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Abstract Desmosomes are intercellular adhesion complexes providing mechanical coupling and tissue integrity. Previously, a correlation of desmosomal molecule expression with invasion and metastasis formation in several tumor entities was described together with a relevance for circulating tumor cell cluster formation. Here, we investigated the contribution of the desmosomal core adhesion molecule desmoglein-2 (DSG2) to the initial steps of liver metastasis formation by pancreatic cancer cells using a novel ex vivo liver perfusion mouse model. We applied the pancreatic ductal adenocarcinoma cell line AsPC-1 with and without a knockout (KO) of DSG2 and generated mouse lines with a hepatocyte-specific KO of the known interacting partners of DSG2 (DSG2 and desmocollin-2). Liver perfusion with DSG2 KO AsPC-1 cells led to smaller circulating cell clusters and a reduced number of cells adhering to murine livers compared to control cells. While this was independent of the expression levels of desmosomal adhesion molecules in hepatocytes, we show that increased cluster size of cancer cells, which correlates with stronger cell–cell adhesion and expression of desmosomal molecules, is a major factor contributing to the early phase of metastatic spreading. In conclusion, impaired desmosomal adhesion results in reduced circulating cell cluster size, which is relevant for seeding and attachment of metastatic cells to the liver.

Abstract Objective Brain tumors and metastases account for approximately 10% of all status epilepticus (SE) cases. This study described the clinical characteristics, treatment, and short- and long-term outcomes of this population. Methods This retrospective, multi-center cohort study analyzed all brain tumor patients treated for SE at the university hospitals of Frankfurt and Marburg between 2011 and 2017. Results The 208 patients (mean 61.5 ± 14.7 years of age; 51% male) presented with adult-type diffuse gliomas (55.8%), metastatic entities (25.5%), intracranial extradural tumors (14.4%), or other tumors (4.3%). The radiological criteria for tumor progression were evidenced in 128 (61.5%) patients, while 57 (27.4%) were newly diagnosed with tumor at admission and 113 (54.3%) had refractory SE. The mean hospital length of stay (LOS) was 14.8 days (median 12.0, range 1–57), 171 (82.2%) patients required intensive care (mean LOS 8.9 days, median 5, range 1–46), and 44 (21.2%) were administered mechanical ventilation. All patients exhibited significant functional status decline (modified Rankin Scale) post-SE at discharge (p

Abstract Lyme borreliosis (LB) is caused by the transmission of Borrelia burgdorferi s.l. from ticks to humans. Climate affects tick abundance, and climate change is projected to promote shifts in abundance in Europe, potentially increasing human exposure. We analyzed serum samples collected between the years 2014–2019 from German National Cohort (NAKO) participants at four study sites (Augsburg, Berlin, Hanover, Münster) for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies using an enzyme‐linked immunosorbent assay (ELISA) and line blot immunoassay as confirmatory test for positive and equivocal ELISA samples. We reported crude and weighted seropositivity proportions for local estimates. We used mixed model analysis to investigate associated factors, such as age, sex, migration background, or animal contacts. We determined the serostatus of 14,207 participants. The weighted seropositivity proportions were 3.4% (IgG) and 0.4% (IgM) in Augsburg, 4.1% (IgG) and 0.6% (IgM) in northern Berlin, 3.0% (IgG) and 0.9% (IgM) in Hanover, and 2.7% (IgG) and 0.6% (IgM) in Münster. We found higher odds for IgG seropositivity with advancing age (p

Background and purposeAutomated perfusion imaging can detect stroke patients with unknown time of symptom onset who are eligible for thrombolysis. However, the availability of this technique is limited. We, therefore, established the novel concept of computed tomography (CT) hypoperfusion-hypodensity mismatch, i.e., an ischemic core lesion visible on cerebral perfusion CT without visible hypodensity in the corresponding native cerebral CT. We compared both methods regarding their accuracy in identifying patients suitable for thrombolysis.MethodsIn a retrospective analysis of the MissPerfeCT observational cohort study, patients were classified as suitable or not for thrombolysis based on established time window and imaging criteria. We calculated predictive values for hypoperfusion-hypodensity mismatch and automated perfusion imaging to compare accuracy in the identification of patients suitable for thrombolysis.ResultsOf 247 patients, 219 (88.7%) were eligible for thrombolysis and 28 (11.3%) were not eligible for thrombolysis. Of 197 patients who were within 4.5 h of symptom onset, 190 (96.4%) were identified by hypoperfusion-hypodensity mismatch and 88 (44.7%) by automated perfusion mismatch (p

Rationale: Early evidence for the benefit of mechanical thrombectomy (MT) in pediatric patients with intracranial large vessel occlusion has been shown in previous retrospective cohorts. Higher-level evidence is needed to overcome the limitations of these studies such as the lack of a control group and the retrospective design. Randomized trials will very likely not be feasible, and several open questions remain, for example, the impact of arteriopathic etiologies or a possible lower age limit for MT. Save ChildS Pro therefore aims to demonstrate the safety and effectiveness of MT in pediatric patients compared to the best medical management and intravenous thrombolysis. Design: Save ChildS Pro is designed as a worldwide multicenter prospective registry comparing the safety and effectiveness of MT to the best medical care alone in the treatment of pediatric arterial ischemic stroke (AIS). It will include pediatric patients (

Abstract Computed-tomography perfusion (CTP) is frequently used to screen acute ischemic stroke (AIS) patients for endovascular treatment (EVT), despite known problems with ischemic “core” overestimation. This potentially leads to the unfair exclusion of patients from EVT. We propose that net water uptake (NWU) can be used in addition to CTP to more accurately assess the extent and/or stage of tissue infarction. Patients treated for AIS between 06/2015 and 07/2020 were retrospectively analyzed. Baseline CTP-derived core volume (pCore) and NWU were determined. Logistic regression tested the relationship between baseline clinical and imaging variables and core-overestimation (primary outcome). The secondary outcomes comprised 90-day functional independence (modified Rankin score) and lesion growth. 284 patients were included. Median NWU was 7.2% (IQR 2.6–12.8). ASPECTS (RR 1.28, 95% CI 1.09–1.51), NWU (RR 0.94, 95% CI 0.89–0.98), onset to recanalization (RR 1.00, 95% CI 0.99–1.00) and imaging (RR 1.00, 95% CI 1.00–1.00) times, and pCore (RR 1.02, 95% CI 1.01–1.02) were significantly associated with core overestimation. Core-overestimation was more likely to occur in patients with large pCores and low NWU at baseline. NWU was significantly correlated with lesion growth. We conclude that NWU can be used as a supplemental tool to CTP during admission imaging to more accurately assess the extent of ischemia, particularly relevant for patients with large CTP-defined cores who would otherwise be excluded from treatment.

Abstract SARS-CoV-2 variants accumulating immune escape mutations provide a significant risk to vaccine-induced protection against infection. The novel variant of concern (VoC) Omicron BA.1 and its sub-lineages have the largest number of amino acid alterations in its Spike protein to date. Thus, they may efficiently escape recognition by neutralizing antibodies, allowing breakthrough infections in convalescent and vaccinated individuals in particular in those who have only received a primary immunization scheme. We analyzed neutralization activity of sera from individuals after vaccination with all mRNA-, vector- or heterologous immunization schemes currently available in Europe by in vitro neutralization assay at peak response towards SARS-CoV-2 B.1, Omicron sub-lineages BA.1, BA.2, BA.2.12.1, BA.3, BA.4/5, Beta and Delta pseudotypes and also provide longitudinal follow-up data from BNT162b2 vaccinees. All vaccines apart from Ad26.CoV2.S showed high levels of responder rates (96–100%) towards the SARS-CoV-2 B.1 isolate, and minor to moderate reductions in neutralizing Beta and Delta VoC pseudotypes. The novel Omicron variant and its sub-lineages had the biggest impact, both in terms of response rates and neutralization titers. Only mRNA-1273 showed a 100% response rate to Omicron BA.1 and induced the highest level of neutralizing antibody titers, followed by heterologous prime-boost approaches. Homologous BNT162b2 vaccination, vector-based AZD1222 and Ad26.CoV2.S performed less well with peak responder rates of 48%, 56% and 9%, respectively. However, Omicron responder rates in BNT162b2 recipients were maintained in our six month longitudinal follow-up indicating that individuals with cross-protection against Omicron maintain it over time. Overall, our data strongly argue for booster doses in individuals who were previously vaccinated with BNT162b2, or a vector-based primary immunization scheme.

Background and Purpose Many patients with stroke cannot receive intravenous thrombolysis because the time of symptom onset is unknown. We tested whether a simple method of computed tomography (CT)-based quantification of water uptake in the ischemic tissue can identify patients with stroke onset within 4.5 hours. Methods This retrospective analysis of the MissPerfeCT study (August 2009 to November 2017) includes consecutive patients with known onset of symptoms from seven tertiary stroke centers. We developed a simplified algorithm based on region of interest (ROI) measurements to quantify water uptake of the ischemic lesion and thereby quantify time of symptom onset within and beyond 4.5 hours. Perfusion CT was used to identify ischemic brain tissue, and its density was measured in non-contrast CT and related to the density of the corresponding area of the contralateral hemisphere to quantify lesion water uptake. Results Of 263 patients, 204 (77.6%) had CT within 4.5 hours. Water uptake was significantly lower in patients with stroke onset within (6.7%; 95% confidence interval [CI], 6.0% to 7.4%) compared to beyond 4.5 hours (12.7%; 95% CI, 10.7% to 14.7%). The area under the curve for distinguishing these patient groups according to percentage water uptake was 0.744 with an optimal cut-off value of 9.5%. According to this cut-off the positive predictive value was 88.8%, sensitivity was 73.5%, specificity 67.8%, negative predictive value was 42.6%. Conclusions Ischemic stroke patients with unknown time of symptom onset can be identified as being within a timeframe of 4.5 hours using a ROI-based method to assess water uptake on admission non-contrast head CT.

Purpose: The Alberta Stroke Program Early CT Score (ASPECTS) is regularly used to guide patient selection for mechanical thrombectomy (MT). Similarly, penumbral imaging based on computed tomography perfusion (CTP) may serve as neuroimaging tool to guide treatment. Yet, patients with a large ischemic core on CTP may show only minor ischemic changes resulting in a high ASPECTS. Aim: We hypothesized twofold: (1) the treatment effect of vessel recanalization in patients with core volume > 50 mL but ASPECTS ⩾ 6 is not different compared to high ASPECTS patients with core volume < 50 mL, and (2) recanalization is associated with core overestimation. Methods: We conducted an observational study analyzing ischemic stroke patients consecutively treated with MT after triage by multimodal CT. Functional endpoint was the rate of functional independence at Day 90 defined as modified Rankin Scale (mRS) 0–2. Imaging endpoint was core overestimation, which was considered when CTP-derived core was larger than the final infarct volume assessed on follow-up imaging. Recanalization was evaluated with the extended Thrombolysis in Cerebral Infarction (eTICI) scale. Multivariable logistic regression analysis and propensity score matching (PSM) were used to assess the association of recanalization (eTICI ⩾ 2b) with functional outcome and core overestimation. Results: Of 630 patients with ASPECTS ⩾ 6, 91 patients (14.4%) had a large ischemic core. Following 1:1 PSM, the treatment effect of recanalization was not different in patients with large core and ASPECTS ⩾ 6 (+ 25.8%, 95% CI: 16.3–35.4, p < 0.001) compared to patients with ASPECTS ⩾ 6 and core volume < 50 mL (+ 14.9%, 95% CI: 5.7–24.1, p = 0.002). Recanalization (aOR: 3.46, 95% CI: 1.85–6.47, p < 0.001) and higher core volume (aOR: 1.03, 95% CI: 1.02–1.04, p < 0.001) were significantly associated with core overestimation. Conclusion: In patients with ASPECTS ⩾ 6, core volumes did not significantly modify outcomes following recanalization. Reperfusion and higher core volume were significantly associated with core overestimation which may explain the treatment effect of MT for patients with a large ischemic core but minor ischemic changes on non-enhanced CT. Data access statement: The data analyzed in this study will be available and shared on reasonable request from any qualified researcher for the purpose of replicating the results after clearance by the local ethics committee. [ABSTRACT FROM AUTHOR]

Ischemic lesion net water uptake (NWU) represents a quantitative imaging biomarker for cerebral edema in acute ischemic stroke. Data on NWU for distinct occlusion locations remain scarce, but might help to improve the prognostic value of NWU. In this retrospective multicenter cohort study, we compared NWU between patients with proximal large vessel occlusion (pLVO; ICA or proximal M1) and distal large vessel occlusion (dLVO; distal M1 or M2). NWU was quantified by densitometric measurements of the early ischemic region. Arterial collateral status was assessed using the Maas scale. Regression analysis was used to investigate the relationship between occlusion location, NWU and ischemic lesion growth. A total of 685 patients met inclusion criteria. Early ischemic lesion NWU was higher in patients with pLVO compared with dLVO (7.7% vs 3.9%, P <.001). The relationship between occlusion location and NWU was partially mediated by arterial collateral status. NWU was associated with absolute ischemic lesion growth between admission and follow-up imaging (β estimate, 5.50, 95% CI, 3.81–7.19, P <.001). This study establishes a framework for the relationship between occlusion location, arterial collateral status, early ischemic lesion NWU and ischemic lesion growth. Future prognostic thresholds for NWU might be optimized by adjusting for the occlusion location. [ABSTRACT FROM AUTHOR]

Background and Purpose The Save ChildS Study demonstrated that endovascular thrombectomy (EVT) is a safe treatment option for pediatric stroke patients with large vessel occlusions (LVOs) with high recanalization rates. Our aim was to determine the long-term cost, health consequences and cost-effectiveness of EVT in this patient population. Methods In this retrospective study, a decision-analytic Markov model estimated lifetime costs and quality-adjusted life years (QALYs). Early outcome parameters were based on the entire Save ChildS Study to model the EVT group. As no randomized data exist, the Save ChildS patient subgroup with unsuccessful recanalization was used to model the standard of care group. For modeling of lifetime estimates, pediatric and adult input parameters were obtained from the current literature. The analysis was conducted in a United States setting applying healthcare and societal perspectives. Probabilistic sensitivity analyses were performed. The willingness-to-pay threshold was set to $100,000 per QALY. Results The model results yielded EVT as the dominant (cost-effective as well as cost-saving) strategy for pediatric stroke patients. The incremental effectiveness for the average age of 11.3 years at first stroke in the Save ChildS Study was determined as an additional 4.02 lifetime QALYs, with lifetime cost-savings that amounted to $169,982 from a healthcare perspective and $254,110 when applying a societal perspective. Acceptability rates for EVT were 96.60% and 96.66% for the healthcare and societal perspectives. Conclusions EVT for pediatric stroke patients with LVOs resulted in added QALY and reduced lifetime costs. Based on the available data in the Save ChildS Study, EVT is very likely to be a cost-effective treatment strategy for childhood stroke.

BackgroundThe eResearch system "Prospective Monitoring and Management App (PIA)" allows researchers to implement questionnaires on any topic and to manage biosamples. Currently, we use PIA in the longitudinal study ZIFCO (Integrated DZIF Infection Cohort within the German National Cohort) in Hannover (Germany) to investigate e.g. associations of risk factors and infectious diseases. Our aim was to assess user acceptance and compliance to determine suitability of PIA for epidemiological research on transient infectious diseases.MethodsZIFCO participants used PIA to answer weekly questionnaires on health status and report spontaneous onset of symptoms. In case of symptoms of a respiratory infection, the app requested participants to self-sample a nasal swab for viral analysis. To assess user acceptance, we implemented the System Usability Scale (SUS) and fitted a linear regression model on the resulting score. For investigation of compliance with submitting the weekly health questionnaires, we used a logistic regression model with binomial response.ResultsWe analyzed data of 313 participants (median age 52.5 years, 52.4% women). An average SUS of 72.0 reveals good acceptance of PIA. Participants with a higher technology readiness score at the beginning of study participation also reported higher user acceptance. Overall compliance with submitting the weekly health questionnaires showed a median of 55.7%. Being female, of younger age and being enrolled for a longer time decreased the odds to respond. However, women over 60 had a higher chance to respond than women under 60, while men under 40 had the highest chance to respond. Compliance with nasal swab self-sampling was 77.2%.DiscussionOur findings show that PIA is suitable for the use in epidemiologic studies with regular short questionnaires. Still, we will focus on user engagement and gamification for the further development of PIA to help incentivize regular and long-term participation.

Background and aims:Assessment of ischemic lesions on computed tomography or MRI diffusion-weighted imaging (DWI) using the Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is widely used to guide acute stroke treatment. However, it has never been defined how many voxels need to be affected to label a DWI-ASPECTS region ischemic. We aimed to assess the effect of various lesion load thresholds on DWI-ASPECTS and compare this automated analysis with visual rating. Materials and methods:We analyzed overlap of individual DWI lesions of 315 patients from the previously published predictive value of fluid-attenuated inversion recovery study with a probabilistic ASPECTS template derived from 221 CT images. We applied multiple lesion load thresholds per DWI-ASPECTS region (>0, >1, >10, and >20% in each DWI-ASPECTS region) to compute DWI-ASPECTS for each patient and compared the results to visual reading by an experienced stroke neurologist. Results:By visual rating, median ASPECTS was 9, 84 patients had a DWI-ASPECTS score ≤7. Mean DWI lesion volume was 22.1 (±35) ml. In contrast, by use of >0, >1-, >10-, and >20%-thresholds, median DWI-ASPECTS was 1, 5, 8, and 10; 97.1% (306), 72.7% (229), 41% (129), and 25.7% (81) had DWI-ASPECTS ≤7, respectively. Overall agreement between automated assessment and visual rating was low for every threshold used (>0%: κw = 0.020 1%: κw = 0.151; 10%: κw = 0.386; 20% κw = 0.381). Agreement for dichotomized DWI-ASPECTS ranged from fair to substantial (≤7: >10% κ = 0.48; >20% κ = 0.45; ≤5: >10% κ = 0.528; and >20% κ = 0.695). Conclusion:Overall agreement between automated and the standard used visual scoring is low regardless of the lesion load threshold used. However, dichotomized scoring achieved more comparable results. Varying lesion load thresholds had a critical impact on patient selection by ASPECTS. Of note, the relatively low lesion volume and lack of patients with large artery occlusion in our cohort may limit generalizability of these findings.

Abstract Background Thrombus histology has become a potential diagnostic tool for the etiology assessment of patients with ischemic stroke caused by embolic proximal vessel occlusion. We validated a classification rule that differentiates between cardiac and arteriosclerotic emboli in individual stroke patients. We aim to describe in detail the development of this classification rule and disclose its reliability. Methods The classification rule is based on the hypothesis that cardiac emboli arise out of separation thrombi and arteriosclerotic emboli result from agglutinative thrombi. 125 emboli recovered by thrombectomy from stroke patients and 11 thrombi serving as references for cardiac (n = 5) and arteriosclerotic emboli (n = 6) were Hematoxylin and eosin, Elastica-van Gieson and CD61 stained and rated independently by two histopathologists blinded to the presumed etiology by several pre-defined criteria. Intra- and interobserver reliabilities of all criteria were determined. Out of the different criteria, three criteria with the most satisfactory reliability values were selected to compose the classification rule that was finally adjusted to the reference thrombi. Reliabilities of the classification rule were calculated by using the emboli of stroke patients. Results The classification rule reached intraobserver reliabilities for the two raters of 92.9% and 68.2%, respectively. Interobserver reliability was 69.9%. Conclusions A new classification rule for emboli obtained from thrombectomy was established. Within the limitations of histological investigations, it is reliable and able to distinguish between cardioembolic and arteriosclerotic emboli.

Abstract Endovascular treatment of strokes caused by large vessel occlusion enables the histopathological investigation of the retrieved embolus, possibly providing a novel opportunity to contribute to the diagnostic workup of etiology and to define secondary prevention measures in strokes with uncertain genesis. We aimed to develop a classification rule based on pathophysiological considerations and adjustment to reference thrombi for distinction between cardiac and arteriosclerotic emboli and to validate this classification rule on a patient cohort. From 125 patients with stroke due to large vessel occlusion and thrombectomy, 82 patients with known etiology (55 cardioembolic and 27 arterioembolic strokes) were included. The corresponding emboli were histologically evaluated by two raters blinded to the etiology of stroke by means of a novel classification rule. Presumed etiology and classification results were compared. Agreement concerning cardiac emboli was 72.2% (95% CI: 58.4–83.5) for rater I and 78.2% (95% CI: 65.0–88.2) for rater II. Agreement concerning arteriosclerotic emboli was 70.4% (95% CI: 49.8–86.3) for rater I and 74.1% (95% CI: 53.7–88.9) for rater II. Overall agreement reached 71.6% (95% CI: 60.5–81.1) for rater I and 76.8% (95% CI: 66.2–85.4) for rater II. Within the limits of generally restricted accuracy of histological evaluations, the classification rule differentiates between cardiac and arteriosclerotic emboli of acute ischemic stroke patients. Further improvement is needed to provide valuable complementary data for stroke etiology workup.

Recent increases in SARS-CoV-2 infections have led to questions about duration and quality of vaccine-induced immune protection. While numerous studies have been published on immune responses triggered by vaccination, these often focus on studying the impact of one or two immunisation schemes within subpopulations such as immunocompromised individuals or healthcare workers. To provide information on the duration and quality of vaccine-induced immune responses against SARS-CoV-2, we analyzed antibody titres against various SARS-CoV-2 antigens and ACE2 binding inhibition against SARS-CoV-2 wild-type and variants of concern in samples from a large German population-based seroprevalence study (MuSPAD) who had received all currently available immunisation schemes. We found that homologous mRNA-based or heterologous prime-boost vaccination produced significantly higher antibody responses than vector-based homologous vaccination. Ad26.CoV2S.2 performance was particularly concerning with reduced titres and 91.7% of samples classified as non-responsive for ACE2 binding inhibition, suggesting that recipients require a booster mRNA vaccination. While mRNA vaccination induced a higher ratio of RBD- and S1-targeting antibodies, vector-based vaccines resulted in an increased proportion of S2-targeting antibodies. Given the role of RBD- and S1-specific antibodies in neutralizing SARS-CoV-2, their relative over-representation after mRNA vaccination may explain why these vaccines have increased efficacy compared to vector-based formulations. Previously infected individuals had a robust immune response once vaccinated, regardless of which vaccine they received, which could aid future dose allocation should shortages arise for certain manufacturers. Overall, both titres and ACE2 binding inhibition peaked approximately 28 days post-second vaccination and then decreased.

Minimally invasive robotic surgery offer benefits such as reduced physical trauma, faster recovery and lesser pain for the patient. For these procedures, visual and haptic feedback to the surgeon is crucial when operating surgical tools without line-of-sight with a robot. External force sensors are biased by friction at the tool shaft and thereby cannot estimate forces between tool tip and tissue. As an alternative, vision-based force estimation was proposed. Here, interaction forces are directly learned from deformation observed by an external imaging system. Recently, an approach based on optical coherence tomography and deep learning has shown promising results. However, most experiments are performed on ex-vivo tissue. In this work, we demonstrate that models trained on dead tissue do not perform well in in vivo data. We performed multiple experiments on a human tumor xenograft mouse model, both on in vivo, perfused tissue and dead tissue. We compared two deep learning models in different training scenarios. Training on perfused, in vivo data improved model performance by 24% for in vivo force estimation.

Randomized trials supporting the benefit of endovascular treatment in acute ischemic stroke patients with a large early infarction are not yet available. Few retrospective studies exist that suggest a potential positive treatment effect on functional outcome, as well as procedural safety. However, potential benefit or harm of MT in patients with low initial ASPECTS is still a subject of current debate, and in particular, how to select these patients for treatment. The purpose of this pilot study was to evaluate how early tissue water uptake in acute ischemic brain might determine lesion fate and functional outcome in low ASPECTS patients undergoing MT. We observed that the degree of early water uptake measured by quantitative NWU was significantly associated with functional outcome in low ASPECTS patients, yielding a higher diagnostic power compared to other parameters such as ASPECTS, age, or NIHSS. No conclusive evidence of a beneficial effect of successful reperfusion was observed in patients with low ASPECTS and high NWU, which highlights the potential of NWU as a tool to specify patient selection.

Introduction: Epidemiological data collection is often challenged by low response and, in the case of cohorts, poor long-term compliance, i.e. a high drop-out. For the correct recording of incident or recurring health events, that are subject to recall difficulties, gathering of data during the event and immediate response of the participants is crucial. This is especially true when biosampling that catches a transient biological situation like COVID-19 is involved. In addition, emerging research topics (e.g. pandemics like the current SARS-CoV-2) demand a flexible approach regarding content while allowing for complex and varying study designs. To meet these needs, we developed an eResearch system for prospective monitoring and management of incident health events (PIA). Methods: Programming PIA focusses on IT security and data protection as well as aiming for a user-friendly and motivating design e.g. through feedback for study participants. The main building blocks of the infrastructure are identical functionalities in web-based, iOS and Android compatible application to strengthen the user acceptance of the participants. The backend consists of services and databases, which are all containerised using Docker containers. All programming is based on the JavaScript ecosystem as this is widely used and well supported. Results: PIA offers complete management of observational epidemiological studies with six different roles: PIA administrator, researcher, participant manager, study nurse, consent manager and participant. Each role has a specific interface, so that different functions e.g. implementation of new questionnaires, administration of biosamples or management of participant contacts can be performed by different personae. PIA can be integrated in the IT system of ongoing studies like the German National Cohort but also used as stand-alone system. The software is open source (AGPL3.0): https://github.com/hzi-braunschweig/pia-system. Discussion: Despite the abundance of existing Electronic Data Capture Systems (EDC systems), we developed our own generic tool that combines monitoring and management in order to use it for specific applications e.g. in certain pre-existing epidemiological studies or for syndromic surveillance in the current pandemic. Hence, PIA is continuously adapted to emerging requirements. Currently, systematic feedback from users is collected. We aim to improve the user experience of PIA as well as provide further feedback and additional elements like gamification in the future.