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Summary Background Chronic kidney disease patients show a high mortality in cases of a severe acute respiratory syndrome coronavirus-2 (SARS-CoV‑2) infection. Thus, information on the sero-status of nephrology personnel might be crucial for patient protection; however, limited information exists about the presence of SARS-CoV‑2 antibodies in asymptomatic individuals. Methods We examined the seroprevalence of SARS-CoV‑2 IgG and IgM antibodies among healthcare workers of a tertiary care kidney center during the the first peak phase of the corona virus disease 2019 (COVID-19) crisis in Austria using an orthogonal test strategy and a total of 12 commercial nucleocapsid protein or spike glycoprotein-based assays as well as Western blotting and a neutralization assay. Results At baseline 60 of 235 study participants (25.5%, 95% confidence interval, CI 20.4–31.5%) were judged to be borderline positive or positive for IgM or IgG using a high sensitivity/low specificity threshold in one test system. Follow-up analysis after about 2 weeks revealed IgG positivity in 12 (5.1%, 95% CI: 2.9–8.8%) and IgM positivity in 6 (2.6%, 95% CI: 1.1–5.6) in at least one assay. Of the healthcare workers 2.1% (95% CI: 0.8–5.0%) showed IgG nucleocapsid antibodies in at least 2 assays. By contrast, positive controls with proven COVID-19 showed antibody positivity among almost all test systems. Moreover, serum samples obtained from healthcare workers did not show SARS-CoV‑2 neutralizing capacity, in contrast to positive controls. Conclusion Using a broad spectrum of antibody tests the present study revealed inconsistent results for SARS-CoV‑2 seroprevalence among asymptomatic individuals, while this was not the case among COVID-19 patients. Trial registration number CONEC, ClinicalTrials.gov number NCT04347694

The nonpathogenic and ubiquitous torque teno virus (TTV) is associated with immunosuppression in solid organ transplant recipients. Studies in kidney transplant patients proposed TTV quantification for risk stratification of graft rejection and infection. In this prospective trial (DRKS00012335) 386 consecutive kidney transplant recipients were subjected to longitudinal per‐protocol monitoring of plasma TTV load by polymerase chain reaction for 12 months posttransplant. TTV load peaked at the end of month 3 posttransplant and reached steady state thereafter. TTV load after the end of month 3 was analyzed in the context of subsequent rejection diagnosed by indication biopsy and infection within the first year posttransplant, respectively. Each log increase in TTV load decreased the odds for rejection by 22% (odds ratio [OR] 0.78, 95% confidence interval [CI] 0.62‐0.97; P = .027) and increased the odds for infection by 11% (OR 1.11, 95% CI 1.06‐1.15; P, This trial defines an optimal plasma level range of the nonpathogenic and ubiquitous torque teno virus, which reflects the immunosuppression of its host, to minimize the risk for rejection and infection in kidney allograft recipients in the first year after transplantation. Fernández‐Ruiz comments on page 1963.

In kidney transplant recipients (KTRs), BK polyomavirus (BKPyV) replication may progress to polyomavirus-associated nephropathy (PVAN). In this retrospective study, we assessed the chemokine CXCL10 in urine and blood samples consecutively acquired from 85 KTRs who displayed different stages of BKPyV replication and eventually developed PVAN. In parallel to progression toward PVAN, CXCL10 gradually increased in blood and urine, from baseline (prior to virus replication) to BKPyV DNAuria (median increase in blood: 42.15 pg/ml, P = 0.0156), from mere DNAuria to low- and high-level BKPyV DNAemia (median increase: 52.60 and 87.26 pg/ml, P = 0.0010 and P = 0.0002, respectively) and peaked with histologically confirmed PVAN (median increase: 145.00 pg/ml, P

BackgroundDialysis patients are at high risk for a severe clinical course after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Safety and early immune responses after mRNA-based vaccination have been reported mostly in patients on hemodialysis (HD), whereas reports of peritoneal dialysis (PD) patients remain rare.MethodsIn this retrospective observational study, 39 PD patients had received two doses of the mRNA-1273 Moderna® vaccine. We analyzed SARS-CoV-2 Spike (S) antibody titers 4 weeks after each dose of mRNA-1273 and report local and systemic side effects in PD patients that occurred within one week after each mRNA-1273 dose. Using a quantile regression model we examined factors that might influence SARS-CoV-2 S antibody levels in PD patients.ResultsFour weeks after the first dose of mRNA-1273 vaccine 33 of 39 (84.6%) PD patients seroconverted and presented with 6.62 U/mL (median; IQR 1.57-22.5) anti-SARS-CoV-2 S antibody titers. After the second dose, 38 of 39 (97.4%) PD patients developed anti-SARS-CoV-2 S antibodies and titers increased significantly (median 968 U/mL; IQR 422.5-2500). Pain at the injection site was the most common local adverse event (AE) (71%). Systemic AEs occurring after the first dose were mostly fatigue (33%) and headache (20%). No severe systemic AEs were reported after the first injection. After the second dose the incidence and the severity of the systemic AEs increased. The most common systemic AEs were: fatigue (40.5%), headache (22.5%), joint pain (20%), myalgia (17.5%) and fever (13%). Lower Davies Comorbidity Score (p=0.04) and shorter dialysis vintage (p=0.017) were associated with higher antibody titers after the first dose. Patients with higher antibody titers after the first dose tended to have higher antibody titers after the second dose (p=1.53x10-05).ConclusionsPeritoneal dialysis patients in this cohort had a high seroconversion rate of 97.4%, showed high antibody titers after full vaccination and tolerated the anti-SARS-CoV-2 mRNA-1273 vaccine well without serious adverse events.

Importance: To our knowledge, little is known about antibody development after SARS-CoV-2 vaccination in immunocompromised individuals, such as patients with cancer. Objective: To determine whether hematooncological patients develop anti-SARS-CoV-2 antibodies after vaccination. Design, Setting, and Participants: This retrospective cohort study included 2 independent cohorts of patients who were treated for hematological and solid malignant tumors between October 2020 and May 2021, comprising 901 samples from 595 patients and 58 health care workers (HCWs). Serum samples were collected from patients who were treated at an academic center and a community hospital in a rural area and a control group of HCWs, all of whom received SARS-CoV-2 vaccination. Main Outcomes and Measures: Total anti-SARS-CoV-2 nucleocapsid (anti-NC) and antispike protein (anti-S) antibodies were measured retrospectively. Results: In total, 595 patients (320 women [53.8%] and 275 men [46.2%]; median [range] age, 67 [19-96] years) and 58 HCWs (40 women [69.0%] and 18 men [31.0%]; median [range] age, 42 [24-60] years) were included. Previous SARS-CoV-2 infection was documented in 43 of 595 (7.2%), while anti-NC antibodies that suggested previous infections were observed in 49 of 573 evaluable patients (8.6%). In both cohorts, anti-S antibody levels were higher in fully vaccinated patients compared with patients who received 1 dose. After the first vaccination, patients with hematological cancer who received B cell-targeting agents had lower anti-S levels (median, 1.6 AU/mL; range: 0-17 244 AU/mL) than patients who received other therapies (median, 191.6 AU/mL; range, 0-40 000; P < .001) or patients with solid tumors (median, 246.4 AU/mL; range, 0-40 000 AU/mL; P < .001). Anti-S levels after the first vaccination differed according to ongoing antineoplastic treatment modalities, with the lowest median levels in patients who received chemotherapy alone (157.7 AU/mL; range, 0-40 000 AU/mL) or in combination with immunotherapy (118.7 AU/mL; range, 14.1-38 727 AU/mL) and the highest levels in patients with no ongoing antineoplastic treatment (median, 634.3 AU/mL; range, 0-40 000 AU/mL; P = .01). Antibody levels after full immunization were higher in HCWs (median, 2500 U/mL; range, 485-2500 U/mL) than in patients with cancer (median, 117.0 U/mL; range, 0-2500 U/mL; P < .001). Conclusions and Relevance: In this cohort study of patients with hematooncological diseases and a control group of HCWs, anti-SARS-CoV-2 antibodies after vaccination could be detected in patients with cancer. Lower antibody levels compared with HCWs and differences in seroconversion in specific subgroups underscore the need for further studies on SARS-CoV-2 vaccination in patients with hematooncological disease.

This study aimed to determine the specific cytokine profile in peripheral blood during the early onset of COVID-19 infection. This was a cross-sectional exploratory, single center study. A total of 55 plasma samples were studied. Serum samples of adults showing symptoms of COVID-19 infection who were tested positive for SARS-CoV-2 infection (CoV+, n=18) at the COVID-19 outpatient clinic of the Medical University of Vienna were screened for immune activation markers by Luminex technology. Additionally, age and gender-matched serum samples of patients displaying COVID-19 associated symptoms, but tested negative for SARS-CoV-2 (CoV-, n=16) as well as healthy controls (HC, n=21) were analyzed. COVID-19 positive (CoV+) patients showed a specific upregulation of BLC (141; 74-189 pg/mL), SCD30 (273; 207-576 pg/mL), MCP-2 (18; 12-30 pg/mL) and IP-10 (37; 23-96 pg/mL), compared to patients with COVID19-like symptoms but negative PCR test (CoV-), BLC (61; 22-100 pg/mL), sCD30L (161; 120-210 pg/mL), MCP-2 (8; 5-12 pg/mL) and IP-10 (9; 6-12 pg/mL) and healthy controls (HC) (BLC 22; 11-36 pg/mL, sCD30 74; 39-108 pg/mL, MCP-2 6; 3-9. pg/mL, IP-10 = 8; 5-13). The markers APRIL, sIL-2R, IL7, MIF, MIP-1b, SCF, SDF-1a, sTNF-RII were elevated in both CoV+ and CoV- patient groups compared to healthy controls. HGF, MDC and VEGF-A were elevated in CoV- but not CoV+ compared to healthy controls. BLC, sCD30, MCP-2 and IP-10 are specifically induced during early stages of COVID-19 infection and might constitute attractive targets for early diagnosis and treatment of this disease.

Simple Summary There is no doubt that immunotherapeutic approaches will change the current treatment landscape of multiple myeloma in the near future; in particular, a wave of BCMA-targeted therapies is currently entering clinical routine. Although the increasing availability of different therapeutic approaches is highly welcome, it also increases the daily challenges in clinical decision making if they all use the same target. Here, we provide a comprehensive summary of BCMA-targeted approaches in myeloma and aim to share some basic concepts in clinical decision making. Abstract Since the introduction of first-generation proteasome inhibitors and immunomodulatory agents, the multiple myeloma (MM) treatment landscape has undergone a remarkable development. Most recently, immunotherapeutic strategies targeting the B cell maturation antigen (BCMA) entered the clinical stage providing access to highly anticipated novel treatment strategies. At present, numerous different approaches investigate BCMA as an effective multi-modal target. Currently, BCMA-directed antibody–drug conjugates, bispecific and trispecific antibodies, autologous and allogeneic CAR-T cell as well as CAR-NK cell constructs are either approved or in different stages of clinical and preclinical development for the treatment of MM. This armamentarium of treatment choices raises several challenges for clinical decision making, particularly in the absence of head-to-head comparisons. In this review, we provide a comprehensive overview of BCMA-targeting therapeutics, deliver latest updates on clinical trial data, and focus on potential patient selection criteria for different BCMA-targeting immunotherapeutic strategies.

Supplemental Digital Content is available in the text., Background. Nonpathogenic torque teno viruses (TTVs) are highly prevalent in transplant recipients and associated with immunosuppression. Studies in kidney transplant patients have proposed assessment of TTV load for risk stratification of clinically overt graft rejection. The value of TTV quantification in the context of subclinical rejection has not been evaluated. Methods. In this prospective trial, 307 consecutive kidney transplant recipients were subjected to per-protocol monitoring of plasma TTV. TTV was analyzed in the context of protocol biopsies (n = 82), scheduled 1 year posttransplantation. Results. TTV load at the time of biopsy was lower in recipients with rejection (n = 19; according to Banff, including borderline changes suspicious for acute T cell-mediated rejection) than those without rejection (n = 63) whereby each log increase in TTV copies/mL decreased the risk for rejection by 9% (risk ratio 0.91, 95% confidence interval, 0.85-0.97; P = 0.004). Development of chronic lesions (cg, cv, ci, ct, ah, ptcml) was associated with the number of days with a TTV load

Introduction: Immunoadsorption (IA) represents a therapeutic option for acute antibody-mediated rejection (ABMR) after kidney transplantation. The addition of membrane filtration (MF) to enhance elimination of macromolecular components that potentially contribute to rejection, such as key complement component C1q and alloreactive IgM, may be an effective strategy to further improve its therapeutic efficiency. Results: Here we present 4 consecutive patients with episodes of HLA donor-specific antibody-positive ABMR nonresponsive to cycles of 6–16 sessions of IA treatment. Rejection episodes were characterized by severe microvascular injury (high-grade microcirculation inflammation and/or signs of thrombotic microangiopathy) and evidence of intense complement activation in peritubular capillaries (diffuse C4d-positivity). IA combined with MF led to substantial morphologic improvement (follow-up biopsies: g + ptc and C4d scores ≤1) and stabilization of allograft function. Conclusions: Our findings provide evidence for an effect of combination of IA + MF in refractory early acute/active ABMR in kidney transplant recipients.

BACKGROUND AND AIMS Despite vaccination recommendations, hepatitis B (HBV) and D (HDV) coinfections are common in HIV+individuals. METHODS HBV immunization status (anti-HBs) as well as HBV (HBsAg/HBV-DNA) and HDV (anti-HDV) coinfection rates were assessed in 1870 HIV+individuals at HIV diagnosis (baseline, BL) and last follow-up (FU). RESULTS Sixty-eight (3.6%) HIV patients were never tested for HBV. At BL, 89/1802 (4.9%) HIV patients were HBV coinfected. Four hundred and fifteen (23.0%) showed virological HBV clearance [HBsAg(-)/anti-HBc(+)/anti-HBs(+)] and 210 (11.7%) presented with anti-HBc(+) only. Seven hundred and ten (39.4%) were HBV naive [HBsAg(-)/anti-HBs(-)/anti-HBc(-)/HBV-DNA(-)], but only 378 (21.0%) received vaccinations with detectable anti-HBs(+) titres. Among the 89 HBV/HIV-coinfected patients, only 52 (58.4%) were tested for HDV: 11/49 (22.4%) had anti-HDV(+) and 3/12 (25.0%) showed HDV-RNA viraemia. During a median FU of 6.5 (IQR 7.2) years, 44 (4.6%) of the 953 retested BL HBV-negative patients acquired new HBV infection (including 15/304, 4.9% of vaccinated patients). Of the 89 patients, 22 (24.7%) patients cleared their HBsAg, resulting in 60/1625 (3.7%) HIV/HBV individuals at FU: 34 (56.7%) showed HBV-DNA suppression and 15 (25.0%) were HBV viraemic, while 12/89 (13.5%) remained without a FU test. Vaccinations induced anti-HBs(+) in 137 of the retested 649 (21.1%) BL HBV-naive patients. CONCLUSION HBV testing is well established among Viennese HIV+patients with HBV coinfection rates around 4%-5%. HBV vaccinations are insufficiently implemented since anti-HBs titres were detected in only 21.1% of HBV-naive HIV(+) patients and new HBV infections occurred in previously vaccinated patients. HDV testing is not systematically performed despite up to 25% of HIV/HBV patients may show HDV coinfection.

Fixed pulmonary hypertension (FPH) is a contraindication for heart transplantation (HTX). However, this condition might be reversed by continuous left-ventricular unloading with a left-ventricular assist device. We present a case of apical hypertrophic cardiomyopathy with extensive left-ventricular endocardial calcification and severe FPH (systolic pulmonary artery pressure, 102 mm Hg). To bridge the patient to candidacy for HTX, two Abbott HeartMate 3 ventricular assist devices were implanted in a total artificial heart (TAH) configuration ("HeartMate 6"). Before TAH implantation, an Abbott CardioMEMS pressure sensor was implanted to assess reversal of FPH before listing for HTX.

BackgroundImmunosuppression in solid organ transplantation is associated with frequent infections. Renal allograft recipients are susceptible to opportunistic infections and can acquire human cytomegalovirus (HCMV) infections even within the allograft. There, HCMV can be found in both the glomerulus and tubular cells, but is mostly restricted to specific and circumscribed sites. Therefore, not all organ infections are identifiable by immunohistology for HCMV proteins in fine needle core biopsies. Thus, we performed a urinalysis study to search for HCMV-specific RNA transcripts in the urine sediment of patients with acute kidney injury.MethodsUrinary sediment of 90 patients with acute kidney injury (AKI), including 48 renal transplant recipients (RTX) and 42 non-transplant recipients (nRTX), was collected from morning urine for RNA extraction and reverse transcription. The copy number of HCMV transcripts was evaluated using a UL132 HCMV-specific probe set and by real-time quantitative polymerase chain reaction (RT-qPCR).ResultsOf the 48 RTX patients, ten showed HCMV copies in their urine sediment cells. Within this group, three recipients had negative HCMV serology and received an allograft from an HCMV-seropositive donor. In addition, all three RTX patients on a belatacept-based immunosuppressive regimen had HCMV transcripts in their urine. Of the 42 nRTX patients, only two had detectable HCMV transcripts in urine sediment cells and both were under immunosuppression.ConclusionsTen immunosuppressed renal allograft recipients and two immunosuppressed non-transplant patients with AKI showed HCMV copies in urine sediment. Thus, HCMV positivity in urinary sediment appears to be associated with immunosuppression. This study describes a novel noninvasive method for detection of HCMV in urinary sediment. Whether all HCMV infections can be detected or only those with viral replication warrants further investigation.

Personal protective equipment and adherence to disinfection protocols are essential to prevent nosocomial severe acute respiratory syndrome coronavirus (SARS-CoV-2) transmission. Here, we evaluated infection control measures in a prospective longitudinal single-center study at the Vienna General Hospital, the biggest tertiary care center in Austria, with a structurally planned low SARS-CoV-2 exposure. SARS-CoV-2-specific antibodies were assessed by Abbott ARCHITECT chemiluminescent assay (CLIA) in 599 health care workers (HCWs) at the start of the SARS-CoV-2 epidemic in early April and two months later. Neutralization assay confirmed CLIA-positive samples. A structured questionnaire was completed at both visits assessing demographic parameters, family situation, travel history, occupational coronavirus disease 2019 (COVID-19) exposure, and personal protective equipment handling. At the first visit, 6 of 599 participants (1%) tested positive for SARS-CoV-2-specific antibodies. The seroprevalence increased to 1.5% (8/553) at the second visit and did not differ depending on the working environment. Unprotected SARS-CoV-2 exposure (p = 0.003), positively tested family members (p = 0.04), and travel history (p = 0.09) were more frequently reported by positively tested HCWs. Odds for COVID-19 related symptoms were highest for congestion or runny nose (p = 0.002) and altered taste or smell (p &lt, 0.001). In conclusion, prevention strategies proved feasible in reducing the risk of transmission of SARS-CoV-2 from patients and among HCWs in a low incidence hospital, not exceeding the one described in the general population.

SummaryBackgroundDuring the second wave of the coronavirus disease 2019 (COVID-19) pandemic Austria suffered one of the highest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rates worldwide. We report performance parameters of a SARS-CoV‑2 screening program established for cancer outpatients at our center.MethodsInstitutional policy recommended routine biweekly SARS-CoV‑2 testing. Adherence to the testing recommendation during the second wave of the COVID-19 pandemic between 1 October and 30 November 2020 was analyzed. The SARS-CoV‑2 infection rate during first wave period (21 March to 4 May 2020) was compared to the one during second wave.ResultsA total of 1577 cancer patients were seen at our outpatient clinic during the second wave. In 1079/1577 (68.4%) patients, at least 1 SARS-CoV2 test was performed. Overall 2833 tests were performed, 23/1577 (1.5%, 95% confidence interval, CI 1.0–2.2%) patients were tested positive for SARS-CoV‑2, which indicates a significant increase compared to the first wave (4/1016; 0.4%, 95% CI 0.1–1.0%) with an odds ratio of 3.9 (95% CI 1.5–10.1;p p p ConclusionWe identified clinical patient parameters influencing SARS-CoV‑2 testing coverage in cancer outpatients. Our data can provide information on generation of standard operating procedures and resource allocation during subsequent infection waves.

Although the risk for nonrelapse mortality (NRM) associated with early cytomegalovirus (CMV) reactivation (CMVR) after allogeneic hematopoietic stem cell transplantation (HSCT) is well established, debate is ongoing on whether CMVR may reduce the risk of primary disease relapse. The aim of this study was to evaluate relapse protection following early CMV reactivation after HSCT in the context of the recipient HLA-C killer cell immunoglobulin-like receptor ligands (KIRLs). In this retrospective bicentric study, 406 matched related or unrelated donor transplantations for acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) were stratified by HLA-C KIRL group (homozygous versus heterozygous) and analyzed separately for the impact of early CMVR on the cumulative incidences of relapse, NRM, and acute and chronic graft-versus-host-disease (GVHD) using landmark and multistate analyses. By landmark analysis of patients alive and relapse-free at 45 days post-HSCT, HLA-C KIRL homozygous recipients (C1/1 or C2/2) had a lower risk of subsequent relapse if CMVR occurred before this landmark (subhazard ratio [sHR], 0.36; P = .002). In contrast, in HLA-C KIRL heterozygous (C1/2) recipients, early CMVR had no impact on subsequent relapse (sHR, 0.88; P = .63). NRM (sHR, 3.31; P.001) and grade III-IV acute GVHD (sHR, 2.60; P = .04) were significantly increased after early CMVR in the homozygous cohort, but not in the heterozygous cohort (NRM: sHR, 1.23; P = .53; grade III-IV acute GVHD: sHR, 1.40; P = .50). Multivariable landmark analyses and a multistate model confirmed the limitation of the relapse-protective effect of early CMVR to the homozygous cohort. Chronic GVHD and overall survival were not influenced in neither cohort. An antileukemic effect of early CMVR after HSCT for AML/MDS was significant but strictly limited to recipients homozygous for HLA-C KIRL. However, particularly in this cohort, CMVR had an adverse impact on aGVHD and NRM.

Respiratory syncytial virus (RSV) testing is generally available in most care centres, but it is rarely performed because clinicians’ seldom suspect RSV to be the underlying pathogen in adults with respiratory disease. Here, we evaluate the impact of broad combined influenza/RSV testing on the clinical practice. Overall, 103 patients were tested positively for RSV. Our study indicates that positively tested patients were mostly of advanced age and suffered from chronic diseases. Mortality was significant in our cohort and higher in patients with advanced age. Further, we report a significant increase in detected RSV cases but also in detection rate. Together, these findings suggest that implementation of a combined influenza/RSV testing led to a significant increase in detection rate, supported clinicians establishing the correct diagnosis and allowed a safe and controlled handling of RSV patients.

Background: The identification of SARS-CoV-2 antigen or RNA in a respiratory specimen collected from a person ≥14 days after completing all recommended doses of authorized COVID-19 vaccine series is a rare condition and defined as „breakthrough infection“. Data on mildly symptomatic or asymptomatic SARS-CoV-2 vaccine breakthrough infection cases especially with respect to viral characteristics and temporal relation to vaccination date is scarce. The purpose of the present investigation was to investigate the prevalence of postvaccination infections in hospital employees and to compare between m-RNA and vector based SARS-CoV-2 vaccines. Methods: At the General Hospital of Vienna 8 553 actively employed staff members participated at an voluntary in-house vaccination program, which took place between January and May 2021 and comprised of application of two doses of either COMIRNATY (BNT162b2; Pfizer/BioNTech, Inc.) or VAXZEVRIA (AstraZeneca, Inc.). Findings: By the end of July 2021 a total of 78 postvaccination infection cases after administration of a minimum of one dose of vaccination had been identified (median age: 40·5 years (IQR: 19-60 years); 53 women) of whom 53 had been vaccinated with VAXZEVRIA and 25 with COMIRNATY. The majority of infections was related to an insufficient or partial vaccination status; the incidence of postvaccination infection ≥14 days after complete vaccination (i.e. breakthrough infection) was 34·8: 10 000 for COMIRNATY and 8·8: 10 000 for VAXZEVRIA. There was no difference in PCR-CT values between the two vaccine brands (24·67 (SD: 7·41) for VAXZEVRIA vaccinated versus 24·0 (SD: 6·53) for COMIRNATY vaccinated persons). Genotyping of positive PCR specimens revealed 42 variant of concerns: B.1.1.7 (n=34); B.1.351 (n=2), B.1.617.2 (n=6). The prevalence of „real brakthrough infections“ (≥14 days after second vaccination) was higher in COMIRNATY vaccinated subjects than in the VAXZEVRIA vaccinated subjects with a ratio of 14:4 (p

Objectives Manual or semi-automated segmentation of the lower extremity arterial tree in patients with Peripheral arterial disease (PAD) remains a notoriously difficult and time-consuming task. The complex manifestations of the disease, including discontinuities of the vascular flow channels, the presence of calcified atherosclerotic plaque in close vicinity to adjacent bone, and the presence of metal or other imaging artifacts currently preclude fully automated vessel identification. New machine learning techniques may alleviate this challenge, but require large and reasonably well segmented training data. Methods We propose a novel semi-automatic vessel tracking approach for peripheral arteries to facilitate and accelerate the creation of annotated training data by expert cardiovascular radiologists or technologists, while limiting the number of necessary manual interactions, and reducing processing time. After automatically classifying blood vessels, bones, and other tissue, the relevant vessels are tracked and organized in a tree-like structure for further visualization. Results We conducted a pilot (N = 9) and a clinical study (N = 24) in which we assess the accuracy and required time for our approach to achieve sufficient quality for clinical application, with our current clinically established workflow as the standard of reference. Our approach enabled expert physicians to readily identify all clinically relevant lower extremity arteries, even in problematic cases, with an average sensitivity of 92.9%, and an average specificity and overall accuracy of 99.9%. Conclusions Compared to the clinical workflow in our collaborating hospitals (28:40 ± 7:45 [mm:ss]), our approach (17:24 ± 6:44 [mm:ss]) is on average 11:16 [mm:ss] (39%) faster.

Background Coronavirus disease 2019 (COVID‐19) interferes with the vascular endothelium. It is not known whether COVID‐19 additionally affects arterial stiffness. Methods This case–control study compared brachial‐ankle pulse wave (baPWV) and carotid‐femoral pulse wave velocities (cfPWV) of acutely ill patients with and without COVID‐19. Results Twenty‐two COVID‐19 patients (50% females, 77 [67–84] years) were compared with 22 age‐ and sex‐matched controls. In COVID‐19 patients, baPWV (19.9 [18.4–21.0] vs. 16.0 [14.2–20.4], P = 0.02) and cfPWV (14.3 [13.4–16.0] vs. 11.0 [9.5–14.6], P = 0.01) were higher than in the controls. In multiple regression analysis, COVID‐19 was independently associated with higher cfPWV (β = 3.164, P = 0.004) and baPWV (β = 3.532, P = 0.003). PWV values were higher in nonsurvivors. In survivors, PWV correlated with length of hospital stay. Conclusion COVID‐19 appears to be related to an enhanced PWV reflecting an increase in arterial stiffness. Higher PWV might be related to an increased length of hospital stay and mortality.

Background Serological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems is often poor, leaving room for false positive and false negative results. However, conventional methods used to increase specificity decrease sensitivity and vice versa. Using SARS-CoV-2 serology as an example, we propose here a novel testing strategy: the "Sensitivity Improved Two-Test" or "SIT2" algorithm. Methods SIT2 involves confirmatory re-testing of samples with results falling in a predefined retesting-zone of an initial screening test, with adjusted cut-offs to increase sensitivity. We verified and compared the performance of SIT2 to single tests and orthogonal testing (OTA) in an Austrian cohort (1,117 negative, 64 post-COVID positive samples) and validated the algorithm in an independent British cohort (976 negatives, 536 positives). Results The specificity of SIT2 was superior to single tests and non-inferior to OTA. The sensitivity was maintained or even improved using SIT2 when compared to single tests or OTA. SIT2 allowed correct identification of infected individuals even when a live virus neutralization assay could not detect antibodies. Compared to single testing or OTA, SIT2 significantly reduced total test errors to 0.46% (0.24-0.65) or 1.60% (0.94-2.38) at both 5% or 20% seroprevalence. Conclusion For SARS-CoV-2 serology, SIT2 proved to be the best diagnostic choice at both 5% and 20% seroprevalence in all tested scenarios. It is an easy to apply algorithm and can potentially be helpful for the serology of other infectious diseases.

Background During the COVID-19 outbreak, healthcare professionals (HCP) are at the frontline of clinical management and at increased risk for infection. The SARS-CoV-2 seroprevalence of oncological HCP and their patients has significant implications for oncological care. Methods HCP and patients with cancer at the Division of Oncology, Medical University of Vienna were included between 21 March and 4 June and tested for total antibodies against SARS-CoV-2 employing the Roche Elecsys Anti-SARS-CoV-2 immunoassay. Reactive samples were confirmed or disproved by the Abbott SARS-CoV-2 IgG test. Additionally, a structured questionnaire regarding basic demographic parameters, travel history and COVID-19-associated symptoms had to be completed by HCP. Results 146 subjects (62 HCP and 84 patients with cancer) were enrolled. In the oncological HCP cohort, 20 (32.3%) subjects were medical oncologists, 28 (45.2%) nurses at our ward and 14 (22.6%) fulfil other functions such as study coordinators. In the patient cohort, most individuals are on active anticancer treatment (96.4%). 26% of the HCP and 6% of the patients had symptoms potentially associated with COVID-19 since the end of February 2020. However, only in 2 (3.2%) HCP and in 3 (3.6%) patients, anti-SARS-Cov-2 total antibodies were detected. The second assay for anti-SARS-Cov-2 IgG antibodies confirmed the positive result in all HCP and in 2 (2.4%) patients, suggesting an initial assay’s unspecific reaction in one case. In individuals with a confirmed test result, an active COVID-19 infection was documented by a positive SARS-CoV-2 RNA PCR test. Conclusion Specific anti-SARS-CoV-2 antibodies were found solely in persons after a documented SARS-CoV-2 viral infection, thus supporting the test methods’ high sensitivity and specificity. The low prevalence of anti-SARS-CoV-2 antibodies in our cohorts indicates a lack of immunity against SARS-CoV-2. It highlights the need for continued strict safety measures to prevent uncontrolled viral spread among oncological HCPs and patients with cancer.

SummaryIn this case report we present a rare case of a patient with multiple risk factors for severe coronavirus disease (COVID 19) in whom intensive glucocorticoid treatment due to incipient nephrotic syndrome coincided with SARS-CoV‑2 infection. Despite this high baseline risk profile and the use of glucocorticoids the patient developed only mild disease including IgG SARS-CoV‑2 seroconversion.

PURPOSE To analyze the prevalence of SARS-CoV-2 infection in patients with cancer in hospital care after implementation of institutional and governmental safety measurements. METHODS Patients with cancer routinely tested for SARS-CoV-2 RNA by nasal swab and real-time polymerase chain reaction between March 21 and May 4, 2020, were included. The results of this cancer cohort were statistically compared with the SARS-CoV-2 prevalence in the Austrian population as determined by a representative nationwide random sample study (control cohort 1) and a cohort of patients without cancer presenting to our hospital (control cohort 2). RESULTS A total of 1,688 SARS-CoV-2 tests in 1,016 consecutive patients with cancer were performed. A total of 270 of 1,016 (26.6%) of the patients were undergoing active anticancer treatment in a neoadjuvant/adjuvant and 560 of 1,016 (55.1%) in a palliative setting. A total of 53 of 1,016 (5.2%) patients self-reported symptoms potentially associated with COVID-19. In 4 of 1,016 (0.4%) patients, SARS-CoV-2 was detected. At the time of testing at our department, all four SARS-CoV-2–positive patients were asymptomatic, and two of them had recovered from symptomatic COVID-19. Viral clearance was achieved in three of the four patients 14-56 days after testing positive. The estimated odds ratio of SARS-CoV-2 prevalence between the cancer cohort and control cohort 1 was 1.013 (95% CI, 0.209 to 4.272; P = 1), and between control cohort 2 and the cancer cohort it was 18.333 (95% CI, 6.056 to 74.157). CONCLUSION Our data indicate that continuation of active anticancer therapy and follow-up visits in a large tertiary care hospital are feasible and safe after implementation of strict population-wide and institutional safety measures during the current COVID-19 pandemic. Routine SARS-CoV-2 testing of patients with cancer seems advisable to detect asymptomatic virus carriers and avoid uncontrolled viral spread.

BackgroundChronic kidney disease patients show a high mortality in case of a SARS-CoV-2 infection. Thus, to be informed on Nephrology personnel’s sero-status might be crucial for patient protection. However, limited information exists about the presence of SARS-CoV-2 antibodies in asymptomatic individuals.MethodsWe examined the seroprevalence of SARS-CoV-2 IgG and IgM antibodies among health care workers of a tertiary care kidney center during the peak phase of the Covid-19 crisis in Austria using an orthogonal test strategy and a total of 12 commercial nucleocapsid protein or spike glycoprotein based assays as well as Western blotting and a neutralization assay.ResultsAt baseline 60 of 235 study participants (25.5%, 95% CI: 20.4-31.5) were judged to be borderline positive or positive for IgM or IgG using a high sensitivity/low specificity threshold in one test system. Follow-up analysis after about two weeks revealed IgG positivity in 12 (5.1%, 95% CI: 2.9-8.8) and IgM positivity in six (2.6%, 95% CI: 1.1-5.6) in at least one assay. 2.1% (95% CI: 0.8-5.0) of health care workers showed IgG nucleocapsid antibodies in at least two assays. By contrast, positive controls with proven Covid-19 showed antibody positivity among almost all test systems. Moreover, serum samples obtained from health care workers did not show SARS-CoV-2 neutralizing capacity, in contrast to positive controls.ConclusionsUsing a broad spectrum of antibody tests the present study revealed inconsistent results for SARS-CoV-2 seroprevalence among asymptomatic individuals, while this was not the case among Covid-19 patients.Trial registration numberCONEC, ClinicalTrials.gov number NCT04347694

To explore the epidemiology and clinical course of hepatitis A virus (HAV) infections at the Vienna General Hospital. We retrospectively identified patients who were tested positive for HAV-IgM at the Vienna General Hospital form Q1/2008 to Q3/2018. Our definition of severe HAV infection was AST and/or ALT > 5 × above the upper limit of normal (ULN); and liver dysfunction as (i) hepatic encephalopathy or ammonia > 100 μmol/L, (ii) coagulopathy with INR > 1.5, or (iii) jaundice with bilirubin > 5 mg/dL. A total of 578 HAV-IgM (+) were identified, including 31 (5.4%) and 38 (6.6%) without and with liver dysfunction, respectively. A proportional increase in severe HAV cases with and without liver dysfunction occurred in 2016/2017 with (21.5% (vs. 8.0% in the years before; p

Background In the context of the COVID-19 pandemic, numerous new serological test systems for the detection of anti-SARS-CoV-2 antibodies rapidly have become available. However, the clinical performance of many of these is still insufficiently described. Therefore, we compared 3 commercial CE-marked, SARS-CoV-2 antibody assays side by side. Methods We included a total of 1154 specimens from pre-COVID-19 times and 65 samples from COVID-19 patients (≥14 days after symptom onset) to evaluate the test performance of SARS-CoV-2 serological assays by Abbott, Roche, and DiaSorin. Results All 3 assays presented with high specificities: 99.2% (98.6–99.7) for Abbott, 99.7% (99.2–100.0) for Roche, and 98.3% (97.3–98.9) for DiaSorin. In contrast to the manufacturers’ specifications, sensitivities only ranged from 83.1% to 89.2%. Although the 3 methods were in good agreement (Cohen’s Kappa 0.71–0.87), McNemar tests revealed significant differences between results obtained from Roche and DiaSorin. However, at low seroprevalences, the minor differences in specificity resulted in profound discrepancies of positive predictive values at 1% seroprevalence: 52.3% (36.2–67.9), 77.6% (52.8–91.5), and 32.6% (23.6–43.1) for Abbott, Roche, and DiaSorin, respectively. Conclusion We found diagnostically relevant differences in specificities for the anti-SARS-CoV-2 antibody assays by Abbott, Roche, and DiaSorin that have a significant impact on the positive predictive values of these tests.

Background Drug-induced immunosuppression in kidney transplant recipients is crucial to prevent allograft rejection, but increases risk for infectious disease. Immunologic monitoring to tailor immunosuppressive drugs might prevent alloreactivity and adverse effects simultaneously. The apathogenic torque teno virus (TTV) reflects the immunocompetence of its host and might act as a potential candidate for a holistic monitoring. Methods We screened all 1010 consecutive patients from the prospective Vienna Kidney Transplant Cohort Study for availability of allograft biopsies and adequately stored sera for TTV quantification by polymerase chain reaction. Results Patients with acute biopsy-proven alloreactivity according to the Banff classification (n = 33) showed lower levels of TTV in the peripheral blood compared to patients without rejection (n = 80) at a median of 43 days before the biopsy. The risk for alloreactivity decreased by 10% per log level of TTV copies/mL (risk ratio, .90 [95% confidence interval, .84–.97]; P = .005). TTV levels >1 × 106 copies/mL exclude rejection with a sensitivity of 94%. Multivariable generalized linear modeling suggests an independent association between TTV level and alloreactivity. Conclusions TTV is a prospective biomarker for risk stratification of acute biopsy-proven alloreactivity in kidney transplant recipients and might be a potential tool to tailor immunosuppressive drug therapy., Torque teno virus level in peripheral blood is associated with the immunocompetence of its host. Low levels of torque teno virus after kidney transplantation might mirror insufficient immunosuppression and thus indicate deleterious alloreactivity in patients with acute graft dysfunction.

Background & aims Increasing numbers of autochthonous hepatitis E virus infections have been reported in Europe. Chronic infections have been shown in immune-compromised patients after solid organ transplantation. Hepatitis E virus might be a possible trigger for autoimmune hepatitis and might cause disease flares or relapses in the further course of disease. Aim of this study was to investigate the presence of hepatitis E virus antibodies and hepatitis E virus RNA, and to analyse their impact on immunosuppressive treatment in patients with autoimmune hepatitis. Methods Sera from 92 autoimmune hepatitis patients (73/79.3% female, age: 42.2 ± 16.3 years [mean ± SD]) were tested. Patients were scored according to the simplified and revised scoring systems of the International Autoimmune Hepatitis Group. The prevalence of anti- hepatitis E virus antibodies (Beijing Wantai Biological Pharmacy Enterprises Co., Ltd, Beijing, China) and hepatitis E virus RNA was determined. Results 19/20.7% autoimmune hepatitis patients tested positive for hepatitis E virus-IgG, which was higher than in previous reports of healthy Austrian individuals (12.4%, P = 0.031); hepatitis E virus RNA was not detectable in any patient. Anti-hepatitis E virus positive patients were older (49.5 ± 9.5 vs 40.4 ± 17.2 years [mean ± SD], P = 0.033) but did not differ in laboratory findings at diagnosis (AST: 14.6 [1.3-70.6] vs 9.5 [0.7-62.7] × ULN [median/range]; P = 0.387, alanine aminotransferase: 18.3 [1.6-62.7] vs. 12.9 [0.8-62.6] × ULN; P = 0.511; IgG: 1.4 [1.0-2.5] vs 1.3 [0.6-3.8] g/dL × ULN; P = 0.278) nor in alanine aminotransferase levels after six months (0.7 [0.5-2.4] vs 1.0 U/L × ULN [0.1-22.4]; P = 0.077). Conclusions No chronic hepatitis E virus infection was observed in our cohort of autoimmune hepatitis patients. Anti- hepatitis E virus-IgG positive patients were older and the seroprevalence was nearly twice as high as reported previously in healthy Austrian individuals, suggesting that hepatitis E virus-infection might act as trigger for the development of autoimmune hepatitis.

Summary Background and aim Hepatitis C virus (HCV) therapy should be considered without delay in all patients with significant (SIGFIB) or advanced liver fibrosis (ADVFIB). We aimed to investigate the rates of treatment initiation with interferon-free regimens within a screening program for SIGFIB/ADVFIB in human immunodeficiency virus/HCV coinfected patients (HIV/HCV). Methods The FIB-4 was calculated in all HIV/HCV from 2014–2016. HIV/HCV were counselled by the HIV clinic and referred to the Division of Gastroenterology and Hepatology for transient elastography (TE) and evaluation for HCV therapy. Patients were stratified by FIB-4 of 7.1 kPa/>9.5 kPa, respectively. Results Among 1348 HIV+ patients, 16% (210/1348) had detectable HCV-RNA. One hundred HIV/HCV had a FIB-4 ≥1.45. Among these, 57% (57/100) underwent TE. The majority of these patients had SIGFIB (75%; 43/57) or ADVFIB (37%; 21/57), however, interferon-free treatment was initiated in only 56% (24/43). In addition, fifty-two percent (57/110) of HIV/HCV with FIB-4

RATIONALE: The immunologic syndrome induced by severe acute coronavirus disease 2019 (COVID-19) is yet not fully understood. Typical patterns of clinical and laboratory features match secondary hemophagocytic lymphohistiocytosis (sHLH). However, the optimal approach to COVID-19 patients testing positive for sHLH is still unclear. PATIENT CONCERNS: Three patients with COVID-19 are reviewed. All showed hyperinflammation and cytokine storm, necessitating intensive care treatment including mechanical ventilation. DIAGNOSIS: Secondary hemophagocytic lymphohistiocytosis due to severe COVID-19; diagnosed via HScore. INTERVENTIONS: A treatment regimen of methylprednisolone, pentaglobin, and anakinra was developed and administered. OUTCOMES: One patient survived the ICU stay. Two other patients, in whom sHLH was diagnosed too late, deceased. LESSONS: A routine screening of COVID-19 patients for secondary HLH by using the HScore is feasible; especially those patients deteriorating clinically with no sufficient response to shock management might be at particular high risk. A stepwise therapeutic approach comprising corticosteroids, immunoglobulins and anakinra, accompanied by immunoadsorption, may dampen cytokine storm effects, and potentially reduce mortality.

OBJECTIVE Vasoactive cardiovascular hormones such as the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are produced upon ventricular stretch and play a central role in neurohumoral pathways of the heart regulating cardiovascular remodeling and volume homeostasis. The impact of HIV infection on these neurohumoral pathways of the heart and its potential reversibility by combinations of antiretroviral therapies remain unclear. METHODS We assessed serum levels of NT-proBNP in 219 antiretroviral therapy-naive HIV-infected patients with a normal cardiac and renal status at treatment initiation and after attainment of viremic control. RESULTS Before antiretroviral therapy, NT-proBNP as a surrogate of myocardial function displayed a significant correlation with absolute CD4 cell count (r = -0.31; P

In this paper, a commercial small-scale boiler designed for wood-chips was modified and redesigned to enable detailed space-resolved extraction of the gaseous compounds above the fuel bed. Therefore, the product gas was extracted at nine different points on the same level over the fuel bed. These experimental measurements are necessary to provide realistic boundary conditions for further freeboard numerical simulations. The space-resolved concentrations also provide excellent data for optimization and validation of fuel bed models. This approach is new in the field of commercial small-scale biomass boilers and shows the requirement of more than only one sampling point to gain the composition of the product gas. Additionally, the positive effect of an air-staged combustion on particle emissions was tested and confirmed for wood-chips with high and highest fine and bark fraction. The experiments were performed for three different fuel moistures and various primary air ratios. During all experiments, the wat...

Background Drug-induced immunosuppression following kidney transplantation is crucial to prevent allograft rejection, but increases risk for infectious disease. Tailoring of drug dosing to prevent both rejection and infection is greatly desirable. The apathogenic and ubiquitous torque teno virus (TTV) reflects immunocompetence of the host and might be a potential candidate for immunologic monitoring. Methods To assess TTV as an infection biomarker, virus load was prospectively quantified in peripheral blood of 169 consecutive renal allograft recipients at the Medical University Vienna. Results Patients with infection showed higher TTV levels compared to patients without infection (4.2 × 108 copies/mL [interquartile range, IQR, 2.7 × 107-1.9 × 109] vs 2.9 × 107 [IQR 1.0 × 106-7.2 × 108]; P = .006). Differences in TTV load became evident almost 3 months before infection (median 77 days, IQR 19-98). Each log level of TTV copies/mL increased the odds ratio for infection by 23% (95% confidence interval 1.04-1.45; P = .014). TTV >3.1 × 109 copies/mL corresponded to 90% sensitivity to predict infections. Logistic regression demonstrated independent association between TTV levels and infection. Conclusions TTV quantification predicts infection after kidney transplantation and might be a potential tool to tailor immunosuppressive drug therapy.

Despite increasing evidence in favor of prophylactic valganciclovir treatment in kidney transplant recipients for the prevention of cytomegalovirus (CMV) infection, the impact of preemptive vs. prophylactic treatment on long-term clinical outcomes is unclear. In this retrospective study, 187 kidney transplant recipients with serologic intermediate-risk constellation (recipient CMV IgG positive) received either preemptive or prophylactic treatment with valganciclovir. Patient survival (primary endpoint), graft survival, viremia rates, and other CMV-related outcomes were analyzed. Prophylactic therapy reduced the rates for CMV viremia during the first year (hazard ratio: 0.48, 95% confidence interval [CI] 0.30-0.75; p < 0.001). There was a trend for higher three-yr patient mortality in the prophylactic group (hazard ratio: 5.08, 95% CI 0.62-41.3; p = 0.091), and the rate of graft loss was not reduced (hazard ratio: 0.93, 95% CI 0.32-2.68; p = 0.894). Estimated glomerular filtration rate over three yr was on average 6.8 mL/min/1.73 m(2) lower in the prophylactic group (95% CI -11.68 to -1.81; p = 0.007) using a multivariate random effects model but showed more improvement over time. Prophylactic valganciclovir treatment reduced the rate of CMV infections during the first year post-transplant but no effects of prophylactic treatment on patient and graft survival or kidney function over three yr were observed.

Bendamustine has demonstrated clinical activity and a favorable safety profile as monotherapy or in combination with rituximab in lymphoid malignancies. As interventional trials do not always reflect clinical reality, we were interested in the treatment modalities and the outcome of bendamustine-based first-line therapy in patients with advanced indolent non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL) in routine practice. Between April 2010 and October 2011, 324 patients were enrolled in a prospective non-interventional multicenter study. Choice of the bendamustine regimen was at the treating physician's discretion. Effectiveness was assessed by best response. Mean age at onset of therapy was 69 years. The majority (94 %) of the patients was treated with bendamustine in combination with rituximab at a median bendamustine dose of 177 mg/m(2) per cycle. Most often, bendamustine was administered on days 1 and 2 (87 %) at 4-week intervals over a median of 6 cycles. Two hundred eighty-one patients qualified for evaluation of response. The overall response rate was 86 % (complete response 43 %, partial response 43 %, stable disease 10 %, progressive disease 4 %). Side effects of all grades were documented for 161 of the 323 patients (50 %), most frequently affecting blood/bone marrow (35 %). Fifty-four (17 %) patients experienced side effects of grade 3 (15 %) or grade 4 (2 %), and two patients grade 5 toxicities. Bendamustine-based first-line treatment of patients with advanced indolent NHL and MCL in clinical routine practice was assessed as effective and well tolerated in our study. Response was comparable to results from interventional clinical trials.

The impact of excess viral RNA on myocardial function and morphology in the setting of acute human immunodeficiency virus (HIV) infection remains unknown. In this study, 49 patients with acute HIV infection showed increased levels of N-terminal prohormone of brain natriuretic peptide, a surrogate of myocardial function, which decreased with viral suppression and normalization of systemic inflammation (79 pg/mL vs 28 pg/mL; P < .001). A comparable change was seen with levels of troponin T, a marker of morphologic myocardial damage (4.9 ng/L vs 1.5 ng/L; P < .001). In conclusion, we observed significant functional and morphological myocardial impairment during acute HIV infection, fueled by inflammatory activation and extensive viral replication, resulting in a reversible subclinical inflammatory cardiomyopathy.

Background and Objective Low-level light therapy (LLLT) has been revealed as a potential means to improve wound healing. So far, most studies are being performed with irradiation in the red to near-infrared spectra. Recently, we showed that blue light (470 nm) can significantly influence biological systems such as nitric oxide (NO) metabolism and is able to release NO from nitrosyl-hemoglobin or mitochondrial protein complexes. Therefore, the aim of this study was to evaluate and compare the therapeutic value of blue or red light emitting diodes (LEDs) on wound healing in an ischemia disturbed rodent flap model. Study Design/Materials and Methods An abdominal flap was rendered ischemic by ligation of one epigastric bundle and subjected to LED illumination with a wavelength of 470 nm (blue, n = 8) or 629 nm (red, n = 8) each at 50 mW/cm2 and compared to a non-treated control group (n = 8). Illumination was performed for 10 minutes on five consecutive days. Results LED therapy with both wavelengths significantly increased angiogenesis in the sub-epidermal layer and intramuscularly (panniculus carnosus muscle) which was associated with significantly improved tissue perfusion 7 days after the ischemic insult. Accordingly, tissue necrosis was significantly reduced and shrinkage significantly less pronounced in the LED-treated groups of both wavelengths. Conclusions LED treatment of ischemia challenged tissue improved early wound healing by enhancing angiogenesis irrespective of the wavelength thus delineating this noninvasive means as a potential, cost effective tool in complicated wounds. Lasers Surg. Med. 46:773–780, 2014. © 2014 Wiley Periodicals, Inc.

The aim of this retrospective study was the identification of clinically useful viral determinants for the prediction of hepatitis B surface antigen (HBsAg) seroclearance and sustained virological response in hepatitis B virus/human immunodeficiency virus (HBV-/HIV)-coinfected patients receiving HBV-active combined antiretroviral therapy (cART). Quantification of HBsAg, HBeAg and HBV DNA before and after initiation of HBV-active cART in a cohort of 59 HIV-/HBV-coinfected patients was performed. Calculations of receiver operating characteristics (ROC) and Kaplan-Meier analysis were used for the identification of predictors of HBsAg seroclearance for HBeAg-positive [HBeAg(+); n = 36] and HBeAg-negative [HBeAg(-);n = 23] patients. HBeAg(+) patients with an HBsAg on-treatment decline ≥ 1 log IU/mL per year achieved higher HBsAg loss rates (P = 0.0294), whereas the quantification of HBeAg had no predictive value for HBsAg seroclearance. Among HBeAg(-) patients, a pretreatment baseline cut-off level of HBsAg ≤ 100 IU/mL was highly predictive for HBsAg seroclearance. No significant influence of the HBV genotype on HBsAg seroclearance was observed among the entire cohort. Quantitative determination of HBsAg provides a clinically useful viral parameter for the prediction of HBsAg seroclearance both in HBeAg(+) and HBeAg(-) HIV-/HBV-coinfected patients receiving HBV-active cART.

BACKGROUND The introduction of direct-acting anti-virals has increased sustained virological response (SVR) rates in chronic hepatitis C genotype 1 infection. At present, data on long-term durability of viral eradication after successful triple therapy are lacking. AIM To evaluate the long-term durability of viral eradication in patients treated with triple therapy, including direct-acting anti-virals. METHODS Patients who participated in randomised, controlled trials or an extended access programme of treatment with peginterferon-α2a/ribavirin in combination with a direct-acting anti-viral (telaprevir, danoprevir, faldaprevir, simeprevir, mericitabine, balapiravir) were followed after achieving SVR. The median follow-up after the patients was 21 (range: 7-64) months. RESULTS One hundred and three patients with chronic hepatitis C genotype 1 infection [f/m: 34/69; GT-1b: 67 GT-1a: 34, GT-4: 2; mean age: 47.6 years (45.5-49.7; 95% CI)] achieving a SVR triple therapy were followed. Two cases of late relapses (2/103, 1.9%; 95% CI: 0.24-6.8) were observed. One patient was cirrhotic, both carried the genotype 1b and completed the prescribed treatment. The relapses occurred 8 and 12 months after cessation of anti-viral treatment. Cloning sequencing revealed identical sequence in both patients. Resistance analysis revealed no presence of viral resistance. CONCLUSION Like the SVR after peginterferon-α2/ribavirin combination treatment, HCV eradication after triple therapy remains durable after long-term follow-up.

Data on the efficacy of lamivudine (LAM)-, tenofovir (TDF)- and emtricitabine (FTC)-based antiretroviral therapy (HAART) in HBV-HIV coinfection are limited. We completed a retrospective analysis of HBV-HIV-coinfected patients treated at the Medical University of Vienna. One-hundred and ten coinfected patients were included, with 57% being initially HBV e-Antigen (HBeAg) positive. Baseline HBV load was significantly higher in HBeAg+ than in HBeAg- patients (5962 ± 3663 vs 20 ± 19 × 10(6) IU/mL; P < 0.0001). Over a median observation period of 83 month (range: 26-183), 87% received HAART and 91% showed a suppression of HBV replication. After 5 years of continuous treatment, HBeAg seroconversion was achieved in 21% of LAM-, 50% of TDF- (P = 0.042 vs LAM) and in 57% of TDF + FTC (P = 0.008 vs LAM)-treated patients, respectively. HBsAg loss after 5 years was found in 8% (LAM), 25% (TDF; P = 0.085 vs LAM) and 29% (TDF + FTC; P = 0.037 vs LAM) of HBeAg+ patients. In HBeAg- patients, HBsAg loss was achieved in 11% (LAM), 27% (TDF; P = 0.263 vs LAM) and 36% (TDF + FTC; P = 0.05 vs LAM), respectively. Pretreatment CD4+ counts did not influence rates of HBeAg seroconversion and of HBsAg loss. Patients with HBsAg loss had lower baseline HBV-DNA levels and higher AST/ALT levels than patients without HBsAg loss. Transient HAART-related hepatotoxicity was found in 32% (Grade I: 21%; II:7%; III:2%; IV:0%). Most HBV-HIV-coinfected patients achieve complete suppression of HBV replication despite high baseline viremia. TDF-based HAART leads to high rates of HBeAg seroconversion and HBsAg loss after 5 years of continuous exposure. One-third of HBV-HIV-coinfected patients may experience transient HAART-related hepatotoxicity.

The responsible politician for environment in Vorarlberg spoke at the Energy Gala in November 2002 in Bregenz and said: “It is necessary not only to discuss central regulations but to invest more in decentralised actions”. The communities are central players in this field because they can act in various ways: as authority, owner of buildings and as motivator for the people. Two examples of strategies in Austria are introduced: e5 - program for energy efficient communities (congruent to the European Energy Award) This program supports communities with high ambitions on energy and sustainability. The program helps to give structure, tools and a quality insurance system, so that even smaller communities can act in a professional and efficient way. Additionally it is a labelling and awarding system, which is quite important because a lot of work in the communities happens voluntarily and it is important to give approval to these actors. Energy point system in housing subsidies In the federal state of Salzburg the energy point system is a subsidy system for energy-saving measures and the use of renewable energy in housing. Quality points are given, depending on the energetic and ecological quality of a building. Every point increases the subvention that is granted by the government of the federal state Salzburg. Additional points exist, for example, for the use of biomass, solar energy and controlled living space ventilation. Using this simple system, the quality of sponsored housing was increased significantly and the use of renewable energies was successfully introduced into social housing. Today more than 80% of the residential buildings in Salzburg are heated by biomass and more than 60% of the buildings are using solar energy for hot water and heating.

AIM This retrospective monocentre study investigates long-term results of the cementless parabolic-shaped HI threaded cup. MATERIAL AND METHODS 678 threaded cups made of titanium were implanted into 641 patients from November 1991 to May 1995. Mean age was 67 years, 65 % female, 35 % male. From December 2005 until October 2006, 165 patients (168 hips) underwent complete clinical and radiological follow-up, data of the remaining group were taken from the files. Using the Kaplan-Meier method, survival rates of the threaded cup were calculated. RESULTS For all patients the average survival time of the cup was 14.2 years, the corresponding survival probability was 93 % (+/- 3.7 %) after 14.5 years. For the patients with complete follow-up, average survival time of the cup was 14.0 years, the corresponding survival probability was 93 % (+/- 5.2 %) after 14.5 years. CONCLUSION Our results are comparable to those of threaded cups with a conical design (Zweymuller), the HI threaded cup can thus be recommended for primary implantation.

White LEDs offer many advantages for use in dental instruments compared to the halogen light sources presently used. However, such LEDs have a very different spectral power distribution than halogen light sources. Therefore, the colour rendering properties of such LEDs have to be evaluated. The CIE colour rendering index is not suitable for this purpose so, in this study, a white LED designed for dental instruments was evaluated using the CIE ▵EL*a*b*2000 method and colour samples representative of teeth. From this evaluation, it is concluded that white LEDs have an advantage compared to halogen light sources for tooth colour evaluation by dentists.

During the last decades, the use of dental implants for tooth replacement became state of the art in dental pros- thetic therapy. The high survival rate of osseointegrated dental implants is well documented, but it is becoming increasingly evident that even successfully integrated implants are susceptible to diseases that finally may lead to implant loss. One of the most frequent reasons for implant failure nowadays is periimplantitis caused by pathological inflammatory changes in the tissue being adjacent to a load bearing implant. Clinically it is associ- ated with pocket formation, suppuration, bleeding and implant mobility. Numerous methods for implant surface decontamination have been suggested as a part of the surgical treatment of periimplantitis. Actually, decontamination of infected implant surfaces can be achieved very effectively by application of laser radiation. Hence, the purpose of our study was to evaluate suitable parameters for laser de- contamination of titanium plasma-sprayed implant surfaces by employing laser pulses in the microsecond range generated by two laser systems (Diode and frequency-doubled Nd:YAG). In this paper the results for tempera- ture development and surface morphology of different laser parameters and their clinical relevance and limita- tions are reported.

Ultra-short laser pulses (USLP) have the potential for materials processing with almost no collateral thermal or mechanical damage. Thus they are well suited for hard tissue preparation in dentistry. But since sharp focusing has to be applied to reach the high intensities required for plasma-mediated ablation, the small focal spot has to be scanned over a larger area representing the cross section of a usual dental drill. This paper investigates cavity shape and morphology for two different pulse lengths, as longer pulses would allow access to cheaper laser sources for later industrial development of a medical device. 700 fs and 12 ps laser pulses were applied on plain human dentine slices with a pulse repetition rate of 35 kHz using a newly developed rotating scanner working in r/φ-coordinates. Cavity shape and morphology of different scanning patterns were evaluated using ESEM and 3D light microscopy.