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1.
Am J Transplant ; 23(12): 1980-1989, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37748554

RESUMEN

Older compatible living donor kidney transplant (CLDKT) recipients have higher mortality and death-censored graft failure (DCGF) compared to younger recipients. These risks may be amplified in older incompatible living donor kidney transplant (ILDKT) recipients who undergo desensitization and intense immunosuppression. In a 25-center cohort of ILDKT recipients transplanted between September 24, 1997, and December 15, 2016, we compared mortality, DCGF, delayed graft function (DGF), acute rejection (AR), and length of stay (LOS) between 234 older (age ≥60 years) and 1172 younger (age 18-59 years) recipients. To investigate whether the impact of age was different for ILDKT recipients compared to 17 542 CLDKT recipients, we used an interaction term to determine whether the relationship between posttransplant outcomes and transplant type (ILDKT vs CLDKT) was modified by age. Overall, older recipients had higher mortality (hazard ratio: 1.632.072.65, P < .001), lower DCGF (hazard ratio: 0.360.530.77, P = .001), and AR (odds ratio: 0.390.540.74, P < .001), and similar DGF (odds ratio: 0.461.032.33, P = .9) and LOS (incidence rate ratio: 0.880.981.10, P = 0.8) compared to younger recipients. The impact of age on mortality (interaction P = .052), DCGF (interaction P = .7), AR interaction P = .2), DGF (interaction P = .9), and LOS (interaction P = .5) were similar in ILDKT and CLDKT recipients. Age alone should not preclude eligibility for ILDKT.


Asunto(s)
Trasplante de Riñón , Humanos , Anciano , Persona de Mediana Edad , Adolescente , Adulto Joven , Adulto , Trasplante de Riñón/efectos adversos , Donadores Vivos , Supervivencia de Injerto , Rechazo de Injerto/etiología , Antígenos HLA , Factores de Riesgo
2.
Biochem Biophys Res Commun ; 686: 149200, 2023 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-37926045

RESUMEN

Stem/progenitor cell therapy is a promising treatment option for patients with type 1 diabetes (T1D) a disease characterized by autoimmune destruction of pancreatic ß cells. Actively injecting cells into an organ is one option for cell delivery, but in the pancreas, this contributes to acute inflammation and pancreatitis. We employed a patch grafting approach to transplant biliary tree stem cells/progenitor cells (BTSC) onto the surface of the pancreas in diabetic mice. The cells engraft and differentiate into ß-like cells reversing hyperglycemia during a four-month period of observation. In addition, C-peptide and insulin gradually increase in blood circulation without detectable adverse effects during this period. Moreover, the patch graft transplant promoted the proliferation and differentiation of pancreatic ß-like cells with co-expression of the ß cell biomarker. CONCLUSION: BTSC transplantation can effectively attenuate T1D over a four-month period that is vital important for clinical applications.


Asunto(s)
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Células Secretoras de Insulina , Humanos , Ratones , Animales , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Experimental/metabolismo , Páncreas/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Diferenciación Celular
3.
Clin Transplant ; 37(3): e14878, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36507574

RESUMEN

BACKGROUND: Several studies show an increase in complications, both cardiac and non-cardiac, and a higher mortality in patients with preexisting cardiac disease when they undergo elective surgery. Due to the high incidence of cardiac dysfunction in patients with concomitant chronic kidney disease, we wanted to determine if the same negative impact is demonstrated in patients undergoing kidney transplantation. METHODS: A retrospective analysis was done on 582 patients who underwent kidney transplant from a single transplant center between 2014 and 2019. Participants for this study were divided into two groups based on cardiac ejection fraction: normal EF (≥40%) (n = 540) and low EF (<40%) (n = 33); exclusion criteria included patients undergoing multi-organ transplants (n = 9). Characteristics and outcomes of patients were compared before and after transplant using chi-square tests for categorical measures, and either Kruskal-Wallis or paired Student's t tests for continuous measures. Overall survival (OS) between groups was assessed using the Kaplan-Meier test. We compared outcomes between the normal EF and low EF groups using logistic regression in raw data, and propensity score matched sample and inverse-probability-weighting to mitigate selection bias. RESULTS: There was no significant difference in survival between patients in the low EF and normal EF groups (p = .33). Among patients with low EF, mean EF after transplant significantly improved (mean: 55.83% ± 5.75%) compared to mean EF before transplant (38.28% ± 7.35%), (p = < .0001). Of the patients with a low EF before transplant, 1 in 5 had a history of CAD, compared to only 1 in 10 among those patients with a normal EF, p = .0657. Post-transplant complications were comparable between the groups. CONCLUSION: Patients undergoing kidney transplantation with a low ejection fraction do not demonstrate an increased incidence of morbidity or mortality in the peri- and post-transplant follow-up compared with patients with a normal ejection fraction. Cardiac events post-transplantation is also comparable between the two groups. Of note, patients with a low EF have a significantly improved EF after kidney transplant which is likely a function of improvement in their physiologic state after the kidney transplant.


Asunto(s)
Cardiopatías , Trasplante de Riñón , Insuficiencia Renal Crónica , Humanos , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Cardiopatías/etiología , Morbilidad , Insuficiencia Renal Crónica/etiología , Resultado del Tratamiento
4.
Clin Transplant ; 36(5): e14609, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35137467

RESUMEN

INTRODUCTION: Aim was to study the early impact of acuity circle-based allocation implementation system on liver transplantation for hepatocellular carcinoma (HCC) patients. METHODS: We assessed characteristics of HCC and non-HCC deceased donor orthotopic liver transplants (OLT) in the year before (2/2019-2/2020) and after (3/2020-2/2021) introduction of the acuity circle policy using the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) database. RESULTS: Total OLTs reduced from 6699 in the preacuity circle era to 6660 in the postacuity circle era (-.6%); this decrease is mostly driven by a decrease in HCC transplants (1529 to 1351; -11.6%). Six out of 11 regions had a reduction in the absolute number and percentage of HCC transplants with significant reductions in regions 2 (-37.8%, p < .001) and 4 (-28.3%, p = .001). DISCUSSION: The introduction of median model for end-stage liver disease (MELD) at transplant minus 3 (MMaT-3) exception points, has created differential opportunities for HCC patients, in low-MELD as opposed to high-MELD areas, despite having the same disease. This effect has become more prominent following the implementation of acuity circle-based allocation system. Ongoing investigation of these trends is needed to ensure that HCC patients are not disparately disadvantaged due to their location.


Asunto(s)
Carcinoma Hepatocelular , Enfermedad Hepática en Estado Terminal , Neoplasias Hepáticas , Trasplante de Hígado , Obtención de Tejidos y Órganos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Índice de Severidad de la Enfermedad , Listas de Espera
5.
Surg Endosc ; 36(10): 7569-7576, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35348874

RESUMEN

BACKGROUND: Laparoscopic-assisted thermal ablation has been used successfully to treat early hepatocellular carcinoma (HCC) tumors, defined as < 3 cm in diameter. This approach allows for ablation of tumors located in areas of the liver that are otherwise inaccessible for a percutaneous approach. Thermal ablation of exophytic tumors remains controversial due to a reported increased risk of tumor seeding of the abdominal cavity and incomplete ablation. METHODS: This cohort study consisted of 663 HCC tumors treated with thermal ablation at a single, quaternary academic medical center between 2/2001 and 1/2021. Post treatment, patients were followed at a defined interval schedule beginning at one month post treatment, then every 3 months for 2 years, every 6 months in year 3, followed by yearly studies. Patients' medical records were reviewed for three years post ablation for evidence of complete ablation and intra-abdominal dissemination of disease. RESULTS: 326 patient records met the inclusion criteria. Comparing the exophytic and non-exophytic groups, there were statistically significant differences in etiology of liver disease (p = 0.048) and TNM stage (p = 0.03), as well as a higher rate of incomplete ablation in the non-exophytic group (10.2% vs 3.3%; p = 0.045). Otherwise, there were no statistically significant differences in baseline characteristics, tumor characteristics, or use of thermal ablation technology. Rates of intra-abdominal dissemination of HCC were low in both groups: 1.1% (n = 1) in the exophytic group and 1.7% (n = 4) in the non-exophytic group. There was no significant difference in intra-abdominal dissemination of HCC between the groups (p > 0.99, RR = 0.66; 95% CI 0.07-5.79). Additionally, no differences were seen in dissemination between microwave ablation and radiofrequency ablation (p > 0.99). CONCLUSION: This study demonstrates that laparoscopic-assisted thermal ablation of small, exophytic tumors is safe and does not increase the risk for disseminated intra-abdominal HCC disease.


Asunto(s)
Cavidad Abdominal , Carcinoma Hepatocelular , Ablación por Catéter , Laparoscopía , Neoplasias Hepáticas , Cavidad Abdominal/patología , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Ablación por Catéter/efectos adversos , Estudios de Cohortes , Humanos , Laparoscopía/efectos adversos , Neoplasias Hepáticas/patología , Resultado del Tratamiento
6.
Am J Transplant ; 21(4): 1612-1621, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33370502

RESUMEN

Incompatible living donor kidney transplant recipients (ILDKTr) have pre-existing donor-specific antibody (DSA) that, despite desensitization, may persist or reappear with resulting consequences, including delayed graft function (DGF) and acute rejection (AR). To quantify the risk of DGF and AR in ILDKT and downstream effects, we compared 1406 ILDKTr to 17 542 compatible LDKT recipients (CLDKTr) using a 25-center cohort with novel SRTR linkage. We characterized DSA strength as positive Luminex, negative flow crossmatch (PLNF); positive flow, negative cytotoxic crossmatch (PFNC); or positive cytotoxic crossmatch (PCC). DGF occurred in 3.1% of CLDKT, 3.5% of PLNF, 5.7% of PFNC, and 7.6% of PCC recipients, which translated to higher DGF for PCC recipients (aOR = 1.03 1.682.72 ). However, the impact of DGF on mortality and DCGF risk was no higher for ILDKT than CLDKT (p interaction > .1). AR developed in 8.4% of CLDKT, 18.2% of PLNF, 21.3% of PFNC, and 21.7% of PCC recipients, which translated to higher AR (aOR PLNF = 1.45 2.093.02 ; PFNC = 1.67 2.403.46 ; PCC = 1.48 2.243.37 ). Although the impact of AR on mortality was no higher for ILDKT than CLDKT (p interaction = .1), its impact on DCGF risk was less consequential for ILDKT (aHR = 1.34 1.621.95 ) than CLDKT (aHR = 1.96 2.292.67 ) (p interaction = .004). Providers should consider these risks during preoperative counseling, and strategies to mitigate them should be considered.


Asunto(s)
Trasplante de Riñón , Funcionamiento Retardado del Injerto/etiología , Rechazo de Injerto/etiología , Supervivencia de Injerto , Humanos , Trasplante de Riñón/efectos adversos , Donadores Vivos , Estudios Retrospectivos , Factores de Riesgo
7.
Transpl Infect Dis ; 23(3): e13562, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33432726

RESUMEN

Donor-derived (DD) herpes simplex virus (HSV) hepatitis in solid organ transplant (SOT) recipients is extremely uncommon but carries a high mortality rate. The diagnosis is challenging due to the non-specific presentation and lack of clinical suspicion. We report a case of DDHSV hepatitis in a HSV2 pre-transplant seronegative kidney recipient who received the organ from a HSV2 seropositive donor. The case is highlighted by a few unusual features, namely severe thrombocytopenia and the development of cutaneous, oral and esophageal HSV lesions several weeks after symptom onset while recovering on appropriate treatment. A review of nine proven and probable DDHSV hepatitis cases (including eight previously published ones) showed that fever is a common presenting feature while gastrointestinal symptoms and cutaneous manifestations are uncommon. The symptoms almost always occurred within 2 weeks of transplant. Six out of the nine DDHSV hepatitis patients, including five patients who were on appropriate treatment, died within a month after transplant.


Asunto(s)
Hepatitis Viral Humana , Herpes Simple , Trasplante de Riñón , Humanos , Simplexvirus , Donantes de Tejidos
8.
Liver Transpl ; 26(2): 203-214, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31677319

RESUMEN

Single hepatocellular carcinoma (HCC) tumors can be successfully eradicated with thermal ablation (TA). We assessed the validity of the Liver Imaging Reporting and Data System Treatment Response (LR-TR) criteria with a retrospective analysis of a single-center database of patients with small HCC tumors (<3 cm in diameter) who underwent both laparoscopic TA and liver transplantation (LT) from 2004 to 2018. Postablation MRIs were assigned LR-TR categories (nonviable, equivocal, and viable) for ablated lesions and Liver Imaging Reporting and Data System (LI-RADS) categories (probable or definite HCC) for untreated lesions. Interpretations were compared with the histopathology of the post-LT explanted liver. There were 45 patients with 81 tumors (59 ablated and 22 untreated; mean size, 2.2 cm), and 23 (39%) of the ablated tumors had viable HCC on histopathology. The sensitivity/specificity of LR-TR categories (nonviable/equivocal versus viable) of ablated tumors was 30%/99%, with a positive predictive value (PPV)/negative predictive value (NPV) of 93%/69%. The sensitivity varied with residual tumor size. The sensitivity/specificity of LI-RADS 4 and 5 diagnostic criteria at detecting new HCC was 65%/94%, respectively, with a PPV/NPV of 85%/84%. The interrater reliability (IRR) was high for LR-TR categories (90% agreement, Cohen's ĸ = 0.75) and for LI-RADS LR-4 and LR-5 diagnostic categories (91% agreement, Cohen's ĸ = 0.80). In patients with HCC <3 cm in diameter, LR-TR criteria after TA had high IRR but low sensitivity, suggesting that the LR-TR categories are precise but inaccurate. The low sensitivity may be secondary to TA's disruption in the local blood flow of the tissue, which could affect the arterial enhancement phase on MRI. Additional investigation and new technologies may be necessary to improve imaging after ablation.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/cirugía , Medios de Contraste , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/efectos adversos , Imagen por Resonancia Magnética , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad
9.
Gene Ther ; 26(12): 504-514, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31570819

RESUMEN

Although therapeutic outcomes have been achieved in hemophilia patients after delivery of clotting factor genes to the liver using adeno-associated virus (AAV) vectors, it is well known that the preclinical results generated from hemophilia animal models have not been directly predictive of successful translation in humans. To address this discrepancy humanized mouse models have recently been used to predict AAV transduction efficiency for human hepatocytes. In this study we evaluated AAV vector transduction from several serotypes in human liver hepatocytes xenografted into chimeric mice. After systemic administration of AAV vectors encoding a GFP transgene in humanized mice, the liver was harvested for either immunohistochemistry staining or flow cytometry assay for AAV human hepatocyte transduction analysis. We observed that AAV7 consistently transduced human hepatocytes more efficiently than other serotypes in both immunohistochemistry assay and flow cytometry analysis. To better assess the future application of AAV7 for systemic administration in the treatment of hemophilia or other liver diseases, we analyzed the prevalence of neutralizing antibodies (NAbs) to AAV7 in sera from healthy subjects and patients with hemophilia. In the general population, the prevalence of NAbs to AAV7 was lower than that of AAV2 or AAV3B. However, a higher prevalence of AAV7 NAbs was found in patients with hemophilia. In summary, results from this study suggest that AAV7 vectors should be considered as an effective vehicle for human liver targeting in future clinical trials.


Asunto(s)
Dependovirus/fisiología , Vectores Genéticos/administración & dosificación , Proteínas Fluorescentes Verdes/genética , Hemofilia A/inmunología , Hepatocitos/virología , Animales , Anticuerpos Neutralizantes/metabolismo , Estudios de Casos y Controles , Línea Celular , Dependovirus/inmunología , Femenino , Proteínas Fluorescentes Verdes/metabolismo , Células HEK293 , Hepatocitos/citología , Humanos , Ratones , Serogrupo , Transducción Genética
10.
N Engl J Med ; 374(10): 940-50, 2016 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-26962729

RESUMEN

BACKGROUND: A report from a high-volume single center indicated a survival benefit of receiving a kidney transplant from an HLA-incompatible live donor as compared with remaining on the waiting list, whether or not a kidney from a deceased donor was received. The generalizability of that finding is unclear. METHODS: In a 22-center study, we estimated the survival benefit for 1025 recipients of kidney transplants from HLA-incompatible live donors who were matched with controls who remained on the waiting list or received a transplant from a deceased donor (waiting-list-or-transplant control group) and controls who remained on the waiting list but did not receive a transplant (waiting-list-only control group). We analyzed the data with and without patients from the highest-volume center in the study. RESULTS: Recipients of kidney transplants from incompatible live donors had a higher survival rate than either control group at 1 year (95.0%, vs. 94.0% for the waiting-list-or-transplant control group and 89.6% for the waiting-list-only control group), 3 years (91.7% vs. 83.6% and 72.7%, respectively), 5 years (86.0% vs. 74.4% and 59.2%), and 8 years (76.5% vs. 62.9% and 43.9%) (P<0.001 for all comparisons with the two control groups). The survival benefit was significant at 8 years across all levels of donor-specific antibody: 89.2% for recipients of kidney transplants from incompatible live donors who had a positive Luminex assay for anti-HLA antibody but a negative flow-cytometric cross-match versus 65.0% for the waiting-list-or-transplant control group and 47.1% for the waiting-list-only control group; 76.3% for recipients with a positive flow-cytometric cross-match but a negative cytotoxic cross-match versus 63.3% and 43.0% in the two control groups, respectively; and 71.0% for recipients with a positive cytotoxic cross-match versus 61.5% and 43.7%, respectively. The findings did not change when patients from the highest-volume center were excluded. CONCLUSIONS: This multicenter study validated single-center evidence that patients who received kidney transplants from HLA-incompatible live donors had a substantial survival benefit as compared with patients who did not undergo transplantation and those who waited for transplants from deceased donors. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases.).


Asunto(s)
Histocompatibilidad , Trasplante de Riñón , Donadores Vivos , Supervivencia de Injerto , Antígenos HLA , Prueba de Histocompatibilidad , Humanos , Trasplante de Riñón/mortalidad , Análisis de Supervivencia , Obtención de Tejidos y Órganos , Listas de Espera
11.
Liver Transpl ; 25(5): 734-740, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30693668

RESUMEN

Marijuana is legalized for either medical or recreational use in over half of the states in the United States and in Canada, but many transplant centers will not list patients who are using marijuana. However, the effect of marijuana on transplant outcomes remains unclear. Thus, we performed a retrospective analysis of all adult (≥18 years old) liver transplant patients treated at our center between 2007 and 2017. Patients were grouped according to their marijuana use and tobacco smoking status. We also evaluated tobacco smoking status for the comparative evaluation. Posttransplant morbidity, mortality, and graft survival were evaluated. In total, 316 patients were included: 171 (54%) patients were tobacco smokers (70 current; 101 former), 81 (26%) patients were marijuana smokers (13 current; 68 former), and 64 (20#x0025;) patients were both marijuana and tobacco smokers. A total of 136 (43%) reported never smoking marijuana or tobacco. After adjustment, current tobacco users were over 3 times as likely to die within 5 years compared with never users (hazard ratio [HR], 3.25; 95% confidence interval [CI], 1.63-6.46; P < 0.001), but no difference was seen between current/former and never marijuana users (HR, 0.52; 95% CI, 0.26-1.04; P = 0.06). No significant differences in inpatient respiratory complications, reintubation, or >24-hour intubation was seen. Overall, pretransplant marijuana use, past or current, does not appear to impact liver transplant outcomes, though tobacco smoking remains detrimental.


Asunto(s)
Enfermedad Hepática en Estado Terminal/mortalidad , Trasplante de Hígado/efectos adversos , Fumar Marihuana/efectos adversos , Fumar Tabaco/efectos adversos , Receptores de Trasplantes/estadística & datos numéricos , Adolescente , Adulto , Enfermedad Hepática en Estado Terminal/diagnóstico , Enfermedad Hepática en Estado Terminal/cirugía , Femenino , Supervivencia de Injerto , Humanos , Trasplante de Hígado/estadística & datos numéricos , Masculino , Fumar Marihuana/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Fumar Tabaco/epidemiología , Estados Unidos/epidemiología , Adulto Joven
12.
Clin Transplant ; 33(6): e13554, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30927288

RESUMEN

BACKGROUND: Post-transplant diabetes mellitus (PTDM) is common after liver transplantation (LT). Yet, how PTDM relates to graft outcomes and survival needs elucidation as more individuals are transplanted for nonalcoholic fatty liver disease (NAFLD). METHODS: This single-center, retrospective study of adult LT recipients (2003-2016) identified PTDM incidence and associations with graft steatosis, rejection, and post-LT patient survival. Multivariable analysis investigated predictors of PTDM. Kaplan-Meier curves depicted patient survival 5 years post-LT. RESULTS: Among 415 adult LT recipients, 23% had pre-LT DM and 13% were transplanted for NAFLD. PTDM incidence was 34.7%, 46.9%, and 56.2% and overall survival was 90%, 80.9%, and 71.7% at 1, 3, and 5 years, respectively. Over a third of non-NAFLD patients developed PTDM. Half of PTDM cases developed by 6 months and 75% by 12 months. The PTDM group had more rejection episodes compared to no PTDM (31.9% vs 21.8%, P = 0.055), with trends toward worse patient survival 5 years post-LT (log-rank test P = 0.254). Age was the only significant predictor of PTDM. CONCLUSIONS: Post-transplant diabetes mellitus occurs rapidly in the post-LT period and is a significant problem for both NAFLD and non-NAFLD LT recipients. Age is a significant risk factor for PTDM. Outcomes trended toward increased rejection and worse survival among PTDM individuals, suggesting the benefit of early strategies targeting glucose control.


Asunto(s)
Diabetes Mellitus/mortalidad , Rechazo de Injerto/mortalidad , Hepatopatías/mortalidad , Trasplante de Hígado/mortalidad , Complicaciones Posoperatorias/mortalidad , Adulto , Diabetes Mellitus/epidemiología , Diabetes Mellitus/fisiopatología , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Incidencia , Hepatopatías/cirugía , Trasplante de Hígado/efectos adversos , Masculino , Persona de Mediana Edad , North Carolina/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/patología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia
13.
Mycopathologia ; 184(1): 155-158, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30062389

RESUMEN

Hepatic mucormycosis is a disease caused by a ubiquitous fungus which is especially important in patients with hematologic malignancies. We present a case of an adult patient with acute myeloid leukemia who developed the infection after undergoing chemotherapy. His successful management was an integrated approach of a minimally invasive surgical resection with anti-fungal therapy. We describe the management of this patient and a review of the literature.


Asunto(s)
Antifúngicos/administración & dosificación , Leucemia Mieloide Aguda/complicaciones , Hepatopatías/diagnóstico , Hepatopatías/terapia , Hígado/cirugía , Mucormicosis/diagnóstico , Mucormicosis/terapia , Adulto , Biopsia , Histocitoquímica , Humanos , Imagen por Resonancia Magnética , Masculino , Microscopía , Radiografía Abdominal , Resultado del Tratamiento
14.
Am J Transplant ; 18(3): 650-658, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28834181

RESUMEN

Thirty percent of kidney transplant recipients are readmitted in the first month posttransplantation. Those with donor-specific antibody requiring desensitization and incompatible live donor kidney transplantation (ILDKT) constitute a unique subpopulation that might be at higher readmission risk. Drawing on a 22-center cohort, 379 ILDKTs with Medicare primary insurance were matched to compatible transplant-matched controls and to waitlist-only matched controls on panel reactive antibody, age, blood group, renal replacement time, prior kidney transplantation, race, gender, diabetes, and transplant date/waitlisting date. Readmission risk was determined using multilevel, mixed-effects Poisson regression. In the first month, ILDKTs had a 1.28-fold higher readmission risk than compatible controls (95% confidence interval [CI] 1.13-1.46; P < .001). Risk peaked at 6-12 months (relative risk [RR] 1.67, 95% CI 1.49-1.87; P < .001), attenuating by 24-36 months (RR 1.24, 95% CI 1.10-1.40; P < .001). ILDKTs had a 5.86-fold higher readmission risk (95% CI 4.96-6.92; P < .001) in the first month compared to waitlist-only controls. At 12-24 (RR 0.85, 95% CI 0.77-0.95; P = .002) and 24-36 months (RR 0.74, 95% CI 0.66-0.84; P < .001), ILDKTs had a lower risk than waitlist-only controls. These findings of ILDKTs having a higher readmission risk than compatible controls, but a lower readmission risk after the first year than waitlist-only controls should be considered in regulatory/payment schemas and planning clinical care.


Asunto(s)
Incompatibilidad de Grupos Sanguíneos/inmunología , Antígenos HLA/inmunología , Fallo Renal Crónico/cirugía , Trasplante de Riñón/métodos , Donadores Vivos/provisión & distribución , Readmisión del Paciente/estadística & datos numéricos , Complicaciones Posoperatorias , Adulto , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Supervivencia de Injerto , Hospitalización/estadística & datos numéricos , Humanos , Isoanticuerpos/sangre , Isoanticuerpos/inmunología , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo
15.
Am J Pathol ; 184(2): 556-71, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24300950

RESUMEN

Accumulating evidence supports that circulating fibrocytes play important roles in angiogenesis. However, the specific role of fibrocytes in angiogenesis and the underlying mechanisms remain unclear. In this study, we found that fibrocytes stabilized newly formed blood vessels in a mouse wound-healing model by inhibiting angiogenesis during the proliferative phase and inhibiting blood vessel regression during the remodeling phase. Fibrocytes also inhibited angiogenesis in a Matrigel mouse model. In vitro study showed that fibrocytes inhibited both the apoptosis and proliferation of vascular endothelial cells (VECs) in a permeable support (Transwell) co-culture system. In a three-dimensional collagen gel, fibrocytes stabilized the VEC tubes by decreasing VEC tube density on stimulation with growth factors and preventing VEC tube regression on withdrawal of growth factors. Further mechanistic investigation revealed that fibrocytes expressed many prosurvival factors that are responsible for the prosurvival effect of fibrocytes on VECs and blood vessels. Fibrocytes also expressed angiogenesis inhibitors, including thrombospondin-1 (THBS1). THBS1 knockdown partially blocked the fibrocyte-induced inhibition of VEC proliferation in the Transwell co-culture system and recovered the fibrocyte-induced decrease of VEC tube density in collagen gel. Purified fibrocytes transfected with THBS1 siRNA partially recovered the fibrocyte-induced inhibition of angiogenesis in both the wound-healing and Matrigel models. In conclusion, our findings reveal that fibrocytes stabilize blood vessels via prosurvival factors and anti-angiogenic factors, including THBS1.


Asunto(s)
Vasos Sanguíneos/patología , Movimiento Celular , Fibroblastos/patología , Neovascularización Fisiológica , Comunicación Paracrina , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Técnicas de Cocultivo , Colágeno/metabolismo , Colágeno/farmacología , Combinación de Medicamentos , Células Endoteliales/patología , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/ultraestructura , Técnicas de Silenciamiento del Gen , Humanos , Laminina/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Modelos Biológicos , Necrosis , Neovascularización Fisiológica/efectos de los fármacos , Comunicación Paracrina/efectos de los fármacos , Proteoglicanos/metabolismo , Trombospondina 1/metabolismo , Cicatrización de Heridas/efectos de los fármacos
16.
Abdom Imaging ; 40(6): 1405-14, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25906343

RESUMEN

PURPOSE: The purpose of the study was to evaluate the feasibility and protocol optimization of whole-body hybrid MR-PET system performed 1-month after post-locoregional thermoablative procedures for hepatocellular carcinomas (HCCs). MATERIALS AND METHODS: Eight patients (6 men and 2 women; mean age, 56.6 ± 5.5 years) with 9 ablated HCCs constituted our study population. Three readers interpreted the studies to determine the presence or absence of residual malignancy. Two readers independently assessed the fused MR-PET images to compare registration accuracy of two types of T2-weighted (triggered T2 half-Fourier acquisition single-shot turbo spin-echo and turbo spin-echo) and T1-weighted [Cartesian and radial 3D gradient echo (GRE)]. Image quality evaluation of both 3D-GRE T1-weighted sequences was evaluated. Kappa statistics were used to measure inter-observer agreement. Non-parametric Kruskal-Wallis and Wilcoxon signed-rank tests were used for qualitative data analysis. RESULTS: Definite residual tumor was observed in 3/9 ablations; two were PET positive. All residual tumors were isovascular on MRI. Radial 3D-GRE demonstrated significantly superior MR-PET subjective co-registration in comparison with the remaining sequences and showed a non-significant trend toward higher image quality scores than Cartesian GRE. CONCLUSION: Whole-body hybrid MR-PET is feasible as a part of 1-month follow-up post-locoregional thermoablative treatment for HCC. Radial 3D-GRE offers improved co-registration with PET data, with overall good image quality.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Ablación por Catéter , Neoplasias Hepáticas/cirugía , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Complicaciones Posoperatorias/diagnóstico , Estudios de Factibilidad , Femenino , Humanos , Hígado/diagnóstico por imagen , Hígado/patología , Hígado/cirugía , Masculino , Persona de Mediana Edad , Imagen Multimodal , Variaciones Dependientes del Observador , Periodo Posoperatorio , Reproducibilidad de los Resultados , Resultado del Tratamiento , Imagen de Cuerpo Entero
17.
Hepatology ; 57(2): 775-84, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22996260

RESUMEN

Cell therapies are potential alternatives to organ transplantation for liver failure or dysfunction but are compromised by inefficient engraftment, cell dispersal to ectopic sites, and emboli formation. Grafting strategies have been devised for transplantation of human hepatic stem cells (hHpSCs) embedded into a mix of soluble signals and extracellular matrix biomaterials (hyaluronans, type III collagen, laminin) found in stem cell niches. The hHpSCs maintain a stable stem cell phenotype under the graft conditions. The grafts were transplanted into the livers of immunocompromised murine hosts with and without carbon tetrachloride treatment to assess the effects of quiescent versus injured liver conditions. Grafted cells remained localized to the livers, resulting in a larger bolus of engrafted cells in the host livers under quiescent conditions and with potential for more rapid expansion under injured liver conditions. By contrast, transplantation by direct injection or via a vascular route resulted in inefficient engraftment and cell dispersal to ectopic sites. Transplantation by grafting is proposed as a preferred strategy for cell therapies for solid organs such as the liver.


Asunto(s)
Hígado/cirugía , Trasplante de Células Madre/métodos , Animales , Intoxicación por Tetracloruro de Carbono/cirugía , Células Cultivadas , Humanos , Ácido Hialurónico/metabolismo , Ácido Hialurónico/uso terapéutico , Hígado/citología , Ratones
18.
Abdom Imaging ; 39(2): 269-82, 2014 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24375021

RESUMEN

PURPOSE: To describe the natural history of liver adenomatosis (LA), including complications and changes in lesion size over time. MATERIALS AND METHODS: Eighteen patients with clinical diagnosis of LA were included. Clinical and biochemical information were collected. The initial and follow-up MR studies were reviewed retrospectively to determine change in lesion size and imaging features. RESULTS: Seventeen patients were women (94.4%). The mean age of the initial MR study was 37.0 years (18-52 years). The median size of the largest lesion was 6.7 cm (range 3.0-13.5 cm). Intratumoral bleeding was detected on MRI in 9 lesions, in 7 patients (38.8%). The median size for hemorrhagic lesions was 7.6 cm (range 4.1-13.5 cm). During the mean follow-up period of 29.4 (range 4-98) months, 10 patients had stable disease (55.6%), and 8 patients had tumor regression (44.4%). Of 8 patients who were followed without intervention, 3 patients (37.5%) had spontaneous regression. No malignant transformation or lesion progression was occurred. CONCLUSION: During an over 2-year follow-up period, the majority of lesions of LA appeared to remain stable or showed tumor regression. Spontaneous tumor regression can be observed in approximately 37% of individuals in the age range of 28-53 years.


Asunto(s)
Adenoma/patología , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética/métodos , Adenoma/terapia , Adolescente , Adulto , Medios de Contraste , Progresión de la Enfermedad , Femenino , Gadolinio DTPA , Humanos , Neoplasias Hepáticas/terapia , Masculino , Meglumina/análogos & derivados , Persona de Mediana Edad , Compuestos Organometálicos , Remisión Espontánea , Estudios Retrospectivos
19.
Surg Innov ; 21(4): 419-26, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24201739

RESUMEN

BACKGROUND: The Explorer Minimally Invasive Liver (MIL) system uses imaging to create a 3-dimensional model of the liver. Intraoperatively, the system displays the position of instruments relative to the virtual liver. A prospective clinical study compared it with intraoperative ultrasound (iUS) in laparoscopic liver ablations. METHODS: Patients undergoing ablations were accrued from 2 clinical sites. During the procedures, probes were positioned in the standard fashion using iUS. The position was synchronously recorded using the Explorer system. The distances from the probe tip to the tumor boundary and center were measured on the ultrasound image and in the corresponding virtual image captured by the Explorer system. RESULTS: Data were obtained on the placement of 47 ablation probes during 27 procedures. The absolute difference between iUS and the Explorer system for the probe tip to tumor boundary distance was 5.5 ± 5.6 mm, not a statistically significant difference. The absolute difference for probe tip to tumor center distance was 8.6 ± 7.0 mm, not statistically different from 5 mm. DISCUSSION: The initial clinical experience with the Explorer MIL system shows a strong correlation with iUS for the positioning of ablation probes. The Explorer MIL system is a promising tool to provide supplemental guidance information during laparoscopic liver ablation procedures.


Asunto(s)
Ablación por Catéter/métodos , Hepatectomía/instrumentación , Laparoscopía/métodos , Cirugía Asistida por Computador/métodos , Ultrasonografía Doppler/métodos , Anciano , Femenino , Estudios de Seguimiento , Hepatectomía/métodos , Humanos , Cuidados Intraoperatorios/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Estudios Prospectivos , Medición de Riesgo , Resultado del Tratamiento
20.
JAMA Netw Open ; 7(2): e240694, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38421644

RESUMEN

Importance: With the increasing prevalence of hepatocellular carcinoma (HCC), ablative therapy is a critical treatment option to achieve a cancer-free state. The anatomic location of the tumor can be a challenge, and select hepatic locations of a tumor require laparoscopic-assisted strategies to safely reach and treat the lesion. Objective: To assess the association of real-time ultrasonography-augmented navigation for HCC ablation with patient survival, operative time, and rate of incomplete ablations. Design, Setting, and Participants: This retrospective case-control study was conducted among a prospectively collected database of more than 750 patients with HCC who were treated with ablation therapy with and without the use of navigation at a single quaternary medical center from June 2011 to January 2021. Data were analyzed from October 2022 through June 2023. Exposure: Real-time ultrasonography-augmented navigation. Main Outcomes and Measures: The primary outcome was rate of incomplete ablations in patients undergoing HCC ablation with vs without navigation. Secondary outcomes included overall survival (OS), progression-free survival (PFS), and operative time. Results: The analytic cohort included 467 patients (mean [SD] age, 62.4 [7.8] years; 355 male [76.0%]; 21 Hispanic [4.5%], 67 non-Hispanic Black [14.5%], and 347 Non-Hispanic White [75.0%] among 463 patients with race and ethnicity data). The most common etiology of liver disease was hepatitis C infection (187 patients with etiology data [40.0%]), and 348 of 458 patients with TMN staging data (76.0%) had TNM stage 1 disease. There were 187 individuals treated with navigation and 280 individuals treated without navigation. Patients who underwent navigation-assisted ablation were more likely to have stage 2 disease based on TNM staging (62 of 183 patients [33.9%] vs 47 of 275 patients [17.1%] with TMN data; P < .002) and had a higher mean (SD) number of lesions (1.3 [0.5] vs 1.2 [0.5] lesions; P = .002) and a longer mean (SD) operation time (113.2 [29.4] vs 109.6 [32.3] minutes; P = .04). Patients who underwent navigation were also more likely to have tumors in segment 8 (59 patients [32.1%] vs 53 of 275 patients with segment data [19.3%] with segment data; P = .005) and less likely to have tumors in segment 4 (20 patients [10.9%] vs 54 patients with segment data [19.6%]; P = .005). Overall mean (SD) time to recurrence after treatment was 10.0 (12.5) months, with similar rates for patients with navigation vs no navigation. There were no differences in incomplete ablation rate (10 patients [9.2%] vs 10 patients [10.5%]; P = .32), OS, or PFS between patients undergoing ablation with and without navigation. Conclusions and Relevance: In this study, use of navigation was associated with comparable outcomes to undergoing ablation without navigation, although patients with navigation had more locally advanced disease. These findings suggest that use of real-time navigation in laparoscopic-assisted ablation of liver cancer should be considered as a useful tool for treating challenging tumors.


Asunto(s)
Carcinoma Hepatocelular , Laparoscopía , Neoplasias Hepáticas , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Hepatocelular/cirugía , Estudios de Casos y Controles , Estudios Retrospectivos , Neoplasias Hepáticas/cirugía
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