Comparison of post-COVID-19 symptoms in patients infected with the SARS-CoV-2 variants delta and omicron-results of the Cross-Sectoral Platform of the German National Pandemic Cohort Network (NAPKON-SUEP).

PURPOSE: The influence of new SARS-CoV-2 variants on the post-COVID-19 condition (PCC) remains unanswered. Therefore, we examined the prevalence and predictors of PCC-related symptoms in patients infected with the SARS-CoV-2 variants delta or omicron. METHODS: We compared prevalences and risk factors of acute and PCC-related symptoms three months after primary infection (3MFU) between delta- and omicron-infected patients from the Cross-Sectoral Platform of the German National Pandemic Cohort Network. Health-related quality of life (HrQoL) was determined by the EQ-5D-5L index score and trend groups were calculated to describe changes of HrQoL between different time points. RESULTS: We considered 758 patients for our analysis (delta: n = 341; omicron: n = 417). Compared with omicron patients, delta patients had a similar prevalence of PCC at the 3MFU (p = 0.354), whereby fatigue occurred most frequently (n = 256, 34%). HrQoL was comparable between the groups with the lowest EQ-5D-5L index score (0.75, 95% CI 0.73-0.78) at disease onset. While most patients (69%, n = 348) never showed a declined HrQoL, it deteriorated substantially in 37 patients (7%) from the acute phase to the 3MFU of which 27 were infected with omicron. CONCLUSION: With quality-controlled data from a multicenter cohort, we showed that PCC is an equally common challenge for patients infected with the SARS-CoV-2 variants delta and omicron at least for the German population. Developing the EQ-5D-5L index score trend groups showed that over two thirds of patients did not experience any restrictions in their HrQoL due to or after the SARS-CoV-2 infection at the 3MFU. CLINICAL TRAIL REGISTRATION: The cohort is registered at ClinicalTrials.gov since February 24, 2021 (Identifier: NCT04768998).

Dynamics of virological and immunological markers of HIV persistence after allogeneic haematopoietic stem-cell transplantation in the IciStem cohort: a prospective observational cohort study.

BACKGROUND: Allogeneic haematopoietic stem-cell transplantation (allo-HSCT) markedly reduces HIV reservoirs, but the mechanisms by which this occurs are only partly understood. In this study, we aimed to describe the dynamics of virological and immunological markers of HIV persistence after allo-HSCT. METHODS: In this prospective observational cohort study, we analysed the viral reservoir and serological dynamics in IciStem cohort participants with HIV who had undergone allo-HSCT and were receiving antiretroviral therapy, ten of whom had received cells from donors with the CCR5Δ32 mutation. Participants from Belgium, Canada, Germany, Italy, the Netherlands, Spain, Switzerland, and the UK were included in the cohort both prospectively and retrospectively between June 1, 2014 and April 30, 2019. In the first 6 months after allo-HSCT, participants had monthly assessments, with annual assessments thereafter, with the protocol tailored to accommodate for the individual health status of each participant. HIV reservoirs were measured in blood and tissues and HIV-specific antibodies were measured in plasma. We used the Wilcoxon signed-rank test to compare data collected before and after allo-HSCT in participants for whom longitudinal data were available. When the paired test was not possible, we used the Mann-Whitney U test. We developed a mathematical model to study the factors influencing HIV reservoir reduction in people with HIV after allo-HSCT. FINDINGS: We included 30 people with HIV with haematological malignancies who received a transplant between Sept 1, 2009 and April 30, 2019 and were enrolled within the IciStem cohort and included in this analysis. HIV reservoirs in peripheral blood were reduced immediately after full donor chimerism was achieved, generally accompanied by undetectable HIV-DNA in bone marrow, ileum, lymph nodes, and cerebrospinal fluid, regardless of donor CCR5 genotype. HIV-specific antibody levels and functionality values declined more slowly than direct HIV reservoir values, decaying significantly only months after full donor chimerism. Mathematical modelling suggests that allogeneic immunity mediated by donor cells is the main viral reservoir depletion mechanism after massive reservoir reduction during conditioning chemotherapy before allo-HSCT (half-life of latently infected replication-competent cells decreased from 44 months to 1·5 months). INTERPRETATION: Our work provides, for the first time, data on the effects of allo-HSCT in the context of HIV infection. Additionally, we raise the question of which marker can serve as the last reporter of the residual viraemia, postulating that the absence of T-cell immune responses might be a more reliable marker than antibody decline after allo-HSCT. FUNDING: amfAR (American Foundation for AIDS Research; ARCHE Program), National Institutes of Health, National Institute of Allergy and Infectious Diseases, and Dutch Aidsfonds.

Definition of the Post-COVID syndrome using a symptom-based Post-COVID score in a prospective, multi-center, cross-sectoral cohort of the German National Pandemic Cohort Network (NAPKON).

PURPOSE: The objective examination of the Post-COVID syndrome (PCS) remains difficult due to heterogeneous definitions and clinical phenotypes. The aim of the study was to verify the functionality and correlates of a recently developed PCS score. METHODS: The PCS score was applied to the prospective, multi-center cross-sectoral cohort (in- and outpatients with SARS-CoV-2 infection) of the "National Pandemic Cohort Network (NAPKON, Germany)". Symptom assessment and patient-reported outcome measure questionnaires were analyzed at 3 and 12 months (3/12MFU) after diagnosis. Scores indicative of PCS severity were compared and correlated to demographic and clinical characteristics as well as quality of life (QoL, EQ-5D-5L). RESULTS: Six hundred three patients (mean 54.0 years, 60.6% male, 82.0% hospitalized) were included. Among those, 35.7% (215) had no and 64.3% (388) had mild, moderate, or severe PCS. PCS severity groups differed considering sex and pre-existing respiratory diseases. 3MFU PCS worsened with clinical severity of acute infection (p = .011), and number of comorbidities (p = .004). PCS severity was associated with poor QoL at the 3MFU and 12MFU (p < .001). CONCLUSION: The PCS score correlated with patients' QoL and demonstrated to be instructive for clinical characterization and stratification across health care settings. Further studies should critically address the high prevalence, clinical relevance, and the role of comorbidities. TRAIL REGISTRATION NUMBER: The cohort is registered at www. CLINICALTRIALS: gov under NCT04768998.

In-hospital mortality during the wild-type, alpha, delta, and omicron SARS-CoV-2 waves: a multinational cohort study in the EuCARE project.

Background: Investigating outcomes of hospitalised COVID-19 patients throughout the pandemic is crucial to understand the impact of different SARS-CoV-2 variants. We compared 28-day in-hospital mortality of Wild-type, Alpha, Delta, and Omicron variant infections. Whether the difference in risk by variant varied by age was also evaluated. Methods: We conducted a cohort study including patients ≥18 years, hospitalised between 2020 and 02-01 and 2022-10-15 with a SARS-CoV-2 positive test, from nine countries. Variant was classified based on sequenced viruses or from national public metadata. Mortality was compared using the cumulative incidence function and subdistribution hazard ratios (SHR) adjusted for age, sex, calendar time, and comorbidities. Results were shown age-stratified due to effect measure modification (P < 0.0001 for interaction between age and variant). Findings: We included 38,585 participants: 19,763 Wild-type, 6387 Alpha, 3640 Delta, and 8795 Omicron. The cumulative incidence of mortality decreased throughout the study period. Among participants ≥70 years, the adjusted SHR (95% confidence interval) for Delta vs. Omicron was 1.66 (1.29-2.13). This estimate was 1.66 (1.17-2.36) for Alpha vs. Omicron, and 1.34 (0.92-1.95) for Wild-type vs. Omicron. These were 1.21 (0.81-1.82), 1.21 (0.68-2.17), and 0.98 (0.53-1.82) among unvaccinated participants. When comparing Omicron sublineages, the aSHR for BA.1 was 1.92 (1.43-2.58) compared to BA.2 and 1.52 (1.11-2.08) compared to BA.5. Interpretation: The herein observed decrease in in-hospital mortality seems to reflect a combined effect of immunity from vaccinations and previous infections, although differences in virulence between SARS-CoV-2 variants may also have contributed. Funding: European Union's Horizon Europe Research and Innovation Programme.

Disease Course and Pulmonary Involvement of COVID-19 during the Delta Variant Period in Germany: A Comparative Study of Vaccinated and Unvaccinated Patients at a Tertiary Hospital.

Background: Despite the availability of vaccines, there is an increasing number of SARS-CoV-2-breakthrough-infections. OBJECTIVE: The aim of this study was to determine whether there is a radiological difference in lung parenchymal involvement between infected vaccinated and unvaccinated patients. Additionally, we aimed to investigate whether vaccination has an impact on the course of illness and the need for intensive care. METHODS: This study includes all patients undergoing chest computed tomography (CT) or x-ray imaging in case of a proven SARS-CoV-2 infection between September and November 2021. Anonymized CT and x-ray images were reviewed retrospectively and in consensus by two radiologists, applying an internal severity score scheme for CT and x-ray as well as CARE and BRIXIA scores for x-ray. Radiological findings were compared to vaccination status, comorbidities, inpatient course of the patient's illness and the subjective onset of symptoms. RESULTS: In total, 38 patients with acute SARS-CoV-2 infection underwent a CT scan, and 168 patients underwent an x-ray examination during the study period. Of these, 32% were vaccinated in the CT group, and 45% in the x-ray group. For the latter, vaccinated patients exhibited significantly more comorbidities (cardiovascular (p=0.002), haemato-oncological diseases (p=0.016), immunosuppression (p=0.004)), and a higher age (p<0.001). Vaccinated groups showed significantly lower extent of lung involvement (severity scores in CT cohort and x-ray cohort both p≤0.020; ARDS 42% in unvaccinated CT cohort vs. 8% in vaccinated CT cohort). Furthermore, vaccinated patients in the CT cohort had significantly less need for intensive care treatment (p=0.040). CONCLUSION: Our data suggest that vaccination, in the case of breakthrough infection, favours a milder course of illness concerning lung parenchymal involvement and the need for intensive care, despite negative predictors, such as immunosuppression or other pre-existing conditions.

AIDS-defining events among people living with HIV who have been under continuous antiretroviral therapy for more than one year, a German cohort study 1999-2018.

PURPOSE: This study examined the characteristics, incidence and prognostic factors of the first AIDS-defining condition developed after more than one year of continuous antiretroviral therapy (ART) among people living with HIV (PLHIV). METHODS: We used data from two multicentre observational cohorts of PLHIV in Germany between 1999 and 2018. Our outcome was the first AIDS-defining event that occurred during follow-up after more than one year of continuous ART. Descriptive analyses at ART initiation, at the time of the AIDS event and of the most frequently observed types of AIDS-defining illnesses were performed. We calculated the incidence rate (IR) per 1000 person-years (PY) and used a bootstrap stepwise selection procedure to identify predictors of the outcome. RESULTS: A total of 12,466 PLHIV were included in the analyses. 378 developed the outcome, constituting an overall IR of 5.6 (95% CI 5.1-6.2) AIDS events per 1000 PY. The majority of PLHIV was virally suppressed at the time of the event. Oesophageal candidiasis and wasting syndrome were the most frequently diagnosed AIDS-defining illnesses. We found a low CD4 count at ART initiation, a previous AIDS-defining condition and transmission through intravenous drug use to be meaningful prognostic factors of the outcome. CONCLUSION: The overall rate of AIDS-defining events among PLHIV under long-term ART was low, highlighting the importance of continuous treatment. PLHIV who started ART with indicators of impaired immune functioning were more susceptible to disease progression, suggesting that the public health response should continue to focus on early and sustained treatment for all PLHIV.

[Presentations for HIV post-exposure prophylaxis in emergency departments: guideline and recommendations]. / HIV-Postexpositionsprophylaxe in der Notaufnahme: Vorgehen, Tipps & Tricks.

Patients often present to emergency departments after potential or confirmed exposure to human immunodeficiency virus (HIV) asking for recommendations concerning the initiation of post-exposure prophylaxis (PEP). These presentations may occur after occupational as well as non-occupational exposure. PEP entails taking a triple antiretroviral therapy for 28-30 days. If taken early (ideally within 2 h, but no later than 72 h) and as indicated, HIV infection can be prevented with a high level of probability. Since these presentations occur around the clock, they require basic expertise on the part of the emergency department staff regarding its indication and its side effects as well as standardized procedures in the emergency department to not delay initiation. Patients should present to an infectious disease outpatient clinic or practice specialized in HIV in order to have the indication reviewed by a specialist and, if necessary, adapted to complex cases with the aim of making individual case decisions. This review article aims to summarize core statements of the 2022 German-Austrian guideline on HIV post-exposure prophylaxis and to give emergency department staff necessary knowledge to safely and correctly begin PEP.

Torque Teno Virus load is associated with CDC stage and CD4+ cell count in people living with HIV but unrelated to AIDS-defining events and Human Pegivirus load.

BACKGROUND: Torque Teno Virus (TTV) is a non-enveloped, circular single-strand DNA virus and part of the human virome. The replication of TTV was related to the immune status in patients treated with immunosuppressive drugs after organ transplantation. We hypothesize that TTV load could be an additional marker for immune function in people living with HIV (PLWH). METHODS: In this analysis serum samples of PLWH from the RESINA multicenter cohort were reanalysed for TTV. Investigated clinical and epidemiological parameters included Pegivirus (HPgV) load, age, sex, HIV load, CD4+ cell count (CDC 1, 2, 3) and CDC clinical stages (1993 CDC classification system, A, B, C) before initiation of antiretroviral treatment. Regression analysis was used to detect possible associations among parameters. RESULTS: Our analysis confirmed TTV as a strong predictor of CD4+ cell count and CDC class 3. This relationship was used to propose a first classification of TTV load in regard to clinical stage. We found no association with clinical CDC stages A, B and C. HPgV load was inversely correlated with HIV load but not TTV load. CONCLUSIONS: TTV load was associated with immunodeficiency in PLWH. Neither TTV- nor HIV load were predictive for the clinical categories of HIV infection.

COVID-19 in Patients with Active Cancer: Higher Inflammatory Activity Predicts Poor Outcome.

INTRODUCTION: Active malignancies have been identified as an independent risk factor for severity and mortality in COVID-19. However, direct comparisons between SARS-CoV-2-infected patients with active (acP) and non-active cancers (n-acP) remain scarce. PATIENTS AND METHODS: We retrospectively analyzed a cohort of cancer patients with PCR-confirmed SARS-CoV-2 infection, enrolled from March 16, 2020, to July 31, 2021. Data on demographics, cancer, and laboratory findings were collected. Descriptive and subsequent regression analyses were performed. Endpoints were "deterioration to severe COVID-19" and "infection-associated mortality." RESULTS: In total, 987 cancer patients (510 acP vs. 477 n-acP) were included in our analysis. The majority was >55 years old, more men than women were included. At detection of SARS-CoV-2, 65.5% of patients had mild/moderate symptoms, while deterioration to severe COVID-19 was slightly more common in acP (19 vs. 16%; p = 0.284). COVID-19-associated mortality was significantly higher in acP (24 vs. 17.5%, p < 0.001). In terms of laboratory tests, severe cytopenia and elevated levels of inflammatory markers were common findings in acP at baseline, particularly in those who developed a severe infection or died. Multivariate analysis revealed that ferritin (HR 14.24 [2.1-96], p = 0.006) and CRP (HR 2.85 [1.02-8.02], p = 0.046) were associated with severity and mortality. In n-acP, association was seen for ferritin only (HR 4.1 [1.51-11.17], p = 0.006). CONCLUSION: Comparing patients with active and non-active cancer, the former showed higher mortality rates. Also, inflammatory markers were significantly increased, assuming higher levels of inflammation may play a role in the adverse outcome of COVID-19 in aCP.

Hemophagocytic lymphohistiocytosis-how common and how severe is it as a complication of malaria? Retrospective case series and review of the literature.

BACKGROUND: Infection-associated secondary hemophagocytic lymphohistiocytosis (sHLH) is a potentially life-threatening hyperinflammatory condition caused by various infectious diseases. Malaria has rarely been described as trigger. The aim of this study is to collect data on frequency, clinical spectrum, and outcome of sHLH induced by malaria. METHODS: We collected case numbers on malaria and malaria-associated sHLH from specialized centers in Germany from 2015 to 2022. In addition, we conducted a literature search on published cases of malaria-associated sHLH and systematically analyzed the literature regarding clinical and diagnostic criteria. RESULTS: We obtained data from 13 centers treating 1461 malaria cases with different Plasmodium species, of which 5 patients (0.34%) also were diagnosed with sHLH. The literature search revealed detailed case reports from further 51 patients and case series comprising the description of further 24 patients with malaria-associated sHLH. Most cases (48/80; 60%) were reported from Asia. The median time interval between onset of malaria symptoms and hospital admission was 7 days. Severe complications of sHLH were documented in 36% (20/56) of patients, including two patients with multiple organ failure in our case series. Only 41% (23/56) of patients received specific treatment for sHLH, nevertheless the mortality rate (CFR) of 5% is lower compared to the CFR reported for sHLH triggered by other infectious diseases (e.g., 25% in sHLH due to EBV infection). CONCLUSION: Malaria-associated sHLH appears to have a comparatively good prognosis but may still represent an underdiagnosed and potentially fatal complication of malaria, especially in resource-poor settings.

Prevalence and prognostic value of neurological affections in hospitalized patients with moderate to severe COVID-19 based on objective assessments.

Neurological manifestations of coronavirus disease 2019 (COVID-19) have been frequently described. In this prospective study of hospitalized COVID-19 patients without a history of neurological conditions, we aimed to analyze their prevalence and prognostic value based on established, standardized and objective methods. Patients were investigated using a multimodal electrophysiological approach, accompanied by neuropsychological and neurological examinations. Prevalence rates of central (CNS) and peripheral (PNS) nervous system affections were calculated and the relationship between neurological affections and mortality was analyzed using Firth logistic regression models. 184 patients without a history of neurological diseases could be enrolled. High rates of PNS affections were observed (66% of 138 patients receiving electrophysiological PNS examination). CNS affections were less common but still highly prevalent (33% of 139 examined patients). 63% of patients who underwent neuropsychological testing (n = 155) presented cognitive impairment. Logistic regression models revealed pathology in somatosensory evoked potentials as an independent risk factor of mortality (Odds Ratio: 6.10 [1.01-65.13], p = 0.049). We conclude that hospitalized patients with moderate to severe COVID-19 display high rates of PNS and CNS affection, which can be objectively assessed by electrophysiological examination. Electrophysiological assessment may have a prognostic value and could thus be helpful to identify patients at risk for deterioration.

Early combination therapy of COVID-19 in high-risk patients.

PURPOSE: Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dual therapies may therefore have a synergistic effect. METHODS: This retrospective, multicentre study compared treatment strategies for corona virus disease-19 (COVID-19) with combinations of nirmatrelvir/ritonavir, remdesivir, molnupiravir, and/ or mABs during the Omicron surge. Co-primary endpoints were prolonged viral shedding (≥ 106 copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 106 copies/ml. Therapeutic strategies and risk groups were compared using odds ratios and Fisher's tests or Kaplan-Meier analysis and long-rank tests. Multivariable regression analysis was performed. RESULTS: 144 patients were included with a median duration of SARS-CoV-2 viral load ≥ 106 copies/ml of 8.0 days (IQR 6.0-15.3). Underlying haematological malignancies (HM) (p = 0.03) and treatment initiation later than five days after diagnosis (p < 0.01) were significantly associated with longer viral shedding. Prolonged viral shedding was observed in 14.6% (n = 21/144), particularly in patients with underlying HM (OR 3.5; 95% CI 1.2-9.9; p = 0.02). Clinical courses of COVID-19 were mild to moderate with only few adverse effects potentially related to combination treatment. CONCLUSION: Early combination treatment of COVID-19 effectively prevented prolonged viral shedding in 85.6% of cases. Considering the rapid viral clearance rates and low toxicity, individualized dual therapy approaches may be beneficial in high-risk patients.

EuCARE-hospitalised study protocol: a cohort study of patients hospitalised with COVID-19 in the EuCARE project.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), can lead to hospitalisation, particularly in elderly, immunocompromised, and non-vaccinated or partially vaccinated individuals. Although vaccination provides protection, the duration of this protection wanes over time. Additional doses can restore immunity, but the influence of viral variants, specific sequences, and vaccine-induced immune responses on disease severity remains unclear. Moreover, the efficacy of therapeutic interventions during hospitalisation requires further investigation. The study aims to analyse the clinical course of COVID-19 in hospitalised patients, taking into account SARS-CoV-2 variants, viral sequences, and the impact of different vaccines. The primary outcome is all-cause in-hospital mortality, while secondary outcomes include admission to intensive care unit and length of stay, duration of hospitalisation, and the level of respiratory support required. METHODS: This ongoing multicentre study observes hospitalised adult patients with confirmed SARS-CoV-2 infection, utilising a combination of retrospective and prospective data collection. It aims to gather clinical and laboratory variables from around 35,000 patients, with potential for a larger sample size. Data analysis will involve biostatistical and machine-learning techniques. Selected patients will provide biological material. The study started on October 14, 2021 and is scheduled to end on October 13, 2026. DISCUSSION: The analysis of a large sample of retrospective and prospective data about the acute phase of SARS CoV-2 infection in hospitalised patients, viral variants and vaccination in several European and non-European countries will help us to better understand risk factors for disease severity and the interplay between SARS CoV-2 variants, immune responses and vaccine efficacy. The main strengths of this study are the large sample size, the long study duration covering different waves of COVID-19 and the collection of biological samples that allows future research. TRIAL REGISTRATION: The trial has been registered on ClinicalTrials.gov. The unique identifier assigned to this trial is NCT05463380.

Tecovirimat for the treatment of severe Mpox in Germany.

BACKGROUND: In May 2022, a multi-national mpox outbreak was reported in several non-endemic countries. The only licensed treatment for mpox in the European Union is the orally available small molecule tecovirimat, which in Orthopox viruses inhibits the function of a major envelope protein required for the production of extracellular virus. METHODS: We identified presumably all patients with mpox that were treated with tecovirimat in Germany between the onset of the outbreak in May 2022 and March 2023 and obtained demographic and clinical characteristics by standardized case report forms. RESULTS: A total of twelve patients with mpox were treated with tecovirimat in Germany in the study period. All but one patient identified as men who have sex with men (MSM) who were most likely infected with mpox virus (MPXV) through sexual contact. Eight of them were people living with HIV (PLWH), one of whom was newly diagnosed with HIV at the time of mpox, and four had CD4+ counts below 200/µl. Criteria for treatment with tecovirimat included severe immunosuppression, severe generalized and/or protracted symptoms, a high or increasing number of lesions, and the type and location of lesions (e.g., facial or oral soft tissue involvement, imminent epiglottitis, or tonsillar swelling). Patients were treated with tecovirimat for between six and 28 days. Therapy was generally well-tolerated, and all patients showed clinical resolution. CONCLUSIONS: In this cohort of twelve patients with severe mpox, treatment with tecovirimat was well tolerated and all individuals showed clinical improvement.

Strain energy density as a Gaussian process and its utilization in stochastic finite element analysis: application to planar soft tissues.

Data-based approaches are promising alternatives to the traditional analytical constitutive models for solid mechanics. Herein, we propose a Gaussian process (GP) based constitutive modeling framework, specifically focusing on planar, hyperelastic and incompressible soft tissues. The strain energy density of soft tissues is modeled as a GP, which can be regressed to experimental stress-strain data obtained from biaxial experiments. Moreover, the GP model can be weakly constrained to be convex. A key advantage of a GP-based model is that, in addition to the mean value, it provides a probability density (i.e. associated uncertainty) for the strain energy density. To simulate the effect of this uncertainty, a non-intrusive stochastic finite element analysis (SFEA) framework is proposed. The proposed framework is verified against an artificial dataset based on the Gasser-Ogden-Holzapfel model and applied to a real experimental dataset of a porcine aortic valve leaflet tissue. Results show that the proposed framework can be trained with limited experimental data and fits the data better than several existing models. The SFEA framework provides a straightforward way of using the experimental data and quantifying the resulting uncertainty in simulation-based predictions.

Consultations for HIV post-exposure prophylaxis before and after health insurance coverage of pre-exposure prophylaxis to a university-based emergency department in Germany.

Background: Potential risk contacts for HIV transmission may lead to presentations to the emergency department (ED) for counseling and initiation of post-exposure prophylaxis (PEP).Objective: To examine the impact of German health insurance covering pre-exposure prophylaxis (PrEP) following Sept 1st 2019 for certain risk groups on the frequency and reasons for PEP counseling in a university-based ED in Germany.Methods: In a before-after study design, all persons aged ≥18 years who presented for PEP counseling were analyzed retrospectively. We compared characteristics of presentations in the 18 months prior to PrEP coverage on Sept 1st, 2019, with those in the following 18 months.Results: 154 ED presentations occurred in the first study period, and 155 ED presentations in the second period. Regarding the reasons for ED visits, no statistically significant difference was found [occupational risk contact (18.2 vs. 26.5%, p = 0.081), sexual risk contact (74.7 vs. 69.0%, p = 0.266), other non-occupational risk contact (7.1 vs. 4.5%, p = 0.329)]. For men who have sex with men (MSM), no statistically significant differences were found [38.9 (n = 60) vs. 35.5% (n = 55), p = 0.537]. All persons presenting to the HIV outpatient clinic after ED PEP initiation (n = 60 vs. n = 52) tested negative for HIV 3 months later.Conclusion: In this study, reasons to present for PEP counseling to a university ED showed no change following the implementation of PrEP coverage by health insurances. Therefore, PEP remains an important prevention for HIV transmission and presentations to the ED for PEP counseling may provide an opportunity to educate persons at risk of HIV infection about PrEP, thereby helping to prevent new HIV infections.

Normal values for body composition in adults are better represented by continuous reference ranges dependent on age and BMI.

BACKGROUND & AIMS: Reference values for body composition parameters like skeletal muscle mass index (SMI) depend on age and BMI. To ensure reference intervals reflect these changes, they have traditionally been separated into groups of young adults based on sex and BMI. However, this static stratification oversimplifies the dynamic and gradual changes of body composition with increasing age and BMI. The aim was therefore to provide continuous reference ranges for body composition parameters. METHODS: Cross-sectional data of 1958 healthy men and women with an age between 18 and 97 years and a BMI between 17.1 und 45.6 kg/m2 were obtained between 2011 and 2019. Multiple regression analyses stratified by sex with age, age2 and BMI as independent variables were conducted to predict fat mass index (FMI), visceral adipose tissue (VAT), SMI, appendicular lean soft tissue index (ALSTI) and the ratio between extracellular to total body water (ECW/TBW). RESULTS: The regression models explained between 61 (VAT in women and ALSTI in men) and 93% of the variance in the respective body composition parameters (FMI in women). Age had only a minor impact (2-16%) whereas BMI substantially increased the explained variance of reference models for FMI, VAT and ALSTI (total explained variance 61-93%). In SMI, age is a major determinant of the explained variance (36% in men and 38% in women) with BMI equally contributing to the explained variance (total explained variance 72% in men and 75% in women). For ECW/TBW-ratio, age nearly completely explained the variance (79% in men and 74% in women) whereas BMI added only 2-3% to the explained variance. CONCLUSIONS: In conclusion, the derived continuous reference ranges are expected to improve body composition evaluation especially in very overweight and very old persons. Future studies applying these reference equations need to validate these assumptions. STUDY REGISTRATION, CLINICALTRIALS.GOV: NCT01368640, NCT01481285, NCT03779932, NCT04028648.

AIDS in the era of antiretroviral therapy: Changes in incidence rates and predictors of AIDS among people living with HIV under clinical care in Germany, a cohort study 1999-2018.

OBJECTIVES: This study examined the incidence rates and predictive utility of established prognostic factors for the progression to AIDS among people living with HIV under clinical care. METHODS: We used data from two observational cohorts of people living with HIV in Germany between 1999 and 2018. The outcome measure was the first AIDS-defining event that occurred during follow-up. Incidence rates (IRs) per 1000 person-years (PY) were calculated by years of follow-up and calendar periods. We used Cox models in our prediction analyses, including CD4 count, viral load, and age at baseline to estimate the predictive performance. Additionally, we included transmission mode to examine its predictive utility. RESULTS: A total of 23 299 people living with HIV were included in the analyses. Of these, 1832 developed a first AIDS event during follow-up, constituting an overall rate of 14.6/1000 PY (95% confidence interval [CI] 13.9-15.2). IRs were highest in the first year of follow-up (45.6/1000 PY, 95% CI 42.6-48.8) and then declined continuously. IRs were highest among people living with HIV who enrolled between 1999 and 2003 (36.1/1000 PY, 95% CI 32.6-40.0). A low CD4 count, high viral load, and older age at baseline increased the likelihood of progressing to AIDS. Adding transmission mode to the models did not improve the predictive performance. CONCLUSIONS: The rates of a first AIDS event among people living with HIV have continuously declined in Germany. Health outcomes depend on a person's CD4 count, viral load, and age but not on transmission mode. To further reduce the number of AIDS cases, the focus should be on groups more likely to present in progressed stages of their HIV infection.

Specialized palliative care for hospitalized patients with SARS-CoV-2 infection: an analysis of the LEOSS registry.

PURPOSE: Symptom control for patients who were severely ill or dying from COVID-19 was paramount while resources were strained and infection control measures were in place. We aimed to describe the characteristics of SARS-CoV-2 infected patients who received specialized palliative care (SPC) and the type of SPC provided in a larger cohort. METHODS: From the multi-centre cohort study Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS), data of patients hospitalized with SARS-CoV-2 infection documented between July 2020 and October 2021 were analysed. RESULTS: 273/7292 patients (3.7%) received SPC. Those receiving SPC were older and suffered more often from comorbidities, but 59% presented with an estimated life expectancy > 1 year. Main symptoms were dyspnoea, delirium, and excessive tiredness. 224/273 patients (82%) died during the hospital stay compared to 789/7019 (11%) without SPC. Symptom control was provided most common (223/273; 95%), followed by family and psychological support (50% resp. 43%). Personal contact with friends or relatives before or during the dying phase was more often documented in patients receiving SPC compared to patients without SPC (52% vs. 30%). CONCLUSION: In 3.7% of SARS-CoV-2 infected hospitalized patients, the burden of the acute infection triggered palliative care involvement. Besides complex symptom management, SPC professionals also focused on psychosocial and family issues and aimed to enable personal contacts of dying patients with their family. The data underpin the need for further involvement of SPC in SARS-CoV-2 infected patients but also in other severe chronic infectious diseases.

Percutaneous fractionated radiotherapy of the groin to eliminate lymphatic fistulas after vascular surgery.

BACKGROUND: Vascular surgery of the inguinal area can be complicated by persistent lymphatic fistulas. Rapid and effective treatment is essential to prevent infection, sepsis, bleeding, and possible leg amputation. Current data on irradiation of lymphatic fistulas lack recommendation on the appropriate individual and total dose, the time of irradiation, and the target volume. Presumably, a dose of 0.3-0.5 to 1-12 Gy should be sufficient for the purpose. Currently, radiotherapy is a "can" recommendation, with a level 4 low evidence and a grade C recommendation, according to the DEGRO S2 guidelines. As part of a pilot study, we analyzed the impact and limitations of low-dose radiation therapy in the treatment of inguinal lymphatic fistulas. PATIENTS AND METHODS: As a part of an internal quality control project, patients with lymphatic fistulas irradiated in the groin area after vascular surgery for arterial occlusive disease (AOD) III-IV, repair of pseudo aneurysm or lymph node dissection due to melanoma were selected, and an exploratory analysis on retrospectively collected data performed. RESULTS: Twelve patients (10 males and 2 females) aged 62.83 ± 12.14 years underwent open vascular reconstruction for stage II (n = 2), III (n = 1), and IV (n = 7) arterial occlusive disease (AOD), lymph node dissection for melanoma (n = 1) or repair of a pseudoaneurysm (n = 1). Surgical vascular access was obtained through the groin and was associated with a persistent lymphatic fistula, secreting more than 50 ml/day. Patients were irradiated five times a week up to a maximum of 10 fractions for the duration of the radiation period. Fraction of 0.4 Gy was applied in the first 7 cases, while 5 patients were treated with a de-escalating dose of 0.3 Gy. There was a resolution of the lymphatic fistula in every patient without higher grade complications. CONCLUSION: Low-dose irradiation of the groin is a treatment option for persistent lymphatic fistula after inguinal vascular surgery.