The (cost) effectiveness of a very low-energy diet intervention with the use of eHealth in patients with type 2 diabetes and obesity:study protocol for a randomised controlled non-inferiority trial (E-diet trial)

BACKGROUND: Despite preventive measures, the number of people with type 2 diabetes and obesity is increasing. Obesity increases morbidity and mortality in people with type 2 diabetes, making weight loss a cornerstone of treatment. We previously developed a very low energy diet (VLED) intervention that effectively reduced weight in people with type 2 diabetes in the long term. However, this intervention requires considerable time and manpower, which reduces the number of people who can benefit from it. eHealth offers more efficient solutions but has proven to be less effective than face-to-face interventions. Therefore, we want to investigate whether a blended version of our VLED intervention (in which face-to-face contact is partly replaced by an eHealth (mobile) application (E-VLED)) would be more cost-effective than the current face-to-face intervention. METHODS: We will conduct a randomised, controlled trial with non-inferiority design in patients with type 2 diabetes and obesity (BMI &gt; 30 kg/m2), aged 18-75 years. The control group will receive the usual care VLED intervention, while the intervention group will receive the E-VLED intervention for 1 year, where face-to-face contact will be partly replaced by an eHealth (mobile) application. The main study endpoint is the difference in weight (% change) between the control and intervention group after 1 year, plus the difference between the total costs (euro) of the treatment in the control and intervention groups. The secondary aims are to investigate the effectiveness of the E-VLED diet intervention regarding cardiovascular risk factors, quality of life, patient satisfaction, compliance, and to study whether there is a difference in effectiveness in pre-specified subgroups. General linear models for repeated measurements will be applied for the statistical analysis of the data. DISCUSSION: We hypothesise that the E-VLED intervention will be equally effective compared to the usual care VLED but lower in costs due to less time invested by the dietician. This will enable to help more people with type 2 diabetes and obesity to effectively lose weight and improve their health-related quality of life. TRIAL REGISTRATION: Netherlands Trial Register, NL7832, registered on 26 June 2019.</p

Unraveling Differences in Molecular Mechanisms and Immunological Contrasts between Squamous Cell Carcinoma and Adenocarcinoma of the Cervix

This study aims to refine our understanding of the inherent heterogeneity in cervical cancer by exploring differential gene expression profiles, immune cell infiltration dynamics, and implicated signaling pathways in the two predominant histological types of cervix carcinoma, Squamous Cell Carcinoma (SCC) and Adenocarcinoma (ADC). Targeted gene expression data that were previously generated from samples of primary cervical cancer were re-analyzed. The samples were grouped based on their histopathology, comparing SCC to ADC. Each tumor in the study was confirmed to be high risk human papilloma virus (hrHPV) positive. A total of 21 cervical cancer samples were included, with 11 cases of SCC and 10 of ADC. Data analysis revealed a total of 26 differentially expressed genes, with 19 genes being overexpressed in SCC compared to ADC (Benjamini–Hochberg (BH)-adjusted p-value &lt; 0.05). Importantly, the immune checkpoint markers CD274 and CTLA4 demonstrated significantly higher expression in SCC compared to ADC. In addition, SCC showed a higher infiltration of immune cells, including B and T cells, and cytotoxic cells. Higher activation of a variety of pathways was found in SCC samples including cytotoxicity, interferon signaling, metabolic stress, lymphoid compartment, hypoxia, PI3k-AKT, hedgehog signaling and Notch signaling pathways. Our findings show distinctive gene expression patterns, signaling pathway activations, and trends in immune cell infiltration between SCC and ADC in cervical cancer. This study underscores the heterogeneity within primary cervical cancer, emphasizing the potential benefits of subdividing these tumours based on histological and molecular differences.</p

Porto-sinusoidal vascular disorder and nephrotic-range proteinuria due to venous vasculitis in Behçet's disease

Behçet's disease (BD) is an autoinflammatory disease with multifactorial and polygenic etiology, potentially involving arteries and veins of any size resulting in variable vessel vasculitis. We report a case of an Iranian male who presented with porto-sinusoidal vascular disorder due to venous vasculitis as initial manifestation of BD. Despite immunosuppression, anticoagulation and venous recanalization, he subsequently developed severe nephrotic-range proteinuria mimicking a primary renal disease which was completely and immediately ameliorated by stenting of the vena cava. This demonstrates that the proteinuria was caused by increased intraglomerular pressure due to venous outflow obstruction as a consequence of venous vasculitis. To our knowledge, this is the first report of massive proteinuria caused by venous obstruction of the caval vein in the context of BD. Altogether, this case demonstrates the extensive spectrum of vascular disease in BD.</p

Long-Term Follow-Up of Patients with Scleritis After Rituximab Treatment Including B Cell Monitoring

Purpose: We report the long-term effect of rituximab (RTX) in scleritis and determine the value of B-cell monitoring for the prediction of relapses. Methods: We retrospectively studied 10 patients with scleritis, who were treated with RTX. Clinical characteristics were collected, and blood B-cell counts were measured before the start of RTX, and at various time points after treatment. Results:Clinical activity of scleritis decreased after RTX treatment in all patients within a median time of 8 weeks (range 3–13), and all reached remission. The median follow-up was 101 months (range 9–138). Relapses occurred in 6 out of 10 patients. All relapses, where B-cell counts were measured (11 out of 19), were heralded by returning B cells. However, B cells also returned in patients with long-term remissions.Conclusions: RTX is a promising therapeutic option for scleritis. Recurrence of B cells after initial depletion does not always predict relapse of scleritis.</p

Pelvic floor dysfunction is not a risk factor for febrile urinary tract infection in adults

OBJECTIVE To determine whether pelvic floor dysfunction (PFD) might be a risk factor for or consequence of febrile urinary tract infection (UTI), as UTI in adults is a common infection in which an underlying urological abnormality is often considered, and as in children, PFD is also thought to have a pathophysiological role in adults with UTI. PATIENTS AND METHODS A multicentre case-control study was conducted at 26 primary-care centres and at six Emergency Departments of regional hospitals. Cases were consecutive patients aged >= 18 years, who presented with febrile UTI. Controls were randomly selected subjects who visited their general practitioner for reasons other than UTI or fever. A validated pelvic floor questionnaire (the Pelvic Floor Inventories Leiden, PelFIs) was used to assess pelvic floor function. RESULTS Between October 2006 and December 2007, 153 cases were included; of these, the completed questionnaires of 102 (response rate 67%) were compared to those of 100 of 110 (response rate 91%) controls. The median age of cases and controls was 65 and 58 years, respectively; 40% of cases and controls were men. The percentage of PelFIs outcomes consistent with PFD were comparable between cases and controls, at 21% vs 23%, respectively (odds ratio 0.9, 95% confidence interval, CI, 0.4-1.78). In the multivariate analysis, comorbidity (odds ratio 4.9, 95% CI 2.2-11.1) and a history of UTI (odds ratio 2.5, 95% CI 1.0-6.1) were independent significant risk factors for febrile UTI, whereas PFD was not (odds ratio 1.0, 0.5-2.2). Within the group of cases, PFD was not associated with bacteriuria during assessment of PelFIs (odds ratio 1.1, 95% CI 0.4-3.5) and inversely related to a history of UTI within the previous year (odds ratio 0.2, 0.1-0.9). CONCLUSIONS PFD is common among adults but it does not seem to be a risk factor for febrile UTI.Immunogenetics and cellular immunology of bacterial infectious disease

Prevalence of Positive QuantiFERON-TB Gold In-Tube Test in Uveitis and its Clinical Implications in a Country Nonendemic for Tuberculosis

Purpose: To report on the prevalence and clinical implications of positive QuantiFERON-Gold (QFT-G) test results in the diagnostic evaluation of a large cohort of consecutive patients with uveitis in the Netherlands. Design: Retrospective cross-sectional study. Methods: This study included 710 consecutive patients who all underwent evaluation for uveitis including QFT-G testing. The ocular features, comorbidity, and abnormalities in diagnostic imaging and laboratory tests were registered for QFT-G–positive patients with uveitis. Results: Of all patients, 13% (92/710) were positive for QFT-G. Previously treated tuberculosis (TB) was documented in 2 patients. Of all 92 QFT-G–positive patients, culture-proven active TB was observed in 1 case. The proportion of patients with uveitis of unknown etiology was higher in QFT-G–positive than in the QFT-G–negative patients (54/92, 59% vs 238/618, 39%; P = .0004). The uveitis features of QFT-G–positive patients were mainly nonspecific. Of all QFT-G–positive patients with uveitis, 17 patients had chest imaging changes suggesting either TB or sarcoidosis. Twenty-nine QFT-G–positive patients with otherwise unexplained uveitis completed antituberculous therapy (29/710; 4% of all included patients) with beneficial effect in most cases. Conclusion: The QFT-G tested positive in 13% of patients with uveitis in the Netherlands, whereas only sporadic patients had a documented previous or active TB infection. The proportion of patients with unexplained uveitis was higher in QFT-G–positive patients. Though the association between uveitis and a positive QFT-G test might be coincidental, the majority of treated QFT-G–positive patients with otherwise unexplained severe uveitis cause had a beneficial response to antituberculous therapy

Lack of evidence for a causal role of CALR3 in monogenic cardiomyopathy

The pathogenicity of previously published disease-associated genes and variants is sometimes questionable. Large-scale, population-based sequencing studies have uncovered numerous false assignments of pathogenicity. Misinterpretation of sequence variants may have serious implications for the patients and families involved, as genetic test results are increasingly being used in medical decision making. In this study, we assessed the role of the calreticulin-3 gene (CALR3) in cardiomyopathy. CALR3 has been included in several cardiomyopathy gene panels worldwide. Its inclusion is based on a single publication describing two missense variants in patients with hypertrophic cardiomyopathy. In our national cardiomyopathy cohort (n = 6154), we identified 17 unique, rare heterozygous CALR3 variants in 48 probands. Overall, our patient cohort contained a significantly higher number of rare CALR3 variants compared to the ExAC population (p = 0.0036). However, after removing a potential Dutch founder variant, no statistically significant difference was found (p = 0.89). In nine probands, the CALR3 variant was accompanied by a disease-causing variant in another, well-known cardiomyopathy gene. In three families, the CALR3 variant did not segregate with the disease. Furthermore, we could not demonstrate calreticulin-3 protein expression in myocardial tissues at various ages. On the basis of these findings, it seems highly questionable that variants in CALR3 are a monogenic cause of cardiomyopathy