COVID-19:Prevention, disease and sequelae

The studies in this thesis investigate various aspects of SARS-CoV-2 infection, from preventive strategies to the pathogenesis of both acute and long-term sequelae. Our research emphasizes the critical need to look beyond the acute phase of the disease, even when milder strains are now prevalent globally. During the COVID-19 pandemic, numerous risk factors for severe COVID-19 were identified, yet the underlying mechanisms that make these factors contribute to an increased risk often remained unclear. This thesis shows how the host immune response differs among patients with these risk factors and how these differences may drive severe outcomes. By understanding these variations in immune responses, we can better identify at-risk patients and develop more effective, targeted treatment strategies to mitigate their risk.Furthermore, this thesis explores post-acute sequelae in severe and mild COVID-19 cases, highlighting the distinct clinical phenotypes and underlying pathophysiological mechanisms. Our research underscores the significant differences between post-COVID-19 hospitalization disease and long COVID, particularly in the context of persistent symptoms and immune responses. In severe COVID-19 cases, prolonged hospitalization and ICU admission are associated with ongoing inflammation, which may contribute to prolonged recovery and high readmission rates. In contrast, long COVID, particularly in patients with mild initial infections, is characterized by debilitating symptoms such as post-exertional malaise accompanied by various metabolic disturbances and autoimmunity. This thesis advances our understanding of the pathophysiology of COVID-19 and its long-term sequelae, paving the way for the development of innovative diagnostic and therapeutic approaches

COVID-19:Prevention, disease and sequelae

The studies in this thesis investigate various aspects of SARS-CoV-2 infection, from preventive strategies to the pathogenesis of both acute and long-term sequelae. Our research emphasizes the critical need to look beyond the acute phase of the disease, even when milder strains are now prevalent globally. During the COVID-19 pandemic, numerous risk factors for severe COVID-19 were identified, yet the underlying mechanisms that make these factors contribute to an increased risk often remained unclear. This thesis shows how the host immune response differs among patients with these risk factors and how these differences may drive severe outcomes. By understanding these variations in immune responses, we can better identify at-risk patients and develop more effective, targeted treatment strategies to mitigate their risk.Furthermore, this thesis explores post-acute sequelae in severe and mild COVID-19 cases, highlighting the distinct clinical phenotypes and underlying pathophysiological mechanisms. Our research underscores the significant differences between post-COVID-19 hospitalization disease and long COVID, particularly in the context of persistent symptoms and immune responses. In severe COVID-19 cases, prolonged hospitalization and ICU admission are associated with ongoing inflammation, which may contribute to prolonged recovery and high readmission rates. In contrast, long COVID, particularly in patients with mild initial infections, is characterized by debilitating symptoms such as post-exertional malaise accompanied by various metabolic disturbances and autoimmunity. This thesis advances our understanding of the pathophysiology of COVID-19 and its long-term sequelae, paving the way for the development of innovative diagnostic and therapeutic approaches

Outcomes of submucosal (T1b) esophageal adenocarcinomas removed by endoscopic mucosal resection

AIM: To investigate the outcomes and recurrences of pT1b esophageal adenocarcinoma (EAC) following endoscopic mucosal resection (EMR) and associated treatments. METHODS: Patients undergoing EMR with pathologically confirmed T1b EAC at two academic referral centers were retrospectively identified. Patients were divided into 4 groups based on treatment following EMR: Endoscopic therapy alone (group A), endoscopic therapy with either chemotherapy, radiation or both (group B), surgical resection (group C) or no further treatment/lost to follow-up (< 12 mo) (group D). Pathology specimens were reviewed by a central pathologist. Follow-up data was obtained from the academic centers, primary care physicians and/or referring physicians. Univariate analysis was performed to identify factors predicting recurrence of EAC. RESULTS: Fifty-three patients with T1b EAC underwent EMR, of which 32 (60%) had adequate follow-up ≥ 12 mo (median 34 mo, range 12-103). There were 16 patients in group A, 9 in group B, 7 in group C and 21 in group D. Median follow-up in groups A to C was 34 mo (range 12-103). Recurrent EAC developed overall in 9 patients (28%) including 6 (38%) in group A (median: 21 mo, range: 6-73), 1 (11%) in group B (median: 30 mo, range: 30-30) and 2 (29%) in group C (median 21 mo, range: 7-35. Six of 9 recurrences were local; of the 6 recurrences, 5 were treated with endoscopy alone. No predictors of recurrence of EAC were identified. CONCLUSION: Endoscopic therapy of T1b EAC may be a reasonable strategy for a subset of patients including those either refusing or medically unfit for esophagectomy

Money Talks? Report on the one-day symposium on the impact of corporate funding on information law research

Corporate funding is a contentious issue in information law and policy research. In the fall of 2019, the Institute of Information Law at the University of Amsterdam, and the European Hub of the Network of Centers invited academic research institutions, as well as junior and senior scholars to reflect on the issues around corporate influence on research through money, data, infrastructure, access. The discussion arrived at a number of important conclusions:- The discussion on funding must include data, infrastructure deals, and other forms of indirect funding- Sometimes corporate funding is the only way to get access to critical resources- Transparency is a must, but not a silver bullet to deal with funding- It is difficult to set up universal a priori norms of which type of funding is acceptable in which situations,- Academia may need new institutional solutions to review funding, and manage the potential risks of funders taking over the agenda, research bias, and reputational harms- Public funding bodies are part of the problem as much of the solution

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Susceptibility weighted imaging in intracranial hemorrhage:not all bleeds are black

To correctly recognize intracranial hemorrhage (ICH) and differentiate it from other lesions, knowledge of the imaging characteristics of an ICH on Susceptibility Weighted Imaging (SWI) is essential. It is a common misconception that blood is always black on SWI, and it is important to realize that hemorrhage has a variable appearance in different stages on SWI. Furthermore, the presence of a low signal on SWI does not equal the presence of blood products. In this review the appearance of ICH on SWI during all its stages and common other causes of a low signal on SWI are further discussed and illustrated.</p

Blood-based omic profiling supports female susceptibility to tobacco smoke-induced cardiovascular diseases

We recently reported that differential gene expression and DNA methylation profiles in blood leukocytes of apparently healthy smokers predicts with remarkable efficiency diseases and conditions known to be causally associated with smoking, suggesting that blood-based omic profiling of human populations may be useful for linking environmental exposures to potential health effects. Here we report on the sex-specific effects of tobacco smoking on transcriptomic and epigenetic features derived from genome-wide profiling in white blood cells, identifying 26 expression probes and 92 CpG sites, almost all of which are affected only in female smokers. Strikingly, these features relate to numerous genes with a key role in the pathogenesis of cardiovascular disease, especially thrombin signaling, including the thrombin receptors on platelets F2R (coagulation factor II (thrombin) receptor; PAR1) and GP5 (glycoprotein 5), as well as HMOX1 (haem oxygenase 1) and BCL2L1 (BCL2-like 1) which are involved in protection against oxidative stress and apoptosis, respectively. These results are in concordance with epidemiological evidence of higher female susceptibility to tobacco-induced cardiovascular disease and underline the potential of blood-based omic profiling in hazard and risk assessment