scholarly journals Proceedings From the 2019 Stanford Single Ventricle Scientific Summit: Advancing Science for Single Ventricle Patients: From Discovery to Clinical Applications

Author(s):  
Sushma Reddy ◽  
Stephanie Siehr Handler ◽  
Sean Wu ◽  
Marlene Rabinovitch ◽  
Gail Wright

Abstracts Because of remarkable advances in survival over the past 40 years, the worldwide population of individuals with single ventricle heart disease living with Fontan circulation has grown to ≈70 000, with nearly half aged >18 years. Survival to at least 30 years of age is now achievable for 75% of Fontan patients. On the other hand, single ventricle patients account for the largest group of the 6000 to 8000 children hospitalized with circulation failure, with or without heart failure annually in the United States, with the highest in‐hospital mortality. Because there is little understanding of the underlying mechanisms of heart failure, arrhythmias, pulmonary and lymphatic vascular abnormalities, and other morbidities, there are no specific treatments to maintain long‐term myocardial performance or to optimize overall patient outcomes.

2021 ◽  
Author(s):  
Corbin E. Goerlich ◽  
Bartley P. Griffith ◽  
John A. Treffalls ◽  
Tianshu Zhang ◽  
Avneesh K. Singh ◽  
...  

Abstract There are 5.7 million people in the United States with heart failure, which is life-limiting in 20% of patients.1 While data is most robust in the United States for this cohort, it is known to be a global problem with over 23 million people carrying the diagnosis.1 For end-stage heart failure, many require a heart transplantation, however, there is a shortage in the supply of organ donors. Cardiac xenotransplantation has been proposed to “bridge the gap” in supply for these patients requiring transplantation. Recent pre-clinical success using genetically modified pig donors in baboon recipients has demonstrated survival greater than 6 months.2–5 First-in-human transplantation of a genetically modified pig kidney demonstrated 54 hour rejection-free function when perfused by a deceased human recipient, demonstrating the feasibility of cross-species transplantation and invigorating enthusiasm further to utilize this new organ source for a population that would otherwise die waiting for a human organ.6 While this human study demonstrated proof-of-principle of overcoming hyperacute rejection, further regulatory oversight by Food and Drug Administration (FDA) may be required with pre-clinical trials in large animal models of xenotransplantation with long-term survival. These studies not only require a multi-disciplinary team and expertise in orthotopic transplantation (cardiac surgery, anesthesia and cardiopulmonary bypass), immunology and genetic engineering; but also, specifically handling large animal recipients that cannot communicate their symptoms. Here we detail our approach to pig-to-primate large animal model of orthotopic cardiac xenotransplantation perioperatively and in the months thereafter in long-term surviving animals. We also detail xenograft surveillance methods and common issues that arise in the postoperative period specific to this model and ways to overcome them.


Neurosurgery ◽  
2007 ◽  
Vol 60 (6) ◽  
pp. 1059-1066 ◽  
Author(s):  
Dongsheng Guo ◽  
Kai Shu ◽  
Rudong Chen ◽  
Changshu Ke ◽  
Yanchang Zhu ◽  
...  

Abstract OBJECTIVE The aim of this study was to investigate the microsurgical results of symptomatic sacral perineurial cysts of 11 patients and to discuss the treatment options of the past 10 years. METHODS We retrospectively reviewed the records of 11 patients with symptomatic sacral perineurial cysts who underwent microsurgical treatment at Tongji Hospital, Huazhong University of Science and Technology from 1993 through 2006. The philosophy was to perform total or partial cyst wall removal, to imbricate the remaining nerve sheath if possible, and to repair local defect with muscle, Gelfoam (Pharmacia & Upjohn, Kalamazoo, MI), and fibrin glue. Patient outcomes were assessed by comparing the preoperative and postoperative examination results. The average follow-up time obtained from return visits to the neurosurgery clinic or by telephone questionnaires ranged from 2 months to 13 years. A literature search and analysis of current treatment options were performed. RESULTS Nine of the 11 patients (82%) experienced complete or substantial relief of their preoperative symptoms. One patient (Patient 4) experienced worsening of bladder dysfunction after surgery and recovered slowly to subnormal function during the subsequent 2 months. The symptoms of Patient 9 did not resolve, and magnetic resonance imaging showed that the cyst had reoccurred. The patient underwent reoperation 3 months later without any improvement. One patient (Patient 11) experience a cerebrospinal fluid leakage complication. Neither new postoperative neurological defects nor infection were observed in our series. In the literature, there are six different treatment options under debate and controversially discussed. CONCLUSION Microsurgical treatment yielded the best long-term resolution of patient symptoms to date and should be recommended to appropriately selected patients.


2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Yang K Xiang ◽  
Federica Barbagallo ◽  
Bing Xu ◽  
Qin Fu

Our long-term goal is to understand mechanisms that govern spatiotemporal regulation of cAMP/PKA signaling in cardiac myocytes under physiological and pathophysiological conditions, and their implication in cardiac disease therapy. Here we use a series of biosensors to measure cAMP/PKA activity under βAR subtype regulation. In failing cardiac myocytes, the cAMP and PKA activity are shifted from the plasma membrane to the intracellular sarcoplasmic reticulum and the myofilaments. Meanwhile, β2AR displays an increased role in signaling to the myofilaments in failing myocytes when compared to the control myocytes. Moreover, we show that an increased βAR association with phosphodiesterases promotes the alteration in spatiotemporal propagation of cAMP/PKA signaling in failing myocytes. These observations and the underlying mechanisms and functional implications will be discussed.


PEDIATRICS ◽  
1962 ◽  
Vol 30 (2) ◽  
pp. 194-205
Author(s):  
Theodore C. Doege ◽  
Clark W. Heath ◽  
Ida L. Sherman

Diphtheria attack rates and cases, and to a much lesser extent case-fatality rates, have fallen steadily within the United States during the past 25 years. However, during 1959 and 1960 there was a halt in this long-term trend. Epidemiologic data on 868 clinical cases of diphtheria occurring in 1959 and 873 cases in 1960 were submitted to the Communicable Disease Center by 45 states. The cases and several major outbreaks tended to concentrate in the southern and southwestern states. Attack rates and deaths were highest for children under 10 years, and attack rates were more than five times greater for nonwhite children. Analysis of 1960 immunization data shows that 72% of the patients had received no immunizations. Fifty-five per cent of carriers, but only 18% of persons with bacteriologically confirmed cases, had received a primary series. Only 1 person of 58 fatal cases occurring in 1960 had received a primary series. Certain problems for future investigation, disclosed by the surveillance data, are discussed.


2018 ◽  
Vol 32 (1) ◽  
pp. 77-92 ◽  
Author(s):  
Cynthia A. Jackevicius ◽  
Robert L. Page ◽  
Leo F. Buckley ◽  
Douglas L. Jennings ◽  
Jean M. Nappi ◽  
...  

Heart failure is one of the leading causes of hospitalizations in the United States, with >1 million admissions yearly and a 25% risk of readmissions within 1 month. In order to assist clinicians, we provide an update of the heart failure bibliography that was published in Pharmacotherapy in 2008, which followed the original bibliography published in 2004. A significant number of clinical trials and observational studies have been conducted since the early 1980s to guide management of heart failure patients. Major advances have occurred in the past 10 years, and our understanding of the diagnosis, prevention, and management of heart failure has evolved substantially during this time period. Specific areas of this review include heart failure risk factors, management of comorbid conditions, acute heart failure management, chronic heart failure management, advanced heart failure, device therapy, lifestyle modification, and medication and therapy management, including medication adherence. Key consensus guidelines and statements are also included. This bibliography of key heart failure papers aims to provide clinicians and their trainees with a valuable clinical reference resource and teaching tool that may be used to optimize the care of patients with heart failure.


2020 ◽  
Vol 6 (23) ◽  
pp. eaba2937 ◽  
Author(s):  
Stefan Leyk ◽  
Johannes H. Uhl ◽  
Dylan S. Connor ◽  
Anna E. Braswell ◽  
Nathan Mietkiewicz ◽  
...  

Over the past 200 years, the population of the United States grew more than 40-fold. The resulting development of the built environment has had a profound impact on the regional economic, demographic, and environmental structure of North America. Unfortunately, constraints on data availability limit opportunities to study long-term development patterns and how population growth relates to land-use change. Using hundreds of millions of property records, we undertake the finest-resolution analysis to date, in space and time, of urbanization patterns from 1810 to 2015. Temporally consistent metrics reveal distinct long-term urban development patterns characterizing processes such as settlement expansion and densification at fine granularity. Furthermore, we demonstrate that these settlement measures are robust proxies for population throughout the record and thus potential surrogates for estimating population changes at fine scales. These new insights and data vastly expand opportunities to study land use, population change, and urbanization over the past two centuries.


2000 ◽  
Vol 89 (1) ◽  
pp. 379-384 ◽  
Author(s):  
John B. West

Studies of physiology in microgravity are remarkably recent, with almost all the data being obtained in the past 40 years. The first human spaceflight did not take place until 1961. Physiological measurements in connection with the early flights were crude, but, in the past 10 years, an enormous amount of new information has been obtained from experiments on Spacelab. The United States and Soviet/Russian programs have pursued different routes. The US has mainly concentrated on relatively short flights but with highly sophisticated equipment such as is available in Spacelab. In contrast, the Soviet/Russian program concentrated on first the Salyut and then the Mir space stations. These had the advantage of providing information about long-term exposure to microgravity, but the degree of sophistication of the measurements in space was less. It is hoped that the International Space Station will combine the best of both approaches. The most important physiological changes caused by microgravity include bone demineralization, skeletal muscle atrophy, vestibular problems causing space motion sickness, cardiovascular problems resulting in postflight orthostatic intolerance, and reductions in plasma volume and red cell mass. Pulmonary function is greatly altered but apparently not seriously impaired. Space exploration is a new frontier with long-term missions to the moon and Mars not far away. Understanding the physiological changes caused by long-duration microgravity remains a daunting challenge.


2012 ◽  
Vol 18 (8) ◽  
pp. S73 ◽  
Author(s):  
J.W. Rossano ◽  
D.J. Goldberg ◽  
A.R. Mott ◽  
K.Y. Lin ◽  
R.E. Shaddy ◽  
...  

2006 ◽  
Vol 4 (8) ◽  
pp. 751-757 ◽  
Author(s):  
Laura M. Kulik

Chronic inflammation induced by viral infections and their role in carcinogenesis is well recognized. Two hepatotropic viruses, hepatitis B and hepatitis C (HCV), have been linked worldwide to the development of hepatocellular carcinoma (HCC). Although orthotopic liver transplant offers the best chance for cure and long-term survival, the demand for organs far outweighs the supply. The incidence of HCC in the United States has increased over the past 3 decades. HCV-induced cirrhosis is believed to play a significant role in the rising rate of HCC. Therefore, primary measures to prevent HCC in HCV-infected patients are urgently needed. Numerous studies of the HCV HCC patient have considered primary treatment with interferon-based therapy. However, secondary prevention currently seems to carry more promise. This article evaluates and assesses various treatments for primary and secondary chemoprevention in the setting of HCV.


2020 ◽  
Vol 12 (3) ◽  
pp. 35-45
Author(s):  
M. A. Savchenko ◽  
A. M. Panteleev

Over the past decade, in Russian Federation there has been a steady increase in the incidence of MAC-infection in patients with HIV (the growth of nosology over the past five years, on average, was 57% per year). This determines the interest in this problem, especially in terms of the high inefficiency of treatment for the disease, the long term and cost of treatment. The history of the study of Mycobacterium Avium Complex-infection (MAC) originates in the early eighties in the United States, when the prognosis for a patient with AIDS and mycobacteriosis was extremely poor: mortality within one year after the detection of pathogen reached 71%. The role of infection in the thanatogenesis of patients was, however, established only by the beginning of the nineties. The detection of macrolide activity against the pathogen significantly improved the prognosis for patients, especially in combination with highly active antiretroviral therapy. The widespread introduction of antiviral drugs into practice and the ability to achieve immune reconstitution prevented the development of opportunistic infections, but did not solve the remaining issues of the treatment of the MAC-infection. The main one is the treatment of patients with a clarithromycin-resistant pathogen. There is no consensus on the sensitivity of non-tuberculous mycobacteria to antibacterials.


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