Did ethno-racial disparities in access to transcatheter aortic valve replacement change over time?

Objective: In this study we sought to evaluate whether disparate use of transcatheter aortic valve replacement (TAVR) among non-White patients has decreased over time, and if unequal access to TAVR is driven by unequal access to high-volume hospitals. Methods: From 2013 to 2017, we used the State Inpatient Database across 8 states (Ariz, Colo, Fla, Md, NC, NM, Nev, Wash) to identify 51,232 Medicare beneficiaries who underwent TAVR versus surgical aortic valve replacement. Hospitals were categorized as low- (<50 per year), medium- (50-100 per year), or high-volume (>100 per year) according to total valve procedures (TAVR + surgical aortic valve replacement). Multivariable logistic regression models with interactions were performed to determine the effect of race, time, and hospital volume on the utilization of TAVR. Results: Non-White patients were less likely to receive TAVR than White patients (odds ratio [OR], 0.77; 95% CI, 0.71-0.83). However, utilization of TAVR increased over time (OR, 1.73; 95% CI, 1.73-1.80) for the total population, with non-White patients' TAVR use growing faster than for White patients (OR, 1.06; 95% CI, 1.00-1.12), time × race interaction, P = .034. Further, an adjusted volume-stratified time trend analysis showed that utilization of TAVR at high volume hospitals increased faster for non-White patients versus White patients by 8.6% per year (OR, 1.09; 95% CI, 1.01-1.16) whereas use at low- and medium-volume hospitals did not contribute to any decreasing utilization gap. Conclusions: This analysis shows initial low rates of TAVR utilization among non-White patients followed by accelerated use over time, relative to White patients. This narrowing gap was driven by increased TAVR utilization by non-White patients at high-volume hospitals.

Increased Access to Cardiac Surgery Did Not Improve Outcomes: Early Look Into Medicaid Expansion.

BACKGROUND: Cardiac surgery utilization has increased after passage of the Affordable Care Act. This multistate study examined whether changes in access after Medicaid expansion (ME) have led to improved outcomes, overall and particularly among ethnoracial minorities. METHODS: State Inpatient Databases were used to identify nonelderly adults (ages 18-64 years) who underwent coronary artery bypass grafting, aortic valve replacement, mitral valve replacement, or mitral valve repair in 3 expansion (Kentucky, New Jersey, Maryland) vs 2 nonexpansion states (North Carolina, Florida) from 2012 to 2015. Linear and logistic interrupted time series were used with 2-way interactions and adjusted for patient-level, hospital-level, and county-level factors to compare trends and instantaneous changes at the point of ME implementation (quarter 1 of 2014) for mortality, length of stay, and elective status. Interrupted time series models estimated expansion effect, overall and by race-ethnicity. RESULTS: Analysis included 22 038 cardiac surgery patients from expansion states and 33 190 from nonexpansion states. In expansion states, no significant trend changes were observed for mortality (odds ratio, 1.01; P = .83) or length of stay (ß = -0.05, P = .20), or for elective surgery (odds ratio, 1.00; P = .91). There were similar changes seen in nonexpansion states. Among ethnoracial minorities, ME did not impact outcomes or elective status. CONCLUSIONS: Despite an increase in cardiac surgery utilization after ME, outcomes remained unchanged in the early period after implementation, overall and among ethnoracial minorities. Future research is needed to confirm long-term trends and examine reasons behind this lack of improved outcomes.

Cardiac Surgery Utilization Across Vulnerable Persons After Medicaid Expansion.

BACKGROUND: Medicaid expansion (ME) under the Affordable Care Act has reduced the number of uninsured patients, although its preferential effects on vulnerable populations have been mixed. This study examined whether ME preferentially improved cardiac surgery use by insurance strata, race, and income level. METHODS: Non-elderly adults (aged 18-64 years) who underwent coronary artery bypass grafting, aortic valve replacement, mitral valve replacement, or mitral valve repair were identified in the State Inpatient Databases for 3 expansion states (Kentucky, New Jersey, and Maryland) and 2 non-expansion states (North Carolina and Florida) from 2012 to the third quarter of 2015. We used adjusted Poisson interrupted time series to determine the impact of ME on cardiac surgery use for Medicaid or uninsured (MCD/UIS) patients, racial and ethnic minorities, and individuals from low-income areas. RESULTS: In expansion states, use among non-White MCD/UIS patients had a positive trend after ME (2.3%/quarter; P = .156), whereas use for White MCD/UIS patients fell (-1.7%/quarter; P = .117). In contrast, use among non-White MCD/UIS in non-expansion states decreased by 4.4% (P < .001) which was a greater decline than among White MCD/UIS patients (-1.8%/quarter; P = .057). There was no substantial effect of ME on cardiac surgery use for MCD/UIS patients from low- versus high-income areas. CONCLUSIONS: These findings demonstrate that the use of cardiac surgical procedures was generally unchanged after ME; however, nonsignificant trend differences suggest a narrowing gap between vulnerable and non-vulnerable groups in ME states. These preliminary findings help describe the association of insurance coverage as a driver of cardiac surgery use among vulnerable patients.

Robotic-assisted tracheobronchial surgery.

Robotic technology is positioned to transform the approach to tracheobronchial surgery. With its magnified 3D view, intuitive controls, wristed-instruments, high-fidelity simulation platforms, and the steady implementation of new technical improvement, the robot is well-suited to manage the careful dissection and delicate handling of the airway in tracheobronchial surgery. This innovative technology has the potential to promote the widespread adoption of minimally invasive techniques for this complex thoracic surgery.

The interactive Physical and Cognitive Exercise System (iPACES™): effects of a 3-month in-home pilot clinical trial for mild cognitive impairment and caregivers.

BACKGROUND: Alzheimer's and related dementias are on the rise, and older adults and their families are seeking accessible and effective ways to stave off or ameliorate mild cognitive impairment (MCI). AIM: This pilot clinical trial (ClinicalTrials.gov Identifier: 03069391) examined neuropsychological and neurobiological outcomes of interactive physical and mental exercise. PARTICIPANTS AND METHODS: Older adults (MCI and caregivers) were enrolled in a 3-month, in-home trial of a portable neuro-exergame (the interactive Physical and Cognitive Exercise System [iPACES™]), in which they pedaled and steered along a virtual bike path to complete a list of errands (Memory Lane™). Neuropsychological function and salivary biomarkers were measured at pre-, mid-, and posttrial. Ten older adults complied with the recommended use of iPACES (complete dose; ≥2×/wk, 67% of the 15 who also had pre- and postevaluation data). Statistical analyses compared change over time and also change among those with a complete dose vs inadequate dose. Correlations between change in neuropsychological and biomarker measures were also examined. RESULTS: Executive function and verbal memory increased after 3 months (p = 0.01; no significant change was found with an inadequate dose). Change in salivary biomarkers was moderately associated with increasing cognition (cortisol, r = 0.68; IGF-1, r = 0.37). CONCLUSION: Further research is needed, but these pilot data provide preliminary indications to suggest neuro-exergaming can impact cognitive function, perhaps via neurobiological mechanisms, and as such may provide an effective and practical way to promote healthy aging.

The Enhanced Interactive Physical and Cognitive Exercise System (iPACESTM v2.0): Pilot Clinical Trial of an In-Home iPad-Based Neuro-Exergame for Mild Cognitive Impairment (MCI).

Given increasing longevity worldwide, older adults and caregivers are seeking ways to curb cognitive decline especially for those with mild cognitive impairment (MCI, now mild neurocognitive disorder, mNCD, Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-V). This quasi-experimental, within-subjects pilot clinical trial was designed to replicate and extend the study of cognitive benefits for MCI by improving upon our prior interactive Physical and Cognitive Exercise Study (iPACESTM v1.0) by increasing the usability of the neuro-exergame and exploring possible underlying neurobiological mechanisms. Older adults were enrolled in a three-month, in-home trial of a portable neuro-exergame (iPACES™ v2.0) where participants pedaled and steered along a virtual bike path (Memory Lane™). Neuropsychological function was assessed at baseline after component familiarization intervals (e.g., two weeks of exercise-only, game-only, etc.) and after three months of interactive neuro-exergame intervention. Fourteen participants were enrolled in the study and seven completed the final evaluation. Intent-to-treat analyses were conducted with imputed missing data (total n = 14). Significant improvement in executive function (Stroop) was found (d = 0.68, p = 0.02) only. Changes in salivary biomarkers (cortisol and insulin-like growth factor 1; IGF-1) were significantly associated with improved cognition. Further research is needed, but pilot data suggest that a portable in-home neuro-exergame may be an additional, practical tool to fight back against cognitive decline and dementia.

The Aerobic and Cognitive Exercise Study (ACES) for Community-Dwelling Older Adults With or At-Risk for Mild Cognitive Impairment (MCI): Neuropsychological, Neurobiological and Neuroimaging Outcomes of a Randomized Clinical Trial.

Prior research has found that cognitive benefits of physical exercise and brain health in older adults may be enhanced when mental exercise is interactive simultaneously, as in exergaming. It is unclear whether the cognitive benefit can be maximized by increasing the degree of mental challenge during exercise. This randomized clinical trial (RCT), the Aerobic and Cognitive Exercise Study (ACES) sought to replicate and extend prior findings of added cognitive benefit from exergaming to those with or at risk for mild cognitive impairment (MCI). ACES compares the effects of 6 months of an exer-tour (virtual reality bike rides) with the effects of a more effortful exer-score (pedaling through a videogame to score points). Fourteen community-dwelling older adults meeting screening criteria for MCI (sMCI) were adherent to their assigned exercise for 6 months. The primary outcome was executive function, while secondary outcomes included memory and everyday cognitive function. Exer-tour and exer-score yielded significant moderate effects on executive function (Stroop A/C; d's = 0.51 and 0.47); there was no significant interaction effect. However, after 3 months the exer-tour revealed a significant and moderate effect, while exer-score showed little impact, as did a game-only condition. Both exer-tour and exer-score conditions also resulted in significant improvements in verbal memory. Effects appear to generalize to self-reported everyday cognitive function. Pilot data, including salivary biomarkers and structural MRI, were gathered at baseline and 6 months; exercise dose was associated with increased BDNF as well as increased gray matter volume in the PFC and ACC. Improvement in memory was associated with an increase in the DLPFC. Improved executive function was associated with increased expression of exosomal miRNA-9. Interactive physical and cognitive exercise (both high and low mental challenge) yielded similarly significant cognitive benefit for adherent sMCI exercisers over 6 months. A larger RCT is needed to confirm these findings. Further innovation and clinical trial data are needed to develop accessible, yet engaging and effective interventions to combat cognitive decline for the growing MCI population. ClinicalTrials.gov ID: NCT02237560.

Effect of Anti-TNF Agents on Postoperative Outcomes in Inflammatory Bowel Disease Patients: a Single Institution Experience.

BACKGROUND: Anti-tumor necrosis factor (TNF) agents have been an integral part in the treatment of inflammatory bowel disease. However, a subset of inflammatory bowel disease patients ultimately requires surgery and up to 30 % of them have undergone treatment with anti-TNF agents. Studies assessing the effect of anti-TNF agents on postoperative outcomes have been inconsistent. The aim of this study is to assess postoperative morbidity in inflammatory bowel disease patients who underwent surgery with anti-TNF therapy prior to surgery. METHODS: This is a retrospective review of 282 patients with inflammatory bowel disease undergoing intestinal surgery between 2013 and 2015 at the Mount Sinai Hospital. Patients were divided into two groups based on treatment with anti-TNF agents (infliximab, adalimumab, certolizumab) within 8 weeks of surgery. Thirty-day postoperative outcomes were recorded. Univariate and multivariate statistical analyses were carried out. RESULTS: Seventy-three patients were treated with anti-TNF therapy within 8 weeks of surgery while 209 patients did not have exposure. Thirty-day anastomotic leak, intra-abdominal abscess, wound infection, extra-abdominal infection, readmission, and mortality rates were not significantly different between the two groups. CONCLUSIONS: The use of anti-TNF medications in inflammatory bowel disease patients within 2 months of intestinal surgery is not associated with an increased risk of 30-day postoperative complications.

Aerobic and Cognitive Exercise (ACE) Pilot Study for Older Adults: Executive Function Improves with Cognitive Challenge While Exergaming.

Dementia cases are increasing worldwide; thus, investigators seek to identify interventions that might prevent or ameliorate cognitive decline in later life. Extensive research confirms the benefits of physical exercise for brain health, yet only a fraction of older adults exercise regularly. Interactive mental and physical exercise, as in aerobic exergaming, not only motivates, but has also been found to yield cognitive benefit above and beyond traditional exercise. This pilot study sought to investigate whether greater cognitive challenge while exergaming would yield differential outcomes in executive function and generalize to everyday functioning. Sixty-four community based older adults (mean age=82) were randomly assigned to pedal a stationary bike, while interactively engaging on-screen with: (1) a low cognitive demand task (bike tour), or (2) a high cognitive demand task (video game). Executive function (indices from Trails, Stroop and Digit Span) was assessed before and after a single-bout and 3-month exercise intervention. Significant group × time interactions were found after a single-bout (Color Trails) and after 3 months of exergaming (Stroop; among 20 adherents). Those in the high cognitive demand group performed better than those in the low cognitive dose condition. Everyday function improved across both exercise conditions. Pilot data indicate that for older adults, cognitive benefit while exergaming increased concomitantly with higher doses of interactive mental challenge.

Browpexy through the upper lid (BUL): a new technique of lifting the brow with a standard blepharoplasty incision.

BACKGROUND: Browpexy returns the brow to an anatomical, aesthetically-appealing location on the upper face. Recently, browlifting techniques have evolved from aggressive, open approaches toward less invasive, limited-incision techniques. Browpexy through the upper lid (BUL), an innovative technique based on earlier practices, anchors the underlying brow soft tissue to the bone, allowing for stabilization. Furthermore, this procedure can be performed concomitantly with an upper eyelid blepharoplasty through the same access incision. OBJECTIVE: The authors evaluate the efficacy of BUL in patients with ptotic eyebrows requiring stabilization and/or elevation and in patients with prominent brow fat pads. METHODS: The charts of 21 patients who were treated with BUL by the senior author (HMS) between February 2007 and October 2008 were retrospectively reviewed. RESULTS: The age range of the 21 patients in this study was 54 to 70 years. Twelve patients were men; nine were women. Each patient presented with complaints of tired-appearing or "weighed-down" upper eyelids. All patients were uniformly happy with their postoperative aesthetic results. There were no major immediate or long-term complications (including, but not limited to, uneven postoperative brow position, loss of suspension, frontal nerve injury, hematoma, infection, or wound dehiscence). No patients required reoperation for recurrent brow ptosis or upper lid deformity. CONCLUSIONS: BUL is ideal for patients with ptotic eyebrows who need brow stabilization and/or elevation, as well as for patients with prominent brow fat pads who require stabilization. BUL achieves excellent results through a standard upper eyelid blepharoplasty incision, and allows the surgeon to perform a concomitant upper eyelid blepharoplasty and browpexy without a traditional coronal, scalp, or forehead incision.

Directed self-assembly in laponite/CdSe/polyaniline nanocomposites.

Laponite films provide versatile inorganic scaffolds with materials architectures that direct the self-assembly of CdSe quantum dots (QDs or EviTags) and catalytic surfaces that promote the in situ polymerization of polyaniline (PANI) to yield novel nanocomposites for light emitting diodes (LEDs) and solar cell applications. Water-soluble CdSe EviTags with varying, overlapping emission wavelengths in the visible spectrum were incorporated using soft chemistry routes within Na-Laponite host film platforms to achieve broadband emission in the visible spectrum. QD concentrations, composition and synthesis approach were varied to optimize photophysical properties of the films and to mediate self-assembly, optical cascading and energy transfer. In addition, aniline tetramers coupled to CdSe (QD-AT) surfaces using a dithioate linker were embedded within Cu-Laponite nanoscaffolds and electronically coupled to PANI via vapor phase exposure. Nanotethering and specific host-guest and guest-guest interactions that mediate nanocomposite photophysical behavior were probed using electronic absorption and fluorescence spectroscopies, optical microscopy, AFM, SEM, powder XRD, NMR and ATR-FTIR. Morphology studies indicated that Lap/QD-AT films synthesized using mixed solvent, layer by layer (LbL) methods exhibited anisotropic supramolecular structures with unique mesoscopic ordering that affords bifunctional networks to optimize charge transport.

Human follitropin receptor (FSHR) interacts with the adapter protein 14-3-3tau.

The human follitropin (follicle stimulating hormone, FSH) receptor (FSHR) is a G protein-coupled receptor (GPCR). To identify cytoplasmic proteins that may regulate FSHR function, a yeast-based interaction trap was performed. A linked construct of the first and second intracellular loops (iL1-iL2 bait) of FSHR was used as bait and a human ovarian cDNA library was used as prey. Among the proteins identified that interacted with the bait was 14-3-3tau, a member of a family of homodimeric cytoplasmic adapter proteins. Human granulosa cells, the site of FSHR expression in the ovary, were found to contain 14-3-3tau. Importantly, 14-3-3tau co-immunoprecipitated with FSHR stably expressed in HEK 293 cells. Its association with FSHR was follitropin-dependent. Over-expression of 14-3-3tau resulted in a modest decrease of follitropin-induced cAMP accumulation. Collectively, these data support a role for 14-3-3tau in follitropin action. The finding that 14-3-3tau interacts with FSHR is novel and should lead to new insights into the regulation of GPCR in general and FSHR specifically.

Human follicle-stimulating hormone (FSH) receptor interacts with the adaptor protein APPL1 in HEK 293 cells: potential involvement of the PI3K pathway in FSH signaling.

Selection of a dominant follicle that will ovulate likely occurs by activation of cell survival pathways and suppression of death-promoting pathways in a mechanism involving FSH and its cognate receptor (FSHR). A yeast two-hybrid screen of an ovarian cDNA library was employed to identify potential interacting partners with human FSHR intracellular loops 1 and 2. Among eight cDNA clones identified in the screen, APPL1 (adaptor protein containing PH domain, PTB domain, and leucine zipper motif; also known as APPL or DIP13alpha) was chosen for further analysis. APPL1 appears to coimmunoprecipitate with FSHR in HEK 293 cells stably expressing FSHR (293/FSHR cells), confirming APPL1 as a potential FSHR-interacting partner. The phosphorylation status of members of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway was also examined because of the proposed role of APPL1 in the antiapoptotic PI3K/Akt pathway. FOXO1a, also referred to as forkhead homologue in rhabdomyosarcoma, is a downstream effector in the pathway and tightly linked to expression of proapoptotic genes. FOXO1a, but not the upstream kinase Akt, is rapidly phosphorylated, and FOXO1a is thereby inactivated when 293/FSHR cells are treated with FSH. In addition, FSHR coimmunoprecipitates with Akt. The identification of APPL1 as a potential interactor with FSHR and the finding that FOXO1a is phosphorylated in response to FSH provide a possible link between FSH and PI3K/Akt signaling, which may help to delineate a survival mechanism whereby FSH selects the dominant follicle to survive.

Synergistic repression of anaerobic genes by Mot3 and Rox1 in Saccharomyces cerevisiae.

Two groups of anaerobic genes (genes induced in anaerobic cells and repressed in aerobic cells) are negatively regulated by heme, a metabolite present only in aerobic cells. Members of both groups, the hypoxic genes and the DAN/TIR/ERG genes, are jointly repressed under aerobic conditions by two factors. One is Rox1, an HMG protein, and the second, originally designated Rox7, is shown here to be Mot3, a global C2H2 zinc finger regulator. Repression of anaerobic genes results from co-induction of Mot3 and Rox1 in aerobic cells. Repressor synthesis is triggered by heme, which de-represses a mechanism controlling expression of both MOT3 and ROX1 in anaerobic cells; it includes Hap1, Tup1, Ssn6 and a fourth unidentified factor. The constitutive expression of various anaerobic genes in aerobic rox1Delta or mot3Delta cells directly implies that neither factor can repress by itself at endogenous levels and that stringent aerobic repression results from the concerted action of both. Mot3 and Rox1 are not essential components of a single complex, since each can repress independently in the absence of the other, when artificially induced at high levels. Moreover, the two repression mechanisms appear to be distinct: as shown here repression of ANB1 by Rox1 alone requires Tup1-Ssn6, whereas repression by Mot3 does not. Though artificially high levels of either factor can repress well, the absolute efficiency observed in normal cells when both are present-at much lower levels-demonstrates a novel inhibitory synergy. Evidently, expression levels for the two mutually dependent repressors are calibrated to permit a range of variation in basal aerobic expression at different promoters with differing operator site combinations.

Regulation of follitropin receptor cell surface residency by the ubiquitin-proteasome pathway.

Little is known of the normal physiological processes that govern the cell surface residency of the human follitropin receptor (hFSHR), a G protein-coupled receptor expressed in the ovary and testis. In the hFSHR, the third intracellular (3i) loop is considered to be pivotal in attenuation of ligand activation, particularly internalization. To gain a better understanding of these processes, we used a yeast-based interaction trap to identify cytoplasmic proteins in a human ovarian cDNA library that interacted with the hFSHR 3i loop. Among the cDNA identified, four encoded isoforms of ubiquitin. Immunoprecipitated hFSHR probed with an antiubiquitin antibody revealed that the receptor is ubiquitinated, although not exclusively on the 3i loop. Cell-surface hFSHR levels increased when expressed at nonpermissive temperature in a temperature-sensitive, ubiquitination-defective cell line. Similarly, after treatment with proteasome inhibitors, HEK293 cells stably transfected with an hFSHR expression plasmid showed an increase in follitropin binding. Proteasome inhibitors did not affect the rate of FSH internalization when receptors were saturated before internalization was measured. In contrast, internalization decreased when binding experiments were performed under nonequilibrium conditions. A mutant hFSHR-K555R, which removes the only lysine in the 3i loop available for ubiquitination, was still ubiquitinated, illustrating that, although the third loop enables and interaction with ubiquitin, it is not the sole site of ubiquitination. These observations are consistent with a role for ubiquitination in the regulation of hFSHR cell surface residency. Additionally, it can be inferred that a sequence in the 3i loop is involved in regulating receptor ubiquitination and internalization.

Molecular, structural, and cellular biology of follitropin and follitropin receptor.

Follitropin and the follitropin receptor are essential for normal gamete development in males and females. This review discusses the molecular genetics and structural and cellular biology of the follitropin/follitropin receptor system. Emphasis is placed on the human molecules when possible. The structure and regulation of the genes for the follitropin beta subunit and the follitropin receptor is discussed. Control of systemic and cellular protein levels is explained. The structural biology of each protein is described, including protein structure, motifs, and activity relationships. Finally, the follitropin/follitropin receptor signal transduction system is discussed.