This study sought to evaluate the outcomes of the early experience of transcatheter mitral valve replacement (TMVR) with balloon-expandable valves in patients with severe mitral annular calcification ...(MAC) and reports the first large series from a multicenter global registry.
The risk of surgical mitral valve replacement in patients with severe MAC is high. There are isolated reports of successful TMVR with balloon-expandable valves in this patient population.
We performed a multicenter retrospective review of clinical outcomes of patients with severe MAC undergoing TMVR.
From September 2012 to July of 2015, 64 patients in 32 centers underwent TMVR with compassionate use of balloon-expandable valves. Mean age was 73 ± 13 years, 66% were female, and mean Society of Thoracic Surgeons score was 14.4 ± 9.5%. The mean mitral gradient was 11.45 ± 4.4 mm Hg and the mean mitral area was 1.18 ± 0.5 cm(2). SAPIEN valves (Edwards Lifesciences, Irvine, California) were used in 7.8%, SAPIEN XT in 59.4%, SAPIEN 3 in 28.1%, and Inovare (Braile Biomedica, Brazil) in 4.7%. Access was transatrial in 15.6%, transapical in 43.8%, and transseptal in 40.6%. Technical success according to Mitral Valve Academic Research Consortium criteria was achieved in 46 (72%) patients, primarily limited by the need for a second valve in 11 (17.2%). Six (9.3%) had left ventricular tract obstruction with hemodynamic compromise. Mean mitral gradient post-procedure was 4 ± 2.2 mm Hg, paravalvular regurgitation was mild or absent in all. Thirty-day all-cause mortality was 29.7% (cardiovascular = 12.5% and noncardiac = 17.2%); 84% of the survivors with follow-up data available were in New York Heart Association functional class I or II at 30 days (n = 25).
TMVR with balloon-expandable valves in patients with severe MAC is feasible but may be associated with significant adverse events. This strategy might be an alternative for selected high-risk patients with limited treatment options.
Abstract Objectives This study sought to evaluate the outcomes of the early experience of transcatheter mitral valve replacement (TMVR) with balloon-expandable valves in patients with severe mitral ...annular calcification (MAC) and reports the first large series from a multicenter global registry. Background The risk of surgical mitral valve replacement in patients with severe MAC is high. There are isolated reports of successful TMVR with balloon-expandable valves in this patient population. Methods We performed a multicenter retrospective review of clinical outcomes of patients with severe MAC undergoing TMVR. Results From September 2012 to July of 2015, 64 patients in 32 centers underwent TMVR with compassionate use of balloon-expandable valves. Mean age was 73 ± 13 years, 66% were female, and mean Society of Thoracic Surgeons score was 14.4 ± 9.5%. The mean mitral gradient was 11.45 ± 4.4 mm Hg and the mean mitral area was 1.18 ± 0.5 cm2 . SAPIEN valves (Edwards Lifesciences, Irvine, California) were used in 7.8%, SAPIEN XT in 59.4%, SAPIEN 3 in 28.1%, and Inovare (Braile Biomedica, Brazil) in 4.7%. Access was transatrial in 15.6%, transapical in 43.8%, and transseptal in 40.6%. Technical success according to Mitral Valve Academic Research Consortium criteria was achieved in 46 (72%) patients, primarily limited by the need for a second valve in 11 (17.2%). Six (9.3%) had left ventricular tract obstruction with hemodynamic compromise. Mean mitral gradient post-procedure was 4 ± 2.2 mm Hg, paravalvular regurgitation was mild or absent in all. Thirty-day all-cause mortality was 29.7% (cardiovascular = 12.5% and noncardiac = 17.2%); 84% of the survivors with follow-up data available were in New York Heart Association functional class I or II at 30 days (n = 25). Conclusions TMVR with balloon-expandable valves in patients with severe MAC is feasible but may be associated with significant adverse events. This strategy might be an alternative for selected high-risk patients with limited treatment options.
Neoplasms are among the most common solid-organ transplant complications, occurring in 11.7% of all transplant recipients and in 6% to 15% of heart transplant recipients, according to early studies. ...The skin and lips are the most common sites for neoplasms, but they also appear in the setting of post-transplant lymphoproliferative disease. Post-transplant lymphoproliferative disease (PTLD) is one of the most serious complications of long-term immunosuppression after transplantation. Herein we report the case of a 53-year-old man who underwent orthotopic heart transplantation for Chagas cardiomyopathy and had developed a mass in the left ventricle with symptomatic ventricle outflow obstruction. The patient was initially treated with anti-coagulation but his condition worsened and he was given emergency surgery to remove the mass. The patient recovered well and histologic assessment revealed PTLD as the etiologic culprit. Lymphoproliferative disorders are the second most frequently identified malignant neoplasm after heart transplantation. B-cell tumors are the most common histologically and are associated with infection by Epstein-Barr virus in 80% to 90% of cases.
The 5-enolpyruvylshikimate-3-phosphate synthase catalyses the sixth step of the shikimate pathway that is responsible for synthesizing aromatic compounds and is absent in mammals, which makes it a ...potential target for drugs development against microbial diseases. Here, we report the phosphate binding effects at the structure of the 5-enolpyruvylshikimate-3-phosphate synthase from
Mycobacterium tuberculosis. This enzyme is formed by two similar domains that close on each other induced by ligand binding, showing the occurrence of a large conformation change. We have monitored the phosphate binding effects using analytical ultracentrifugation, small angle X-ray scattering and, circular dichroism techniques. The low resolution results showed that the enzyme in the presence of phosphate clearly presented a more compact structure. Thermal-induced unfolding experiments followed by circular dichroism suggested that phosphate rigidified the enzyme. Summarizing, these data suggested that the phosphate itself is able to induce conformational change resulting in the closure movement in the
M. tuberculosis 5-enolpyruvylshikimate-3-phosphate synthase.
In bacteria, fungi, plants, and apicomplexan parasites, the aromatics compounds, such as aromatics amino acids, are synthesized through seven enzymes from the shikimate pathway, which are absent in ...mammals. The absence of this pathway in mammals make them potential targets for development of new therapy against infectious diseases, such as tuberculosis, which is the world’s second commonest cause of death from infectious disease. The last enzyme of shikimate pathway is the chorismate synthase (CS), which is responsible for conversion of the 5-enolpyruvylshikimate-3-phosphate to chorismate. Here, we report the crystallographic structure of CS from
Mycobacterium tuberculosis (
MtCS) at 2.65
Ǻ resolution. The
MtCS structure is similar to other CS structures, presenting β–α–β sandwich structural topology, in which each monomer of
MtCS consists of a central helical core. The
MtCS can be described as a tetramer formed by a dimer of dimers. However, analytical ultracentrifugation studies suggest the
MtCS is a dimer with a more asymmetric shape than observed on the crystallographic dimer and the existence of a low equilibrium between dimer and tetramer. Our results suggest that the
MtCS oligomerization is concentration dependent and some conformational changes must be involved on that event.
Objective
Blunted tachycardia during hypotension is a characteristic feature of patients with autonomic failure, but the range has not been defined. This study reports the range of orthostatic heart ...rate (HR) changes in patients with autonomic failure caused by neurodegenerative synucleinopathies.
Methods
Patients evaluated at sites of the U.S. Autonomic Consortium (NCT01799915) underwent standardized autonomic function tests and full neurological evaluation.
Results
We identified 402 patients with orthostatic hypotension (OH) who had normal sinus rhythm. Of these, 378 had impaired sympathetic activation (ie, neurogenic OH) and based on their neurological examination were diagnosed with Parkinson disease, dementia with Lewy bodies, pure autonomic failure, or multiple system atrophy. The remaining 24 patients had preserved sympathetic activation and their OH was classified as nonneurogenic, due to volume depletion, anemia, or polypharmacy. Patients with neurogenic OH had twice the fall in systolic blood pressure (SBP; −44 ± 25 vs −21 ± 14 mmHg mean ± standard deviation, p < 0.0001) but only one‐third of the increase in HR of those with nonneurogenic OH (8 ± 8 vs 25 ± 11 beats per minute bpm, p < 0.0001). A ΔHR/ΔSBP ratio of 0.492 bpm/mmHg had excellent sensitivity (91.3%) and specificity (88.4%) to distinguish between patients with neurogenic from nonneurogenic OH (area under the curve = 0.96, p < 0.0001). Within patients with neurogenic OH, HR increased more in those with multiple system atrophy (p = 0.0003), but there was considerable overlap with patients with Lewy body disorders.
Interpretation
A blunted HR increase during hypotension suggests a neurogenic cause. A ΔHR/ΔSBP ratio < 0.5 bpm/mmHg is diagnostic of neurogenic OH. Ann Neurol 2018;83:522–531
Objective
To define the clinical features and biomarkers that predict which patients with pure autonomic failure will develop Parkinson disease, dementia with Lewy bodies, or multiple system atrophy.
...Methods
One hundred patients who presented with pure autonomic failure were recruited at 5 medical centers in the United States. Seventy‐four patients agreed to be followed prospectively. Patients underwent clinical evaluations including neurological rating scales, sleep questionnaires, smell test, and sympathetic and parasympathetic cardiovascular autonomic function tests.
Results
At enrollment, patients were 68 ± 12 years old (median ± interquartile range) and had had autonomic failure for 5 ± 7 years. Within 4 years of follow‐up, 25 of 74 subjects (34%) developed dementia with Lewy bodies (n = 13), Parkinson disease (n = 6), or multiple system atrophy (n = 6). The presence of probable rapid eye movement (REM) sleep behavior disorder was strongly associated with the development of a manifest central nervous system (CNS) synucleinopathy (odds ratio = 7.1). Patients who phenoconverted to multiple system atrophy had younger age at onset of autonomic failure, severe bladder/bowel dysfunction, preserved olfaction, and a cardiac chronotropic response upon tilt > 10 beats per minute. Those who phenoconverted to Parkinson disease or dementia with Lewy bodies had decreased olfaction, a lesser chronotropic response to tilt, and a longer duration of illness. The small group of patients retaining the pure autonomic failure phenotype had very low plasma norepinephrine levels, slow resting heart rate, no REM sleep behavior disorder, and preserved smell.
Interpretation
Patients presenting with pure autonomic failure are at high risk of phenoconverting to a manifest CNS synucleinopathy. Specific clinical features predict future diagnosis. Ann Neurol 2017;81:287–297
Adapting the management of forest resources to climate change involves addressing several crucial aspects to provide a valid basis for decision making. These include the knowledge and belief of ...decision makers, the mapping of management options for the current as well as anticipated future bioclimatic and socioeconomic conditions, and the ways decisions are evaluated and made. We investigate the adaptive management process and develop a framework including these three aspects, thus providing a structured way to analyze the challenges and opportunities of managing forests in the face of climate change. We apply the framework for a range of case studies that differ in the way climate and its impacts are projected to change, the available management options, and how decision makers develop, update, and use their beliefs about climate change scenarios to select among adaptation options, each being optimal for a certain climate change scenario. We describe four stylized types of decision-making processes that differ in how they (1) take into account uncertainty and new information on the state and development of the climate and (2) evaluate alternative management decisions: the “no-change,” the “reactive,” the “trend-adaptive,” and the “forward-looking adaptive” decision-making types. Accordingly, we evaluate the experiences with alternative management strategies and recent publications on using Bayesian optimization methods that account for different simulated learning schemes based on varying knowledge, belief, and information. Finally, our proposed framework for identifying adaptation strategies provides solutions for enhancing forest structure and diversity, biomass and timber production, and reducing climate change-induced damages. They are spatially heterogeneous, reflecting the diversity in growing conditions and socioeconomic settings within Europe.
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