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621.
Yahalom Claudia Blumenfeld Anat Hendler Karen Wussuki-Lior Orly Macarov Michal Shohat Mordechai Khateb Samer 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2018,256(11):2157-2164
Graefe's Archive for Clinical and Experimental Ophthalmology - Aniridia is a rare panocular disorder caused by mutations in the PAX6 gene and characterized mainly by iris hypoplasia. Here, we... 相似文献
622.
Ben Katz Rachel Zaguri Simon Edvardson Channa Maayan Orly Elpeleg Shaya Lev Elyad Davidson Maximilian Peters Shlomit Kfir-Erenfeld Esther Berger Shifa Ghazalin Alexander M. Binshtok Baruch Minke 《The Journal of clinical investigation》2023,133(3)
BACKGROUNDChronic pain is a debilitating illness with currently limited therapy, in part due to difficulties in translating treatments derived from animal models to patients. The transient receptor potential vanilloid 1 (TRPV1) channel is associated with noxious heat detection and inflammatory pain, and reports of adverse effects in human trials have hindered extensive efforts in the clinical development of TRPV1 antagonists as novel pain relievers.METHODSWe examined 2 affected individuals (A1 and A2) carrying a homozygous missense mutation in TRPV1, rendering the channel nonfunctional. Biochemical and functional assays were used to analyze the mutant channel. To identify possible phenotypes of the affected individuals, we performed psychophysical and medical examinations.RESULTSWe demonstrated that diverse TRPV1 activators, acting at different sites of the channel protein, were unable to open the cloned mutant channel. This finding was not a consequence of impairment in the expression, cellular trafficking, or assembly of protein subunits. The affected individuals were insensitive to application of capsaicin to the mouth and skin and did not demonstrate aversive behavior toward capsaicin. Furthermore, quantitative sensory testing of A1 revealed an elevated heat-pain threshold but also, surprisingly, an elevated cold-pain threshold and extensive neurogenic inflammatory, flare, and pain responses following application of the TRPA1 channel activator mustard oil.CONCLUSIONOur study provides direct evidence in humans for pain-related functional changes linked to TRPV1, which is a prime target in the development of pain relievers.FUNDINGSupported by the Israel Science Foundation (368/19); Teva’s National Network of Excellence in Neuroscience grant (no. 0394886) and Teva’s National Network of Excellence in Neuroscience postdoctoral fellowship. 相似文献
623.
Maria Pabon Brian L. Claggett Xiaowen Wang Zi Michael Miao Safia Chatur Ankeet S. Bhatt Muthiah Vaduganathan James C. Fang Akshay S Desai Pardeep Jhund Felipe Martinez Rudolf A. de Boer Mikhail N. Kosiborod Carolyn S.P. Lam Sanjiv J. Shah Adrian F. Hernandez John J.V. McMurray Scott D. Solomon Orly Vardeny 《European journal of heart failure》2023,25(9):1663-1670
Aims
The Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure (DELIVER) trial demonstrated the sodium–glucose cotransporter 2 inhibitor dapagliflozin to be beneficial in patients with symptomatic heart failure (HF) with improved ejection fraction (HFimpEF; those with prior left ventricular ejection fraction ≤40% that had improved to >40% by enrolment). Whether this benefit differs by background medical therapy is unclear. The current study aims to determine the efficacy and safety of dapagliflozin among patients with HFimpEF by background medical therapy.Methods and results
Treatment effects on the primary endpoint (worsening HF or cardiovascular death) were assessed by number of background HF medical therapies (angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor–neprilysin inhibitor, evidence-based beta-blocker, and mineralocorticoid receptor antagonist). Among the 6263 patients randomized in DELIVER, 1151 (18%) had HFimpEF. Of those, 21% of patients were on 0–1 therapies, 44% were on two therapies, and 35% were on three therapies. During 2.3 years of median follow-up, the incidence rate of the primary outcome was 9.7, 8.8, and 8.4 per 100 person-years for patients on 0–1, 2 and 3 HF medications at baseline, respectively. Treatment effects with dapagliflozin on the primary outcome may be greater in patients with HFimpEF on 0–1 therapies at baseline (pinteraction = 0.09), driven mostly by a significant interaction for HF hospitalization (pinteraction = 0.023) with no evidence of effect modification for cardiovascular death (pinteraction = 0.65). Treatment effects of dapagliflozin on the primary outcome were, however, consistent when assessed across the modified Heart Failure Collaboratory Medical Therapy Score integrating both therapeutic use and dosing (pinteraction = 0.39). The use of dapagliflozin was not associated with changes in use or doses of background HF therapies, and among patients on three HF medications at baseline, the addition of dapagliflozin did not lead to higher adverse events.Conclusions
In patients with HFimpEF, the safety and efficacy of dapagliflozin were largely similar by background use and dosing of HF medical therapies. The benefit of dapagliflozin in reducing HF events tended to be greater in those patients on 0-1 medications at baseline. Among patients already on three HF medical therapies, the addition of dapagliflozin was safe without requiring de-escalation of other therapies. 相似文献624.
625.
Adir Shaulov Deborah Rund Dvora Filon Boaz Nachmias Aliaa Khalili Noga Manny Orly Zelig 《Transfusion》2023,63(5):1100-1106
Introduction
Hyperhemolytic syndrome (HHS) is a severe form of delayed transfusion reaction primarily described in sickle cell anemia patients which is characterized by a hemoglobin decrease to pre-transfusion levels or lower, often with reticulocytopenia and no evidence of auto- or allo-antibodies.Case Presentation
We present two cases of severe HHS in patients without sickle cell anemia refractory to treatment with steroids, immunoglobulins, and rituximab. In one case, temporary relief was achieved with eculizumab. In both cases, plasma exchange resulted in a profound and immediate response allowing for splenectomy and resolution of hemolysis.Discussion/Conclusion
We discuss the pathophysiology of HHS, its presentation and treatment and expand on the possible role of plasma exchange in this setting. 相似文献626.
627.
Alexander Peikert Brian L. Claggett KyungMann Kim Jacob A. Udell Jacob Joseph Akshay S. Desai Michael E. Farkouh Sheila M. Hegde Adrian F. Hernandez Deepak L. Bhatt J. Michael Gaziano H. Keipp Talbot Clyde Yancy Inder Anand Lu Mao Lawton S. Cooper Scott D. Solomon Orly Vardeny 《European journal of heart failure》2023,25(2):299-310