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1.
J Card Fail ; 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38754697

RESUMO

BACKGROUND: Living with a left ventricular assist device (LVAD) comes with potentially burdensome aspects posed by, for example, battery packs and device drivelines. We aim to describe the impact of living with a durable LVAD on sexual quality of life (QOL), depression, and anxiety in patients and their partners. METHODS AND RESULTS: In this single-center, prospective, observational study, patients ≥4 months after LVAD implantation and their partners completed the Sexual Activities in Left Ventricular Assist Device Patients or Partners questionnaire to assess their sexual QOL, the 8-item Patient Health Questionnaire (PHQ-8) to assess symptoms of depression and the 7-item Generalized Anxiety Disorder (GAD-7) to assess symptoms of anxiety. Sixty patients and 60 partners completed the questionnaires 2.3 ± 1.9 years after implantation. Eighty-seven percent of the patients and 13% of partners were male. The mean age of patients was 57.4 ± 13.3 years, with 90% living with their partner. Ten percent of patients and 18% of partners had a current diagnosis of a psychological condition, most frequently depression and/or anxiety. Overall, 49% of participants indicated the LVAD influenced their sexual activity (patients 53% vs partners 45%; P = .33). Disturbances from the driveline were the most common problem indicated. Twenty-four percent of participants had scored in the mild to moderate depression range on the PHQ-8 and 28% scored in the mild to severe anxiety range on the GAD-7. The median total GAD-7 (1 [interquartile range (IQR) 0-4.25] vs 2.5 [IQR 0-5]; P = .06) were comparable between patients and partners; whereas patients had a higher total PHQ-8 score (3 [IQR 0-5.25] vs 1 [IQR 0-3.25]; P = .02). A preference to receive information regarding sexuality while on LVAD support was indicated by 54% of participants and did not differ between patients and partners (P > .99). Written resources were the most commonly preferred source of information. CONCLUSIONS: LVADs severely affect the sexual QOL for patients and their partners. The presence of a driveline is a major cause for concern. Patients prefer receiving written information on how to improve their sexual QOL.

2.
Clin Transplant ; 38(3): e15287, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38477177

RESUMO

BACKGROUND: Little is known about the relationship between cytomegalovirus (CMV) infections and donor-derived cell-free DNA (dd-cfDNA) in heart transplant recipients. METHODS: In our study, CMV and dd-cfDNA results were prospectively collected on single-organ heart transplant recipients. If the CMV study was positive, a CMV study with dd-cfDNA was repeated 1-3 months later. The primary aim was to compare dd-cfDNA between patients with positive and negative CMV results. RESULTS: Of 44 patients enrolled between August 2022 and April 2023, 12 tested positive for CMV infections, 25 were included as controls, and seven patients with a viral infection without CMV were excluded. Baseline characteristics did not differ significantly between CMV-positive and CMV-negative patients with the exception of a later median time post-transplant in the CMV-positive group (253 days vs. 120 days, p = .03). Dd-cfDNA levels were significantly higher in patients with CMV infections compared to those without (p < .001) with more patients in the CMV positive group showing dd-cfDNA results ≥.12% (75% vs. 8%, p < .001) and ≥.20% (58% vs. 8%, p = .002). Each 1 log10 copy/ml reduction in CMV viral load from visit 1 to visit 2 was associated with a.23% reduction in log10 dd-cfDNA (p = .002). CONCLUSION: Our findings suggest that active CMV infections may raise dd-cfDNA levels in patients following heart transplantation. Larger studies are needed to validate these preliminary findings.


Assuntos
Ácidos Nucleicos Livres , Infecções por Citomegalovirus , Transplante de Coração , Humanos , Citomegalovirus/genética , Doadores de Tecidos , Transplantados , Rejeição de Enxerto
3.
Clin Transplant ; 37(12): e15151, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37922318

RESUMO

BACKGROUND: Recent innovations in temperature-controlled cardiac transportation allow for static hypothermic preservation of transplant organs during transportation. We assessed differences in donor-derived cell-free DNA (dd-cfDNA) using the SherpaPak cardiac transport system (SCTS) and traditional ice transportation. METHODS: Single-organ heart transplant recipients between January 2020 and January 2022 were included if they had dd-cfDNA measures ≤6 weeks post-transplant along with the baseline biopsy at 6 weeks as part of the surveillance protocol and no biopsy-confirmed rejection ≤90 days. Elevated dd-cfDNA ≥.20% were compared between groups using logistic regression including a subject effect. RESULTS: Of 65 hearts transplanted, 30 were transported with SCTS and 35 on ice. Recipient characteristics were similar between groups. Donors in the SCTS group were older (34 vs. 40 years, p = .04) with a longer total ischemic time (171 vs. 212 min, p = .002). Recipients in the SCTS group had a greater risk of elevated dd-cfDNA unadjusted and adjusted for donor age, and prolonged ischemic times > 3.5 h (Unadjusted odds ratio: 4.9, 95%-CI: 1.08-22.5, p = .039 and Adjusted odds ratio: 5.5, 95%-CI: 1.03-29.6, p = .046). Primary graft dysfunction rates and 1-year mortality were comparable between groups. CONCLUSION: Elevated dd-cfDNA in patients procured with SCTS may indicate that graft injury was not negated relative to ice transport. However, there were no clinical differences noted in short or long-term outcomes including mortality despite a longer ischemic time in the SCTS group.


Assuntos
Ácidos Nucleicos Livres , Transplante de Coração , Humanos , Gelo , Biomarcadores , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/genética , Doadores de Tecidos , Transplante de Coração/efeitos adversos , Transplantados
4.
Artif Organs ; 47(7): 1094-1103, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37012224

RESUMO

BACKGROUND: Right ventricular failure is associated with increased morbidity and mortality. The ProtekDuo (Livanova, Uk) is a dual-lumen cannula that allows for percutaneous right ventricular support and may be connected to a centrifugal blood pump such as the TandemHeart or LifeSparc (Livanova, UK). This systematic review aims to evaluate the safety and efficacy of ProtekDuo right ventricular support and evaluate potential clinical variables that can influence outcomes. METHODS: PubMed, MEDLINE, SCOPUS, EMBASE, and the Cochrane Library were systematically searched. Studies meeting inclusion criteria, where ProtekDuo was used as the right ventricular assist device with reported numerical death counts for mortality as outcome measures. The primary endpoints were in-hospital 30-day and 1-year mortality rates. Secondary endpoints included ICU length of stay, conversion rates to surgical RVADs, ProtekDuo wean rates, duration of use of ProtekDuo, and adverse event rates. RESULTS: Of 49 studies reviewed, 7 met inclusion criteria with study periods between October 2014 and November 2019. ProtekDuo was utilized due to RV failure post-LVAD insertion in 64.8% (68/105) of patients. In-hospital mortality, 30-day mortality, and 1-year mortality ranged between 9%-46%, 15%-40%, and 19%-40%, respectively. Weaning from ProtekDuo and conversion to surgical RVAD ranged between 24%-91% and 11%-35%, respectively. The ICU stay average ranged from 15.8 to 36 days and ProtekDuo mean support duration ranged from 10.5 to 58 days. CONCLUSION: The ProtekDuo cannula is increasingly utilized as a right ventricular support device. Despite the sparse retrospective data available with variable patient characteristics and study design, percutaneous RV mechanical support via ProtekDuo cannula is a safe and feasible option.


Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Disfunção Ventricular Direita , Humanos , Coração Auxiliar/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Insuficiência Cardíaca/cirurgia , Implantação de Prótese , Disfunção Ventricular Direita/cirurgia
5.
Am J Transplant ; 22(10): 2443-2450, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35514138

RESUMO

The Molecular Microscope Diagnostic System (MMDx) analyzes RNA transcripts of transplanted heart tissue to differentiate among T cell-mediated rejection (TCMR), antibody-mediated rejection (AMR), injury, and healthy tissue. However, little is known about its performance in relation to other modalities in a real-world heart transplant population. We evaluated whether MMDx performs in agreement with other validated modalities. Two hundred and twenty-eight corresponding endomyocardial biopsies (EMBx) and MMDx specimens from 135 adult heart transplant patients were retrospectively reviewed with correlating donor-derived cell-free DNA (dd-cfDNA). Rejection was classified on EMBx in 29 specimens (TCMR ≥ 2R and/or AMR ≥ 1), on MMDx in 56 specimens, and in 74 values with dd-cfDNA ≥0.20%. Despite moderate agreement between EMBx and MMDx (84% agreement, Cohen's kappa, 0.48, p < .001), systematic differences were observed (McNemar's test, p < .001) where MMDx classified 32 of 37 discordant cases as rejection. MMDx and dd-cfDNA demonstrated slight agreement (72% agreement, Cohen's kappa, 0.39, p < .001); however, systematic differences were also apparent where MMDx classified 12 of 50 discordant specimens as rejection when dd-cfDNA was <0.20% (McNemar's test, p < .001). Our findings provide insight on the performance of MMDx relative to other modalities in a heart transplant cohort and have implications on the surveillance and workup of allograft rejection in heart transplantation.


Assuntos
Ácidos Nucleicos Livres , Cardiopatias , Transplante de Coração , Transplante de Rim , Adulto , Anticorpos , Ácidos Nucleicos Livres/genética , Doxorrubicina/análogos & derivados , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Transplante de Coração/efeitos adversos , Humanos , Complicações Pós-Operatórias , RNA , Estudos Retrospectivos
6.
Clin Transplant ; 36(3): e14549, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34863042

RESUMO

Donor-derived cell free DNA (dd-cfDNA) has rapidly become part of rejection surveillance following orthotopic heart transplantation. However, some patients show elevated dd-cfDNA without clinical evidence of rejection. With the aim to provide a clinical description of this subpopulation, we retrospectively analyzed 35 cardiac transplant recipients at our center who experienced elevated (≥.20%) dd-cfDNA in the absence of clinical rejection, out of a total 106 recipients who had dd-cfDNA results available during the first year. The median time to first elevated dd-cfDNA level was 46 days, and the highest dd-cfDNA recorded within 1 year was .31% [inter-quartile range, .23-.45]. Twenty-two (63%) patients experienced infections (cytomegalovirus (CMV) or other), and 16 (46%) presented with de novo donor-specific antibodies. Cluster analysis revealed four distinct groups characterized by (a) subclinical rejection with 50% CMV (n = 16), (b) non-CMV infections and the longest time to first elevated dd-cfDNA (187 days) (n = 8), (c) right ventricular dysfunction (n = 6), and (d) women who showed the youngest median age (45 years) and highest median dd-cfDNA (.50%) (n = 5). Continued prospective analysis is needed to determine if these observations warrant changes in patient management to optimize the utilization of this vital non-invasive graft surveillance tool.


Assuntos
Ácidos Nucleicos Livres , Infecções por Citomegalovirus , Transplante de Coração , Transplante de Rim , Aloenxertos , Feminino , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/genética , Transplante de Coração/efeitos adversos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos , Transplantados
7.
Clin Transplant ; 36(3): e14545, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34817905

RESUMO

BACKGROUND: In acute decompensated heart failure (ADHF), noninvasive markers that predict morbidity and mortality are limited. Liver stiffness measurement (LSM) increases with hepatic fibrosis; however, it may be falsely elevated in patients with ADHF in the absence of liver disease. We investigated whether elevated LSM predicts cardiac outcomes in ADHF. METHODS: In a prospective study, we examined 52 ADHF patients without liver disease between 2016 and 2017. Patients underwent liver 2D shear wave elastography (SWE) and were followed for 12 months to assess the outcomes of left ventricular assist device (LVAD), heart transplant (HT) or death. RESULTS: The median LSM was elevated in patients who received an LVAD or HT within 30-days compared to those who did not (median [IQR]: 55.6 [22.5 - 63.4] vs 13.8 [9.5 - 40.3] kPa, p = .049). Moreover, the risk of composite outcome was highest in the 3rd tertile (> 39.8 kPa compared to 1st and 2nd combined, HR 2.83, 95% CI 1.20- 6.67, p = .02). Each 1-kPa increase in LSM was associated with a 1%-increase in the incidence rate of readmissions (IRR 1.01, 95% CI 1.00-1.02, p = .01). CONCLUSIONS: LSM may serve as a novel noninvasive tool to determine LVAD, HT, or death in patients with ADHF.


Assuntos
Técnicas de Imagem por Elasticidade , Insuficiência Cardíaca , Hepatopatias , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/cirurgia , Humanos , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Hepatopatias/patologia , Estudos Prospectivos
8.
J Cardiothorac Vasc Anesth ; 36(8 Pt A): 2303-2312, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34774406

RESUMO

OBJECTIVES: Acute kidney injury (AKI) remains a leading source of morbidity and mortality after cardiothoracic surgery. Insulin-like growth factor-binding protein 7 (IGFBP7), and tissue inhibitor of metalloproteinases-2 (TIMP-2), are novel early-phase renal biomarkers that have been validated as sensitive predictors of AKI. Here the authors studied the efficacy of these biomarkers for predicting AKI after left ventricular assist device (LVAD) implantation and cardiac transplantation. DESIGN/SETTING/PARTICIPANTS/INTERVENTIONS: This was a prospective study of 73 patients undergoing LVAD implantation (n = 37) or heart transplant (n = 36) from 2016 to 2017 at the authors' center. TIMP-2 and IGFBP7 were measured with the NephroCheck Test on urine samples before surgery and one-to-six hours after surgery. NephroCheck scores were assessed as predictors of moderate/severe AKI (Kidney Disease International Global Outcomes 2/3 creatinine criteria) within 48 hours of surgery, and the association with survival to one year was investigated. MEASUREMENTS AND MAIN RESULTS: The LVAD and transplant cohorts overall were similar in demographics and baseline creatinine (p > 0.05), with the exception of having more African-American patients in the LVAD arm (p = 0.003). Eleven (30%) LVAD and 16 (44%) transplant patients developed moderate/severe AKI. Overall, AKI was associated with postsurgery NephroCheck (odds ratio [95% confidence interval] for 0.1 mg/dL increase: 1.36 [1.04-1.79]; p = 0.03), but not with baseline NephroCheck (p = 0.92). When analyzed by cohort, this effect remained for LVAD (1.68 [1.05-2.71]; p = 0.03) but not for transplant (p = 0.15). Receiver operating characteristic analysis showed postoperative NephroCheck to be superior to baseline creatinine in LVAD (p = 0.046). Furthermore, an increase of 0.1 mg/dL in postoperative NephroCheck was associated with a 10% increase in the risk of mortality (adjusted hazard ratio: 1.11 [1.01-1.21]; p = 0.04) independent of age and body mass index. CONCLUSION: Assessment of TIMP-2 and IGFBP7 within six hours after surgery appeared effective at predicting AKI in patients with LVADs. Larger studies are warranted to validate these findings.


Assuntos
Injúria Renal Aguda , Transplante de Coração , Coração Auxiliar , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Biomarcadores/urina , Pontos de Checagem do Ciclo Celular , Creatinina , Transplante de Coração/efeitos adversos , Coração Auxiliar/efeitos adversos , Humanos , Estudos Prospectivos , Inibidor Tecidual de Metaloproteinase-2/urina
9.
Clin Transplant ; 35(11): e14445, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34318517

RESUMO

Mycophenolate mofetil (MMF), the prodrug of mycophenolic acid, is a highly effective immunosuppressive agent in heart transplant therapy. While the FDA approved dose is 1500 mg twice daily, dosing is often reduced due to dose-dependent adverse effects. However, empiric MMF dose reductions may lead to sub-therapeutic dosing and impair clinical outcomes. Our single center protocolized a risk-stratified approach based on age and weight to dose 500 mg twice daily or 1000 mg twice daily to patients after heart transplantation. This retrospective single-center study analyzed 140 consecutive heart transplant patients who were initiated on our risk-stratified MMF protocol post-transplant. The analysis revealed that the composite rate of biopsy-proven rejection, graft loss, or mortality at 1-year post-transplantation was similar between the two groups. Incidence of neutropenia, thrombocytopenia, infection, cardiac allograft vasculopathy, or acute kidney injury by 1-year also showed similar results between the two groups. Risk-stratification of MMF dosing appears to be a safe and effective strategy after heart transplantation.


Assuntos
Transplante de Coração , Transplante de Rim , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores , Ácido Micofenólico , Estudos Retrospectivos
10.
Clin Transplant ; 35(12): e14487, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34529289

RESUMO

Extended-release tacrolimus for prophylaxis of allograft rejection in orthotopic heart transplant (OHT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release tacrolimus (IR-tacrolimus). We compared the efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. Twenty-five prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 1 year was compared using non-inferiority analysis. LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 20% (90% CI: -40%, -.5%; non-inferiority P = .001). Tacrolimus trough levels peaked at 2-3 months and were higher in LCPT (median 14.5 vs. 12.7 ng/ml; P = .03) with similar dose levels (LCPT vs. IR-tacrolimus: .08 vs. .09 mg/kg/day; P = .33). Cardiovascular-related readmissions were reduced by 62% (P = .046) in LCPT patients. The complication rate per transplant admission and all-cause readmission rate did not differ significantly. These results suggest that LCPT is non-inferior in efficacy to IR-tacrolimus with a similar safety profile and improved bioavailability in OHT.


Assuntos
Transplante de Coração , Transplante de Rim , Adulto , Preparações de Ação Retardada , Esquema de Medicação , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/uso terapêutico , Comprimidos , Tacrolimo/uso terapêutico
11.
J Card Surg ; 36(9): 3052-3059, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34080231

RESUMO

BACKGROUND: Surgical site infections (SSIs) after left ventricular assist device (LVAD) implantation are associated with high mortality, while surgical prophylaxis is variable. METHODS: This retrospective study included adult patients who underwent LVAD implantation at a single center. We compared outcomes in patients who received narrow antimicrobial prophylaxis (cefazolin, vancomycin, or both) to those who received broad antimicrobial prophylaxis (any antimicrobial combination targeting gram-positive and gram-negative organisms not included in the narrow group) at 30-day and 1-year postimplantation. Cox-proportional hazards models and log-rank tests were used for survival analysis. RESULTS: Among the 39 and 65 patients comprising narrow and broad groups respectively, there was no difference in rate of SSI at 30 days (6.2% vs. 12.8%, p = .290) and 1 year (16.9% vs. 25.6%, p = .435). Comparing narrow to broad prophylaxis, the risk of mortality (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.15-1.35, logrank p = .14), and composite of mortality and infection was reduced (HR = 0.92, 95% CI = 0.45-1.88, logrank p = .83), but did not reach statistical significance. Most culture positive infections were due to gram-positive bacteria (70%) and the most common organisms were the Staphylococcus spp (47%). There were no significant differences in the rate of SSI at 1-year (p = 1.00) and mortality (p = .33) by device type. CONCLUSIONS: The rates of infection and all-cause mortality were not different between patients who received narrow or broad prophylaxis. This highlights an opportunity for institutions to narrow their surgical infection prophylaxis protocols to primarily cover gram-positive organisms.


Assuntos
Anti-Infecciosos , Coração Auxiliar , Adulto , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Antibioticoprofilaxia , Humanos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle
12.
J Antimicrob Chemother ; 75(2): 392-399, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31713607

RESUMO

OBJECTIVES: Animal models have suggested that the combination of pretomanid with pyrazinamide and moxifloxacin (PaMZ) may shorten TB therapy duration to 3-4 months. Here, we tested that in the hollow-fibre system model of TB (HFS-TB). METHODS: A series of HFS-TB experiments were performed to compare the kill rates of the PaMZ regimen with the standard three-drug combination therapy. HFS-TB experiments were performed with bacilli in log-phase growth treated for 28 days, intracellular bacilli treated daily for 28 days and semi-dormant Mycobacterium tuberculosis treated with daily therapy for 56 days for sterilizing effect. Next, time-to-extinction equations were employed, followed by morphism transformation and Latin hypercube sampling, to determine the proportion of patients who achieved a time to extinction of 3, 4 or 6 months with each regimen. RESULTS: Using linear regression, the HFS-TB sterilizing effect rates of the PaMZ regimen versus the standard-therapy regimen during the 56 days were 0.18 (95% credible interval=0.13-0.23) versus 0.15 (95% credible interval=0.08-0.21) log10 cfu/mL/day, compared with 0.16 (95% credible interval=0.13-0.18) versus 0.11 (95% credible interval=0.09-0.13) log10 cfu/mL/day in the Phase II clinical trial, respectively. Using time-to-extinction and Latin hypercube sampling modelling, the expected percentages of patients in which the PaMZ regimen would achieve sterilization were 40.37% (95% credible interval=39.1-41.34) and 72.30% (95% credible interval=71.41-73.17) at 3 and 4 months duration of therapy, respectively, versus 93.67% (95% credible interval=93.18-94.13) at 6 months for standard therapy. CONCLUSIONS: The kill rates of the PaMZ regimen were predicted to be insufficient to achieve cure in less than 6 months in most patients.


Assuntos
Moxifloxacina/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Nitroimidazóis/uso terapêutico , Pirazinamida/uso terapêutico , Tuberculose/tratamento farmacológico , Antituberculosos/uso terapêutico , Quimioterapia Combinada , Humanos , Matemática
13.
J Infect Dis ; 219(6): 975-985, 2019 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-30597040

RESUMO

Drug-resistant tuberculosis represents a global emergency, requiring new drugs. We found that minocycline was highly potent in laboratory strains of Mycobacterium tuberculosis and that 30 drug-susceptible and multidrug/extensively drug-resistant clinical strains were susceptible to clinically achievable concentrations. In the hollow fiber system model, lung concentration-time profiles of 7 mg/kg/day human-equivalent minocycline dose achieved bacterial kill rates equivalent to those of first-line antituberculosis agents. Minocycline killed extracellular bacilli directly. Minocycline also killed intracellular bacilli indirectly, via concentration-dependent granzyme A-driven apoptosis. Moreover, minocycline demonstrated dose-dependent antiinflammatory activity and downregulation of extracellular matrix-based remodeling pathways and, thus, could protect patients from tuberculosis immunopathology. In RNA sequencing of repetitive samples from the hollow fiber system and in independent protein abundance experiments, minocycline demonstrated dose-dependent inhibition of sonic hedgehog-patched-gli signaling. These findings have implications for improved lung remodeling and for dual immunomodulation and direct microbial kill-based treatment shortening regimens for drug-susceptible and drug-resistant latent and active M. tuberculosis infection.


Assuntos
Antituberculosos/farmacologia , Minociclina/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Granzimas/metabolismo , Proteínas Hedgehog , Humanos , Testes de Sensibilidade Microbiana , Transdução de Sinais , Células THP-1 , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/imunologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
14.
Transpl Immunol ; 83: 102009, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38325525

RESUMO

BACKGROUND: Extended-release tacrolimus for prophylaxis of allograft rejection in heart transplant (HT) recipients is currently not FDA-approved. One such extended-release formulation of tacrolimus known as LCPT allows once-daily dosing and improves bioavailability compared to immediate-release (IR-) tacrolimus. We compared long-term efficacy and safety of LCPT to IR-tacrolimus applied de novo in adult OHT recipients. METHODS: 25 prospective recipients on LCPT at our center from 2017 to 2019 were matched 1:2 with historical control recipients treated with IR-tacrolimus based on age, gender, and baseline creatinine. The primary composite outcome of death, acute cellular rejection, and/or new graft dysfunction within 3 years following transplant was compared between groups using non-inferiority analysis. RESULTS: LCPT demonstrated non-inferiority to IR-tacrolimus, with a primary outcome risk reduction of 16% (90%CI, -37%, -1%, non-inferiority p = 0.002) up to 3 years following heart transplant. Up to 3-years post-transplant, 14 patients remained on once-daily LCPT and 10 patients were switched to IR-tacrolimus due to lack of insurance coverage. There were no significant differences in the rate of chronic kidney disease requiring dialysis, cytomegalovirus requiring treatment, cardiac allograft vasculopathy, and malignancy within 3 years following transplant. CONCLUSION: LCPT is non-inferior in efficacy to IR-tacrolimus in heart transplantation with a similar safety profile. Narrowly-constrained FDA labels specific to kidney transplant remain a barrier to consistent access to many immunosuppressant medications for recipients of non-kidney solid organs. We recommend the FDA consider developing facile pathways for expanding the approved label of extended-release tacrolimus formulations to heart transplant recipients.


Assuntos
Transplante de Coração , Tacrolimo , Adulto , Humanos , Tacrolimo/uso terapêutico , Imunossupressores/uso terapêutico , Diálise Renal , Rejeição de Enxerto/tratamento farmacológico , Comprimidos , Preparações de Ação Retardada
15.
Proc (Bayl Univ Med Cent) ; 37(2): 205-209, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38343487

RESUMO

Background: Conduction abnormality requiring the implantation of a permanent pacemaker (PPM) is a well-known and clinically important complication of transcatheter aortic valve replacement (TAVR). However, PPM implantation may result in lead-associated tricuspid valve regurgitation (TR). This study sought to determine the incidence and progression of TR following PPM implantation after TAVR. Methods: This was a retrospective review of all echocardiograms of patients who underwent PPM following TAVR at the Baylor Scott & White hospitals from 2012 to 2021. The primary endpoint was TR progression at 30 days and 1 year. A subanalysis comparing the change in TR progression between small and large TAVR devices was also conducted. Secondary outcomes included all-cause death at 30 days and 1 year. Results: Out of the 2744 patients who underwent TAVR between April 2012 and August 2021, 177 patients (6.5%) subsequently received a new PPM. There was a statistically significant progression of TR at 1-year follow-up (McNemar's P value = 0.02). TR progression rates were comparable between the small and large valve groups at 1-year follow-up (4% vs 11%, P = 0.09, respectively). Conclusion: In this single healthcare system study, we demonstrated a significant progression of TR in patients with PPM post TAVR at 1 year.

16.
Transpl Immunol ; 81: 101924, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37648034

RESUMO

PURPOSE: Little is known about clinical decision making among discordant findings concerning for rejection with endomyocardial biopsy (EMBx) and Molecular Microscope Diagnostic System (MMDx) in patients following heart transplantation. METHODS: Two hundred and twenty-eight corresponding EMBx and MMDx specimens from 135 adult heart transplant patients were retrospectively reviewed. Rejection was classified as t-cell mediated rejection ≥2R and/or antibody mediated rejection ≥1. Clinical decision making among concordant and discordant cases of EMBx and MMDx results were reviewed. RESULTS: Patient characteristics were comparable between concordant and discordant patient groups (median age 60 yrs., 76% male, and 71% White). A total of 167/228 specimens (73%) were concordant for no rejection with 98% agreement in clinical decision making and 25/228 (11%) concordant for rejection with 64% agreement in clinical decision making. Among the 36/228 (16%) discordant samples, clinical decision-making agreed on treatment for rejection in five of the MMDx samples and three of the EMBx samples. CONCLUSIONS: MMDx can be an additional tool to diagnose rejection not detected by the traditional EMBx and influence clinical decision making in guiding appropriate treatment. Ongoing investigation into the clinical utility of MMDx is warranted to determine the significance of discordant findings among diagnostic modalities when assessing for rejection.


Assuntos
Transplante de Coração , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Biópsia , Raciocínio Clínico , Rejeição de Enxerto , Miocárdio/patologia
17.
World Neurosurg ; 175: e780-e789, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37061032

RESUMO

BACKGROUND: The rate of complications remains significant after craniotomy for supratentorial primary malignant brain tumors despite recent advances. OBJECTIVE: The goal of this study is to characterize factors associated with these complications. METHODS: Data were extracted from the National Surgical Quality Improvement Program database from 2016 to 2019. Patients who underwent a craniotomy for resection of supratentorial primary malignant brain tumors were included. Covariates included demographics/comorbidities, preoperative laboratory values, American Society of Anesthesiologists (ASA) classification, operative time, and postoperative complications. Multivariable logistic regression with backward and forward selection was used to evaluate independent predictors of death, prolonged hospitalization, postoperative stroke with neurologic deficit (CVA), and unplanned readmission. Predictive fit of the model was evaluated using the area under the receiver operating curve (AUC). RESULTS: Of 8965 included cases, the 30-day postoperative risks were 1.9% for CVA, 10.1% for unplanned readmission, 1.2% for prolonged hospitalization, and 2.4% for death. Age, ASA category, disseminated cancer, preoperative functional dependence, and postoperative respiratory complications were predictors of 30-day mortality (AUC, 0.83; P < 0.001). CVA was best predicted by increased operation time (P < 0.001), age, ASA category, and recent weight loss (AUC, 0.63; P = 0.009). Prolonged hospitalization was predicted by nonelective surgery status, time from admission to surgery, reintubation, and postoperative sepsis (AUC, 0.78; P < 0.001). Unplanned readmission was predicted by chronic steroid use, postoperative thrombotic complications after surgery, organ/space surgical site infection, deep vein thrombosis, postoperative systemic sepsis, and septic shock (AUC, 0.68; P < 0.001). CONCLUSIONS: Our study identifies predictors of major 30-day complications after craniotomy for this subset of patients with brain tumor.


Assuntos
Neoplasias Encefálicas , Sepse , Humanos , Adulto , Melhoria de Qualidade , Craniotomia/efeitos adversos , Infecção da Ferida Cirúrgica/cirurgia , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/complicações , Sepse/complicações , Readmissão do Paciente , Fatores de Risco , Complicações Pós-Operatórias/etiologia
18.
Transplantation ; 107(11): e305-e317, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37291721

RESUMO

BACKGROUND: Bioimpedance spectroscopy yields measurements of fat-free mass, fat mass, phase angle, and other measures. Bioimpedance spectroscopy has been validated as a preoperative assessment tool in cardiac surgical studies, in which low phase angle predicted morbidity and mortality. No studies have evaluated bioimpedance spectroscopy following heart transplantation. METHODS: We evaluated body composition, nutrition status (Subjective Global Assessment, body mass index, midarm muscle circumference, and triceps skinfolds), and functional status (handgrip strength and 6-min walk test) in 60 adults. Body composition measurements via a 256-frequency bioimpedance spectroscopy device included fat and fat-free mass as well as phase angle calculated at 50 kHz. Testing was completed at baseline and 1, 3, 6, and 12 mo following heart transplantation. Mortality and hospital readmissions were analyzed. RESULTS: Phase angle and fat mass increased while fat-free mass decreased; grip strength and 6-min walk test improved after transplantation (all P < 0.001). Improvement in phase angle in the first month postoperatively was associated with reduced risk of readmission. Low perioperative and 1-mo phase angles were associated with prolonged posttransplant length of stay (median: 13 versus 10 d, P = 0.03), increased infection-related readmissions (40% versus 5%, P = 0.001), and increased 4-y mortality (30% versus 5%, P = 0.01). CONCLUSIONS: Phase angle, grip strength, and 6-min walk test distance improved after heart transplantation. Low phase angle appears to be associated with suboptimal outcomes and may be a feasible and affordable method to predict outcomes. Further research should ascertain whether preoperative phase angle can predict outcomes.

19.
JACC Case Rep ; 16: 101877, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37396326

RESUMO

Little is known about the development of human leukocyte antigen antibodies with use of the temporary transvalvular pump 5.5 mechanical circulatory support device. This case reports a patient who developed de novo antibodies prior to his heart transplantation and remains free of any episodes of rejection post transplantation to date. (Level of Difficulty: Advanced.).

20.
Am J Cardiol ; 191: 8-13, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36621055

RESUMO

Untreated sleep disorders form a risk of coronary artery disease, hypertension, obesity, and diabetes mellitus. Access to polysomnography is limited, especially during the COVID-19 pandemic, with home sleep apnea testing (HSAT) being a potentially viable alternative. We describe an HSAT protocol in patients with advanced heart failure (HF). In a single-center, observational analysis between 2019 and 2021 in patients with advanced HF and heart transplant (HT), 135 screened positive on the STOP-Bang sleep survey and underwent a validated HSAT (WatchPAT, ZOLL-Itamar). HSAT was successful in 123 patients (97.6%), of whom 112 (91.1%; 84 HF and 28 HT) tested positive for sleep apnea. A total of 91% of sleep apnea cases were obstructive, and 63% were moderate to severe. Multivariable linear regression showed that the apnea hypopnea index was 34% lower in the HT group than in the HF group (p = 0.046) after adjusting for gender, and that this effect persisted in White patients but not among African-Americans. Patient characteristics were similar between groups, with coronary artery disease, diabetes mellitus, and hypertension as the most prevalent co-morbidities. In conclusion, sleep apnea remains prevalent in patients with HF with a high co-morbidity burden. HSAT is a feasible and effective tool for screening and diagnosis in this population.


Assuntos
COVID-19 , Doença da Artéria Coronariana , Insuficiência Cardíaca , Hipertensão , Síndromes da Apneia do Sono , Apneia Obstrutiva do Sono , Humanos , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Pandemias , COVID-19/complicações , COVID-19/epidemiologia , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Sono , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia
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