Kidney Associates

Hypokalemic Periodic Paralysis in a Young Woman with Mast Cell Activation Syndrome: Atypical Presentation Associated with an Ultra-Rare CACNA1S VariantAli Moradi, Yasmin Aboutaleb, Saba Noreen, Abdullah Sahyouni, Hasin Sharma, Olugbenga Oyesanmi, Ian

Abstract Background Pragmatic randomized controlled trials (RCTs) must be embedded within routine clinical workflows, which requires monitoring strategies that are feasible in everyday practice. Incremental hemodialysis—initiating treatment twice weekly in patients with preserved residual kidney function and escalating frequency as needed—differs from conventional thrice-weekly initiation. Implementing this approach in a pragmatic trial among providers and dialysis staff unfamiliar with incremental dialysis necessitated additional preparation and oversight. The TwoPlus trial is a multicenter pragmatic RCT evaluating incremental versus conventional initiation of chronic hemodialysis. We describe the patient monitoring framework developed for TwoPlus, which integrates digital infrastructure, human touchpoints, and provider engagement to ensure participant safety. Methods/Design TwoPlus is an ongoing multicenter RCT enrolling adults initiating chronic hemodialysis with residual kidney function (urine urea clearance ≥2.0 mL/min and urine output ≥500 mL/24 hours). Participants are randomized to incremental hemodialysis—twice-weekly treatment supported by diuretics and sodium bicarbonate, with transition to thrice-weekly as clinically indicated—or conventional thrice-weekly initiation. The primary outcome is a composite of all-cause death, hospitalization, or emergency department visits. Secondary outcomes include preservation of residual kidney function and treatment adherence. The monitoring framework combines automated dialysis data downloads, manual data abstraction, assessments conducted by investigators or clinical research coordinators and reviewed at the site level, structured team reviews, and regular communication with treating providers. Discussion This layered monitoring model balances feasibility, safety, and fidelity in a pragmatic trial where provider engagement and site-specific adaptation were essential. The monitoring approach adopted in TwoPlus will inform the design of monitoring frameworks for future pragmatic nephrology trials. Trial registration: NCT05828823

Abstract Background:This research focuses on improving communication between emergency doctors and deaf and dumb patients in Yemen.Which the effective social communication with all patients in the emergency department is essential for case management. If there are any problems or obstacles in this communication, the patient's safety is at risk. This study aims to raise the culture of the Yemeni doctor and feed the community awareness especially for the deaf and dumb category and improve the level of medical quality and address the problems that occur during communication between them as it helps emergency doctors and deaf and dumb patients to understand each other.Methodology:A cross-sectional and descriptive study analysis was conducted on emergency physicians working in the general emergency department. Data were collected from physicians working in 8 different government centers in 8 governorates around Yemen (Sana'a, Hadramout, Aden, Al Hodeida, Thamar, Ibb, Taiz, Amran). Data analysis was conducted using the SPSS statistical program.Results:The majority of the participants in this study were emergency physicians (38%), while the percentage of resident physicians in the emergency department was 43% and volunteers in the emergency department was 19%. They reported that they met the most deaf and mute cases (90.59%), which makes the subject common and therefore we find that most doctors feel anxious when dealing with these cases because they are not prepared or do not have the capabilities that help them deal with them. A large number of them recommended holding awareness workshops and training courses (47%). Another study confirmed that (83.7%) would help them develop their dealings with these cases, in addition to adopting a book that helps them know the basics of dealing with this segment to provide them with appropriate healthcare. This was praised by 94%.Conclusion:This study has proven the importance of dealing with deaf and dumb cases, and the extent of the spread of these cases with the lack of knowledge and important skills to communicate with the deaf and dumb segment. We also recommend teaching doctors medical sign language, as well as holding awareness and training workshops and adopting a book that contains the basics of medical sign language, which will raise readiness to deal with cases.

BACKGROUND:Diabetic hyperglycemia promotes vasoconstriction by activating an ATP-dependent P2Y11L (P2Y11-like receptor)/AC5 (adenylyl cyclase 5)/AKAP5 (A-kinase anchoring protein 5)/PKA (protein kinase A)/CaV1.2 (L-type voltage-dependent calcium channel 1.2) nanocomplex in arterial myocytes, but upstream mechanisms are unclear. We hypothesized that Panx1 (pannexin 1) channels, which facilitate ATP release, are associated with the complex in arterial myocytes and mediate its activation to induce vasoconstriction during diabetic hyperglycemia.METHODS:Multidisciplinary approach using extracellular ATP and cAMP biosensors, patch-clamp electrophysiology, super-resolution nanoscopy, proximity ligation assay, pressure myography, and laser speckle imaging to test premises in arterial myocytes and vessels from wild-type and genetically modified mice, including an inducible smooth muscle–specific Panx1 knockout and a global AKAP5 knockout.RESULTS:We found that elevating extracellular glucose (eg, high glucose, hyperglycemia) triggered an increase in extracellular ATP levels, and this was reduced in the presence of the Panx1 inhibitor spironolactone, in inducible smooth muscle–specific Panx1 knockout cells, and by inhibiting glucose metabolism. Panx1 was found in complex with P2Y11L, AC5, AKAP5, PKA, and CaV1.2 in arterial myocytes. The protein complex was strengthened in response to hyperglycemia, which required Panx1 and AKAP5. Hyperglycemia–induced cAMP production, CaV1.2 potentiation, sustained vasoconstriction, and in vivo changes in cerebral artery myogenic tone and blood flow were ameliorated by spironolactone and in inducible smooth muscle–specific Panx1 knockout samples. Panx1 expression was elevated in arterial lysates from a mouse model of type 1 diabetes (eg, streptozotocin), and increased CaV1.2 activity and enhanced ex vivo and in vivo myogenic tone were prevented in arterial myocytes and arteries from inducible smooth muscle–specific Panx1 knockout mice.CONCLUSIONS:These results suggest a key role for Panx1 in controlling ATP signaling through the P2Y11L/AC5/AKAP5/PKA/CaV1.2 axis in arterial myocytes. This Panx1-led complex modulates cAMP levels, CaV1.2 activity, and vascular reactivity in response to diabetic hyperglycemia. Thus, Panx1 could be a new therapeutic target to mitigate vascular complications during diabetes.