Cohort In Germany Research Articles

Association between Chronic Hepatitis B/C and Incidence of Osteoporosis and Bone Fractures: Results from a Retrospective Cohort Study.

Background: Osteoporosis and bone fractures affect health and quality of life. Since bone disease is multifactorial, identifying risk factors is key in prevention. There are multiple reports on how viral hepatitis, especially chronic hepatitis B (CHB) and chronic hepatitis C (CHC), are affecting bone disease, but results vary. Here, we analyzed the potential association between CHB/CHC and osteoporosis or bone fractures in a large outpatient cohort in Germany. Methods: We included 3136 outpatients with CHB and 15,608 matched non-hepatitis individuals as well as 2867 outpatients with CHC and 14,335 matched non-hepatitis individuals from the Disease Analyzer Database between 2005 and 2022. The main outcome was the 5-year cumulative incidence of osteoporosis and bone fractures as a function of either CHB or CHC. Results: Within 5 years of the index date, 2.9% vs. 1.6% of patients with and without CHB were diagnosed with osteoporosis (p = 0.001) and 1.0% vs. 0.4% were diagnosed with bone fractures (p < 0.001). Moreover, 3.3% of CHC patients and 2.2% of individuals without hepatitis C were diagnosed with osteoporosis (p = 0.002). In Cox regression analyses, CHB was significantly associated with an increased risk for osteoporosis (HR: 1.76) and fractures (HR:2.43) and CHC with osteoporosis (HR: 1.54). For both CHB and CHC, the association with osteoporosis was restricted to the female subgroup. Conclusions: CHB and CHC are associated with osteoporosis in women. CHB in male patients is associated with a higher risk of fractures. More research is needed to understand the underlying pathophysiological mechanisms.

Major depression recurrence is associated with differences in obesity-related traits in women, but not in men.

Obesity-related cardiometabolic comorbidity is common in major depressive disorder (MDD). However, sex differences and MDD recurrence may modify the MDD-obesity-link. Sex-specific associations of MDD recurrence (single [MDDS] or recurrent episodes [MDDR]) and obesity-related traits were analyzed in 4.100 adults (51.6% women) from a cross-sectional population-based cohort in Germany (SHIP-Trend-0). DSM-IV-based lifetime MDD diagnoses and MDD recurrence status were obtained through diagnostic interviews. Obesity-related outcomes included anthropometrics (weight, body mass index, waist- and hip-circumference, waist-to-hip ratio, waist-to-height ratio), bioelectrical impedance analysis of body fat mass and fat-free mass, and subcutaneous (SAT) and visceral adipose tissue (VAT) from abdominal magnetic resonance imaging. Sex-stratified linear regression models predicting obesity-related traits from MDD recurrence status were adjusted for age, education, and current depressive symptoms. 790 participants (19.3%) fulfilled lifetime MDD criteria (23.8% women vs. 14.5% men, p<0.001). In women, MDDS was inversely associated with anthropometric indicators of general and central obesity, while MDDR was positively associated with all obesity-related traits, except waist-to-hip ratio and fat-free mass. In women, MDDR versus MDDS was associated with higher levels of obesity across all outcomes except fat-free mass. In men, MDD was positively associated with SAT regardless of MDD recurrence. Additionally, lifetime MDD was positively associated with VAT in men. Results remained significant in sensitivity analyses after exclusion of participants with current use of antidepressants. The MDD-obesity association is modified by MDD recurrence and sex independent of current depressive symptoms. Accounting for sex and MDD recurrence may identify individuals with MDD at increased cardiometabolic risk.

Cost-Effectiveness Analysis of Routine Childhood Immunization with 20-Valent versus 15-Valent Pneumococcal Conjugate Vaccines in Germany.

This study aimed to evaluate the cost-effectiveness of routine childhood immunization with the 20-valent pneumococcal conjugate vaccine (PCV20) in a four-dose regimen (3 + 1 schedule) versus the 15-valent PCV (PCV15/V114) in a three-dose regimen (2 + 1) in Germany. The study utilized a decision-analytic Markov model to estimate lifetime costs and effectiveness outcomes for a single birth cohort in Germany. The model tracked the incidence of acute pneumococcal infections and long-term pneumococcal meningitis sequelae for both vaccination strategies. The vaccine effectiveness data were derived from published clinical trials and observational studies of PCV7 and PCV13. Indirect effects, such as herd protection and serotype replacement, were included in the model. The model adopted a societal perspective, including direct medical, direct non-medical, and indirect costs. Scenario and sensitivity analyses were performed. In the base case, PCV20 prevented more pneumococcal disease cases and deaths, with an expected gain of 96 quality-adjusted life years (QALYs) compared to V114. However, PCV20 was associated with a total incremental cost of EUR 48,358,424, resulting in an incremental cost-effectiveness ratio (ICER) of EUR 503,620/QALY. Most of the scenario and sensitivity analyses estimated that the ICER for PCV20 exceeded EUR 150,000/QALY. Routine childhood immunization with PCV20 instead of V114 may not be an economically efficient use of healthcare resources in Germany.

Association between Helicobacter pylori and its eradication and the development of cancer

BackgroundHelicobacter pylori (H. pylori) is a gram-negative gastrointestinal pathogen that colonises the human stomach and is considered a major risk factor for gastric cancer and mucosa-associated lymphoid tissue lymphoma. Furthermore,...

Association of Clinical Relapses With Disease Outcomes in Multiple Sclerosis Patients Older Than 50 Years.

Relapse and MRI activity usually decline with aging but are replaced by progression independent of relapse activity (PIRA) in patients with multiple sclerosis (PwMS). However, several older PwMS continue to experience clinical relapses, and the impact on their disease remains undetermined. We aimed to determine the impact of an index relapse on disease outcomes in patients older than 50 years and to identify risk factors of disadvantageous outcomes. We performed a secondary analysis from 3 prospective cohorts in Germany. We evaluated all PwMS 50 years and older with a relapse ≤60 days before a baseline visit and at least 18 months of follow-up compared with a control cohort of PwMS without a relapse. Patients were stratified according to age ("50-54" vs "55-59" vs "60+") or disease outcomes ("stable" vs "active" vs "progressive," according to the Lublin criteria). We analyzed relapses, MRI activity, relapse-associated worsening, and PIRA. Regression analysis was performed to evaluate the association of specific baseline risk factors and treatment regimen changes with disease outcomes at month 18. A total of 681 patients were included in the "relapse cohort" (50+: 361; 55+: 220; 60+: 100). The "control cohort" comprised 232 patients (50+: 117; 55+: 71; 60+: 44). Baseline epidemiologic parameters were balanced among cohorts and subgroups. We observed increased abundance of inflammatory activity and relapse-independent disability progression in the "relapse" vs "control" cohort. In the "relapse" cohort, we identified 273 patients as "stable" (59.7%), 114 patients as "active" (24.9%), and 70 patients as "progressive" (15.3%) during follow-up. Cardiovascular risk factors (CVRFs) and older age at baseline were identified as risk factors of progressive, whereas disease-modifying treatment (DMT) administration at baseline favored stable disease. DMT during follow-up was associated with stable over active, but not over progressive disease. A relapse-suggesting underlying active disease-in PwMS older than 50 years was associated with continued disease activity and increased risk of PIRA. Presence of CVRF and absence of DMT at baseline appeared as risk factors of disadvantageous disease courses. An escalation of DMT switch was associated with stable over active but not progressive disease.

A Transcriptomic Biomarker Predicting Linezolid-Associated Neuropathy During Treatment of Drug-Resistant Tuberculosis.

Neuropathic adverse events occur frequently in linezolid-containing regimens, some of which remain irreversible after drug discontinuation. We aimed to identify and validate a host RNA-based biomarker that can predict linezolid-associated neuropathy before multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) treatment initiation and to identify genes and pathways that are associated with linezolid-associated neuropathy. Adult patients initiating MDR/RR-TB treatment including linezolid were prospectively enrolled in 3 independent cohorts in Germany. Clinical data and whole blood RNA for transcriptomic analysis were collected. The primary outcome was linezolid-associated optic and/or peripheral neuropathy. A random forest algorithm was used for biomarker identification. The biomarker was validated in an additional fourth cohort of patients with MDR/RR-TB from Romania. A total of 52 patients from the 3 identification cohorts received linezolid treatment. Of those, 24 (46.2%) developed peripheral and/or optic neuropathies during linezolid treatment. The majority (59.3%) of the episodes were of moderate (grade 2) severity. In total, the expression of 1,479 genes differed significantly at baseline of treatment. Suprabasin (SBSN) was identified as a potential biomarker to predict linezolid-associated neuropathy. In the validation cohort, 10 of 42 (23.8%) patients developed grade ≥3 neuropathies. The area under the curve for the biomarker algorithm prediction of grade ≥3 neuropathies was 0.63 (poor; 95% confidence interval: 0.42 - 0.84). We identified and preliminarily validated a potential clinical biomarker to predict linezolid-associated neuropathies before the initiation of MDR/RR-TB therapy. Larger studies of the SBSN biomarker in more diverse populations are warranted.

Real-world therapy management of patients with multiple sclerosis receiving cladribine tablets beyond year 4 – Results from a German cladribine cohort

BackgroundThe current approval of oral cladribine covers four years, with two treatment courses in the first two years, followed by two treatment-free years. For decision-making in year 5, experts recommend three scenarios: Extending the treatment-free period, retreatment with cladribine, or therapy switch. ObjectiveTo assess the implementation of the three year-5-scenarios in clinical practice in a large multicentric real-world cohort in Germany. MethodsData from adult patients diagnosed with highly active RMS (first dose between 8/2017 and 8/2018) were included. The primary outcome was the percentages of patients who remained treatment-free in year 5, were retreated with cladribine, or switched to another therapy. ResultsIn total, 187 patients (75 % female, mean age 38.6 years, median EDSS 2.5, 21 % DMT-naive) were evaluated. Overall, 27 (14 %) switched treatment within year 1–4, 36 (19 %) continued therapy with cladribine tablets in year 5, and 8 (4 %) switched therapy in year 5. All other patients (n = 118, 63 %) continued to be monitored without therapy in year 5. ConclusionThe recommended three treatment scenarios in year 5 appear to be feasible in clinical practice. Treatment-free structured monitoring is the most frequently applied strategy, highly likely due to the prospect of continuing low disease activity under cladribine treatment.

Differences in Anthropometric Measures Based on Sex, Age, and Health Status.

Obesity is a worldwide health problem. We conducted detailed analyses of anthropometric measures in a comprehensive, population-based, current cohort in Germany. In the German National Cohort (NAKO), we analyzed cross-sectional data on body mass index (BMI), waist and hip circumference, subcutaneous (SAT) and visceral adipose tissue (VAT) as measured by ultrasound, and body fat percentage. The data were stratified by sex, age, and self-reported physicians' diagnoses of cardiovascular diseases (CVD), metabolic diseases (MetD), cardiometabolic diseases (CMD), and cancer. Data were available from 204 751 participants (age, 49.9 ± 12.8 years; 50.5% women). Body size measures generally increased with age. Men had a higher BMI, larger waist circumference, and more VAT than women, while women had a larger hip circumference, more SAT, and a higher body fat percentage than men. For example, the mean BMI of participants over age 60 was 28.3 kg/m2 in men and 27.6 kg/m2 in women. CVD, MetD, and CMD were associated with higher anthropometric values, while cancer was not. For example, the mean BMI was 25.3 kg/m2 in healthy women, 29.4 kg/m2 in women with CMD, and 25.4 kg/m2 in women with cancer. Obesity is widespread in Germany, with notable differences between the sexes in anthro - pometric values. Obesity was more common in older participants and those with chronic diseases other than cancer. Elevated values were especially common in multimorbid individuals.

BMI-Stratified Exploration of the 'Obesity Paradox': Heart Failure Perspectives from a Large German Insurance Database.

Background: The global rise of obesity and its association with cardiovascular risk factors (CVRF) have highlighted its connection to chronic heart failure (CHF). Paradoxically, obese CHF patients often experience better outcomes, a phenomenon known as the 'obesity paradox'. This study evaluated the 'obesity paradox' within a large cohort in Germany and explored how varying degrees of obesity affect HF outcome. Methods: Anonymized health claims data from the largest German insurer (AOK) for the years 2014-2015 were utilized to analyze 88,247 patients hospitalized for myocardial infarction. This analysis encompassed baseline characteristics, comorbidities, interventions, complications, and long-term outcomes, including overall survival, freedom from CHF, and CHF-related rehospitalization. Patients were categorized based on body mass index. Results: Obese patients encompassed 21.3% of our cohort (median age 68.69 years); they exhibited a higher prevalence of CVRF (p < 0.001) and comorbidities than non-obese patients (median age 70.69 years). Short-term outcomes revealed lower complication rates and mortality (p < 0.001) in obese compared to non-obese patients. Kaplan-Meier estimations for long-term analysis illustrated increased incidences of CHF and rehospitalization rates among the obese, yet with lower overall mortality. Multivariable Cox regression analysis indicated that obese individuals faced a higher risk of developing CHF and being rehospitalized due to CHF but demonstrated better overall survival for those classified as having low-level obesity (p < 0.001). Conclusions: This study underscores favorable short-term outcomes among obese individuals. The 'obesity paradox' was confirmed, with more frequent CHF cases and rehospitalizations in the long term, alongside better overall survival for certain degrees of obesity.

Patient-reported outcomes in advanced NSCLC before and during the COVID-19 pandemic: Real-world data from the German prospective CRISP Registry (AIO-TRK-0315).

Patients with lung cancer under treatment have been associated with a high risk of COVID-19 infection and potentially worse outcome, but real-world data on patient-reported outcomes (PROs) are rare. We assess patients' characteristics and PROs before and during the COVID-19 pandemic in an advanced non-small cell lung cancer (NSCLC) cohort in Germany. Patients with locally advanced or metastatic NSCLC from the prospective, multicentre, observational CRISP Registry (NCT02622581) were categorised as pre-pandemic (March 2019 to Feb 2020, n = 1621) and pandemic (March 2020 to Feb 2021, n = 1317). From baseline to month 15, patients' health-related quality of life (HRQoL) was assessed by FACT-L, anxiety and depression by PHQ-4. Association of pandemic status with time to deterioration (TTD) in QoL scales adjusted for potential covariates was estimated using Cox modelling. PROs were documented for 1166 patients (72%) in the pre-pandemic, 979 (74%) in the pandemic group. Almost 60% of patients were male, median age was 66 years, comorbidities occurred in 85%. Regarding HRQoL, mean-change-from-baseline plots hardly differed between both samples. Approximately 15%-21% of patients reported anxiety, about 19%-27% signs of depression. For the pandemic group, TTD was slightly, but statistically significantly, worse for the physical well-being-FACT-G subscale (HR 1.15 [95%CI 1.02-1.30]) and the anxiety-GAD-2 subscale (HR 1.14 [95%CI 1.01-1.29]). These prospectively collected real-world data provide valuable insights into PROs before and during the COVID-19 pandemic in advanced NSCLC. For the patients, the pandemic seemed to be less of a burden than the disease itself, as there was a considerable proportion of patients with anxiety and depression in both groups.

Psychiatric disorder and its association with gastrointestinal cancer: a retrospective cohort study with 45,842 patients in Germany.

Psychiatric disorders and cancer are both common, and comorbidity has detrimental impacts on cancer outcomes. Previous studies focus on affective disorders which arise after cancer diagnosis, not on the impact of psychiatric disorders on cancer risk. We investigate the association between psychiatric disorders and subsequent gastrointestinal cancer in a large cohort in Germany. This case-control study used secondary data (electronic medical records) from the national IQVIA Disease Analyzer database.We evaluated the association between previous psychiatric diagnosis in 44,582 matched patients with and without gastrointestinal (GI) cancer. Regression analyses were stratified by psychiatric diagnosis and adjusted by chronic comorbidities and previous psychiatric treatments. No association between any previous psychiatric disease and GI cancers was found (OR = 0.98 (0.95-1.02 95%CL, p = 0.39). Previous psychosomatic disorder and GI cancer showed a significant negative association (OR: 0.86, 0.81-0.90 95%CL, p < 0.0001). No association was found between previous diagnosis with depression or PTSD and GI cancer. These results remained consistent when including previous psychiatric treatments in the regression analyses. Psychiatric disease was not associated with GI cancer risk. Further investigation into the pathways linking psychiatric disease and cancer needs to be conducted, taking into consideration psychiatric treatments administered, to enhance our understanding of the relationship between these two common and devastating diseases.

Association between gout and epilepsy in adults – a retrospective cohort study with 244,964 primary care outpatients

BackgroundRecently there has been a rising interest in the identification of possible risk factors for epilepsies. In the present study, we investigated the potential association between gout and epilepsy in an outpatient cohort in Germany. MethodsUsing the IQVIA Disease Analyzer database, we identified 112,482 patients with gout treated in outpatient departments. These were matched 1:1 to non-gout patients based on sex, age, yearly consultation frequency during the follow-up period, and diagnoses associated with an increased epilepsy risk documented prior to or on the index date. Cox regression models were used to evaluate the association between gout and epilepsy. ResultsWithin 10 years after the index date, epilepsy had been diagnosed in 2.2% of gout and 1.6% of non-gout patients (log-rank p<0.001). In the regression analysis, we observed a significant association between gout and subsequent epilepsy (HR: 1.32; 95% CI: 1.21–1.44). The association was significant in all age groups, but strongest in the youngest age group (18–50) (HR: 1.86; 95% CI: 1.44–1.2.41). ConclusionOur study demonstrates that gout is associated with an increased incidence of epilepsy. This finding could help us to understand the mechanisms of epilepsy and better protect affected individuals in the future.

Analysis of volume and topography of adipose tissue in the trunk: Results of MRI of 11,141 participants in the German National Cohort

This research addresses the assessment of adipose tissue (AT) and spatial distribution of visceral (VAT) and subcutaneous fat (SAT) in the trunk from standardized magnetic resonance imaging at 3 T, thereby demonstrating the feasibility of deep learning (DL)-based image segmentation in a large population-based cohort in Germany (five sites). Volume and distribution of AT play an essential role in the pathogenesis of insulin resistance, a risk factor of developing metabolic/cardiovascular diseases. Cross-validated training of the DL-segmentation model led to a mean Dice similarity coefficient of >0.94, corresponding to a mean absolute volume deviation of about 22 ml. SAT is significantly increased in women compared to men, whereas VAT is increased in males. Spatial distribution shows age- and body mass index-related displacements. DL-based image segmentation provides robust and fast quantification of AT (≈15 s per dataset versus 3 to 4 hours for manual processing) and assessment of its spatial distribution from magnetic resonance images in large cohort studies.

Predictors of changes in physical activity and sedentary behavior during the COVID-19 pandemic in a Turkish migrant cohort in Germany

Predictors of changes in physical activity and sedentary behavior during the COVID-19 pandemic in a Turkish migrant cohort in Germany

Depression Is Associated with an Increased Risk of Subsequent Cancer Diagnosis: A Retrospective Cohort Study with 235,404 Patients.

Background: Depression and cancer share common risk factors and mechanisms of disease. The current literature has not explored the effect of depression on cancer risk. We assessed the difference in cancer risk in patients with and without depression in a large cohort in Germany. Methods: We compared cancer risk and incidence in patients with and without depression aged 18 or above diagnosed between 2015 and 2018 documented in the Disease Analyzer Database. Patients from a comparator group were matched 1:1 to patients with depression based on propensity scores. Patients with previous bipolar disorder (F31), mania (F30) or schizophrenia (F20-29) and cancer diagnosis 3 years prior to index date were excluded. Analyses were stratified by cancer type, age group, and gender. Results: A total of 117,702 patients with depression were included and matched 1:1, resulting in a cohort overall of 235,404. 4.9% of patients with depression compared to 4.1% without depression received at least one cancer diagnosis over 3.9 years median follow-up. The depression group showed an 18% increase in risk for a cancer diagnosis overall, with largest increased risk in lung cancer (HR: 1.39 [1.21-1.60], p < 0.0001), cancers of the gastro-intestinal-tract (HR: 1.30 [1.15-1.46], p < 0.0001), breast (HR: 1.23 [1.12-1.35], p < 0.0001) and urinary (HR: 1.23 [1.06-1.43], p < 0.01). Similarly, the incidence of cancer diagnosis overall increased by 22% for depressed patients. IRs showed no difference across cancer types. Conclusions: Depression increased the risk for cancer diagnosis consistently independent of the comparison method used. The potential mediating factors or shared mechanisms of the disease require further investigation.

The association of early regulatory problems with behavioral problems and cognitive functioning in adulthood: two cohorts in two countries.

Regulatory problems (RPs; excessive crying, sleeping, or feeding difficulties) that co-occur (i.e., multiple) or are persistent have been associated with cognitive and behavioral problems in childhood. However, it remains unknown if multiple or persistent RPs are associated with cognitive and behavioral problems in adulthood. This large prospective longitudinal study (N=759) was conducted in two cohorts in Germany (N=342) and Finland (N=417). RPs were assessed at 5, 20, and 56 months via the same standardized parental interviews and neurological examinations. In young adulthood, questionnaires were used to assess behavioral problems. Cognitive functioning was assessed with IQ tests. We examined the effects of multiple or persistent RPs on the outcomes via analysis of covariance tests and logistic regression controlled for the influence of cohort. Of 163 participants with RPs, 89 had multiple and 77 had persistent RPs. Adults who had early multiple or persistent RPs (N=151) reported more internalizing (p=.001), externalizing (p=.020), and total behavioral problems (p=.001), and, specifically, more depressive (p=.012), somatic (p=.005), avoidant personality (p < .001), and antisocial personality problems (p=.006) than those who never had RPs (N=596). Participants with multiple or persistent RPs were more likely to receive any ADHD diagnoses (p=.017), particularly of hyperactive/impulsive subtype (p=.032). In contrast, there were no associations between multiple or persistent RPs and IQ scores in young adulthood. The results indicate long-lasting associations between multiple or persistent RPs and behavioral problems. Thus, screening for early RPs could help to identify children who are at risk for later behavioral problems.

Age-period-cohort analysis of depression trends: are depressive symptoms increasing across generations in Germany?

Several studies have examined trends in depression, but only few have explicitly considered possible generational differences. I examined changes in the burden of depressive symptoms between 2002 and 2017 according to age, time period and birth cohort in Germany. I used population-based data drawn from the German Aging Survey (N = 33,723, 54% female, ages 40 +) from 2002, 2008, 2011, 2014, and 2017. Depressive symptoms were measured via the CES-D 15. Hierarchical age-period-cohort models were used to examine trends in depression. I found that depressive symptoms changed across age, time period and birth cohorts. While there was a general decrease across time periods, strong evidence for a U-shaped cohort effect was also found: Younger generations, beginning with cohorts born after the World War II, increasingly report more depressive symptoms than older generations. This U-shaped cohort trend appeared most pronounced for the somatic symptoms subscale. Contrarily, only minimal cohort differences were found regarding the positive affect subscale. Therefore, depressive symptoms, and especially somatic symptoms, seem to increase in more recent birth cohorts in Germany, who might thus be at risk to experience more mental health problems in the future. Potential reasons for these trends and the generalizability of the results to other countries should be investigated by future studies.

Explaining employment sector choices of doctoral graduates in Germany

Abstract Previous research in different national contexts has shown that individual preferences for certain job attributes, objective labour market conditions, subjective career prospects, and external encouragement shape doctoral graduates’ career decisions. For Germany, where the number of awarded doctoral degrees is highest within the European Union and where no established academic tenure-track system exists, the determinants of doctoral graduates’ sector choices are still largely unexplored. This article aims to shed light on the determinants of sector choices of doctoral graduates in Germany. By deriving the determinants from the wide version of rational choice theory and by measuring the determinants prior to employment sectors, we overcome the conceptual and methodological limitations of previous research. Using data from a nationally representative panel survey with doctoral graduates of the 2014 cohort in Germany, we differentiate between five distinct employment sectors and carry out multinomial logistic regression analysis. As expected, and in line with previous research from other countries, the results confirm that the sector choices of doctoral graduates in Germany depend on their preferences as well as various objective and subjective constraints. The article helps to better understand how doctoral graduates select into different employment sectors and thus provides important insights into postdoctoral career trajectories.

Lp(a) is not associated with arterial stiffness: a Mendelian randomization study

Abstract Background Deeper understanding of the potential causal relationship between Lp(a) and vascular injury will provide further insight to related pathways to be monitored and targeted by emerging treatments. Accumulating evidence supports the causal association of lipoprotein(a) [Lp(a)] with cardiovascular disease and calcific aortic valve disease (AVD). Arterial stiffening is mechanistically linked with cardiovascular disease and AVD severity. We hypothesized that Lp(a) may be causally associated with pulse-wave velocity (PWV) as the gold-standard marker of arterial stiffness. Aim To investigate the potential causal association of Lp(a) levels with PWV. Methods We performed a two sample Mendelian randomization (MR) analysis of LP(a) on PWV by combining the summary data of two independent Genetic-Wide Association Study (GWASs). Genetic variants associated with Lp(a) were retrieved from the UK Biobank (N=220,497). A GWAS based on a cohort in Germany (N=7,000) was used to obtain genetic associations for PWV index (outcome). We assessed two different measures of arterial stiffness, brachial ankle (baPWV) and carotid femoral pulse (cfPWV) wave velocity. In total, we used 170 SNPs as Instrument Variables (IV's) and applied a two sample MR with the main technique of Inverse Variance Weighting method (IVW). We conducted sensitivity analyses (MR-Egger and Median based) to detect pleiotropy of the causal variants and to test for robustness of our findings. Results Our analyses based on all 170 SNP's did not find evidence for causal relationship between Lp(a) and PWV for neither measurement [bivw (baPWV) = −0.0005, CI (−0.0043, 0.0034), P=0.8 and bivw (cfPWV) = −0.006, CI (−0.013, 0.002), P=0.16 for brachial ankle and carotid-femoral PWV, respectively]. Sensitivity analyses, including weighted median and mode-based estimation, did not show significant association of Lp (a) with neither baPWV nor cfPWV. Conclusions Lp(a) is not causally associated with arterial stiffness. These findings suggest that arterial stiffening is not involved Lp(a)-mediated cardiovascular and aortic valve disease. Funding Acknowledgement Type of funding sources: None.

Clinical characteristics of monkeypox virus infections among men with and without HIV: A large outbreak cohort in Germany.

Since May 2022, increasing numbers of monkeypox virus (MPXV) infections have been reported from across Europe and North America. Studies, mainly from Africa, have suggested a higher risk for severe MPXV cases in people living with HIV. This was a retrospective study of all confirmed MPXV infections observed in the participating centres since 19 May 2022. We conducted a chart review to evaluate clinical characteristics, comorbidities, and coinfections, including HIV, viral hepatitis, and sexually transmitted infections (STIs). By 30 June 2022, a total of 546 MPXV infections were reported from 42 German centres. All patients were men who have sex with men (MSM), of whom 256 (46.9%) were living with HIV, mostly with a preserved immune system and with viral suppression. In total, 232 (42.5%) MSM were also taking HIV pre-exposure prophylaxis (PrEP) and 58 (10.6%) MSM had no known HIV infection or PrEP use. The median age was 39 years (range 20-67), and comorbidities were rare. However, 52.4% and 29.4% of all patients had been diagnosed with at least one STI within the last 6months or within the last 4 weeks, respectively. The most frequent localizations of MPXV infection were genital (49.9%) and anal (47.9%), whereas fever (53.2%) and lymphadenopathy (42.6%) were the most frequent general symptoms. The hospitalization rate was low (4.0%), and no fatal course was observed. The clinical picture showed no apparent differences between MSM with or without HIV. In this preliminary cohort analysis from a current large outbreak among MSM in Germany, the clinical picture of MPXV infection did not differ between MSM with and without HIV infection. Severe courses were rare and hospitalization rates were low. However, most patients were relatively healthy, and only a few people living with HIV were viremic or severely immunosuppressed.