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There are an estimated 14,000 randomized trials published in chronic kidney disease. The most frequently reported outcomes are biochemical endpoints, rather than clinical and patient-reported outcomes including cardiovascular disease, mortality, and quality of life. While many trials have focused on optimizing kidney health, the heterogeneity and uncertain relevance of outcomes reported across trials may limit their policy and practice impact. The international Standardized Outcomes in Nephrology (SONG) Initiative was formed to identify core outcomes that are critically important to patients and health professionals, to be reported consistently across trials. We convened a SONG Implementation Workshop to discuss the implementation of core outcomes. Eighty-two patients/caregivers and health professionals participated in plenary and breakout discussions. In this report, we summarize the findings of the workshop in two main themes: socializing the concept of core outcomes, and demonstrating feasibility and usability. We outline implementation strategies and pathways to be established through partnership with stakeholders, which may bolster acceptance and reporting of core outcomes in trials, and encourage their use by end-users such as guideline producers and policymakers to help improve patient-important outcomes.

Introduction: Previous studies suggest that crimping causes permanent structural damage to the leaflet tissues of transcatheter heart valves (THV). However, this damage is not yet known to facilitate calcification process. Hypothesis: Our hypothesis is to test whether crimp-induced damage promotes valvular calcification. Methods: Self-expandable THVs with Glutaraldehye-fixed bovine pericardial leaflets was used. The valves were divided into two groups; crimped and uncrimped, and each group was split into two to be exposed either to a calcifying solution or to a control -normal phosphate buffered saline- solution. For the crimped group, the valves were carefully crimped with a standard crimper at 14Fr and held crimped for 20 minutes. The calcifying solution contains ionic concentrations corresponding to normal human plasma. All groups were maintained at pH 7.5, 37°C, on an orbital shaker at 400 rpm for 7 weeks. At the end, each tissue sample was individually embedded, sectioned and stained for calcium stain (Von Kossa), Verhoff’s Van Geison (VVG) stain for elastin and collagen stain (trichrome III). Results: Fig 1A show the normal bovine pericardium with arranged collagen layers in blue whereas intermittent striations are seen across the collagen fibers in the crimped group (Fig 1B). VVG stains show similar results with continuous elastin fibers (black) in the uncrimped group (Fig 1C) versus fragmented elastin fibers in the crimped group (Fig 1D). Of most significance are the results from the von kossa stains where crimped samples in saline show minimal hydroxyapatite deposition (Fig 1E) while crimped samples in calcifying buffer show brown deposits of hydroxyapatite along the crimped regions (Fig 1F). No hydroxyapatite deposition was observed in uncrimped group exposed to calcifying solution. Conclusions: Our results indicate that severe structural changes due to crimping are associated with greater levels of calcium deposition along the crimped sites.

The extracellular matrix of the atrioventricular (AV) valves' leaflets has a key role in the ability of these valves to properly remodel in response to constantly varying physiological loads. While the loading on mitral and tricuspid valves is significantly different, no information is available on how collagen fibers change their orientation in response to these loads. This study delineates the effect of physiological loading on AV valves' leaflets microstructures using Second Harmonic Generation (SHG) microscopy. Fresh natural porcine tricuspid and mitral valves' leaflets (n = 12/valve type) were cut and prepared for the experiments. Histology and immunohistochemistry were performed to compare the microstructural differences between the valves. The specimens were imaged live during the relaxed, loading, and unloading phases using SHG microscopy. The images were analyzed with Fourier decomposition to mathematically seek changes in collagen fiber orientation. Despite the similarities in both AV valves as seen in the histology and immunohistochemistry data, the microstructural arrangement, especially the collagen fiber distribution and orientation in the stress-free condition, were found to be different. Uniaxial loading was dependent on the arrangement of the fibers in their relaxed mode, which led the fibers to reorient in-line with the load throughout the depth of the mitral leaflet but only to reorient in-line with the load in deeper layers of the tricuspid leaflet. Biaxial loading arranged the fibers in between the two principal axes of the stresses independently from their relaxed states. Unlike previous findings, this study concludes that the AV valves' three-dimensional extracellular fiber arrangement is significantly different in their stress-free and uniaxially loaded states; however, fiber rearrangement in response to the biaxial loading remains similar.

Byline: Priyanka. Madaan, Prashant. Jauhari, Shruthi. Michael, Aditi. Sinha, Biswaroop. Chakrabarty, Sheffali. Gulati Sir, Pediatric arterial ischemic stroke (AIS) is relatively uncommon and often under-recognized. It comprises 5%-10% of all [...]

Background Sequential rituximab (RTX) administration has emerged as an important strategy to sustain remission of disease in patients with difficult-to-treat nephrotic syndrome. Methods We report the efficacy and safety of sequential therapy with two or more courses of intravenous RTX in 250 patients with difficult-to-treat steroid dependence (n  = 127) and calcineurin inhibitor (CNI)-dependent or CNI-refractory steroid resistance (n  = 123) managed at one center during 2015–2021. Subsets of patients were cross-sectionally tested for hypogammaglobulinemia, seroprotection against and hyporesponsiveness to vaccines for hepatitis B and tetanus, BK/JC viruria and human antichimeric antibodies (HACAs). Results Sequential RTX therapy, initiated at a median of 10 years [interquartile range (IQR) 7.3–14.4], was administered for 1.8 courses/person-year [95% confidence interval (CI) 1.7–2.0] over 2.0 years (95% CI 1.2–3.0). Therapy was associated with postponement of relapses by a median of 3 years in patients with steroid-sensitive disease and 2 years in those with steroid resistance. Relapses were reduced by a mean of 2.0 relapses/person-year (95% CI 1.8–2.2), enabling a reduction in prednisolone dose to 0.04 mg/kg/day (95% CI 0.01–0.11) and withdrawal of additional immunosuppression in 154 (62%) patients. RTX-associated adverse events, occurring at 0.20 events/person-year (95% CI 0.17–0.23), were chiefly comprised of infusion reactions (n  = 108) and infections (n  = 46); serious adverse events were observed in 10.8% patients, at 0.03 events/person-year (95% CI 0.02–0.05). Hypogammaglobulinemia was observed in 35% of 177 patients and was moderate to severe in 8.5% of cases. Rates of seroprotection at baseline and response following vaccination were lower for hepatitis B [1.9% and 29.4% (n  = 52)] than tetanus [65.5% and 34.5% (n  = 58)]. BK/JC viruria, without viremia, was observed in 7.3% of 109 cases. A total of 19 of 107 patients (17.8%) had HACAs, which were associated with B cell nondepletion and serum sickness. Age at therapy of <9–10 years was associated with a risk of early relapse, treatment failure and hypogammaglobulinemia following RTX therapy. Conclusions Sequential therapy with RTX effectively reduces relapses in patients with difficult-to-treat steroid- and/or CNI-dependent or CNI-refractory nephrotic syndrome. Therapy is associated with high rates of hypogammaglobulinemia and infusion reactions. [ABSTRACT FROM AUTHOR]

Objectives To assess the awareness and practice of two-wheeler riders regarding the helmet use, and to determine the association of awareness and practices with selected variables. Setting and Design This article is a descriptive survey, which was completed at All India Institute of Medical Sciences (AIIMS) premises, New Delhi, India. Materials and Methods The pretested and validated tools developed by researcher consisted of demographic sheet (8 items) along with structured awareness and practice questionnaire. Results and Conclusions Maximumparticipants were male (71.06%) with majority riding for 8 years. Asmuch as 48%of the sample population had accidentswhile driving. Only 2.9% of them reported to have sustained severe injury during these accidents. The mean awareness and practice score related to helmet use were 49.58±6.019.75±5.56. There was weak correlation between awareness and practice. Association of awareness and practices with selected variables could not be observed (p-value--0.4870). Although public awareness is present, but law needs to be more stringent. Accidents are fatal and it can happen anywhere and anytime, irrespective of long or short distance, and wearing of helmet can save a person from major injuries. [ABSTRACT FROM AUTHOR]

Background More than 50% of children with chronic kidney disease (CKD) have uncontrolled hypertension, increasing their long-term risk of cardiovascular disease and progression to kidney failure. Children receiving medications or dialysis may also experience acute blood pressure fluctuations accompanied by debilitating symptoms. We aimed to describe the perspectives of children with CKD and their parental caregivers on blood pressure to inform patient-centered care. Methods Secondary thematic analysis was conducted on qualitative data from the Standardized Outcomes in Nephrology—Children and Adolescents initiative, encompassing 16 focus groups, an international Delphi survey and two consensus workshops. We analyzed responses from children with CKD (ages 8–21 years) and caregivers (of children ages 0–21 years) pertaining to blood pressure. Results Overall, 120 patients and 250 caregivers from 22 countries participated. We identified five themes: invisibility and normalization (reassured by apparent normotension, absence of symptoms and expected links with CKD), confused by ambiguity (hypertension indistinguishable from cardiovascular disease, questioning the need for prophylactic intervention, frustrated by inconsistent messages and struggling with technical skills in measurement), enabling monitoring and maintaining health (gaging well-being and preventing vascular complications), debilitating and constraining daily living (provoking anxiety and agitation, helpless and powerless and limiting life activities) and burden of medications (overwhelmed by the quantity of tablets and distress from unexpected side effects). Conclusions For children with CKD and their caregivers, blood pressure was an important heath indicator, but uncertainty around its implications and treatment hampered management. Providing educational resources to track blood pressure and minimizing symptoms and treatment burden may improve outcomes in children with CKD. [ABSTRACT FROM AUTHOR]

Tufted angioma and kaposiform hemangioendothelioma are considered to represent two ends of the spectrum of benign vascular neoplasms that predominantly present during infancy or early childhood. We report a rare case of a 5-month-old infant with complicated vascular neoplasm involving the pericardial cavity and skin over cervical region, masquerading as infective pericarditis with cellulitis. The patient responded dramatically to therapy with oral prednisolone and sirolimus, with a significant reduction of size of skin lesions and complete resolution of pericardial effusion over 8 weeks. The report also highlights the importance of a multidisciplinary team in managing such complicated cases. [ABSTRACT FROM AUTHOR]