Immunotherapy: A new standard in the treatment of metastatic clear cell renal cell carcinoma

Renal cell cancer (RCC) represents 2%-3% of all adulthood cancers and is the most common malignant neoplasm of the kidney (90%). In the mid-nineties of the last century, the standard of treatment for patients with metastatic RCC was cytokines. Sunititib and pazopanib were registered in 2007 and 2009, respectively, and have since been the standard first-line treatment for metastatic clear cell RCC (mccRCC). Renal cell cancer is a highly immunogenic tumor with tumor infiltrating cells, including CD8+ T lymphocytes, dendritic cells, natural killer cells (NK) and macrophages. This observation led to the design of new clinical trials in which patients were treated with immunotherapy. With the growing evidence that proangiogenic factors can have immunomodulatory effects on the host’s immune system, the idea of combining angiogenic drugs with immunotherapy has emerged, and new clinical trials have been designed. In the last few years, several therapeutic options have been approved [immunotherapy and immunotherapy/tyrosine kinase inhibitors (TKI)] for the first-line treatment of mccRCC. Nivolumab/ipilimumab is approved for the treatment of patients with intermediate and poor prognoses. Several checkpoint inhibitors (pembrolizumab, nivolumab, avelumab) in combination with TKI (axitinib, lenvatinib, cabozantinib) are approved for the treatment of patients regardless of their International mRCC Database Consortium prognostic group and PD-L1 expression. There is no specific and ideal biomarker that could help in selecting the ideal patient for the appropriate first-line treatment.     

COVID-19-Impfintention von Eltern bezogen auf ihre Kinder

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Mit Beginn der Impfkampagne hat eine neue Phase der Bewältigung der Coronapandemie begonnen. Zulassung und Empfehlung...     

Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site

Background Cervical cancer (CC) remains a leading cause of gynaecological cancer-related mortality with infection by human papilloma virus (HPV) being the most important risk factor. We analysed the association between different viral integration signatures, clinical parameters and outcome in pre-treated CCs.Methods Different integration signatures were identified using HPV double capture followed by next-generation sequencing (NGS) in 272 CC patients from the BioRAIDs study [{"type":"clinical-trial","attrs":{"text":"NCT02428842","term_id":"NCT02428842"}}NCT02428842]. Correlations between HPV integration signatures and clinical, biological and molecular features were assessed.Results Episomal HPV was much less frequent in CC as compared to anal carcinoma (p < 0.0001). We identified >300 different HPV-chromosomal junctions (inter- or intra-genic). The most frequent integration site in CC was in MACROD2 gene followed by MIPOL1/TTC6 and TP63. HPV integration signatures were not associated with histological subtype, FIGO staging, treatment or PFS. HPVs were more frequently episomal in PIK3CA mutated tumours (p = 0.023). Viral integration type was dependent on HPV genotype (p < 0.0001); HPV18 and HPV45 being always integrated. High HPV copy number was associated with longer PFS (p = 0.011).Conclusions This is to our knowledge the first study assessing the prognostic value of HPV integration in a prospectively annotated CC cohort, which detects a hotspot of HPV integration at MACROD2; involved in impaired PARP1 activity and chromosome instability.Subject terms: Oncology, Molecular medicine, Biomarkers, Molecular biology     

Discordant Electrocardiogram Left Ventricular Wall Thickness and Strain Findings in Influenza Myocarditis

A 42‐year‐old man presented with a viral prodrome and tested positive for influenza A. He rapidly deteriorated developing cardiogenic shock, rhabdomyolysis, and acute kidney injury. Patient improved 1 week later with supportive measures including vasopressors, inotropes, and an intraaortic balloon pump. We report this case as it highlights the discordance between echocardiographic ventricular wall thickening as a result of myocardial edema, and electrocardiographic findings at presentation, with a reversal in findings at time of resolution. Additionally, there was some suggestion of a regional pattern to the reduced longitudinal strain.     

Determination of potential biotin interference on accuracy of results of serologic assays for various viral hepatitis markers

Biotin taken orally can interfere with some diagnostic immunoassays, including those for thyroid hormones, ferritin, and markers of infectious disease. Assays affected are ones that use streptavidin-biotin in their design. The goal of our study was to examine the effect of biotin concentrations of up to 1200 ng/mL on three serological assays performed on VITROS 3600 system, Immunoglobulin M (IgM) antibodies to hepatitis A virus (anti-HAV), total anti-HAV, and IgM antibodies to hepatitis B virus core antigen (anti-HBc), by spiking serum samples with variable amounts of biotin. No false-negative results were generated with either concentration of biotin for total anti-HAV (65/65). Likewise, biotin caused no false-positive IgM anti-HAV results (59/59) with either concentration of biotin; however, 6.7% false negativity was found for IgM anti-HAV when samples were spiked with 1200 ng/mL of biotin. Conversely, 100% false positivity (30/30) was produced by biotin interference in total anti-HAV negative specimens with both concentrations of biotin. False negativity rate was 87.5% in IgM anti-HBc positive samples when biotin levels were at 1200 ng/mL. These data show that individuals taking biotin-containing supplements may test false-positive in some serologic assays using streptavidin-biotin chemistries. Further studies are warranted to determine the extent of biotin interference resulting in false-positive and negative results and their impact, if any, on surveillance and diagnostic settings.     

Diabetes treatment and hypoglycaemic episodes in elderly patients at nursing homes in Uppsala County

Aim: The aim of this study was to examine the situation for elderly patients with diabetes living in nursing homes with regard to diabetes treatment, clinical variables, and vascular complications associated with diabetes. A second aim was to evaluate if the patients were at risk of hypoglycaemia.

Methods: This was a cross-sectional study including diabetes patients from all 30 nursing homes in Uppsala County, Sweden. Current antidiabetic medications, HbA_1c, hypoglycaemic events, and diabetes complications were registered from the medical records. The patients were stratified into a general group and divided into three groups according to HbA_1c (<52, 52–73, and >73?mmol/mol).

Results: Of 1,350 individuals, 218 patients were identified with diabetes mellitus. The diabetes duration was 11.2?±?9.4 years and their serum HbA_1c concentration 56.0?±?1.2?mmol/mol. Hypoglycaemic events were reported in 24% of the diabetic individuals, and 43.1% of them had HbA_1c <52?mmol/mol (mean value 44.0?±?1.1?mmol/mol). Of these, 36% were taking antidiabetic drugs. Another 35.8% of the patients had HbA_1c values between 52–73?mmol/mol (mean value 60.0?±?1.1?mmol/mol), and 82% of these patients were taking antidiabetic drugs. Almost 80% of the diabetic patients had either micro- or macrovascular complications, with diabetes duration as an association for both micro- or macrovascular complications and hypoglycaemic events.

Conclusions: A reduction of the use of antidiabetic drugs with follow-up of HbA_1c level should be considered, especially for multimorbid elderly patients with low HbA_1c and hypoglycaemia.