Short-term transfer effects of Tetris on mental rotation: Review and registered report - A Bayesian approach.

The existence of transfer effects of video games on cognitive performance are controversially discussed in experimental psychology. Whereas recent meta-analyses suggest the absence of far transfer effects, empirical evidence regarding near transfer effects is more controversial. This conceptual replication investigated the short-term near transfer effect of playing Tetris on mental rotation abilities. The design of the conceptual replication was based on a comprehensive compilation of the methods used by previous literature on this topic and advanced in order to reach a high scientific state-of-the-art standard. We ran a high-powered conceptual replication study with 366 participants randomly assigned to either an experimental group playing Tetris or a control group playing Solitaire. Both groups completed three commonly used mental rotation tests in a pre- and a posttest session. Additionally, the experimental group played Tetris while the control group played Solitaire. Playing time was 10 hours in total within 4 weeks. Based on previous research, we hypothesized that this might generate a short-term transfer effect of Tetris on mental rotation. While participants showed a repeated testing effect for the mental rotation tests in both groups, we found evidence that Tetris does not produce a short-term transfer effect on mental rotation. Both gender and expected outcomes did not influence this effect. Our study suggests that playing Tetris does not improve mental rotation skills.

The chemicals between us-First results of the cluster analyses on anatomy embalming procedures in the German-speaking countries.

Hands-on courses utilizing preserved human tissues for educational training offer an important pathway to acquire basic anatomical knowledge. Owing to the reevaluation of formaldehyde limits by the European Commission, a joint approach was chosen by the German-speaking anatomies in Europe (Germany, Austria, Switzerland) to find commonalities among embalming protocols and infrastructure. A survey comprising 537 items was circulated to all anatomies in German-speaking Europe. Clusters were established for "ethanol"-, formaldehyde-based ("FA"), and "other" embalming procedures, depending on the chemicals considered the most relevant for each protocol. The logistical framework, volumes of chemicals, and infrastructure were found to be highly diverse between the groups and protocols. Formaldehyde quantities deployed per annum were three-fold higher in the "FA" (223 L/a) compared to the "ethanol" (71.0 L/a) group, but not for "other" (97.8 L/a), though the volumes injected per body were similar. "FA" was strongly related to table-borne air ventilation and total fixative volumes ≤1000 L. "Ethanol" was strongly related to total fixative volumes >1000 L, ceiling- and floor-borne air ventilation, and explosion-proof facilities. Air ventilation was found to be installed symmetrically in the mortuary and dissection facilities. Certain predictors exist for the interplay between the embalming used in a given infrastructure and technical measures. The here-established cluster analysis may serve as decision supportive tool when considering altering embalming protocols or establishing joint protocols between institutions, following a best practice approach to cater toward best-suited tissue characteristics for educational purposes, while simultaneously addressing future demands on exposure limits.

In Vitro Simulated Neuronal Environmental Conditions Qualify Umbilical Cord Derived Highly Potent Stem Cells for Neuronal Differentiation.

The healing of neuronal injuries is still an unachieved goal. Medicine-based therapies can only extend the survival of patients, but not finally lead to a healing process. Currently, a variety of stem cell-based tissue engineering developments are the subject of many research projects to bridge this gap. As yet, neuronal differentiation of induced pluripotent stem cells (iPS), embryonic cell lines, or neuronal stem cells could be accomplished and produce functional neuronally differentiated cells. However, clinical application of cells from these sources is hampered by ethical considerations. To overcome these hurdles numerous studies investigated the potential of adult mesenchymal stem cells (MSCs) as a potential stem cell source. Adult MSCs have been approved as cellular therapeutical products due to their regenerative potential and immunomodulatory properties. Only a few of these studies could demonstrate the capacity to differentiate MSCs into active firing neuron like cells. With this study we investigated the potential of Wharton's Jelly (WJ) derived stem cells and focused on the intrinsic pluripotent stem cell pool and their potential to differentiate into active neurons. With a comprehensive neuronal differentiation protocol comprised of mechanical and biochemical inductive cues, we investigated the capacity of spontaneously forming stem cell spheroids (SCS) from cultured WJ stromal cells in regard to their neuronal differentiation potential and compared them to undifferentiated spheroids or adherent MSCs. Spontaneously formed SCSs show pluripotent and neuroectodermal lineage markers, meeting the pre-condition for neuronal differentiation and contain a higher amount of cells which can be differentiated into cells whose functional phenotypes in calcium and voltage responsive electrical activity are similar to neurons. In conclusion we show that up-concentration of stem cells from WJ with pluripotent characteristics is a tool to generate neuronal cell replacement.

Processing spatial configurations in visuospatial working memory is influenced by shifts of overt visual attention.

When memorizing multiple objects, humans process them in relation to each other, proposing a configuration benefit. Shifts in overt visual attention through eye movements might influence the processing of spatial configurations. Whereas some research suggests that overt visual attention aids the processing of spatial representations, other research suggests a snapshot-like processing of spatial configurations, thus likely not relying on eye movements. In the first experiment, we focused on the comparison between an enforced fixation and a free view condition regarding configurational effects. Participants encoded objects' locations and were asked for changes at retrieval. One object was displaced in half of the trials and was either accompanied by a configuration or was displayed alone. In the second experiment, we expanded this idea by enforcing fixation during different task phases, namely encoding, maintenance and retrieval. We investigated if a fixed gaze during one specific phase drives the influence of eye movements when processing spatial configurations. We observed reliable configuration benefits for the free view conditions. Whereas a fixed gaze throughout the whole trial reduced the effect, enforced fixations during the task phases did not break the configuration benefit. Our findings suggest that whereas the processing of spatial configurations in memory is supported by the ability of performing shifts of overt visual attention, configurational processing does not rely on these shifts occurring throughout the task. Our results indicate a reciprocal relationship of visuospatial working memory and eye movements.

SARS-CoV-2 seroprevalence and determinants of infection in young adults: a population-based seroepidemiological study.

OBJECTIVES: Most SARS-CoV-2 seroprevalence studies have focussed on adults and high-risk populations, and little is known about young adults. The objective of the present study was to provide evidence on the SARS-CoV-2 seroprevalence among young adults in Germany and to explore determinants associated with seropositivity in general and, specifically, with previously undetected infections. STUDY DESIGN: This was a population-based SARS-CoV-2 seroprevalence study. METHODS: In November 2020, a population-based study on SARS-CoV-2 seroprevalence in young adults (aged 18-30 years) was conducted in a large German city. Serum samples were obtained to analyse the SARS-CoV-2 antibody status using the Elecsys Anti-SARS-CoV-2 immunoassay. Descriptive statistics and odds ratios (ORs) of seropositivity and of previously undetected infections in relation to different determinants were calculated. RESULTS: Among 2186 participants, SARS-CoV-2 antibodies were detected in 72 individuals, equalling a test performance-adjusted seroprevalence of 3.1% (95% confidence interval [CI]: 2.4-4.0). Based on reported COVID-19 cases to the public health authority, a moderate underascertainment rate of 1.7 was calculated. Seropositivity was higher among individuals who sought COVID-19-related information from social media (OR: 1.83, 95% CI: 1.2-3.1), and undetected COVID-19 infections were more prevalent among men and those not adhering to social distancing. CONCLUSIONS: The results show a substantial underascertainment of SARS-CoV-2 infections among young adults and indicate that seroprevalence is likely to be much higher than the reported COVID-19 prevalence based on confirmed COVID-19 cases in Germany. Preventive efforts should consider the heterogeneity of risk profiles among the young adult population.

Acute or chronic pulmonary emphysema? Or both?-A contribution to the diagnosis of death due to violent asphyxiation in cases with pre-existing chronic emphysema.

The diagnosis of death due to violent asphyxiation may be challenging if external injuries are missing, and a typical acute emphysema (AE) "disappears" in pre-existing chronic emphysema (CE). Eighty-four autopsy cases were systematically investigated to identify a (histo-) morphological or immunohistochemical marker combination that enables the diagnosis of violent asphyxiation in cases with a pre-existing CE ("AE in CE"). The cases comprised four diagnostic groups, namely "AE", "CE", "acute and chronic emphysema (AE + CE)", and "no emphysema (NE)". Samples from all pulmonary lobes were investigated by conventional histological methods as well as with the immunohistochemical markers Aquaporin 5 (AQP-5) and Surfactant protein A1 (SP-A). Particular attention was paid to alveolar septum ends ("dead-ends") suspected as rupture spots, which were additionally analyzed by transmission electron microscopy. The findings in the four diagnostic groups were compared using multivariate analysis and 1-way ANOVA analysis. All morphological findings were found in all four groups. Based on histological and macroscopic findings, a multivariate analysis was able to predict the correct diagnosis "AE + CE" with a probability of 50%, and the diagnoses "AE" and "CE" with a probability of 86% each. Three types of "dead-ends" could be differentiated. One type ("fringed ends") was observed significantly more frequently in AE. The immunohistochemical markers AQP-5 and SP-A did not show significant differences among the examined groups. Though a reliable identification of AE in CE could not be achieved using the examined parameters, our findings suggest that considering many different findings from the macroscopical, histomorphological, and molecular level by multivariate analysis is an approach that should be followed.

Underascertainment of COVID-19 cases among first responders: a seroepidemiological study.

BACKGROUND: Providing frontline support places first responders at a high risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. AIMS: This study was aimed to determine the anti-SARS-CoV-2 seroprevalence in a cohort of first responders (i.e. firefighters/paramedics), to detect the underascertainment rate and to assess risk factors associated with seropositivity. METHODS: We conducted a serological survey among 745 first responders in Germany during 27 November and 4 December 2020 to determine the anti-SARS-CoV-2 seroprevalence using Elecsys® Anti-SARS-CoV-2 immunoassay (Roche Diagnostics, Mannheim, Germany). As part of the examination, participants were asked to provide information on coronavirus disease 2019 (COVID-19)-like-symptoms, information on sociodemographic characteristics and workplace risk factors for a SARS-CoV-2 infection and any prior COVID-19 infection. Descriptive statistics and logistic regression analysis were performed and seroprevalence estimates were adjusted for test sensitivity and specificity. RESULTS: The test-adjusted seroprevalence was 4% (95% CI 3.1-6.2) and the underascertainment rate was 2.3. Of those tested SARS-CoV-2 antibody positive, 41% were aware that they had been infected in the past. Seropositivity was elevated among paramedics who worked in the emergency rescue team providing first level of pre-hospital emergency care (6% [95% CI 3.4-8.6]) and those directly exposed to a COVID-19 case (5% [95% CI 3.5-8.1]). Overall, the seroprevalence and the underascertainment rate were higher among first responders than among the general population. CONCLUSIONS: The high seroprevalence and underascertainment rate highlight the need to mitigate potential transmission within and between first responders and patients. Workplace control measures such as increased and regular COVID-19-testing and the prompt vaccination of all personnel are necessary.

Torque Teno Virus plasma level as novel biomarker of retained immunocompetence in HIV-infected patients.

PURPOSE: To predict the course of immune recovery (IR) in HIV-1-infected patients after initiation of combined antiretroviral therapy (cART) by determination of the plasma concentration of Torque Teno Virus (TTV). TTV has been identified as marker for risk assessment in immunosuppressed patients after transplantation procedures. Here, TTV was analyzed in HIV-1-infected therapy-naïve patients to evaluate its use as predictor of the course of IR for guidance of individualized treatment. METHODS: TTV DNA was quantified in plasma samples of 301 therapy-naïve HIV-1-infected patients and correlated to CD4+ cell count, HIV viral load, presence of the herpes viruses CMV, EBV and HHV-8, age and sex. Patients were classified according to their initial CD4+ cell count and to the extent of CD4+ T-cell increase within the first year of cART. RESULTS: TTV DNA was detectable in 96% of the patients' plasma samples with a median TTV plasma concentration of 5.37 log10 cop/ml. The baseline CD4+ cell count was negatively correlated with TTV plasma concentration (p = 0.003). In patients with a CD4+ cell recovery < 50 cells/µl, the median TTV plasma concentration was significantly higher compared to patients with a CD4+ cell recovery of > 200 CD4+ cells/µl (5.68 log10 cop/ml versus 4.99 log10 cop/ml; p = 0.011). TTV plasma concentration in combination with baseline CD4+ cell count were significantly correlated to CD4+ cell recovery (p = 0.004). For all other parameters considered, no significant correlation for CD4+ cell recovery was found. CONCLUSION: Within the cohort, the significantly elevated TTV plasma concentration in patients with diminished CD4+ cell recovery indicates a more profound immune defect. Baseline TTV plasma concentrations and CD4+ cell count are predictive for the course of immune recovery in HIV-1-infected patients with severe immunodeficiency.

Assessment of Psychosocial Functioning in a Large Cohort of Patients with Schizophrenia.

BACKGROUND: This study addresses the question of whether psychosocial functioning measured by the Personal and Social Performance (PSP) Scale is related to various psychopathological measures in a cohort of patients with schizophrenia. METHODS: The 'Neuroleptic Strategy Study' (NeSSy) performed at 14 German hospitals between 2010 and 2013 compared two treatment strategies instead of individual drugs. Secondary end-points were the two PSP scales as well as measures of quality of life (SF-36) and the Positive and Negative Syndrome Scale (PANSS). RESULTS: 149 patients were randomised. There was no difference between the two treatment strategies (first-generation versus second-generation antipsychotics) with regard to the PSP. There were differences in doctors' assessments regarding psychosocial functioning compared with patients' own assessments. Furthermore, there were relationships between the PSP and quality of life, level of skills (ICF), and severity of disease (PANSS), level of sexual activities and poor well-being under antipsychotic medication but not with cognitive changes. CONCLUSIONS: The findings on psychosocial functioning of patients with schizophrenia related to severity and skill level could be confirmed. Further findings were the correlation between psychosocial functioning and quality of life, well-being under treatment, and sexuality what emphasizes the substantial importance of a reduced psychosocial functioning.

Do group ensemble statistics bias visual working memory for individual items? A registered replication of Brady and Alvarez (2011).

We performed a registered and precise replication of Experiment 1 reported in Brady and Alvarez (Psychological Science, 22, 384-392, 2011). The original experiment found that participants, who were asked to memorize the size of differently colored circles, reported the size of a probed circle biased toward the mean size of the same-colored group. Because our previous three unpublished replication attempts failed to find this effect, we powered the present registered replication using a Bayes Factor Design Analysis such that it provided compelling evidence regarding the presence or absence of the reported bias with a high probability, even under the assumption of smaller effect sizes. Thus, we recruited 663 participants through Amazon Mechanical Turk. We observed both a significant bias and strong Bayesian evidence in favor of the existence of a bias over the null hypothesis. Thus, our results can be considered a successful replication of the original findings, although with a considerably smaller effect size. We discuss the role of data quality when recruiting participants with Amazon Mechanical Turk. The present findings corroborate the idea that memory representations of individual objects are influenced by summary statistics.

(Re-)organisation of spatial configurations in visual working memory: The fate of objects rendered relevant or irrelevant by selective attention.

People maintain object locations not as independent absolute positions but based on inter-object relations in the form of a spatial configuration in visual working memory (VWM). Initial evidence suggests that spatial configurations can be reorganised during maintenance; however, this mechanism is not well understood. We report three experiments investigating this reorganisation process. First, we found that directing spatial attention with a retro cue triggers a reorganisation of spatial configurations during maintenance (Experiment 1). Second, we investigated the role of contextual objects rendered either relevant or irrelevant through the retro cue by manipulating the locations of the context at retrieval both within a partial display (Experiment 2a) and a whole display (Experiment 2b). Whereas the similar impairment of memory performance by changing the relevant and global context suggests a complete reorganisation of spatial configurations in VWM, this interpretation was challenged by the observation of impaired memory performance with changes of the irrelevant objects in a whole display that retains the relevant locations. Thus, we suggest that reorganisation should be considered to be the formation of a partial configuration based on the objects rendered relevant by the retro cue in addition to the originally encoded global configuration, with both configurations affecting memory performance.

Engineering Biocompatible Interfaces via Combinations of Oxide Films and Organic Self-Assembled Monolayers.

In this paper, we demonstrate that cell adhesion and neuron maturation can be guided by patterned oxide surfaces functionalized with organic molecular layers. It is shown that the difference in the surface potential of various oxides (SiO2, Ta2O5, TiO2, and Al2O3) can be increased by functionalization with a silane, (3-aminopropyl)-triethoxysilane (APTES), which is deposited from the gas phase on the oxide. Furthermore, it seems that only physisorbed layers (no chemical binding) can be achieved for some oxides (Ta2O5 and TiO2), whereas self-assembled monolayers (SAM) form on other oxides (SiO2 and Al2O3). This does not only alter the surface potential but also affects the neuronal cell growth. The already high cell density on SiO2 is increased further by the chemically bound APTES SAM, whereas the already low cell density on Ta2O5 is even further reduced by the physisorbed APTES layer. As a result, the cell density is ∼8 times greater on SiO2 compared to Ta2O5, both coated with APTES. Furthermore, neurons form the typical networks on SiO2, whereas they tend to cluster to form neurospheres on Ta2O5. Using lithographically patterned Ta2O5 layers on SiO2 substrates functionalized with APTES, the guided growth can be transferred to complex patterns. Cell cultures and molecular layers can easily be removed, and the cell experiment can be repeated after functionalization of the patterned oxide surface with APTES. Thus, the combination of APTES-functionalized patterned oxides might offer a promising way of achieving guided neuronal growth on robust and reusable substrates.

Reorganization of spatial configurations in visual working memory: A matter of set size?

Humans process single objects in relation to other simultaneously maintained objects in visual working memory. This interdependence is called spatial configuration. Humans are able to reorganize global spatial configurations into relevant partial configurations. We conducted three experiments investigating the process underlying reorganization by manipulating memory set size and the presence of configurations at retrieval. Participants performed a location change detection task for a single object probed at retrieval. At the beginning of each trial, participants memorized the locations of all objects (set size: 4, 8, 12, or 16). During maintenance, a valid retro cue highlighted the side containing the object probed at retrieval, thus enabling participants to reorganize the memorized global spatial configuration to the partial cued configuration. At retrieval, the object probed was shown together with either all objects (complete configuration; Experiment 1a), the cued objects only (congruent configuration; all Experiments), the non-cued objects only (incongruent configuration, all Experiments) or alone (no configuration; Experiment 1b). We observed reorganization of spatial configurations as indicated by a superior location change detection performance with a congruent partial configuration than an incongruent partial configuration across all three experiments. We also observed an overall decrease in accuracy with increasing set size. Most importantly, however, we did not find evidence for a reliable impairment of reorganization with increasing set size. We discuss these findings with regard to the memory representation underlying spatial configurations.

MEA Recordings and Cell-Substrate Investigations with Plasmonic and Transparent, Tunable Holey Gold.

Microelectrode arrays are widely used in different fields such as neurobiology or biomedicine to read out electrical signals from cells or biomolecules. One way to improve microelectrode applications is the development of novel electrode materials with enhanced or additional functionality. In this study, we fabricated macroelectrodes and microelectrode arrays containing gold penetrated by nanohole arrays as a conductive layer. We used this holey gold to optically excite surface plasmon polaritons, which lead to a strong increase in transparency, an effect that is further enhanced by the plasmon's interaction with cell culture medium. By varying the nanohole diameter in finite-difference time domain simulations, we demonstrate that the transmission can be increased to above 70% with its peak at a wavelength depending on the holey gold's lattice constant. Further, we demonstrate that the novel transparent microelectrode arrays are as suitable for recording cellular electrical activity as standard devices. Moreover, we prove using spectral measurements and finite-difference time domain simulations that plasmonically induced transmission peaks of holey gold red-shift upon sensing medium or cells in close vicinity (<30 nm) to the substrate. Thus, we establish plasmonic and transparent holey gold as a tunable material suitable for cellular electrical recordings and biosensing applications.

Improvements of Microcontact Printing for Micropatterned Cell Growth by Contrast Enhancement.

Patterned neuronal cell cultures are important tools for investigating neuronal signal integration, network function, and cell-substrate interactions. Because of the variable nature of neuronal cells, the widely used coating method of microcontact printing is in constant need of improvements and adaptations depending on the pattern, cell type, and coating solutions available for a certain experimental system. In this work, we report on three approaches to modify microcontact printing on borosilicate glass surfaces, which we evaluate with contact angle measurements and by determining the quality of patterned neuronal growth. Although background toxification with manganese salt does not result in the desired pattern enhancement, a simple heat treatment of the glass substrates leads to improved background hydrophobicity and therefore neuronal patterning. Thirdly, we extended a microcontact printing process based on covalently linking the glass surface and the coating molecule via an epoxysilane. This extension is an additional hydrophobization step with dodecylamine. We demonstrate that shelf life of the silanized glass is at least 22 weeks, leading to consistently reliable neuronal patterning by microcontact printing. Thus, we compared three practical additions to microcontact printing, two of which can easily be implemented into a workflow for the investigation of patterned neuronal networks.

Reorganization of spatial configurations in visual working memory.

Human beings have to constantly process multiple objects in visual working memory (VWM). Positional relations to other objects known as spatial configurations contribute significantly to the organization of information in VWM. The aim of our study was to clarify whether spatial configurations can be reorganized to a subset of objects during maintenance. Participants were shown an array of objects, and afterwards the objects disappeared. A valid cue was shown either during encoding or maintenance to highlight the side of the following probed object. Afterwards, the objects reappeared and participants were instructed to detect whether or not a particular object changed its location. We manipulated the configurations at retrieval regarding the number of objects, ranging from all objects to a single object. Our first and second experiment investigated reorganization for a number of six and 12 objects, respectively. In the third experiment, we used a retro cue only and manipulated eye movements (free view vs. enforced fixation). While showing that reorganization of spatial configurations during maintenance is possible in principle, we found some boundary conditions. There was no spatial configuration effect when participants had to fixate. Thus, eye movements are required for a configuration effect to occur.

Outcome of a hepatitis B vaccination program for clients of a drug consumption facility.

BACKGROUND: Intravenous drug users (IDUs) are a risk group for hepatitis B. In Germany, the hepatitis B virus (HBV) vaccination rates in IDUs are low. OBJECTIVES: In this study the implementation and success of HBV vaccination in a drug consumption facility (DCF) was evaluated. STUDY DESIGN: Clients attending a DCF were asked regarding their HBV status. In case of no known HBV infection and no previous vaccination, clients interested in HBV vaccination were offered a HBV blood testing. HBV vaccination was administered to susceptible clients in months 0, 1, 6. Booster vaccinations were offered to clients without seroconversion (anti-HBs < 100 U/l). RESULTS: 193 out of 364 clients reported on a known HBV infection or immunity after vaccination. 95 (55.6%) out of 171 eligible clients underwent a HBV serology. According to HBV serology 31 (32.6%) out of 95 clients were not susceptible for vaccination (mainly due to an unknown HBV infection). 47 (73.4%) out of 64 clients susceptible were administered 3 vaccinations. 10 clients received at least one further vaccination. For those showing up for testing (36 out of 47 clients) the seroconversion rate was 69.4% (> 100 IU/l) and 83.3% (> 10 IU/l), respectively. DISCUSSION: Only a minority of clients of a DCF was susceptible for HBV vaccination. 47 out of 64 (73.4%) susceptible clients underwent at least three administrations of the vaccine, mostly resulting in seroconversion. Even in IDUs attending a DCF, a clientele with unstable social and health conditions, HBV vaccination can be carried out successfully.

Establishment and Characterization of a Novel Cell Line Derived from a Small Cell Neuroendocrine Carcinoma of the Anal Canal.

BACKGROUND: Gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) are biologically aggressive tumors, associated with a very poor survival. Due to their rarity, our knowledge on GEP-NEC biology is very limited. The aim of this study was to establish a GEP-NEC cell line model that might contribute to a better understanding of this rare malignant disease to further develop novel therapeutic approaches in preclinical studies. METHODS: Small cell neuroendocrine cancer cell line NEC-DUE3 was derived from a lymph node metastasis of a neuroendocrine carcinoma (NEC) located at the anal canal. Morphological characteristics and the expression of neuroendocrine markers were comprehensively investigated. For genetic profiling, NEC-DUE3 cells were analyzed by DNA fingerprinting. Chromosomal aberrations were mapped by array comparative genomic hybridization. NEC-DUE3 cell tumorigenicity was evaluated in vivo and the sensitivity to chemotherapeutic agents was assessed in vitro. RESULTS: NEC-DUE3 cells were characterized by the expression of molecular markers that are commonly observed in GEP-NECs, were sensitive to treatment with cisplatin, and able to form tumors in immunodeficient mice. CONCLUSION: We established and characterized the first small cell GEP-NEC cell line that may serve as a valuable tool to create a better understanding of the biology of these rare tumors and to develop novel treatment strategies.

High efficacy of sofosbuvir/velpatasvir and impact of baseline resistance-associated substitutions in hepatitis C genotype 3 infection.

BACKGROUND: Twelve weeks of the pangenotypic direct-acting antiviral (DAA) combination sofosbuvir/velpatasvir (SOF/VEL) was highly efficient in patients with hepatitis C virus (HCV) genotype 3 (GT3) infection in the ASTRAL-3 approval study. However, presence of resistance-associated substitutions (RASs) in the HCV nonstructural protein 5A (NS5A) was associated with lower treatment response. AIM: To assess the efficacy and safety of SOF/VEL ± ribavirin (RBV) and the impact of NS5A RASs and RBV use on treatment outcome in HCV GT3 infection in a real-world setting. METHODS: In this multicentre cohort study, GT3 patients from ten treatment centres across Germany were included. Sustained virological response was assessed 12 weeks after end-of-treatment (SVR12) in modified intention-to-treat (mITT) and per-protocol analysis (PP). NS5A RASs were tested by population-based sequencing. RESULTS: A total of 293 GT3 patients were included. The median age was 48 years, 70% were male, 25.3% were cirrhotic, 9.2% were HCV/HIV co-infected and 21.8% were treatment-experienced, including 4.1% with DAA experience. Baseline NS5A RASs (Y93H, A30K, L31M) were detected in 11.2%. RBV was added in 5% of noncirrhotic and 58.9% of cirrhotic patients, respectively. SVR12 rates for SOF/VEL±RBV were 95.9% (mITT) and 99.5% (PP), respectively. Only 1 virological relapse occurred in a cirrhotic patient previously treated with SOF/RBV. No treatment-related major adverse events occurred. CONCLUSION: Twelve weeks of SOL/VEL±RBV was safe and highly efficient in HCV GT3 across a diverse patient population. Baseline NS5A RASs were rarely observed and presence did not seem to impact SVR, regardless of the use of RBV.