Group testing in mediation analysis

We consider the scenario where there is an exposure, multiple biologically defined sets of biomarkers, and an outcome. We propose a new two-step procedure that tests if any of the sets of biomarkers mediate the exposure/outcome relationship, while maintaining a prespecified familywise error rate. The first step of the proposed procedure is a screening step that removes all groups that are unlikely to be strongly associated with both the exposure and the outcome. The second step adapts recent advances in postselection inference to test if there are true mediators in each of the remaining candidate sets. We use simulation to show that this simple two-step procedure has higher statistical power to detect true mediating sets when compared with existing procedures. We then use our two-step procedure to identify a set of Lysine-related metabolites that potentially mediate the known relationship between increased body mass index and the increased risk of estrogen-receptor positive breast cancer in postmenopausal women.     

Risk factors for Epstein–Barr virus reactivation after renal transplantation: Results of a large,multi-centre study

Epstein–Barr virus (EBV) reactivation is a very common and potentially lethal complication of renal transplantation. However, its risk factors and effects on transplant outcome are not well known. Here, we have analysed a large, multi-centre cohort (N = 512) in which 18.4% of the patients experienced EBV reactivation during the first post-transplant year. The patients were characterized pre-transplant and two weeks post-transplant by a multi-level biomarker panel. EBV reactivation was episodic for most patients, only 12 patients showed prolonged viraemia for over four months. Pre-transplant EBV shedding and male sex were associated with significantly increased incidence of post-transplant EBV reactivation. Importantly, we also identified a significant association of post-transplant EBV with acute rejection and with decreased haemoglobin levels. No further severe complications associated with EBV, either episodic or chronic, could be detected. Our data suggest that despite relatively frequent EBV reactivation, it had no association with serious complications during the first post-transplantation year. EBV shedding prior to transplantation could be employed as biomarkers for personalized immunosuppressive therapy. In summary, our results support the employed immunosuppressive regimes as relatively safe with regard to EBV. However, long-term studies are paramount to support these conclusions.     

Online determination of sulfide using an optical immersion probe combined with headspace liquid-phase microextraction

A new design for headspace liquid phase microextraction in combination with an optical immersion probe (HS-LPME-OIP) was proposed and successfully tested for the determination of sulfide in wine and water samples. The developed method is based on the release of hydrogen sulfide from the aqueous phase after the addition of orthophosphoric acid and its extraction with an aqueous solution of 5,5′-dithiobis-(2-nitrobenzoic) acid (DTNB). The analytical signal was recorded using an optical probe immersed in a vial containing 200 μL of 0.1 mM DTNB solution. Using the optical immersion probe in combination with HS-LPME allowed to register the analytical signal online and significantly improve the reproducibility of sulfide determination compared to known microextraction approaches. In the proposed approach, the problems with drop stability, limitations in mixing rate or extraction time, too small volume of the acceptor phase and stability of the holding the acceptor phase in the hole of the optical probe were also satisfactorily solved. The calibration graph was linear in the range of 16–256 μg L⁻¹ with a correlation coefficient of 0.9992. The limit of detection was 6 μg L⁻¹.

A new design for headspace liquid phase microextraction combined with an optical probe.     

Perception of COVID-19 Pandemic Among IBD Clinicians and IBD Surgeons in Black Sea Region: A Cross-Sectional Questionnaire Study

Background:Since December 2019, the COVID-19 pandemic has created an increasing challenge in managing inflammatory bowel disease patients both medically and surgically. Although several international and national medical/surgical associations published guidelines in this area, there is still a huge difference between daily practices and these guidelines, especially depending on regional practices and governmental policies. Therefore, we aimed to investigate and define gastroenterologists’ and surgeons’ fear of COVID-19 and how they have managed inflammatory bowel disease patients during this pandemic in the Black Sea region.Methods:A 20-question survey was administered to 70 gastroenterology specialists and 80 general surgeons who are mainly focused on the management of inflammatory bowel disease in 5 countries in the Black Sea region.Results:The majority of respondents (81.3%) mentioned that they have concerns that their inflammatory bowel disease patients were at risk of contracting COVID-19. In addition, the majority of respondents (80.3%) believed that inflammatory bowel disease itself, independent of medications, might increase the risk of contracting COVID-19. The majority of gastroenterologists told that they did not stop inflammatory bowel disease medications due to the COVID-19 pandemic unless patients had COVID-19 disease. Surgeons overwhelmingly reached a consensus on how to test patients for COVID-19 perioperatively and came to a conclusion on which of the patients cannot wait to be operated. Both gastroenterologists and general surgeons, usually have similar perceptions.Conclusion:Despite the increasing number of definitive studies, it seems that there are still regional differences in the perception of COVID-19 and inflammatory bowel disease patient care during the pandemic.     

Pulmonary pattern in systemic vasculitis: granulomatosis,lung cancer or both?

As clinical manifestations of systemic vasculitides share many common features with other conditions, the rate of diagnostic errors and delayed diagnoses is high. Hence we performed an analysis of the available data regarding misdiagnosis of vasculitis as lung cancer and vice versa, as well as coexistence of vasculitis and lung cancer. The present case-based review highlights the diagnostic challenges encountered when granulomatosis with polyangiitis (GPA) mimics lung cancer. The importance of a multidisciplinary team approach to patients with pulmonary involvement and multisystem manifestations is essential for appropriate planning of further diagnostic steps and for minimizing the delay in correct diagnosis and treatment. In the present case, although computed tomography raised suspicion for lung cancer, further biopsies and laboratory screening for systemic vasculitides rejected malignancy and confirmed the diagnosis of GPA.     

Is Isolated Systolic Hypertension Worse Than Combined Systolic/Diastolic Hypertension?

J Clin Hypertens (Greenwich). 2012;14:808–809. ©2012 Wiley Periodicals, Inc. New developments in cardiovascular translational sciences have significantly advanced our understanding of the endovascular biology of blood pressure. Reductions in vascular elasticity and vessel compliance of conduit arteries are key components of both ISH and SDH. Vascular changes from the matrix metalloproteinase family of enzymes are involved in arterial wall remodeling and vascular stiffness. This new translational information helps further our understanding of both ISH and SDH.     

Repeated Valsalva maneuvers promote symptomatic manifestations of cerebral microhemorrhages: implications for the pathogenesis of vascular cognitive impairment in older adults

Multifocal cerebral microhemorrhages (CMHs, also known as “cerebral microbleeds”), which are associated with rupture of small intracerebral vessels, have been recognized as an important cause for cognitive decline in older adults. Although recent studies demonstrate that CMHs are highly prevalent in patients 65 and older, many aspects of the pathogenesis and clinical significance of CMHs remain obscure. In this longitudinal observational study, a case of a 77-year-old man with multifocal CMHs is described, in whom the rupture of intracerebral vessels could be linked to repeatedly performing extended Valsalva maneuvers. This patient was initially seen with acute aphasia after performing a prolonged Valsalva maneuver during underwater swimming. T2-weighted magnetic resonance imaging revealed a left acute frontal intracerebral hemorrhage (ICH) with multiple CMHs. The aphasia was resolved and no cognitive impairment was present. Two years later, he developed unsteadiness and confusion after performing two prolonged Valsalva maneuvers during underwater swimming separated by about 12 days. Repeat brain imaging revealed an acute right and a subacute left ICH, with a marked interval increase in the number of CMHs. The patient also exhibited manifest memory loss after the second admission and was diagnosed with dementia. These observations suggest that prolonged Valsalva maneuver is potentially a common precipitating cause of both CMHs and symptomatic ICHs. The Valsalva maneuver both increases the systolic arterial pressure and gives rise to a venous pressure wave transmitted to the brain in the absence of the competent antireflux jugular vein valves. This pressure increase is superimposed on existing hypertension and/or increases in blood pressure due to exercise and increased venous return due to immersion of the body in water. We advocate that further studies are needed to distinguish between CMHs with arterial and venous origins and their potential to lead to ICH induced by Valsalva maneuver as well as to determine whether these lesions have a predilection for a particular location.