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PURPOSE OF REVIEW: To review findings related to phantom genital sensation, emphasizing phantom sensation in the transgender and gender diverse (TGD) population. We discuss prevalence, presentation and potential implications for sensory outcomes in genital gender-affirming surgery. RECENT FINDINGS: There is a high prevalence of phantom genital sensations in the TGD population. The prevalence varies by body part, approaching 50% in the most frequently reported transgender phantom - the phantom penis. Unlike genital phantoms that occur after trauma or surgery which are often painful, transgender phantoms are typically neutral and often erogenous in experience. Phantom sensation in the TGD population can be an affirming experience and important part of sexual well being and embodiment. SUMMARY: Recent studies have begun to characterize the prevalence and presentations of phantom genital sensations in TGD people, informing our evolving understanding of the sensory experiences of the transgender and gender diverse population. Targeting integration of these centrally-mediated phantom genital sensations with the peripherally generated sensation from genital stimulation may represent one potential avenue to improve sensation and embodiment following genital gender-affirming surgical procedures. Additionally, emerging techniques in modern peripheral nerve surgery targeting phantom pain may offer potential treatment options for painful phantom sensation seen after cases of genital surgery or trauma.
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Cirugía de Reasignación de Sexo , Humanos , Masculino , Femenino , Cirugía de Reasignación de Sexo/métodos , Cirugía de Reasignación de Sexo/efectos adversos , Personas Transgénero/psicología , Prevalencia , Transexualidad/cirugía , Transexualidad/psicología , Transexualidad/fisiopatología , Miembro Fantasma/epidemiología , Miembro Fantasma/etiología , Miembro Fantasma/fisiopatología , SensaciónRESUMEN
INTRODUCTION: Some patients pursuing gender-affirming mastectomy prefer to forgo autologous nipple and areolar reconstruction, instead choosing a "no nipple" option. The objective of this study is to evaluate the motives and influences contributing to this decision. METHODS: A retrospective survey-based study of patients undergoing gender-affirming mastectomy over a 4.6-year period was conducted. All patients were offered nipple and areolar reconstruction. A survey was distributed to those who elected to forgo nipple and areolar reconstruction exploring the factors influencing that choice and postoperative satisfaction. RESULTS: Five hundred thirty-six patients underwent gender-affirming mastectomy and 13% chose to forgo nipple and areolar reconstruction. The survey response rate was 72%. Most respondents identified as nonbinary (48%) or transmasculine (42%). Body image, defined in the context of this study as an improvement in body image satisfaction due to achievement of a more gender-congruent appearance, was the most highly cited and most heavily weighted decision-making factor. Concerns about nipple graft outcomes were frequently cited as important but carried less weight. There were no differences between transmasculine and nonbinary patients in terms of motivations for choosing this surgical option. Fifty-eight percent of respondents pursued or planned to pursue chest tattoos, whereas 42% preferred no further chest modifications. Patient satisfaction was high postoperatively (98%), and 82% of respondents would choose to forgo nipple and areolar reconstruction again even if surgical outcomes of free nipple grafts were improved. CONCLUSIONS: Gender-affirming mastectomy without nipple and areolar reconstruction was requested by 13% of patients presenting for gender-affirming chest surgery over the study period and had high postoperative satisfaction among patients who chose this option. This modification of gender-affirming mastectomy is a variation that surgical teams should be aware of. Many reasons to forgo nipple preservation were cited, most of which related to body image. Secondary factors were easier recovery and/or concern about outcomes of free nipple grafts. Many patients wished information about this surgical option was more widely available.
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Mamoplastia , Mastectomía , Pezones , Satisfacción del Paciente , Humanos , Femenino , Estudios Retrospectivos , Pezones/cirugía , Masculino , Adulto , Persona de Mediana Edad , Mamoplastia/métodos , Mastectomía/métodos , Satisfacción del Paciente/estadística & datos numéricos , Cirugía de Reasignación de Sexo/métodos , Encuestas y Cuestionarios , Conducta de Elección , Imagen CorporalRESUMEN
BACKGROUND: Significant improvements in myocardial structure and function have been reported in some patients with advanced heart failure (termed responders [R]) following left ventricular assist device (LVAD)-induced mechanical unloading. This therapeutic strategy may alter myocardial energy metabolism in a manner that reverses the deleterious metabolic adaptations of the failing heart. Specifically, our previous work demonstrated a post-LVAD dissociation of glycolysis and oxidative-phosphorylation characterized by induction of glycolysis without subsequent increase in pyruvate oxidation through the tricarboxylic acid cycle. The underlying mechanisms responsible for this dissociation are not well understood. We hypothesized that the accumulated glycolytic intermediates are channeled into cardioprotective and repair pathways, such as the pentose-phosphate pathway and 1-carbon metabolism, which may mediate myocardial recovery in R. METHODS: We prospectively obtained paired left ventricular apical myocardial tissue from nonfailing donor hearts as well as R and nonresponders at LVAD implantation (pre-LVAD) and transplantation (post-LVAD). We conducted protein expression and metabolite profiling and evaluated mitochondrial structure using electron microscopy. RESULTS: Western blot analysis shows significant increase in rate-limiting enzymes of pentose-phosphate pathway and 1-carbon metabolism in post-LVAD R (post-R) as compared with post-LVAD nonresponders (post-NR). The metabolite levels of these enzyme substrates, such as sedoheptulose-6-phosphate (pentose phosphate pathway) and serine and glycine (1-carbon metabolism) were also decreased in Post-R. Furthermore, post-R had significantly higher reduced nicotinamide adenine dinucleotide phosphate levels, reduced reactive oxygen species levels, improved mitochondrial density, and enhanced glycosylation of the extracellular matrix protein, α-dystroglycan, all consistent with enhanced pentose-phosphate pathway and 1-carbon metabolism that correlated with the observed myocardial recovery. CONCLUSIONS: The recovering heart appears to direct glycolytic metabolites into pentose-phosphate pathway and 1-carbon metabolism, which could contribute to cardioprotection by generating reduced nicotinamide adenine dinucleotide phosphate to enhance biosynthesis and by reducing oxidative stress. These findings provide further insights into mechanisms responsible for the beneficial effect of glycolysis induction during the recovery of failing human hearts after mechanical unloading.
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Glucosa/metabolismo , Insuficiencia Cardíaca/metabolismo , Miocardio/metabolismo , Comorbilidad , Metabolismo Energético , Glucólisis , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/fisiopatología , Corazón Auxiliar , Humanos , Redes y Vías Metabólicas , Metaboloma , Metabolómica/métodos , Oxidación-Reducción , Volumen SistólicoAsunto(s)
Colgajos Tisulares Libres , Cirugía de Reasignación de Sexo , Humanos , Masculino , Antebrazo/cirugía , Faloplastia , Pene/cirugíaRESUMEN
Adverse myocardial remodeling can be reversed by medical, surgical, and device therapies leading to reduced heart failure (HF) morbidity and mortality and significant improvements in the structure and function of the failing heart. The growing population of HF patients who experience a degree of myocardial improvement should be better studied in terms of long-term outcomes and underlying biology to more clearly define the difference between recovery and remission. These investigations should also be focused in determining whether in chronic HF patients complete myocardial recovery is achievable at a meaningful rate and help us better understand, predict, and manipulate cardiac recovery.
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Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Rehabilitación Cardiaca , Femenino , Humanos , Masculino , Investigación Biomédica Traslacional , Remodelación VentricularRESUMEN
Symptomatic neuromas of the superficial radial nerve (SRN) can cause debilitating pain. Traditional surgical management options have demonstrated inconsistent outcomes prompting a search for alternatives. Recent reports have emerged on the use of targeted muscle reinnervation (TMR) for neuromas of the SRN using donors that are well established in hand surgery, such as the brachioradialis (BR) or extensor capri radialis longus or brevis. Use of the brachioradialis or extensor capri radialis longus motor targets can require surgery at or above the level of the antecubital fossa, and denervation of these muscle groups may be undesirable in cases of complex upper extremity injury where these donors may be needed for tendon or nerve transfer. The supinator is an expendable and often overlooked donor nerve that has not been assessed as a target for TMR of the SRN. In this case series, three patients with SRN neuromas whose conservative management failed and who did not have an SRN lesion amenable to reconstruction were managed with TMR to the nerves to supinator. At latest follow-up (9-22 months), no patients had deficits in supination or evident donor site morbidity. Two patients reported complete resolution of their SRN neuroma pain, and one patient reported partial improvement. This case series reports early results of TMR of the SRN using nerves to supinator in cases of SRN neuromas not amenable to reconstruction, demonstrating technical feasibility, improvements in neuroma pain, and no discernible donor morbidity.
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Gender-affirming vaginoplasty (GAV) comprises the construction of a vulva and a neovaginal canal. Although technical nuances of vulvar construction vary between surgeons, vulvar construction is always performed using the homologous penile and scrotal tissues to construct the corresponding vulvar structures. Therefore, the main differentiating factor across gender-affirming vaginoplasty techniques is the tissue that is utilized to construct the neovaginal canal. These tissue types vary markedly in their availability, histology, and ease of harvest and have different advantages and disadvantages to their use as neovaginal lining. In this narrative review, the authors provide a comprehensive overview of the tissue types and associated operative approaches used for construction of the neovagina in GAV. Tissue choice is guided by several factors, such as histological similarity to natal vaginal mucosa, tissue availability, lubrication potential, additional donor site morbidity, and the specific goals of each patient. Skin is used to construct the neovagina in most cases with a combination of pedicled penile skin flaps and scrotal and extra-genital skin grafts. However, skin alternatives such as peritoneum and intestine are increasing in use. Peritoneum and intestine are emerging as options for primary vaginoplasty in cases of limited genital skin or revision vaginoplasty procedures. The increasing number of gender-affirming vaginoplasty procedures performed and the changing patient demographics from factors such as pubertal suppression have resulted in rapidly evolving indications for the use of these differing vaginoplasty techniques. This review sheds light on the use of less frequently utilized tissue types described for construction of the neovaginal canal, including mucosal tissues such as urethral and buccal mucosa, the tunica vaginalis, and dermal matrix allografts and xenografts. Although the body of evidence for each vaginoplasty technique is growing, there is a need for large prospective comparison studies of outcomes between these techniques and the tissue types used to line the neovaginal canal to better define indications and limitations.
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Importance: Carpal tunnel release (CTR) technique may influence the likelihood of revision surgery. Prior studies of revision CTR following endoscopic CTR (ECTR) compared with open CTR (OCTR) have been limited by sample size and duration of follow-up. Objective: To estimate the incidence of revision CTR following ECTR compared with OCTR in a national cohort. Design, Setting, and Participants: This retrospective cohort study used data from the US Veterans Health Administration. Participants included all adults (age ≥18 years) undergoing at least 1 outpatient CTR from October 1, 1999, to May 20, 2021. Data were analyzed from May 21, 2021, to November 27, 2023. Exposure: Index CTR technique. Main Outcomes and Measures: The primary outcome was time to revision CTR, defined as repeat ipsilateral CTR during the study period. Secondary outcomes were indications for revision, findings during revision, and additional procedures performed during revision. Results: Among 134â¯851 wrists from 103â¯455 patients (92â¯510 [89.4%] male; median [IQR] age, 62 [53-70] years) undergoing at least 1 CTR, 1809 wrists underwent at least 1 revision at a median (IQR) of 2.5 (1.0-3.8) years. In competing-risks analysis, the cumulative incidence of revision was 1.06% (95% CI, 0.99%-1.12%) at 5 years and 1.59% (95% CI, 1.51%-1.67%) at 10 years. ECTR was associated with increased hazard of revision CTR compared with OCTR (adjusted hazard ratio [aHR], 1.56; 95% CI, 1.34-1.81; P < .001). The risk difference for revision CTR associated with ECTR compared with OCTR was 0.57% (95% CI, 0.31%-0.84%) at 5 years (number needed to harm, 176) and 0.72% (95% CI, 0.36%-1.07%) at 10 years (number needed to harm, 139). Regardless of index CTR technique, the most common indication for revision was symptom recurrence (1062 wrists [58.7%]). A reconstituted transverse carpal ligament (TCL) was more common after ECTR compared with OCTR, whereas scarring of the overlying tissues and of the median nerve itself were more common following OCTR. Incomplete transverse-carpal-ligament release was observed in 251 of the wrists undergoing revision CTR (13.94%) and was more common among revisions following ECTR (odds ratio, 1.62; 95% CI, 1.11-2.37; P = .01). Conclusions and Relevance: In this cohort study of revision CTR in the Veterans Health Administration, ECTR was associated with increased risk of revision compared with OCTR, but the absolute risk was low regardless of technique. Intraoperative findings at revision varied significantly according to index CTR technique.
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Síndrome del Túnel Carpiano , Endoscopía , Adulto , Humanos , Masculino , Persona de Mediana Edad , Adolescente , Femenino , Estudios de Cohortes , Estudios Retrospectivos , Procedimientos Neuroquirúrgicos/métodos , Síndrome del Túnel Carpiano/epidemiología , Síndrome del Túnel Carpiano/cirugía , DescompresiónRESUMEN
Gender-affirming phalloplasty involves flap tubularization, placing unique stresses on the vascularity of the flap. Tubularization renders the flap susceptible to postoperative edema that can lead to excessive turgor that, if left untreated, can compromise perfusion and threaten the viability of the phallic reconstruction. This phenomenon has not been formally described in our literature. We aim to define this entity, described here as "Excessive Phallic Turgor" (EPT), and to outline its incidence, frequency of its underlying etiologies, and sequelae. We conducted a single-center, retrospective review of all phalloplasty operations involving flap transfer performed from December 2016 to May 2023. All patients requiring emergent intervention (bedside suture release, reoperation, or both) due to excessive phallic swelling and impending flap compromise were considered to have EPT. Variables compared between groups included underlying etiology (categorized as congestion, hematoma or swelling), patient demographics, flap type and size, management, length of stay, and postoperative outcomes. Over the study period, 147 phalloplasty operations involving flap transfer for shaft creation were performed. Of those, 15% developed EPT. Age, BMI, flap length, flap circumference, flap surface area, single vs multistage operation, flap tubularization (shaft-only vs tube-within-tube), and flap donor site were not significantly different between the cohort that developed EPT and that which did not. Development of EPT was associated with higher rates of phallic hematoma, surgical site infection, shaft fistula requiring repair, and longer inpatient stays. When EPT develops, prompt diagnosis and alleviation of intraphallic pressure are paramount for mitigating short- and long-term morbidity.
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Cirugía de Reasignación de Sexo , Humanos , Masculino , Cirugía de Reasignación de Sexo/efectos adversos , Faloplastia , Uretra/cirugía , Colgajos Quirúrgicos/cirugía , Hematoma/cirugía , Pene/cirugíaRESUMEN
A key component of success of a nerve transfer is the innervation density, which is directly affected by the donor nerve axonal density and donor-to-recipient (D:R) axon ratio. Optimal D:R axon ratio for a nerve transfer is quoted at 0.7:1 or greater. In phalloplasty surgery, there are currently minimal data available to help inform selection of donor and recipient nerves, including unavailability of axon counts. Methods: Five transmasculine people who underwent gender-affirming radial forearm phalloplasty had nerve specimens processed with histomorphometric evaluation to determine axon counts and approximate donor-to-recipient axon ratios. Results: Mean axon counts for recipient nerves were 6957 ± 1098 [the lateral antebrachial (LABC)], 1866 ± 590 [medial antebrachial (MABC)], and 1712 ± 121 [posterior antebrachial cutaneous (PABC)]. Mean axon counts for donor nerves were 2301 ± 551 [ilioinguinal (IL)] and 5140 ± 218 [dorsal nerve of the clitoris (DNC)]. D:R axon ratios using mean axon counts were DNC:LABC 0.739 (0.61-1.03), DNC:MABC 2.754 (1.83-5.91), DNC:PABC 3.002 (2.71-3.53), IL:LABC 0.331 (0.24-0.46), IL:MABC 1.233 (0.86-1.17), and IL:PABC 1.344 (0.85-1.82). Conclusions: The DNC is the more powerful donor nerve with greater than two times the axon count of the IL. The IL nerve may be under-powered to re-innervate the LABC based on an axon ratio consistently less than 0.7:1. All other mean D:R are more than 0.7:1. DNC axon counts may be excessive for re-innervation of the MABC or PABC alone with D:R of more than 2.5:1, potentially increasing risk of neuroma formation at the coaptation site.
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Sensate flaps are increasingly used in diverse areas of plastic surgery. Concurrently, modern techniques in neuroma prevention have emerged, such as regenerative peripheral nerve interface (RPNI). Despite increasing use of sensate flaps, the combined use of donor-site neuroma prevention techniques has yet to be described. We report on the use of primary donor-site RPNI at the time of sensate anterolateral thigh (ALT) reconstructions. In ALT flaps, the vastus lateralis muscle can be segmentally devascularized from perforator dissection. These segments of devascularized vastus lateralis muscle can easily be used and repurposed as the free muscle grafts needed for RPNI, providing a physiologic target for the regenerating neurons. Donor-site neuroma has not been shown to be a significant issue at standard ALT flap donor sites. Sensate ALT flaps involve harvest of the lateral femoral cutaneous nerve and/or additional femoral sensory branches at a more proximal location close to the level of the anterior superior iliac spine, where injury to the lateral femoral cutaneous nerve may be associated with pain. In this series, eight patients underwent senate ALT flaps with the use of primary RPNI at the sensate ALT donor site. At a mean follow-up of 16.3 months (range 5-25 months), there was minimal to no nerve pain and no clinical evidence of donor-site neuroma. As sensate flap reconstructions are increasingly performed in plastic surgery and data on neuroma prevention techniques continue to grow, we propose consideration of their combined use.
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Breast cancer patients have reported restricted mobility, pain, lymphedema, and impaired sensation and strength after breast reconstruction surgery. Many studies have demonstrated benefits of early exercise intervention (within the first 2 weeks) for functional recovery after breast surgery. From the surgeon's perspective, there is a concern that early postoperative exercise can potentially lead to complications or even reconstruction failure. The purpose of this study was to evaluate current trends and practices related to patient exercise after breast reconstruction among plastic surgeons in the United States. METHODS: An anonymous, electronic survey was sent to a random cohort of 2336 active members of the American Society of Plastic Surgeons. The survey consisted of 23 questions and was used to assess how plastic surgeons currently manage patients postoperatively after breast reconstruction. RESULTS: Responses were received from 228 plastic surgeons. Thirty-six (18%) respondents reported never prescribing physical therapy (PT) postoperatively. In total, 154 (76%) prescribe PT to less than 50% of their patients, and those who do most commonly prescribe it more than 3 weeks postoperatively. There was no difference in perceived rate of complications by respondents who prescribe early versus late exercise (χ 2 (5) = 8.815, P = 0.117). CONCLUSIONS: Based on our survey results, only a small percentage of plastic and reconstructive surgeons support early initiation of exercise, and PT is being prescribed to a minority of patients. Surgeons and physical therapists must work together to devise a recovery program that maximizes functional outcomes for patients while also limiting complications.
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BACKGROUND: Breast reconstruction may result in significant functional compromise and pain. Postoperative exercise and physical therapy can mitigate these morbidities, but it is infrequently recommended by healthcare providers. This study asked how many breast reconstruction patients are instructed to perform postoperative at-home exercises or physical therapy, how many reported following through with these instructions, and what timeline they were given for these activities. METHODS: A 16-question multiple-choice anonymous online survey was distributed to a private breast cancer survivor Facebook group (Diep C. Foundation). RESULTS: A total of 150 breast reconstruction patients responded to our survey. The majority of respondents in our sample were not provided with specific instructions regarding postoperative at-home exercises (N = 70, 54.3%) or physical therapy (N = 77, 63.6%). Approximately 13 of 59 respondents (22%) who had been instructed to participate in postoperative at-home exercises were directed to begin at 2-3 weeks. Approximately 15 of 44 respondents (34.1%) who had been instructed to participate in physical therapy were directed to begin these at 4-5 weeks. CONCLUSIONS: To the best of our knowledge, this is the first study of how often postoperative at-home exercises and physical therapy are recommended to breast reconstruction patients. Despite robust evidence of these activities' benefits, most women are not instructed to participate in postoperative at-home exercises or physical therapy. This is likely to impede breast reconstruction patients' recovery and delay their return to activities of daily living. More studies are needed of how to actively engage breast reconstruction patients in postoperative at-home exercises and physical therapy.
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We have investigated the structure sensitivity of methanol electrooxidation on eight transition metals (Au, Ag, Cu, Pt, Pd, Ir, Rh, and Ni) using periodic, self-consistent density functional theory (DFT-GGA). Using the adsorption energies of 16 intermediates on two different facets of these eight face-centered-cubic transition metals, combined with a simple electrochemical model, we address the differences in the reaction mechanism between the (111) and (100) facets of these metals. We investigate two separate mechanisms for methanol electrooxidation: one going through a CO* intermediate (the indirect pathway) and another that oxidizes methanol directly to CO(2) without CO* as an intermediate (the direct pathway). A comparison of our results for the (111) and (100) surfaces explains the origin of methanol electrooxidation's experimentally-established structure sensitivity on Pt surfaces. For most metals studied, on both the (111) and (100) facets, we predict that the indirect mechanism has a higher onset potential than the direct mechanism. Ni(111), Au(100), and Au(111) are the cases where the direct and indirect mechanisms have the same onset potential. For the direct mechanism, Rh, Ir, and Ni show a lower onset potential on the (111) facet, whereas Pt, Cu, Ag, and Au possess lower onset potential on the (100) facet. Pd(100) and Pd(111) have the same onset potential for the direct mechanism. These results can be rationalized by the stronger binding energy of adsorbates on the (100) facet versus the (111) facet. Using linear scaling relations, we establish reactivity descriptors for the (100) surface similar to those recently developed for the (111) surface; the free energies of adsorbed CO* and OH* can describe methanol electrooxidation trends on various metal surfaces reasonably well.
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BACKGROUND: The coronary vasculature encounters a reduction in pulsatility after implementing durable continuous-flow left ventricular assist device (CF-LVAD) circulatory support. Evidence exists that appropriate pulsatility is required to maintain endothelial cell homeostasis. We hypothesized that coronary artery endothelial function would be impaired after CF-LVAD intervention. METHODS AND RESULTS: Coronary arteries from patients with end-stage heart failure caused by ischemic cardiomyopathy (ICM; n=16) or non-ICM (n=22) cardiomyopathy were isolated from the left ventricular apical core, which was removed for the CF-LVAD implantation. In 11 of these patients, paired coronary arteries were obtained from an adjacent region of myocardium after the CF-LVAD intervention (n=6 ICM, 5 non-ICM). Vascular function was assessed ex vivo using isometric tension procedures in these patients and in 7 nonfailing donor controls. Maximal endothelium-dependent vasorelaxation to BK (bradykinin; 10-6-10-10 M) was blunted (P<0.05) in arteries from patients with ICM compared with non-ICM and donor controls, whereas responses to sodium nitroprusside (10-4-10-9 M) were similar among the groups. Contrary to our hypothesis, vasorelaxation responses to BK and sodium nitroprusside were similar before and 219±37 days after CF-LVAD support. Of these patients, an exploratory subgroup analysis revealed that BK-induced coronary artery vasorelaxation was greater (P<0.05) after (87±6%) versus before (54±14%) CF-LVAD intervention in ICM patients, whereas sodium nitroprusside-evoked responses were similar. CONCLUSIONS: Coronary artery endothelial function is not impaired by durable CF-LVAD support and in ICM patients appears to be improved. Investigating coronary endothelial function using in vivo approaches in a larger patient population is warranted.
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Cardiomiopatías/complicaciones , Vasos Coronarios/fisiopatología , Endotelio Vascular/fisiopatología , Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Isquemia Miocárdica/complicaciones , Vasodilatación/fisiología , Biopsia , Cardiomiopatías/fisiopatología , Cardiomiopatías/terapia , Vasos Coronarios/patología , Ecocardiografía , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/fisiopatología , Isquemia Miocárdica/terapia , Miocardio/patologíaRESUMEN
BACKGROUND: Immunosuppression is a known risk for post-transplant infections. Little data exist on the risk contributions of specific agents for various infections. METHODS: A triply robust propensity score-adjusted analysis was performed in a renal transplant cohort between February 2006 and January 2014. The study was performed to identify the incidence and the risk factors for developing a post-transplant infection. After initial bivariate analysis, a triply robust propensity score-adjusted multivariate logistic regression was performed. RESULTS: The mean age of the 717 renal transplant recipients was 50.0 ± 13.3 years, with the majority being male (61.6%) and 349 (48.7%) experiencing at least 1 post-transplant infection. Neither race, graft type, nor insurance status was associated with an increased incidence or risk of infection. In a fully adjusted regression model, the immunosuppressants mycophenolic acid mofetil (OR 0.38, 95% CI 0.21-0.71; P < .001) and alemtuzumab (OR 0.40, 95% CI 0.19-0.85; Pâ¯=â¯.020) were protective. CONCLUSION: Alemtuzumab and mycophenolic acid mofetil as immunosuppressant agents in a multiagent protocol appear to decrease the incidence of infection. Cytomegalovirus antigenemia was the greatest risk for infection and mycophenolic acid mofetil possessed the greatest protective effect on viral infections.
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Alemtuzumab/efectos adversos , Inmunosupresores/efectos adversos , Infecciones/etiología , Trasplante de Riñón/efectos adversos , Ácido Micofenólico/efectos adversos , Virosis/etiología , Adulto , Estudios de Casos y Controles , Infecciones Comunitarias Adquiridas/etiología , Infección Hospitalaria/etiología , Femenino , Glucocorticoides/efectos adversos , Humanos , Infecciones/microbiología , Masculino , Persona de Mediana Edad , Infecciones Oportunistas/etiología , Puntaje de Propensión , Estudios Retrospectivos , Factores de Riesgo , Tacrolimus/efectos adversos , Virosis/virologíaRESUMEN
AIMS: Adjuvant heart failure (HF) drug therapy in patients undergoing chronic mechanical circulatory support (MCS) is often used in conjunction with a continuous-flow left ventricular assist device (LVAD), but its potential impact is not well defined. The objective of the present study was to examine the effects of conventional HF drug therapy on myocardial structure and function, peripheral organ function and the incidence of adverse events in the setting of MCS. METHODS AND RESULTS: Patients with chronic HF requiring LVAD support were prospectively enrolled. Paired myocardial tissue samples were obtained prior to LVAD implantation and at transplantation for histopathology. The Meds group comprised patients treated with neurohormonal blocking therapy (concurrent beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and aldosterone antagonist), and the No Meds group comprised patients on none of these. Both the Meds (n = 37) and No Meds (n = 44) groups experienced significant improvements in cardiac structure and function over the 6 months following LVAD implantation. The degree of improvement was greater in the Meds group, including after adjustment for baseline differences. There were no differences between the two groups in arrhythmias, end-organ injury, or neurological events. In patients with high baseline pre-LVAD myocardial fibrosis, treatment with HF drug therapy was associated with a reduction in fibrosis. CONCLUSIONS: Clinical and histopathological evidence showed that adjuvant HF drug therapy was associated with additional favourable effects on the structure and function of the unloaded myocardium that extended beyond the beneficial effects attributed to LVAD-induced unloading alone. Adjuvant HF drug therapy did not influence the incidence of major post-LVAD adverse events during the follow-up period.
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Fármacos Cardiovasculares/uso terapéutico , Insuficiencia Cardíaca/terapia , Ventrículos Cardíacos/diagnóstico por imagen , Corazón Auxiliar , Miocardio/patología , Función Ventricular Izquierda/fisiología , Cateterismo Cardíaco , Ecocardiografía , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Periodicidad , Estudios Retrospectivos , Factores de TiempoRESUMEN
This study sought to investigate the effects of mechanical unloading on myocardial energetics and the metabolic perturbation of heart failure (HF) in an effort to identify potential new therapeutic targets that could enhance the unloading-induced cardiac recovery. The authors prospectively examined paired human myocardial tissue procured from 31 advanced HF patients at left ventricular assist device (LVAD) implant and at heart transplant plus tissue from 11 normal donors. They identified increased post-LVAD glycolytic metabolites without a coordinate increase in early, tricarboxylic acid (TCA) cycle intermediates. The increased pyruvate was not directed toward the mitochondria and the TCA cycle for complete oxidation, but instead, was mainly converted to cytosolic lactate. Increased nucleotide concentrations were present, potentially indicating increased flux through the pentose phosphate pathway. Evaluation of mitochondrial function and structure revealed a lack of post-LVAD improvement in mitochondrial oxidative functional capacity, mitochondrial volume density, and deoxyribonucleic acid content. Finally, post-LVAD unloading, amino acid levels were found to be increased and could represent a compensatory mechanism and an alternative energy source that could fuel the TCA cycle by anaplerosis. In summary, the authors report evidence that LVAD unloading induces glycolysis in concert with pyruvate mitochondrial oxidation mismatch, most likely as a result of persistent mitochondrial dysfunction. These findings suggest that interventions known to improve mitochondrial biogenesis, structure, and function, such as controlled cardiac reloading and conditioning, warrant further investigation to enhance unloading-induced reverse remodeling and cardiac recovery.
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We report that alkali ions (sodium or potassium) added in small amounts activate platinum adsorbed on alumina or silica for the low-temperature water-gas shift (WGS) reaction (H(2)O + CO â H(2) + CO(2)) used for producing H(2). The alkali ion-associated surface OH groups are activated by CO at low temperatures (~100°C) in the presence of atomically dispersed platinum. Both experimental evidence and density functional theory calculations suggest that a partially oxidized Pt-alkali-O(x)(OH)(y) species is the active site for the low-temperature Pt-catalyzed WGS reaction. These findings are useful for the design of highly active and stable WGS catalysts that contain only trace amounts of a precious metal without the need for a reducible oxide support such as ceria.