Detection of Excercise-Induced Ischemia by Measurement of NT-proBNP

Electrocardiographic exercise testing is the most widely used non-invasive screening test for coronary artery disease (CAD); however, both positive and negative predictive values for this procedure are hampered by relatively low sensitivity and specificity, leading to significant numbers of false negative and false positive studies. We hypothesized that NT-proBNP, a Neuro hormone secreted by cardiac myocytes in the ventricular wall in response to increased wall stress, would rise as a result of exercise-induced ischemia. If this were true, the enhancement of exercise testing by analysis of this plasma biomarker may offer significant improvement in the diagnostic accuracy of this procedure

Pharmacogenetic allele nomenclature: International workgroup recommendations for test result reporting

This manuscript provides nomenclature recommendations developed by an international workgroup to increase transparency and standardization of pharmacogenetic (PGx) result reporting. Presently, sequence variants identified by PGx tests are described using different nomenclature systems. In addition, PGx analysis may detect different sets of variants for each gene, which can affect interpretation of results. This practice has caused confusion and may thereby impede the adoption of clinical PGx testing. Standardization is critical to move PGx forward

Endocrine Testing Protocols: Hypothalamic Pituitary Adrenal Axis

Abnormalities in the hypothalamic pituitary adrenal (HPA) axis are identified by a careful analysis of both direct and non-stimulated measurements of the hormones as well as provocative tests. Dynamic testing is useful to determine if elevated levels are suppressible and whether there is sufficient hormone reserve when low levels are measured under stimulation. A combination of all these analyses can distinguish between normal physiology and the consequences of clinical disease in the HPA axis. While clinical suspicion drives the testing performed, arrival at the correct diagnosis by laboratory testing is crucial for cure of the patient. Knowledge of the methodologies used in measuring cortisol and ACTH and associated hormones and binding proteins is essential for correct interpretation of the tests. In this review we compare methodologies available, sensitivity and specificity of the various assays and volumes of sample needed. There are at least 7 different types of dexamethasone suppression testing and they are compared and described in detail. Confirmation of the anatomic source of the hormone is necessary. Petrosal sinus sampling and adrenal vein sampling are reviewed and the clinical indications for each discussed. Finally, once the endocrine diagnosis is reached based on endocrine testing, imaging studies are then reviewed which can confirm the endocrine diagnosis. An abnormality in the HPA axis is a laboratory diagnosis and radiologic imaging is reserved for the last step in the diagnosis of endocrine disease. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG

Optimal management of upper tract urothelial carcinoma : current perspectives

Introduction: Upper tract urothelial carcinoma (UTUC) is a relatively uncommon urologic malignancy for which there has not been significant improvement in survival over the past few decades, highlighting the need for optimal multi-modality management. Methods: A non-systematic review of the latest literature was performed to include relevantarticles up to June 2019. It summarizes the epidemiologic risk factors associated with UTUC,including smoking, carcinogenic aromatic amines, arsenic, aristolochic acid, and Lynchsyndrome. Molecular pathways underlying UTUC and potential druggable targets are outlined. Results: Surgical management for UTUC includes kidney-sparing surgery (KSS) for low-risk disease and radical nephroureterectomy (RNU) for high-risk disease. Endoscopic man-agement of UTUC may include ureteroscopic or percutaneous resection. Topical instillationtherapy post-KSS aims to reduce recurrence, progression and to treat carcinoma-in-situ; thismay be achieved retrogradely (via ureteric catheterization), antegradely (via percutaneousnephrostomy) or via reflux through double-J stent. RNU, which may be performed via open,laparoscopic or robot-assisted approaches, is the gold standard treatment for high-riskUTUC. The distal cuff may be dealt with extravesical, transvesical or endoscopic techniques.Peri-operative chemotherapy and immunotherapy are increasingly utilized; level 1 evidenceexists for adjuvant chemotherapy, but neoadjuvant chemotherapy is favored as kidneyfunction is better prior to RNU. Immunotherapy is primarily reserved for metastatic UTUCbut is currently being investigated in the perioperative setting. Conclusion: The optimal management of UTUC includes afirm understanding of theepidemiological factors and molecular pathways. Surgical management includes KSS forlow-risk disease and RNU for high-risk disease. Peri-operative immunotherapy and che-motherapy may be considered as evidence mounts.Published versio

Longitudinal SARS-CoV-2 antibody study using the Easy Check COVID-19 IgM/IgG™ lateral flow assay

Since the initial identification of the novel coronavirus SARS-CoV-2 in December of 2019, researchers have raced to understand its pathogenesis and begun devising vaccine and treatment strategies. An accurate understanding of the body’s temporal immune response against SARS-CoV-2 is paramount to successful vaccine development and disease progression monitoring. To provide insight into the antibody response against SARS-CoV-2, plasma samples from 181 PCR-confirmed COVID-19 patients collected at various timepoints post-symptom onset (PSO) were tested for the presence of anti-SARS-CoV-2 IgM and IgG antibodies via lateral flow. Additionally, 21 donors were tracked over time to elucidate patient-specific immune responses. We found sustained levels of anti-SARS-CoV-2 antibodies past 130 days PSO, with 99% positivity observed at 31–60 days PSO. By 61–90 days PSO, the percentage of IgM-/IgG+ results were nearly equal to that of IgM+/IgG+ results, demonstrating a shift in the immune response with a decrease in IgM antibody levels. Results from this study not only provide evidence that the antibody response to COVID-19 can persist for over 4 months, but also demonstrates the ability of Easy Check™ to monitor seroconversion and antibody response of patients. Easy Check was sufficiently sensitive to detect antibodies in patient samples as early as 1–4 days PSO with 86% positivity observed at 5–7 days PSO. Further studies are required to determine the longevity and efficacy of anti-SARS-CoV-2 antibodies, and whether they are protective against re-infection

Pharmacogenomics and personalized medicine in clinical practice

The Santorini Conference on prospective biology, genomics and pharmacogenomics occurs every 2 years. On 30 September to 2nd October 2010, the fifth meeting in this series took place in Santorini, Greece. This conference has established a tradition of organizing a workshop each time to address the most recent developments and key issues in pharmacogenomics. This year, the workshop was chaired by Bryan Dechairo and Alain Huriez, and was titled 'Pharmacogenomics and personalized medicine in clinical practice'