A Pilot Study of the Effect of Transcutaneous Spinal Cord Stimulation on Micturition-Related Brain Activity and Lower Urinary Tract Symptoms After Stroke.

PURPOSE: Transcutaneous spinal cord stimulation (TSCS) is a novel neuromodulation modality developed to promote functional restoration in patients with neurological injury or disease. Previous pilot data suggest that lower urinary tract dysfunction (LUTD) due to stroke may be partially alleviated by TSCS. In this study, we examine the mechanism of this effect by evaluating bladder-related brain activity in patients before and after TSCS therapy and comparing it to healthy volunteers. MATERIALS AND METHODS: Patients who developed storage LUTD after a stroke and healthy volunteers without LUTD were recruited. Patients and healthy volunteers underwent simultaneous urodynamics and functional MRI. Patients then completed 24 biweekly sessions of TSCS and underwent another simultaneous urodynamics-functional MRI study. Clinical outcomes were assessed using validated questionnaires and voiding diary. RESULTS: Fifteen patients and 16 healthy volunteers completed the study. Following TSCS, patients exhibited increased blood-oxygen-level-dependent activity in areas including periaqueductal grey, the insula, the lateral prefrontal cortex, and motor cortex. Prior to TSCS therapy, healthy controls exhibited higher blood-oxygen-level-dependent activity in 17 regions, including multiple regions in the prefrontal cortex and basal ganglia. These differences were attenuated after TSCS with no frontal brain differences remaining between healthy volunteers and stroke participants who completed therapy. Neuroimaging changes were complemented by clinically significant improvements in questionnaire scores and voiding diary parameters. CONCLUSIONS: TSCS therapy modulated bladder-related brain activity, reducing differences between healthy volunteers and stroke patients with LUTD. These changes, alongside improved clinical outcomes, suggest TSCS as a promising approach for LUTD management.

Epistemic uncertainty in Bayesian predictive probabilities.

Bayesian predictive probabilities have become a ubiquitous tool for design and monitoring of clinical trials. The typical procedure is to average predictive probabilities over the prior or posterior distributions. In this paper, we highlight the limitations of relying solely on averaging, and propose the reporting of intervals or quantiles for the predictive probabilities. These intervals formalize the intuition that uncertainty decreases with more information. We present four different applications (Phase 1 dose escalation, early stopping for futility, sample size re-estimation, and assurance/probability of success) to demonstrate the practicality and generality of the proposed approach.

The flaw of averages: Bayes factors as posterior means of the likelihood ratio.

As an alternative to the Frequentist p-value, the Bayes factor (or ratio of marginal likelihoods) has been regarded as one of the primary tools for Bayesian hypothesis testing. In recent years, several researchers have begun to re-analyze results from prominent medical journals, as well as from trials for FDA-approved drugs, to show that Bayes factors often give divergent conclusions from those of p-values. In this paper, we investigate the claim that Bayes factors are straightforward to interpret as directly quantifying the relative strength of evidence. In particular, we show that for nested hypotheses with consistent priors, the Bayes factor for the null over the alternative hypothesis is the posterior mean of the likelihood ratio. By re-analyzing 39 results previously published in the New England Journal of Medicine, we demonstrate how the posterior distribution of the likelihood ratio can be computed and visualized, providing useful information beyond the posterior mean alone.

Electric Field Navigated 1-Hz rTMS for Poststroke Motor Recovery: The E-FIT Randomized Controlled Trial.

BACKGROUND: To determine if low-frequency repetitive transcranial magnetic stimulation targeting the primary motor cortex contralateral (M1CL) to the affected corticospinal tract in patients with hemiparetic stroke augments intensive training-related clinical improvement; an extension of the NICHE trial (Navigated Inhibitory rTMS to Contralesional Hemisphere Trial) using an alternative sham coil. METHODS: The present E-FIT trial (Electric Field Navigated 1Hz rTMS for Post-stroke Motor Recovery Trial) included 5 of 12 NICHE trial outpatient US rehabilitation centers. The stimulation protocol remained identical (1 Hz repetitive transcranial magnetic stimulation, M1CL, preceding 60-minute therapy, 18 sessions/6 wks; parallel arm randomized clinical trial). The sham coil appearance mimicked the active coil but without the weak electric field in the NICHE trial sham coil. Outcomes measured 1 week, and 1, 3, and 6 months after the end of treatment included the following: upper extremity Fugl-Meyer (primary, 6 months after end of treatment), Action Research Arm Test, National Institutes of Health Stroke Scale, quality of life (EQ-5D), and safety. RESULTS: Of 60 participants randomized, 58 completed treatment and were included for analysis. Bayesian analysis of combined data from the E-FIT and the NICHE trials indicated that active treatment was not superior to sham at the primary end point (posterior mean odds ratio of 1.94 [96% credible interval of 0.61-4.80]). For the E-FIT intent-to-treat population, upper extremity Fugl-Meyer improvement ≥5 pts occurred in 60% (18/30) active group and 50% (14/28) sham group. Participants enrolled 3 to 6 months following stroke had a 67% (31%-91% CI) response rate in the active group at the 6-month end point versus 50% in the sham group (21.5%-78.5% CI). There were significant improvements from baseline to 6 months for both active and sham groups in upper extremity Fugl-Meyer, Action Research Arm Test, and EQ-5D (P<0.05). Improvement in National Institutes of Health Stroke Scale was observed only in the active group (P=0.004). Ten serious unrelated adverse events occurred (4 active group, 6 sham group, P=0.72). CONCLUSIONS: Intensive motor rehabilitation 3 to 12 months after stroke improved clinical impairment, function, and quality of life; however, 1 Hz-repetitive transcranial magnetic stimulation was not an effective treatment adjuvant in the present sample population with mixed lesion location and extent. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03010462.

Post-stroke outcomes predicted from multivariate lesion-behaviour and lesion network mapping.

Clinicians and scientists alike have long sought to predict the course and severity of chronic post-stroke cognitive and motor outcomes, as the ability to do so would inform treatment and rehabilitation strategies. However, it remains difficult to make accurate predictions about chronic post-stroke outcomes due, in large part, to high inter-individual variability in recovery and a reliance on clinical heuristics rather than empirical methods. The neuroanatomical location of a stroke is a key variable associated with long-term outcomes, and because lesion location can be derived from routinely collected clinical neuroimaging data there is an opportunity to use this information to make empirically based predictions about post-stroke deficits. For example, lesion location can be compared to statistically weighted multivariate lesion-behaviour maps of neuroanatomical regions that, when damaged, are associated with specific deficits based on aggregated outcome data from large cohorts. Here, our goal was to evaluate whether we can leverage lesion-behaviour maps based on data from two large cohorts of individuals with focal brain lesions to make predictions of 12-month cognitive and motor outcomes in an independent sample of stroke patients. Further, we evaluated whether we could augment these predictions by estimating the structural and functional networks disrupted in association with each lesion-behaviour map through the use of structural and functional lesion network mapping, which use normative structural and functional connectivity data from neurologically healthy individuals to elucidate lesion-associated networks. We derived these brain network maps using the anatomical regions with the strongest association with impairment for each cognitive and motor outcome based on lesion-behaviour map results. These peak regional findings became the 'seeds' to generate networks, an approach that offers potentially greater precision compared to previously used single-lesion approaches. Next, in an independent sample, we quantified the overlap of each lesion location with the lesion-behaviour maps and structural and functional lesion network mapping and evaluated how much variance each could explain in 12-month behavioural outcomes using a latent growth curve statistical model. We found that each lesion-deficit mapping modality was able to predict a statistically significant amount of variance in cognitive and motor outcomes. Both structural and functional lesion network maps were able to predict variance in 12-month outcomes beyond lesion-behaviour mapping. Functional lesion network mapping performed best for the prediction of language deficits, and structural lesion network mapping performed best for the prediction of motor deficits. Altogether, these results support the notion that lesion location and lesion network mapping can be combined to improve the prediction of post-stroke deficits at 12-months.

The Study of Alanine Transaminase Activity in Tissues of Silkworm (Bombyx mori) via Direct Analysis in Real-Time (DART) Mass Spectrometry.

Alanine transaminase (ALT) is an important amino acid-metabolizing enzyme in silkworm Bombyx mori L., and is mainly involved in transferring glutamate to alanine (serving as an essential precursor in silk protein synthesis) through transamination. Therefore, it is generally believed that silk protein synthesis in the silk gland and the cocoon quantity increase with the increase in ALT activity to a certain extent. Here, a novel analytical method was developed to determine the ALT activity in several key tissues of Bombyx mori L. including the posterior silk gland, midgut, fat body, middle silk gland, trachea and hemolymph, by combining the direct-analysis-in-real-time (DART) ion source with a triple-quadrupole mass spectrometer. In addition, a traditional ALT activity assay, the Reitman-Frankel method, was also used to measure ALT activity for comparison. The ALT activity results obtained via the DART-MS method are in good agreement with those obtained via the Reitman-Frankel method. However, the present DART-MS method provides a more convenient, rapid and environmentally friendly quantitative method for ALT measurement. Especially, this method can also monitor ALT activity in different tissues of Bombyx mori L. in real time.

The Neurophysiological Representation of Imagined Somatosensory Percepts in Human Cortex.

Intracortical microstimulation (ICMS) in human primary somatosensory cortex (S1) has been used to successfully evoke naturalistic sensations. However, the neurophysiological mechanisms underlying the evoked sensations remain unknown. To understand how specific stimulation parameters elicit certain sensations we must first understand the representation of those sensations in the brain. In this study we record from intracortical microelectrode arrays implanted in S1, premotor cortex, and posterior parietal cortex of a male human participant performing a somatosensory imagery task. The sensations imagined were those previously elicited by ICMS of S1, in the same array of the same participant. In both spike and local field potential recordings, features of the neural signal can be used to classify different imagined sensations. These features are shown to be stable over time. The sensorimotor cortices only encode the imagined sensation during the imagery task, while posterior parietal cortex encodes the sensations starting with cue presentation. These findings demonstrate that different aspects of the sensory experience can be individually decoded from intracortically recorded human neural signals across the cortical sensory network. Activity underlying these unique sensory representations may inform the stimulation parameters for precisely eliciting specific sensations via ICMS in future work.SIGNIFICANCE STATEMENT Electrical stimulation of human cortex is increasingly more common for providing feedback in neural devices. Understanding the relationship between naturally evoked and artificially evoked neurophysiology for the same sensations will be important in advancing such devices. Here, we investigate the neural activity in human primary somatosensory, premotor, and parietal cortices during somatosensory imagery. The sensations imagined were those previously elicited during intracortical microstimulation (ICMS) of the same somatosensory electrode array. We elucidate the neural features during somatosensory imagery that significantly encode different aspects of individual sensations and demonstrate feature stability over almost a year. The correspondence between neurophysiology elicited with or without stimulation for the same sensations will inform methods to deliver more precise feedback through stimulation in the future.

Frequency-specific medial septal nucleus deep brain stimulation improves spatial memory in MK-801-treated male rats.

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.

Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial.

BACKGROUND: Long-term loss of arm function after ischaemic stroke is common and might be improved by vagus nerve stimulation paired with rehabilitation. We aimed to determine whether this strategy is a safe and effective treatment for improving arm function after stroke. METHODS: In this pivotal, randomised, triple-blind, sham-controlled trial, done in 19 stroke rehabilitation services in the UK and the USA, participants with moderate-to-severe arm weakness, at least 9 months after ischaemic stroke, were randomly assigned (1:1) to either rehabilitation paired with active vagus nerve stimulation (VNS group) or rehabilitation paired with sham stimulation (control group). Randomisation was done by ResearchPoint Global (Austin, TX, USA) using SAS PROC PLAN (SAS Institute Software, Cary, NC, USA), with stratification by region (USA vs UK), age (≤30 years vs >30 years), and baseline Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score (20-35 vs 36-50). Participants, outcomes assessors, and treating therapists were masked to group assignment. All participants were implanted with a vagus nerve stimulation device. The VNS group received 0·8 mA, 100 µs, 30 Hz stimulation pulses, lasting 0·5 s. The control group received 0 mA pulses. Participants received 6 weeks of in-clinic therapy (three times per week; total of 18 sessions) followed by a home exercise programme. The primary outcome was the change in impairment measured by the FMA-UE score on the first day after completion of in-clinic therapy. FMA-UE response rates were also assessed at 90 days after in-clinic therapy (secondary endpoint). All analyses were by intention to treat. This trial is registered at ClinicalTrials.gov, NCT03131960. FINDINGS: Between Oct 2, 2017, and Sept 12, 2019, 108 participants were randomly assigned to treatment (53 to the VNS group and 55 to the control group). 106 completed the study (one patient for each group did not complete the study). On the first day after completion of in-clinic therapy, the mean FMA-UE score increased by 5·0 points (SD 4·4) in the VNS group and by 2·4 points (3·8) in the control group (between group difference 2·6, 95% CI 1·0-4·2, p=0·0014). 90 days after in-clinic therapy, a clinically meaningful response on the FMA-UE score was achieved in 23 (47%) of 53 patients in the VNS group versus 13 (24%) of 55 patients in the control group (between group difference 24%, 6-41; p=0·0098). There was one serious adverse event related to surgery (vocal cord paresis) in the control group. INTERPRETATION: Vagus nerve stimulation paired with rehabilitation is a novel potential treatment option for people with long-term moderate-to-severe arm impairment after ischaemic stroke. FUNDING: MicroTransponder.

Improvements and Gaps in Financial Risk Protection Among Veterans Following the Affordable Care Act.

BACKGROUND: Despite public perception, most of the nearly 20 million US veterans have health coverage outside the Veterans Health Administration (VHA), and VHA eligibility and utilization vary across veterans. Out-of-pocket healthcare spending thus remains a potential source of financial hardship for veterans. The Affordable Care Act (ACA) aimed to expand health insurance access, but its effect on veterans' financial risk protection has not been explored. OBJECTIVE: To evaluate whether ACA implementation was associated with changes in veterans' risk of catastrophic health expenditures, and to characterize drivers of catastrophic health spending among veterans post-ACA. DESIGN: Using multivariable linear probability regression, we examined changes in likelihood of catastrophic health spending after ACA implementation, stratifying by age (18-64 vs 65+), household income tercile, and payer (VHA vs non-VHA). Among veterans with catastrophic spending post-ACA, we evaluated sources of out-of-pocket spending. PARTICIPANTS: Nationally representative sample of 13,030 veterans aged 18+ from the 2010 to 2017 Medical Expenditure Panel Survey. INTERVENTION: ACA implementation, January 1, 2014. MAIN MEASURES: Likelihood of catastrophic health expenditures, defined as household out-of-pocket spending exceeding 10% of household income. KEY RESULTS: Among veterans aged 18-64, ACA implementation was associated with a 26% decrease in likelihood of catastrophic health expenditures (absolute change, -1.4 percentage points [pp]; 95% CI, -2.6 to -0.2; p=0.03), which fell from 5.4% pre-ACA to 3.9% post-ACA. This was driven by a 38% decrease in catastrophic spending among veterans with non-VHA coverage (absolute change, -1.8pp; 95% CI, -3.0 to -0.6; p=0.003). In contrast, catastrophic expenditure rates among veterans aged 65+ remained high, at 13.0% pre- and 12.5% post-ACA. Major drivers of veterans' spending post-ACA include dental care, prescription drugs, and home care. CONCLUSIONS: ACA implementation was associated with reduced household catastrophic health expenditures for younger but not older veterans. These findings highlight gaps in veterans' financial protection and areas amenable to policy intervention.

Impact of cerebrovascular accidents on lung transplant survival.

BACKGROUND: Cerebrovascular accidents (CVA) are a source of postoperative morbidity. Existing data on CVA after lung transplantation (LT) are limited. We aimed to evaluate the impact of CVA on LT survival. METHODS: A retrospective analysis of LT recipients at the University of Texas Southwestern Medical Center was performed. Data was obtained from the institutional thoracic transplant database between January 2012 and December 2018, which consisted of 476 patients. Patients were stratified by the presence of a postoperative CVA. Univariate comparisons of baseline characteristics, operative variables, and postoperative outcomes between the cohorts were performed. Survival was analyzed by Kaplan-Meier method. Aalen's additive regression model was utilized to assess mortality hazard over time. RESULTS: The incidence of CVA was 4.2% (20/476). Lung allocation score was higher in the CVA cohort (46.2 [41.7, 57.3] vs. 41.5 [35.8, 52.2], p = 0.04). There were no significant differences in operative variables. CVA patients had longer initial intensive care unit (ICU) stays (316 h [251, 557] vs. 124 [85, 218], p < 0.001) and longer length of stay (22 days [17, 53] vs. 15 [11, 26], p = 0.007). CVA patients required more ICU readmissions (35% vs. 15%, p = 0.02) and had a lower rates of home discharge (35% vs. 71%, p < 0.001). Thirty-day mortality was higher in the CVA cohort (20% vs. 1.3%, p < 0.001). Overall survival was lower in the CVA cohort (log rank p = 0.044). CONCLUSIONS: Postoperative CVA following LT was associated with longer ICU stays, more ICU readmissions, longer length of stay, and fewer home discharges. Thirty day and long-term mortality were significantly higher in the CVA group.

Neuromodulation in Beta-Band Power Between Movement Execution and Inhibition in the Human Hippocampus.

INTRODUCTION: The hippocampus is thought to be involved in movement, but its precise role in movement execution and inhibition has not been well studied. Previous work with direct neural recordings has found beta-band (13-30 Hz) modulation in both movement execution and inhibition throughout the motor system, but the role of beta-band modulation in the hippocampus during movement inhibition is not well understood. Here, we perform a Go/No-Go reaching task in ten patients with medically refractory epilepsy to study human hippocampal beta-power changes during movement. MATERIALS AND METHODS: Ten epilepsy patients (5 female; ages 21-46) were implanted with intracranial depth electrodes for seizure monitoring and localization. Local field potentials were sampled at 2000 Hz during a Go/No-Go movement task. Comparison of beta-band power between Go and No-Go conditions was conducted using Wilcoxon signed-rank hypothesis testing for each patient. Sub-analyses were conducted to assess differences in the anterior vs posterior contacts, ipsilateral vs contralateral contacts, and male vs female beta-power values. RESULTS: Eight out of ten patients showed significant beta-power decreases during the Go movement response (p < 0.05) compared to baseline. Eight out of ten patients also showed significant beta-power increases in the No-Go condition, occurring in the absence of movement. No significant differences were noted between ipsilateral vs contralateral contacts nor in anterior vs posterior hippocampal contacts. Female participants had a higher task success rate than males and had significantly greater beta-power increases in the No-Go condition (p < 0.001). CONCLUSION: These findings indicate that increases in hippocampal beta power are associated with movement inhibition. To the best of our knowledge, this study is the first to report this phenomenon in the human hippocampus. The beta band may represent a state-change signal involved in motor processing. Future focus on the beta band in understanding human motor and impulse control will be vital.

Impact of the Affordable Care Act Insurance Marketplaces on Out-of-Pocket Spending Among Surgical Patients.

OBJECTIVE: To evaluate the association between the introduction of the Affordable Care Act (ACA) Health Insurance Marketplaces ("Marketplaces") and financial protection for patients undergoing surgery. BACKGROUND: The ACA established Marketplaces through which individuals could purchase subsidized insurance coverage. However, the effect of these Marketplaces on surgical patients' healthcare spending remains largely unknown. METHODS: We analyzed a nationally representative sample of adults aged 19-64 who underwent surgery in 2010-2017, using the Medical Expenditure Panel Survey. Low-income patients eligible for cost-sharing and premium subsidies in the Marketplaces [income 139%-250% federal poverty level (FPL)] and middle-income patients eligible only for premium subsidies (251%-400% FPL) were compared to high-income controls ineligible for subsidies (>400% FPL) using a quasi-experimental difference-in-differences approach. We evaluated 3 main outcomes: (1) out-of-pocket spending, (2) premium contributions, and (3) likelihood of experiencing catastrophic expenditures, defined as out-of-pocket plus premium spending exceeding 19.5% of family income. RESULTS: Our sample included 5450 patients undergoing surgery, representing approximately 69 million US adults. Among low-income patients, Marketplace implementation was associated with $601 lower [95% confidence interval (CI): -$1169 to -$33; P = 0.04) out-of-pocket spending; $968 lower (95% CI: -$1652 to -$285; P = 0.006) premium spending; and 34.6% lower probability (absolute change: -8.3 percentage points; 95% CI: -14.9 to -1.7; P = 0.01) of catastrophic expenditures. We found no evidence that health expenditures changed for middle-income surgical patients. CONCLUSIONS: The ACA's insurance Marketplaces were associated with improved financial protection among low-income surgical patients eligible for both cost-sharing and premium subsidies, but not in middle-income patients eligible for only premium subsidies.

Cardiac transplantation in adults with congenital heart disease: A single center case series.

BACKGROUND: Adult congenital heart disease (CHD) transplant recipients historically experienced worse survival early after transplantation. We aim to review updated trends in adult CHD transplantation. METHODS: We performed a single center case series of adult cardiac transplants from January 2013 through July 2020. Outcomes of patients with CHD were compared to non-CHD. The primary outcome was overall survival. Secondary outcomes included a variety of post-operative complications. RESULTS: 18/262 (7%) transplants were CHD recipients. CHD patients were younger with median age 41 (32-47) versus 58 (48-65) (P < .001). Fontan circulation for single ventricle physiology was present in 4/18 (22%) of CHD recipients, while 16/18 (89%) had systemic right ventricles. CHD recipients had higher rates of previous cardiovascular operations (94% vs. 51%, P < .001). 9/18 (50%) of CHD patients required reconstructive procedures at the time of transplant. Operative and cardiopulmonary bypass times were longer for the CHD cohort (7.5 h [6.6-8.5] vs. 5.6 h [4.6-7] P < .001) and (197 min [158-240] vs. 130 [105-167] P < .001), respectively. There were no differences in operative complications or survival between CHD and non-CHD recipients. CONCLUSIONS: These data highlight the added technical challenges of performing adult CHD transplants. However, similar outcomes can be achieved as for non-CHD recipients. SUMMARY: Modern advances in palliation of congenital heart defects (CHD) has led to increased survival into adulthood. Many of these patients require heart transplantation as adults. There are limited data on adult CHD transplantation. Historically, these patients have had worse perioperative outcomes with improved long-term survival. We retrospectively analyzed 262 heart transplants at a single center, 18 of which were for adult CHD. Here, we report our series of 18 CHD recipients. We detail the palliative history of all CHD patients and highlight the added technical challenges for each of the 18 patients at transplant. In our analysis, CHD patients had more prior cardiovascular surgeries as well as longer transplant operative and bypass times. Despite this, there were no differences in perioperative and long-term outcomes. We have added patient and institution specific data for transplanting patients with adult CHD. We hope that our experience will add to the growing body of literature on adult CHD transplantation.

Surgical, Obstetric, and Anesthetic Mortality Measurement at a Ugandan Secondary Referral Hospital.

BACKGROUND: The health care systems of low-income countries have severely limited capacity to treat surgical diseases and conditions. There is limited information about which hospital mortality outcomes are suitable metrics in these settings. METHODS: We did a 1-year observational cohort study of patient admissions to the Surgery and the Obstetrics and Gynecology departments and of newborns delivered at a Ugandan secondary referral hospital. We examined the proportion of deaths captured by standardized metrics of mortality. RESULTS: There were 17,015 admissions and 9612 deliveries. A total of 847 deaths were documented: 385 (45.5%) admission deaths and 462 (54.5%) perinatal deaths. Less than one-third of admission deaths occurred during or after an operation (n = 126/385, 32.7%). Trauma and maternal mortality combined with perioperative mortality produced 79.2% (n = 305/385) of admission deaths. Of 462 perinatal deaths, 412 (90.1%) were stillborn, and 50 (10.9%) were early neonatal deaths. The combined metrics of the trauma mortality rate, maternal mortality ratio, thirty-day perioperative mortality rate, and perinatal mortality rate captured 89.8% (n = 761/847) of all deaths documented at the hospital. CONCLUSIONS: The combination of perinatal, maternal, trauma, and perioperative mortality metrics captured most deaths documented at a Ugandan referral hospital.

Deep Brain Stimulation for Alzheimer's Disease: Tackling Circuit Dysfunction.

OBJECTIVES: Treatments for Alzheimer's disease are urgently needed given its enormous human and economic costs and disappointing results of clinical trials targeting the primary amyloid and tau pathology. On the other hand, deep brain stimulation (DBS) has demonstrated success in other neurological and psychiatric disorders leading to great interest in DBS as a treatment for Alzheimer's disease. MATERIALS AND METHODS: We review the literature on 1) circuit dysfunction in Alzheimer's disease and 2) DBS for Alzheimer's disease. Human and animal studies are reviewed individually. RESULTS: There is accumulating evidence of neural circuit dysfunction at the structural, functional, electrophysiological, and neurotransmitter level. Recent evidence from humans and animals indicate that DBS has the potential to restore circuit dysfunction in Alzheimer's disease, similarly to other movement and psychiatric disorders, and may even slow or reverse the underlying disease pathophysiology. CONCLUSIONS: DBS is an intriguing potential treatment for Alzheimer's disease, targeting circuit dysfunction as a novel therapeutic target. However, further exploration of the basic disease pathology and underlying mechanisms of DBS is necessary to better understand how circuit dysfunction can be restored. Additionally, robust clinical data in the form of ongoing phase III clinical trials are needed to validate the efficacy of DBS as a viable treatment.

Acute Kidney Injury in Patients Undergoing Cardiopulmonary Bypass for Lung Transplantation.

BACKGROUND: Cardiopulmonary bypass (CPB) is often used to support patients undergoing lung transplantation who are intolerant of anatomic manipulation or single lung ventilation during the procedure. However, CPB may be associated with adverse outcomes. We evaluated the hypothesis that CPB is associated with increased acute kidney injury (AKI) and postoperative mortality after lung transplantation. MATERIALS AND METHODS: This was a retrospective review of our institutional lung transplant database at the University of Texas Southwestern Medical Center from 2012 to 2018. Patients were grouped based on their need for CPB. The primary outcome was AKI within 48 h of transplantation, which was defined as Kidney Disease Improving Global Outcomes stage 1 or greater. Secondary outcomes included all-cause mortality. RESULTS: A total of 426 patients underwent lung transplantation with 39.0% (n = 166) requiring CPB. There were no differences in demographics and comorbidities, including baseline renal function, between CPB and no CPB. CPB use was higher in recipients with interstitial lung diseases and primary pulmonary hypertension. Median lung allocation score was higher in those needing CPB (47 [interquartile range, 40-59] versus 39 [interquartile range, 35-47]). Patients requiring CPB were significantly more likely to experience AKI (61.44% versus 36.5.3%, P < 0.01) and postoperative hemodialysis (6.6% versus 0.4%, P < 0.01). On multivariable analysis, CPB was significantly associated with postoperative AKI (odds ratio, 1.66; 95% CI, 1.01-2.75; P = 0.04). Thirty-day mortality was higher in patients undergoing CPB (4.2% versus 0.8%, P = 0.03). CONCLUSIONS: CPB for lung transplantation is associated with a higher incidence of AKI, renal failure requiring hemodialysis, and 30-d mortality. CPB should be used selectively for lung transplantation.

The effect of stroke on micturition associated brain activity: A pilot fMRI study.

OBJECTIVE: Cerebral stroke is a unique model for studying the role of the brain in lower urinary tract (LUT) control. By its nature, stroke must change the activity of the brain to cause LUT dysfunction. The objective of this study was to describe changes in micturition-related brain activity in patients who develop LUT symptoms (LUTS) after a cerebral stroke. MATERIALS AND METHODS: Healthy controls (HC, n = 10) and patients who developed storage LUTS after a cerebral stroke (n = 7) were recruited. Functional magnetic resonance imaging was used to assess brain activity in each subject. In the task-based block design, blood-oxygen-level-dependent (BOLD) signal was detected during rest, active bladder filling, and bladder voiding. BOLD signal intensity was compared between HCs and stroke subjects during bladder filling, voiding, and voiding initiation. RESULTS: Stroke subjects exhibited higher activity in the periaqueductal gray and cerebellum during bladder filling and bladder voiding. HCs exhibited more intense activity in higher centers, such as the cingulate cortex, motor cortex, and the dorsolateral prefrontal cortex in each of the phases examined. CONCLUSIONS: Subjects with stroke-related LUTS exhibit a specific pattern of brain activity during bladder filling and voiding. There appears to be a greater reliance on primitive centers (cerebellum, midbrain) than in healthy controls during both phases of the micturition cycle. We hypothesize that these findings may reflect loss of connectivity with higher brain centers after a stroke.

Improving neuropsychological seizure lateralization in Spanish-speaking people with epilepsy in the US: The need to account for education and demographic differences.

OBJECTIVE: The objective of the study was to investigate the predictive seizure lateralization ability of the Neuropsychological Screening Battery for Hispanics (NeSBHIS) in an optimally, demographically matched cohort of primarily immigrant Spanish-speaking people with epilepsy (PWE) living in the US. Linguistically and culturally appropriate neuropsychological measures for Spanish-speaking people are increasingly needed in the US, especially as this diverse, international population grows. The NeSBHIS was developed to meet this need. Previous studies were inconclusive regarding its utility in epilepsy lateralization with PWE. Sample size and demographic variables, particularly educational levels, which anchor neuropsychological normative data and guide clinical use, limited the conclusions of earlier studies. METHODS: A retrospective study, the NeSBHIS battery's ability to predict seizure lateralization in a large cohort of Spanish-speaking PWE (n = 108) was conducted using normative data based on refined, smaller education ranges suggested by the author of the NeSBHIS, Pontón. RESULTS: Regression analysis revealed that four NeSBHIS subtests representing different cognitive domains produced the best model for predicting lateralization: 1) language, 2) attention/mental control, 3) visual memory recall, and 4) verbal memory recall. Prediction accuracy overall was 62% (67.3% for left hemisphere (LH) and 55.8% for right hemisphere (RH)). CONCLUSION: This study demonstrated the clinical utility of the NeSBHIS in seizure lateralization in a large cohort of Spanish-speaking PWE by analyzing standardized scores based on refined, education-based normative samples. These results also highlight that demographic variables, in particular, education, which varies greatly across Spanish-speaking nations in terms of compulsory educational opportunity and quality, must be accounted for more carefully in clinical and research practice.

Clinical Effectiveness and Resource Utilization of Surgery versus Endovascular Therapy for Chronic Limb-Threatening Ischemia.

BACKGROUND: The clinical effectiveness of surgical versus endovascular therapy for chronic limb-threatening ischemia (CLTI) continues to be debated, and the resources required for each therapy are unclear. METHODS: Systematic review of randomized controlled trials (RCTs) and observational studies comparing surgery with endovascular therapy for CLTI, which reported clinical effectiveness and resource utilization. Short-term and long-term clinical outcomes were examined. RESULTS: The search yielded 4,231 titles, of which 17 publications met our inclusion criteria. Five publications were all from 1 RCT, and 12 publications were observational studies. In the RCT, the surgical approach had greater resource use in the first year (total hospital days across all admissions for surgery versus angioplasty: 46.14 ± 53.87 vs. 36.35 ± 51.39; P < 0.001; also true for days in high-dependency and intensive therapy units), but differences were not statistically significant in subsequent years. All-cause mortality presented a nonsignificant difference favoring angioplasty in the first 2 years (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [95% CI], 0.75-2.15), but after 2 years, it favored surgical treatment (aHR, 0.34; 95% CI, 0.17-0.71). The observational studies reported short-term effectiveness and resource utilization favoring endovascular therapy, but most differences were not statistically significant. Long-term outcomes were more mixed; in particular, mortality outcomes generally favored surgery, although concluding that cause and effect is not possible as endovascularly treated patients tended to be older and may have had a shorter life expectancy regardless of therapy. CONCLUSIONS: The clinical effectiveness and resource utilization of surgery compared with endovascular therapy for CLTI is not known with certainty and will not be known until ongoing trials report results. It is likely that findings will vary by the time horizon, where initial outcomes and utilization tend to favor endovascular interventions, but long-term outcomes favor surgical revascularization.