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1.
J Card Fail ; 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-38103723

ABSTRACT

BACKGROUND: Although sustained ventricular arrhythmias (VAs) are a common complication after durable left ventricular assist device (LVAD) implantation, the incidence, risk factors, and prognostic implications of postoperative early VAs (EVAs) in contemporary patients with LVAD are poorly understood. METHODS AND RESULTS: A single-center retrospective analysis was performed of patients who underwent LVAD implantation from October 1, 2006, to October 1, 2022. EVA was defined as an episode of sustained VA identified ≤30 days after LVAD implantation. A total of 789 patients underwent LVAD implantation (mean age 62.9 ± 0. years 5, HeartMate 3 41.4%, destination therapy 43.3%). EVAs occurred in 100 patients (12.7%). A history of end-stage renal disease (odds ratio [OR] 5.6, 95% confidence interval [CI] 1.45-21.70), preoperative electrical storm (OR 2.82, 95% CI 1.11-7.16), and appropriate implantable cardiac defibrillator therapy before implantation (OR 2.8, 95% CI 1.26-6.19) are independently associated with EVAs. EVA was associated with decreased 30-day survival (hazard ratio 3.02, 95% CI 1.1-8.3, P = .032). There was no difference in transplant-free survival time between patients with and without EVAs (hazard ratio 0.82, 95% CI 0.5-1.4, P = .454). CONCLUSIONS: EVAs are common after durable LVAD implantation and are associated with an increased risk of 30-day mortality.

2.
Curr Cardiol Rep ; 25(4): 213-227, 2023 04.
Article in English | MEDLINE | ID: mdl-36847990

ABSTRACT

PURPOSE OF REVIEW: Cardiogenic shock (CS) is a complex clinical entity that continues to carry a high risk of mortality. The landscape of CS management has changed with the advent of several temporary mechanical circulatory support (MCS) devices designed to provide hemodynamic support. It remains challenging to understand the role of different temporary MCS devices in patients with CS, as many of these patients are critically ill, requiring complex care with multiple MCS device options. Each temporary MCS device can provide different types and levels of hemodynamic support. It is important to understand the risk/benefit profile of each one of them for appropriate device selection in patients with CS. RECENT FINDINGS: MCS may be beneficial in CS patients through augmentation of cardiac output with subsequent improvement of systemic perfusion. Selecting the optimal MCS device depends on several variables including the underlying etiology of CS, clinical strategy of MCS use (bridge to recovery, bridge to transplant or durable MCS, or abridge to decision), amount of hemodynamic support needed, associated respiratory failure, and institutional preference. Furthermore, it is even more challenging to determine the appropriate time to escalate from one MCS device to another or combine different MCS devices. In this review, we discuss the current available data published in the literature on the management of CS and propose a standardized approach for escalation of MCS devices in patients with CS. Shock teams can play an important role to help in hemodynamic-guided management and algorithm-based step-by-step approach in early initiation and escalation of temporary MCS devices at different stages of CS. It is important to define the etiology of CS, and stage of shock and recognize univentricular vs biventricular shock for appropriate device selection and escalation of therapy.


Subject(s)
Extracorporeal Membrane Oxygenation , Heart-Assist Devices , Humans , Shock, Cardiogenic/therapy , Risk Assessment , Hemodynamics
3.
Neurobiol Dis ; 170: 105756, 2022 08.
Article in English | MEDLINE | ID: mdl-35584727

ABSTRACT

BACKGROUND: Few treatments exist for the cognitive symptoms of schizophrenia. Pharmacological agents resulting in glutamate N-methyl-d-aspartate (NMDA) receptor hypofunction, such as MK-801, mimic many of these symptoms and disrupt neural activity. Recent evidence suggests that deep brain stimulation (DBS) of the medial septal nucleus (MSN) can modulate medial prefrontal cortex (mPFC) and hippocampal activity and improve spatial memory. OBJECTIVE: Here, we examine the effects of acute MK-801 administration on oscillatory activity within the septohippocampal circuit and behavior. We also evaluate the potential for MSN stimulation to improve cognitive behavioral measures following MK-801 administration. METHODS: 59 Sprague Dawley male rats received either acute intraperitoneal (IP) saline vehicle injections or MK-801 (0.1 mg/kg). Theta (5-12 Hz), low gamma (30-50 Hz) and high frequency oscillatory (HFO) power were analyzed in the mPFC, MSN, thalamus and hippocampus. Rats underwent MSN theta (7.7 Hz), gamma (100 Hz) or no stimulation during behavioral tasks (Novel object recognition (NOR), elevated plus maze, Barnes maze (BM)). RESULTS: Injection of MK-801 resulted in frequency-specific changes in oscillatory activity, decreasing theta while increasing HFO power. Theta, but not gamma, stimulation enhanced the anxiolytic effects of MK-801 on the elevated plus maze. While MK-801 treated rats exhibited spatial memory deficits on the Barnes maze, those that also received MSN theta, but not gamma, stimulation found the escape hole sooner. CONCLUSIONS: These findings demonstrate that acute MK-801 administration leads to altered neural activity in the septohippocampal circuit and impaired spatial memory. Further, these findings suggest that MSN theta-frequency stimulation improves specific spatial memory deficits and may be a possible treatment for cognitive impairments caused by NMDA hypofunction.


Subject(s)
Deep Brain Stimulation , Septal Nuclei , Animals , Deep Brain Stimulation/methods , Dizocilpine Maleate/pharmacology , Hippocampus , Male , Memory Disorders/chemically induced , Memory Disorders/therapy , N-Methylaspartate/pharmacology , Rats , Rats, Sprague-Dawley , Spatial Memory
4.
J Card Fail ; 28(7): 1116-1124, 2022 07.
Article in English | MEDLINE | ID: mdl-34998703

ABSTRACT

BACKGROUND: Acute decompensation of heart failure (HF) is often marked by fluid retention, and weight loss is a marker of successful diuresis. We examined the relationship between in-hospital weight loss and post-discharge outcomes in patients with HF. METHODS: We conducted a propensity score-matched study of 8830 patients hospitalized for decompensated HF in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, in which 4415 patients in the weight-loss group and 4415 patients in the no-weight-loss group were balanced on 75 baseline characteristics. We defined weight loss as an admission-to-discharge weight loss of 1-30 kilograms, and we defined no weight loss as a weight gain or loss of < 1 kilogram. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with weight loss were estimated. RESULTS: Patients had a mean age of 78 years, 57% were women, and 11% were African American. The median weight loss in the weight-loss group was 3.6 (interquartile range, 2.0-6.0) kilograms. HRs and 95% CIs for 30-day all-cause mortality, all-cause readmission and HF readmission associated with weight loss were 0.75 (0.63-0.90), 0.90 (0.83-0.99) and 0.83 (0.72-0.96), respectively. Respective 60-day HRs (95% CIs) were 0.80 (0.70-0.92), 0.91 (0.85-0.98) and 0.88 (0.79-0.98). These associations were attenuated and lost significance during 6 months of follow-up. CONCLUSIONS: Among older patients hospitalized for decompensated HF, in-hospital weight loss was associated with a lower risk of mortality and hospital readmission. These findings suggest that in-hospital weight loss, a marker of successful diuresis and decongestion, is also a marker of improved clinical outcomes.


Subject(s)
Heart Failure , Aftercare , Aged , Female , Heart Failure/diagnosis , Heart Failure/epidemiology , Heart Failure/therapy , Hospitals , Humans , Male , Medicare , Patient Discharge , Patient Readmission , United States/epidemiology
5.
J Card Fail ; 28(1): 65-70, 2022 01.
Article in English | MEDLINE | ID: mdl-34419597

ABSTRACT

BACKGROUND: A low right ventricular ejection fraction (RVEF) is a marker of poor outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Beta-blockers improve outcomes in HFrEF, but whether this effect is modified by RVEF is unknown. METHODS AND RESULTS: Of the 2798 patients in Beta-Blocker Evaluation of Survival Trial (BEST), 2008 had data on baseline RVEF (mean 35%, median 34%). Patients were categorized into an RVEF of less than 35% (n = 1012) and an RVEF of 35% or greater (n = 996). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) within each RVEF subgroup and formally tested for interactions between bucindolol and RVEF. The effect of bucindolol on all-cause mortality in 2008 patients with baseline RVEF (HR 0.88, 95% CI 0.75-1.02) is consistent with that in 2798 patients in the main trial (HR 0.90, 95% CI 0.78-1.02). Bucindolol use was associated with a lower risk of all-cause mortality in patients with an RVEF of 35% or greater (HR 0.70, 95% CI 0.55-0.89), but not in those with an RVEF of less than 35% (HR 1.02, 95% CI 0.83-1.24, P for interaction = .022). Similar variations were observed for cardiovascular mortality (P for interaction = .009) and sudden cardiac death (P for interaction = .018), but not for pump failure death (P for interaction = .371) or HF hospitalization (P for interaction = .251). CONCLUSIONS: The effect of bucindolol on mortality in patients with HFrEF was modified by the baseline RVEF. If these hypothesis-generating findings can be replicated using approved beta-blockers in contemporary patients with HFrEF, then RVEF may help to risk stratify patients with HFrEF for optimization of beta-blocker therapy.


Subject(s)
Heart Failure , Adrenergic beta-Antagonists/therapeutic use , Hospitalization , Humans , Stroke Volume , Ventricular Function, Right
6.
J Card Fail ; 28(8): 1309-1317, 2022 08.
Article in English | MEDLINE | ID: mdl-35447337

ABSTRACT

BACKGROUND: Continuous infusion of ambulatory inotropic therapy (AIT) is increasingly used in patients with end-stage heart failure (HF). There is a paucity of data concerning the concomitant use of beta-blockers (BB) in these patients. METHODS: We retrospectively reviewed all patients discharged from our institution on AIT. The cohort was stratified into 2 groups based on BB use. The 2 groups were compared for differences in hospitalizations due to HF, ventricular arrhythmias and ICD therapies (shock or antitachycardia pacing). RESULTS: Between 2010 and 2017, 349 patients were discharged on AIT (95% on milrinone); 74% were males with a mean age of 61 ± 14 years. BB were used in 195 (56%) patients, whereas 154 (44%) did not receive these medications. Patients in the BB group had longer duration of AIT support compared to those in the non-BB group (141 [1-2114] vs 68 [1-690] days). After adjusting for differences in baseline characteristics and indication for AIT, patients in the BB group had significantly lower rates of hospitalizations due to HF (hazard ratio [HR] 0.61 (0.43-0.86); P = 0.005), ventricular arrhythmias (HR 0.34 [0.15-0.74]; P = 0.007) and ICD therapies (HR 0.24 [0.07-0.79]; P = 0.02). CONCLUSION: In patients with end-stage HF on AIT, the use of BB with inotropes was associated with fewer hospitalizations due to HF and fewer ventricular arrhythmias.


Subject(s)
Heart Failure , Adrenergic beta-Antagonists/therapeutic use , Aged , Arrhythmias, Cardiac , Female , Hospitalization , Humans , Male , Middle Aged , Retrospective Studies
7.
Artif Organs ; 46(3): 460-470, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34516000

ABSTRACT

BACKGROUND: Due to anatomic and physiologic concerns, prior generations of the left ventricular assist devices (LVAD) have frequently been denied to patients with small body size. However, outcomes in patients with small body surface area (BSA) following HeartMate 3 (HM3) LVAD implantation remain relatively unknown. METHODS: A cohort of 220 patients implanted at a single center was divided into two groups: BSA ≤1.8 m2 (small BSA, n = 37) and BSA >1.8 m2 (large BSA, n = 183). We investigated baseline characteristics and clinical outcomes including survival and incidence of adverse events. RESULTS: Small BSA patients were older (60 vs. 57 years), more likely female (60% vs. 20%), had a lower body mass index (24 vs. 32 kg/m2 ), lower incidence of diabetes (32% vs. 51%), history of stroke (5% vs. 19%), and left ventricular thrombus (0% vs. 11%). They had smaller left ventricular end diastolic diameter (64.8 vs. 69.3 mm). Pump speed and pump flows at discharge were lower in the small BSA group. Survival at 1 year and 2 years was 86% versus 87% and 86% versus 79% for small versus large BSA groups (p = 0.408), respectively. The rates of adverse events were similar between groups and there were no cases of confirmed pump thrombosis. The incidence of readmissions for low flow alarms was higher in the small BSA group (0.55 vs. 0.24 EPPY). CONCLUSIONS: These findings demonstrate comparable outcomes in patients with small body size and suggest that this parameter should not be an exclusion criterion on patients who are otherwise candidates for HM3 LVAD implantation.


Subject(s)
Body Surface Area , Heart-Assist Devices , Body Mass Index , Cohort Studies , Diabetes Mellitus/epidemiology , Diastole , Female , Humans , Male , Middle Aged , Patient Readmission , Retrospective Studies , Stroke/epidemiology , Thrombosis/epidemiology
8.
J Cardiovasc Electrophysiol ; 32(3): 862-866, 2021 03.
Article in English | MEDLINE | ID: mdl-33484203

ABSTRACT

Sustained ventricular tachycardia and ventricular fibrillation (VF) are life-threatening arrhythmias which remain highly prevalent in patients with advanced heart failure. These ventricular arrhythmias may impair the support provided by continuous-flow left ventricular assist devices (CF-LVADs) and lead to frequent hospitalizations, antiarrhythmic medication use, external defibrillations, and need for heart transplantation. We report a case in which a patient with a CF-LVAD and an implantable cardioverter defibrillator at end of life presented with asymptomatic low-flow alarms and was found to have VF of unknown duration. Unique in our case was the presence of apparent organized contractility and rhythmic opening of the mitral valve on echocardiogram despite VF on electrocardiogram.


Subject(s)
Defibrillators, Implantable , Heart Failure , Heart-Assist Devices , Arrhythmias, Cardiac , Defibrillators, Implantable/adverse effects , Heart Failure/diagnostic imaging , Heart Failure/therapy , Heart-Assist Devices/adverse effects , Humans , Ventricular Fibrillation/diagnostic imaging , Ventricular Fibrillation/etiology
9.
J Card Surg ; 36(7): 2541-2542, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33855770

ABSTRACT

Iatrogenic chordal rupture with severe mitral regurgitation is a rare but serious complication associated with the use of Impella device. We present a case of a 47-year-old man with ischemic cardiomyopathy who required insertion of an Impella 5.0 device. During Impella support, he developed acute pulmonary edema secondary to newly diagnosed posterior mitral valve chordal rupture and subsequent severe mitral regurgitation. He underwent implantation of a durable left ventricular assist device with concomitant edge-to-edge mitral valve repair through the apex.


Subject(s)
Heart Rupture , Mitral Valve Insufficiency , Chordae Tendineae/surgery , Heart Rupture/etiology , Heart Rupture/surgery , Humans , Iatrogenic Disease , Male , Middle Aged , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Mitral Valve Insufficiency/etiology , Mitral Valve Insufficiency/surgery
10.
Curr Opin Neurol ; 33(1): 93-105, 2020 02.
Article in English | MEDLINE | ID: mdl-31809331

ABSTRACT

PURPOSE OF REVIEW: Optic neuropathies refer to a collection of diseases in which retinal ganglion cells (RGCs), the specialized neuron of the retina whose axons make up the optic nerve, are selectively damaged. Blindness secondary to optic neuropathies is irreversible as RGCs do not have the capacity for self-renewal and have a limited capacity for self-repair. Numerous strategies are being developed to either prevent further RGC degeneration or replace the cells that have degenerated. In this review, we aim to discuss known limitations to regeneration in central nervous system (CNS), followed by a discussion of previous, current, and future strategies for optic nerve neuroprotection as well as approaches for neuro-regeneration, with an emphasis on developments in the past two years. RECENT FINDINGS: Neuro-regeneration in the CNS is limited by both intrinsic and extrinsic factors. Environmental barriers to axon regeneration can be divided into two major categories: failure to clear myelin and formation of glial scar. Although inflammatory scars block axon growth past the site of injury, inflammation also provides important signals that activate reparative and regenerative pathways in RGCs. Neuroprotection with neurotrophins as monotherapy is not effective at preventing RGC degeneration likely secondary to rapid clearance of growth factors. Novel approaches involve exploiting different technologies to provide sustained delivery of neurotrophins. Other approaches include application of anti-apoptosis molecules and anti-axon retraction molecules. Although stem cells are becoming a viable option for generating RGCs for cell-replacement-based strategies, there are still many critical barriers to overcome before they can be used in clinical practice. Adjuvant treatments, such as application of electrical fields, scaffolds, and magnetic field stimulation, may be useful in helping transplanted RGCs extend axons in the proper orientation and assist with new synapse formation. SUMMARY: Different optic neuropathies will benefit from neuro-protective versus neuro-regenerative approaches. Developing clinically effective treatments for optic nerve disease will require a collaborative approach that not only employs neurotrophic factors but also incorporates signals that promote axonogenesis, direct axon growth towards intended targets, and promote appropriate synaptogenesis.


Subject(s)
Nerve Regeneration/physiology , Neuroprotection/physiology , Optic Nerve Diseases/physiopathology , Optic Nerve Injuries/physiopathology , Optic Nerve/physiopathology , Animals , Axons/physiology , Humans , Optic Nerve Diseases/therapy , Optic Nerve Injuries/therapy
11.
Am J Ther ; 27(3): e235-e242, 2020.
Article in English | MEDLINE | ID: mdl-30299270

ABSTRACT

BACKGROUND: Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs-ARBs) improve outcomes in heart failure (HF). Less is known about this association in nursing home (NH) residents. METHODS: Of the 8024 hospitalized HF patients, 542 were NH residents, of whom 250 received ACEIs-ARBs. We assembled a propensity score-matched cohort of 157 pairs of NH residents receiving and not receiving ACEIs-ARBs balanced on 29 baseline characteristics (mean age, 83 years, 74% women, 17% African American), in which we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with ACEI-ARB use. We then checked for interaction in a matched cohort of 5130 patients (378 were NH residents) assembled from the 8024 patients. RESULTS: Among 314 matched NH residents, HRs (95% CIs) for 30-day all-cause readmission, HF readmission, and all-cause mortality were 0.78 (0.47-1.28), 0.68 (0.29-1.60), and 1.26 (0.70-2.27), respectively. Respective HRs (95% CIs) at 1 year were 0.76 (0.56-1.02), 0.68 (0.42-1.09), and 1.04 (0.78-1.38). Among 5130 matched patients, ACEI-ARB use was associated with a significantly lower risk of all outcomes at both times, with no significant interactions, except for 1-year mortality, which was only significant in the non-NH subgroup (P for interaction, 0.026). CONCLUSIONS: We found no evidence that the use of ACEIs or ARBs is associated with improved outcomes in patients with HF in the NH setting. However, we also found no evidence that this association is different in NH residents with HF versus non-NH patients with HF. Future larger studies are needed to demonstrate effectiveness of these drugs in the NH setting.


Subject(s)
Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Heart Failure/drug therapy , Nursing Homes/statistics & numerical data , Aged , Aged, 80 and over , Alabama/epidemiology , Drug Therapy, Combination/methods , Female , Heart Failure/mortality , Humans , Kaplan-Meier Estimate , Male , Patient Readmission/statistics & numerical data , Registries/statistics & numerical data , Treatment Outcome
12.
J Neuroophthalmol ; 40(2): 234-242, 2020 06.
Article in English | MEDLINE | ID: mdl-32282513

ABSTRACT

BACKGROUND: Restoration of vision in patients blinded by advanced optic neuropathies requires technologies that can either 1) salvage damaged and prevent further degeneration of retinal ganglion cells (RGCs), or 2) replace lost RGCs. EVIDENCE ACQUISITION: Review of scientific literature. RESULTS: In this article, we discuss the different barriers to cell-replacement based strategies for optic nerve regeneration and provide an update regarding what progress that has been made to overcome them. We also provide an update on current stem cell-based therapies for optic nerve regeneration. CONCLUSIONS: As neuro-regenerative and cell-transplantation based strategies for optic nerve regeneration continue to be refined, researchers and clinicians will need to work together to determine who will be a good candidate for such therapies.


Subject(s)
Nerve Regeneration/physiology , Optic Nerve Injuries/physiopathology , Optic Nerve/physiopathology , Axons , Cell Survival , Humans
13.
J Arthroplasty ; 33(10): 3354-3361, 2018 10.
Article in English | MEDLINE | ID: mdl-30232017

ABSTRACT

BACKGROUND: The proximal femur represents the most common site of metastatic bone disease in the appendicular skeleton, and associated pathologic pertrochanteric femur fractures contribute to cancer-related morbidity and mortality. Controversy exists as to whether these injuries are best managed with intramedullary nailing (IMN) or with arthroplasty. METHODS: A systematic review of the literature was performed using a PubMed search following PRISMA guidelines to identify studies performed within the last 20 years regarding treatment of proximal femur metastatic lesions with either nailing or arthroplasty with a reported reoperation rate. Sixteen studies were selected for inclusion containing 1414 patients. Pooled estimates and 95% confidence intervals (CIs) for reoperation rates associated with IMN and endoprosthetic reconstruction (EPR) were separately calculated. RESULTS: The pooled estimate for reoperation for IMN was a median of 9% (95% CI, 5%-14%) and the pooled estimate for reoperation for EPR was a median of 7% (95% CI, 5%-11%). Significant heterogeneity was present in studies reporting on both treatment modalities: for IMN, I2 = 55%, and for EPR, I2 = 51%. CONCLUSION: This systematic literature review identified 16 eligible, nonrandomized, retrospective studies that reported on the results of surgical treatment for proximal femur metastatic disease. The pooled estimate of reoperation was similar between patients treated with IMN and EPR. Inconsistencies among follow-up and the study designs used limited evidence-based conclusions. As the oncologic care of patients with metastatic disease continues to evolve and improve, patient-specific needs must be carefully considered when selecting an optimal treatment strategy. LEVEL OF EVIDENCE: Level III.


Subject(s)
Arthroplasty, Replacement, Hip/statistics & numerical data , Fracture Fixation, Intramedullary/statistics & numerical data , Fractures, Spontaneous/surgery , Hip Fractures/surgery , Reoperation/statistics & numerical data , Bone Neoplasms/complications , Bone Neoplasms/secondary , Bone Neoplasms/surgery , Femoral Fractures , Femur/surgery , Fractures, Spontaneous/etiology , Hip Fractures/etiology , Humans , Retrospective Studies , Thigh , Treatment Outcome
14.
Heart Fail Clin ; 13(3): 581-587, 2017 07.
Article in English | MEDLINE | ID: mdl-28602373

ABSTRACT

Heart failure is a disease of poor prognosis marked by frequent hospitalizations, premature death, and impaired quality of life. Despite advances in medical therapy for patients with heart failure and reduced ejection fraction, mortality and hospitalizations with advanced disease are still increased and the quality of life continues to be poor in this population. The advent of cardiac resynchronization therapy has led to a significant improvement in both survival and symptom management in patients with heart failure and reduced ejection fraction. Its beneficial effects in the elderly population, however, are not well-defined.


Subject(s)
Cardiac Resynchronization Therapy/methods , Heart Failure/therapy , Age Factors , Aged , Humans , Middle Aged
15.
Heart Fail Clin ; 13(3): 527-534, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28602370

ABSTRACT

Positive inotropic drugs have long been studied for their potential benefits in patients with heart failure and reduced ejection fraction (HFrEF). Although there has been an extensive amount of research about the clinical effects of these drugs in general, few studies examined their effect in older patients. Therefore, there is little or no evidence to guide the use of positive inotropes in older patients with HFrEF. However, recommendations from national heart failure guidelines may be generalized to older HFrEF patients on an individual basis, taking into consideration the basic geriatric principles of pharmacotherapy: start low and go slow.


Subject(s)
Cardiotonic Agents/administration & dosage , Heart Failure/drug therapy , Heart Failure/physiopathology , Age Factors , Aged , Cardiotonic Agents/adverse effects , Humans , Randomized Controlled Trials as Topic , Stroke Volume
16.
J Nat Prod ; 78(11): 2768-75, 2015 Nov 25.
Article in English | MEDLINE | ID: mdl-26510047

ABSTRACT

Four new elaiophylin macrolides (1-4), together with five known elaiophylins (5-9), have been isolated from cultures of the Indonesian soil bacterium Streptomyces sp. ICBB 9297. The new compounds have macrocyclic skeletons distinct from those of the known dimeric elaiophylins in that one or both of the polyketide chains contain(s) an additional pendant methyl group. Further investigations revealed that 1 and 2 were derived from 3 and 4, respectively, during isolation processes. Compounds 1-3 showed comparable antibacterial activity to elaiophylin against Staphylococcus aureus. However, interestingly, only compounds 1 and 3, which contain a pendant methyl group at C-2, showed activity against Mycobacterium smegmatis, whereas compound 2, which has two pendant methyl groups at C-2 and C-2', and the known elaiophylin analogues (5-7), which lack pendant methyl groups at C-2 and/or C-2', showed no activity. The production of 3 and 4 in strain ICBB 9297 indicates that one of the acyltransferase (AT) domains in the elaiophylin polyketide synthases (PKSs) can recruit both malonyl-CoA and methylmalonyl-CoA as substrates. Bioinformatic analysis of the AT domains of the elaiophylin PKSs revealed that the ela_AT7 domain contains atypical active site amino acid residues, distinct from those conserved in malonyl-CoA- or methylmalonyl-CoA-specific ATs.


Subject(s)
Macrolides/isolation & purification , Streptomyces/chemistry , Acyl Coenzyme A/metabolism , Acyltransferases/metabolism , Anti-Bacterial Agents/chemistry , Catalytic Domain , Indonesia , Macrolides/chemistry , Microbial Sensitivity Tests , Molecular Structure , Mycobacterium smegmatis/drug effects , Polyketide Synthases/metabolism , Soil Microbiology
17.
Cardiol Rev ; 2024 Feb 29.
Article in English | MEDLINE | ID: mdl-38421170

ABSTRACT

Understanding noncardiovascular comorbidities and geriatric syndromes in elderly patients with heart failure (HF) is important as the average age of the population increases. Healthcare professionals need to consider these complex dynamics when managing older adults with HF, especially those older than 80. A number of small studies have described associations between HF and major geriatric domains. With information on patients' cognitive, functional decline, and ability to adhere to therapy, physicians can plan for individualized treatment goals and recommendations for these patients.

18.
ESC Heart Fail ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38873749

ABSTRACT

AIMS: Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD-code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients. METHODS AND RESULTS: The model development cohort (n = 20 000: training, 16 000; validation 2000; testing, 2000) included 10 000 patients with HF and 10 000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60 days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP-HF) and non-HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF-related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP-HF as cases (PPV, 0.86; sensitivity, 0.86). From the 'HF ICD-code universe', we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP + ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP + ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54). CONCLUSIONS: These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation.

19.
Eur J Heart Fail ; 26(5): 1251-1260, 2024 May.
Article in English | MEDLINE | ID: mdl-38700246

ABSTRACT

AIMS: According to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline, the definition of chronic kidney disease (CKD) requires the presence of abnormal kidney structure or function for >3 months with implications for health. CKD in patients with heart failure (HF) has not been defined using this definition, and less is known about the true health implications of CKD in these patients. The objective of the current study was to identify patients with HF who met KDIGO criteria for CKD and examine their outcomes. METHODS AND RESULTS: Of the 1 419 729 Veterans with HF not receiving kidney replacement therapy, 828 744 had data on ≥2 ambulatory serum creatinine >90 days apart. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (n = 185 821) or urinary albumin-to-creatinine ratio (uACR) >30 mg/g (n = 32 730) present twice >3 months apart. Normal kidney function (NKF) was defined as eGFR ≥60 ml/min/1.73 m2, present for >3 months, without any uACR >30 mg/g (n = 365 963). Patients with eGFR <60 ml/min/1.73 m2 were categorized into four stages: 45-59 (n = 72 606), 30-44 (n = 74 812), 15-29 (n = 32 077), and <15 (n = 6326) ml/min/1.73 m2. Five-year all-cause mortality occurred in 40.4%, 57.8%, 65.6%, 73.3%, 69.7%, and 47.5% of patients with NKF, four eGFR stages, and uACR >30mg/g (albuminuria), respectively. Compared with NKF, hazard ratios (HR) (95% confidence intervals [CI]) for all-cause mortality associated with the four eGFR stages and albuminuria were 1.63 (1.62-1.65), 2.00 (1.98-2.02), 2.49 (2.45-2.52), 2.28 (2.21-2.35), and 1.22 (1.20-1.24), respectively. Respective age-adjusted HRs (95% CIs) were 1.13 (1.12-1.14), 1.36 (1.34-1.37), 1.87 (1.84-1.89), 2.24 (2.18-2.31) and 1.19 (1.17-1.21), and multivariable-adjusted HRs (95% CIs) were 1.11 (1.10-1.12), 1.24 (1.22-1.25), 1.46 (1.43-1.48), 1.42 (1.38-1.47), and 1.13 (1.11-1.16). Similar patterns were observed for associations with hospitalizations. CONCLUSION: Data needed to define CKD using KDIGO criteria were available in six out of ten patients, and CKD could be defined in seven out of ten patients with data. HF patients with KDIGO-defined CKD had higher risks for poor outcomes, most of which was not explained by abnormal kidney structure or function. Future studies need to examine whether CKD defined using a single eGFR is characteristically and prognostically different from CKD defined using KDIGO criteria.


Subject(s)
Glomerular Filtration Rate , Heart Failure , Renal Insufficiency, Chronic , Veterans , Humans , Male , Female , Heart Failure/physiopathology , Heart Failure/epidemiology , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/physiopathology , Aged , Veterans/statistics & numerical data , United States/epidemiology , Middle Aged , Creatinine/blood , Retrospective Studies
20.
J Clin Med ; 12(17)2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37685783

ABSTRACT

Metastatic bony disease is a significant health issue, with approximately 700,000 new cases annually that tend to metastasize to bones. The proximal femur in the appendicular skeleton is commonly affected. Our study aimed to investigate mortality rates and hospital stay duration in patients with pathologic proximal femur fractures treated with either intramedullary nailing or arthroplasty within the Veterans Health Administration system. In total, 679 patients (265 arthroplasty, 414 intramedullary nails) were identified through ICD-9 and CPT codes from 30 September 2010 to 1 October 2015. Hospital stays were similar for both groups (arthroplasty: 10.5 days, intramedullary nails: 11 days, p = 0.1). Mortality was associated with increased age and Gagne comorbidity scores (p < 0.001). Arthroplasty showed a survival benefit in the log-rank test (p = 0.018), and this difference persisted in the multivariate analysis after adjusting for age and comorbidities, with a hazard ratio of 1.3. Our study reported evidence that arthroplasty is associated with increased patient survival even when accounting for age and comorbidities in treating metastatic disease of the proximal femur.

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