats, Rhinolophus sinicus and Rhinolophus affinis, and the hepevirus was found in the whiskered bat Myotis davidii. The full-length genomic sequences were determined for one of the two hepadnaviruses identified in R. sinicus (designated BtHBVRs3364) and the hepevirus (designated BtHEVMd2350). A sequence identity analysis indicated that BtHBVRs3364 had the highest degree of identity with a previously reported hepadnavirus from the roundleaf bat, Hipposideros pomona, from China, and BtHEVMd2350 had the highest degree of identity with a hepevirus found in the serotine bat, Eptesicus serotinus, from Germany, but it exhibited high levels of divergence at both the nucleotide and the amino acid levels. CONCLUSIONS: This is the first study to report that the Chinese horseshoe bat and the Chinese whiskered bat have been found to carry novel hepadnaviruses and a novel hepevirus, respectively. The discovery of BtHBVRs3364 further supports the significance of host switches evolution while opposing the co-evolutionary theory associated with hepadnaviruses. According to the latest criterion of the International Committee on Taxonomy of Viruses (ICTV), we hypothesize that BtHEVMd2350 represents an independent genotype within the species Orthohepevirus D of the family Hepeviridae.

Double-Wire versus Single-Wire Sternal Closure in Obese Patients: a Randomized Prospective Study.

Background Sternal instability after coronary artery bypass grafting (CABG) is a serious complication. Obese patients are at high risk for sternal instability after CABG. This study was conducted to assess the positive impact of double-wire sternal closure on sternal instability. Methods A total of 200 obese patients with a body mass index ≥ 30 kg/m2 undergoing isolated CABG with left internal mammary artery (LIMA) graft were randomly assigned to sternal closure either by eight single wires (n = 100) or by a combination of four double wires and four single wires. Results There was a total of 21 cases with sternal instability: 5 cases (i.e., 5%) in the double-wire group versus 16 cases (16%) in the single-wire group (p = 0.019). Logistic regression analysis showed sternal closure via double wires as an independent protection factor (odds ratio [OR]: 0.276; p = 0.029). Smoking (OR: 5.5; p = 0.006) and postoperative delirium (OR: 3.5; p = 0.033) turned out to be independent risk factors for the development of sternal instability. Conclusion Double-wire sternal closure significantly reduces postoperative sternal instability in obese patients undergoing isolated CABG with LIMA graft.

High variability of HIV and HCV seroprevalence and risk behaviours among people who inject drugs: results from a cross-sectional study using respondent-driven sampling in eight German cities (2011-14).

BACKGROUND: People who inject drugs (PWID) are at increased risk of acquiring and transmitting HIV and Hepatitis C (HCV) due to sharing injection paraphernalia and unprotected sex. To generate seroprevalence data on HIV and HCV among PWID and related data on risk behaviour, a multicentre sero- and behavioural survey using respondent driven sampling (RDS) was conducted in eight German cities between 2011 and 2014. We also evaluated the feasibility and effectiveness of RDS for recruiting PWID in the study cities. METHODS: Eligible for participation were people who had injected drugs within the last 12 months, were 16 years or older, and who consumed in one of the study cities. Participants were recruited, using low-threshold drop-in facilities as study sites. Initial seeds were selected to represent various sub-groups of people who inject drugs (PWID). Participants completed a face-to-face interview with a structured questionnaire about socio-demographics, sexual and injecting risk behaviours, as well as the utilisation of health services. Capillary blood samples were collected as dried blood spots and were anonymously tested for serological and molecular markers of HIV and HCV. The results are shown as range of proportions (min. and max. values (%)) in the respective study cities. For evaluation of the sampling method we applied criteria from the STROBE guidelines. RESULTS: Overall, 2,077 PWID were recruited. The range of age medians was 29-41 years, 18.5-35.3 % of participants were female, and 9.2-30.6 % were foreign born. Median time span since first injection were 10-18 years. Injecting during the last 30 days was reported by 76.0-88.4 % of participants. Sharing needle/syringes (last 30 days) ranged between 4.7 and 22.3 %, while sharing unsterile paraphernalia (spoon, filter, water, last 30 days) was reported by 33.0-43.8 %. A majority of participants (72.8-85.8 %) reported incarceration at least once, and 17.8-39.8 % had injected while incarcerated. Between 30.8 and 66.2 % were currently in opioid substitution therapy. Unweighted HIV seroprevalence ranged from 0-9.1 %, HCV from 42.3-75.0 %, and HCV-RNA from 23.1-54.0 %. The implementation of RDS as a recruiting method in cooperation with low-threshold drop in facilities was well accepted by both staff and PWID. We reached our targeted sample size in seven of eight cities. CONCLUSIONS: In the recruited sample of mostly current injectors with a long duration of injecting drug use, seroprevalence for HIV and HCV varied greatly between the city samples. HCV was endemic among participants in all city samples. Our results demonstrate the necessity of intensified prevention strategies for blood-borne infections among PWID in Germany.

Soluble MICB protein levels and platelet counts during hepatitis B virus infection and response to hepatocellular carcinoma treatment.

BACKGROUND: The human major histocompatibility complex class I polypeptide-related sequence B (MICB) is a protein that modulates the NK and T cell activation through the NKG2D receptor and is related to several diseases including cancer. METHODS: The study investigated the prognostic role of soluble MICB (sMICB) protein in the progression of HBV-related liver diseases and to HBV-related HCC treatment. The sMICB serum levels were measured in 266 chronic HBV-infected Vietnamese patients and in healthy controls, and correlated with clinical and laboratory parameters and with therapeutic interventions for HBV-related HCC. RESULTS: Significant differences in both clinical and laboratory parameters were observed among the patient groups with different stages of hepatitis. The platelet counts were significantly decreased with disease progression (P < 0.001). The sMICB serum levels were significantly increased in HBV patients compared to healthy controls (P < 0.0001). Among the patients with different stages of hepatitis, asymptomatic individuals (ASYM) revealed higher sMICB serum levels while liver cirrhosis (LC) patients revealed lower sMICB serum levels (P < 0.0001) compared to other patient groups. Notably, the sMICB serum levels were decreased in treated HCC patient group compared to not-treated HCC patient group (P = 0.05). Additionally, the sMICB levels were significantly correlated with platelet counts in ASYM and HCC patients (r = -0.37, P = 0.009; and r = 0.22, P = 0.025, respectively). CONCLUSIONS: Our results demonstrate a potential role of sMICB serum levels and platelet counts during immune response to the HBV infection, liver disease progression and response to the HCC treatment.

A multicentre sero-behavioural survey for hepatitis B and C, HIV and HTLV among people who inject drugs in Germany using respondent driven sampling.

BACKGROUND: People who inject drugs are at high risk for hepatitis B, hepatitis C and HIV. HTLV was reported by neighboring countries to be prevalent in this population, but the situation for Germany is unclear. To generate seroprevalence and related behavioural data and to enhance prevention efforts against these infections for drug users in Germany, a multicentre sero- and behavioural survey was initiated. People who inject drugs are not well reached by services for testing and counselling for blood-borne infections in Germany. An interventional part of the study is intended to prove feasibility and acceptance of testing and counselling in low-threshold drop-in settings. METHODS/DESIGN: Between May 2011 and March 2015, eligible participants (persons having injected drugs within the last 12 months, aged 16 years+, and living in the study city) are recruited by respondent driven sampling, using low-threshold drop-in facilities as study-sites in eight German cities with large drug scenes. Calculated sample size is 2,033 participants. Capillary blood samples collected as dried blood spots are anonymously tested for serological and molecular markers of hepatitis B and C, HIV, and HTLV I and II. A detailed face-to-face-interview about hepatitis- and HIV-related knowledge, former testing, imprisonment, sexual and injecting risk behaviour is conducted with participants. Staff is trained to offer pre- and post-test-counselling of blood-borne infections and HIV rapid testing to participants. DISCUSSION: We chose respondent driven sampling for recruitment of participants to improve representativeness of results. Persons, who are not reached by the facility where the study is conducted, are aimed to be included by recruitment through their personal social network of injecting drug users. To reduce differential biases in the questions on knowledge of transmission and prevention of infections, we present true statements on hepatitis B, C and HIV, their possible routes of transmission and measures of prevention to participants. Participants are told that the statements are true and are asked to answer if they knew this fact already or if it is new to them. In case of knowledge gaps they are offered free targeted counselling as well as free HIV rapid testing and post-test counselling of HIV and hepatitis test results.

Genetic determinants of host- and virus-derived insertions for hepatitis E virus replication.

Hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans. Recent data suggest that HEV has a very heterogeneous hypervariable region (HVR), which can tolerate major genomic rearrangements. In this study, we identify insertions of previously undescribed sequence snippets in serum samples of a ribavirin treatment failure patient. These insertions increase viral replication while not affecting sensitivity towards ribavirin in a subgenomic replicon assay. All insertions contain a predicted nuclear localization sequence and alanine scanning mutagenesis of lysine residues in the HVR influences viral replication. Sequential replacement of lysine residues additionally alters intracellular localization in a fluorescence dye-coupled construct. Furthermore, distinct sequence patterns outside the HVR are identified as viral determinants that recapitulate the enhancing effect. In conclusion, patient-derived insertions can increase HEV replication and synergistically acting viral determinants in and outside the HVR are described. These results will help to understand the underlying principles of viral adaptation by viral- and host-sequence snatching during the clinical course of infection.

Risk Factors for Hepatitis E Virus Infection and Eating Habits in Kidney Transplant Recipients.

There is a significant risk for ongoing and treatment-resistant courses of hepatitis E virus (HEV) infection in patients after solid organ transplantation. The aim of this study was to identify risk factors for the development of hepatitis E, including the dietary habits of patients. We conducted a retrospective single-center study with 59 adult kidney and combined kidney transplant recipients who were diagnosed with HEV infection between 2013 and 2020. The outcomes of HEV infections were analyzed during a median follow-up of 4.3 years. Patients were compared with a control cohort of 251 transplant patients with elevated liver enzymes but without evidence of an HEV infection. Patients' alimentary exposures during the time before disease onset or diagnosis were assessed. Previous intense immunosuppression, especially treatment with high-dose steroids and rituximab, was a significant risk factor to acquire hepatitis E after solid organ transplantation. Only 11 out of 59 (18.6%) patients reached remission without further ribavirin (RBV) treatment. A total of 48 patients were treated with RBV, of which 19 patients (39.6%) had either viral rebounds after the end of treatment or did not reach viral clearance at all. Higher age (>60 years) and a BMI ≤ 20 kg/m2 were risk factors for RBV treatment failure. Deterioration in kidney function with a drop in eGFR (p = 0.046) and a rise in proteinuria was more common in patients with persistent hepatitis E viremia. HEV infection was associated with the consumption of undercooked pork or pork products prior to infection. Patients also reported processing raw meat with bare hands at home more frequently than the controls. Overall, we showed that the intensity of immunosuppression, higher age, a low BMI and the consumption of undercooked pork meat correlated with the development of hepatitis E.

Interferon-ß Suppresses Transcriptionally Active Parvovirus B19 Infection in Viral Cardiomyopathy: A Subgroup Analysis of the BICC-Trial.

Human parvovirus B19 (B19V) is the predominant virus currently detected in endomyocardial biopsies (EMBs). Recent findings indicate that, specifically, transcriptionally active B19V with detectable viral RNA is of prognostic relevance in inflammatory viral cardiomyopathy. We aimed to evaluate B19V replicative status (viral RNA) and beneficial effects in a sub-collective of the prospective randomized placebo-controlled phase II multi-center BICC-Trial (Betaferon In Chronic Viral Cardiomyopathy) after interferon beta-1b (IFN-ß) treatment. EMBs of n = 64 patients with B19V mono-infected tissue were retrospectively analyzed. Viral RNA could be detected in n = 18/64 (28.1%) of B19V DNA positive samples (mean age 51.7 years, 12 male), of whom n = 13 had been treated with IFN-ß. Five patients had received placebo. PCR analysis confirmed in follow-up that EMBs significantly reduced viral RNA loads in n = 11/13 (84.6%) of IFN-ß treated patients (p = 0.001), independently from the IFN-ß dose, in contrast to the placebo group, where viral RNA load was not affected or even increased. Consequently, a significant improvement of left ventricular ejection fraction (LVEF) after treatment with IFN-ß was observed (LVEF mean baseline 51.6 ± 14.1% vs. follow-up 61.0 ± 17.5%, p = 0.03). In contrast, in the placebo group, worsening of LVEF was evaluated in n = 4/5 (80.0%) of patients. We could show for the first-time the beneficial effects from treatment with IFN-ß, suppressing B19V viral RNA and improving the hemodynamic course. Our results need further verification in a larger prospective randomized controlled trial.

Effectiveness of different types, delivery modes and extensiveness of exercise in patients with breast cancer receiving systemic treatment - A systematic review and meta-analysis.

BACKGROUND: Effects of exercise in patients with breast cancer have been thoroughly investigated. The aim was to explore differences in effects regarding type, delivery mode and extensiveness (e.g. intensity; volume) of the interventions. METHODS: We searched for randomised controlled trials including patients with breast cancer receiving systemic treatment, exercise-based interventions, and measures on patient reported- and objectively measured outcomes. RESULTS: Exercise showed significant and moderate effects on the primary outcomes quality of life and physical function, Standardised Mean Difference: 0.52 (95 % CI 0.38-0.65) and 0.52 (95 % CI 0.38-0.66), respectively. Type of exercise had little influence on the effects, however combined aerobic- and resistance exercise seemed superior for increasing physical function, compared to aerobic or resistance exercise. Supervised interventions were superior to partly and unsupervised. Extensiveness of the intervention only influenced physical function. CONCLUSIONS: Supervised interventions, more than type or extensiveness of interventions, seem to increase effects.

Identification of a Putative Novel Genotype of Avian Hepatitis E Virus from Apparently Healthy Chickens in Southwestern Nigeria.

Avian hepatitis E virus (aHEV) is the major etiological agent of hepatitis-splenomegaly syndrome (HSS), big liver and spleen disease (BLSD), and hepatic rupture hemorrhage syndrome (HRHS) in chickens. Infections with aHEV cause a significant decrease in egg production and increased mortality in chickens worldwide. However, studies on the prevalence of aHEV in Nigeria are scarce. In this study, serum (n = 88) and fecal samples (n = 110) obtained from apparently healthy layer chickens from three states in southwestern Nigeria were analyzed by nested reverse transcription-polymerase chain reaction (nRT-PCR) targeting the helicase and capsid gene for the presence of aHEV. Avian HEV was detected in 12.5% (n = 11/88) of serum samples and 9.1% (n = 10/110) of fecal samples tested. Phylogenetic analysis showed that five of the twelve identified aHEV sequences belonged to genotype 2. The remaining seven sequences were only distantly related to other known aHEV isolates. After amplification of the near-complete ORF2 fragment (1618 bp) and part of the ORF1 (582 bp) of isolate YF40_aHEV_NG phylogenetic analysis revealed a nucleotide sequence identity between 79.0 and 82.6% and 80.1 and 83.5%, respectively, to other known aHEV strains, indicating that the Nigerian isolate YF40_aHEV_NG belongs to a novel aHEV genotype. This is the first report of co-circulation of aHEV genotypes in chickens in Nigeria.