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1.
Transpl Int ; 37: 12320, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38357216

RESUMEN

The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90 mg/kg IV x6 doses, n = 13), etanercept (50 mg then 25 mg SQ x 5 doses, n = 14), or standard care (n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2 years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group (p = 0.027). A1AT increased after IAT in all groups (p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2 years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period.


Asunto(s)
Diabetes Mellitus , Trasplante de Islotes Pancreáticos , Humanos , Etanercept/uso terapéutico , Autoinjertos , Trasplante Autólogo , Insulina , Inflamación , Citocinas , ADN , Pancreatectomía , Resultado del Tratamiento
2.
HPB (Oxford) ; 26(5): 664-673, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38368218

RESUMEN

BACKGROUND: Total pancreatectomy with islet autotransplant (TPIAT) can improve quality of life for individuals with pancreatitis but creates health risks including diabetes, exocrine insufficiency, altered intestinal anatomy and function, and asplenia. METHODS: We studied survival and causes of death for 693 patients who underwent TPIAT between 2001 and 2020, using the National Death Index with medical records to ascertain survival after TPIAT, causes of mortality, and risk factors for death. We used Kaplan Meier curves to examine overall survival, and Cox regression and competing-risks methods to determine pre-TPIAT factors associated with all-cause and cause-specific post-TPIAT mortality. RESULTS: Mean age at TPIAT was 33.6 years (SD = 15.1). Overall survival was 93.1% (95% CI 91.2, 95.1%) 5 years after surgery, 85.2% (95% CI 82.0, 88.6%) at 10 years, and 76.2% (95% CI 70.8, 82.3%) at 15 years. Fifty-three of 89 deaths were possibly related to TPIAT; causes included chronic gastrointestinal complications, malnutrition, diabetes, liver failure, and infection/sepsis. In multivariable models, younger age, longer disease duration, and more recent TPIAT were associated with lower mortality. CONCLUSIONS: For patients undergoing TPIAT to treat painful pancreatitis, careful long-term management of comorbidities introduced by TPIAT may reduce risk for common causes of mortality.


Asunto(s)
Causas de Muerte , Trasplante de Islotes Pancreáticos , Pancreatectomía , Humanos , Pancreatectomía/efectos adversos , Pancreatectomía/mortalidad , Femenino , Masculino , Trasplante de Islotes Pancreáticos/efectos adversos , Adulto , Factores de Riesgo , Persona de Mediana Edad , Trasplante Autólogo , Adulto Joven , Estudios Retrospectivos , Medición de Riesgo , Factores de Tiempo , Adolescente , Resultado del Tratamiento , Pancreatitis/mortalidad , Pancreatitis/etiología , Pancreatitis Crónica/cirugía , Pancreatitis Crónica/mortalidad
3.
Pancreatology ; 23(1): 57-64, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36443174

RESUMEN

BACKGROUND: In total pancreatectomy with islet auto-transplantation, successful diabetes outcomes are limited by islet loss from the instant blood mediated inflammatory response. We hypothesized that blockade of the inflammatory response with either etanercept or alpha-1-antitrypsin would improve islet function and insulin independence. METHODS: We randomized 43 participants to receive A1AT (90 mg/kg x 6 doses, n = 13), or etanercept (50 mg then 25 mg x 5 doses, n = 14), or standard care (n = 16), aiming to reduce detrimental effects of innate inflammation on early islet survival. Islet graft function was assessed using mixed meal tolerance testing, intravenous glucose tolerance testing, glucose-potentiated arginine-induced insulin secretion studies, HbA1c, and insulin dose 3 months and 1 year post-TPIAT. RESULTS: We observed the most robust acute insulin response (AIRglu) and acute C-peptide response to glucose (ACRglu) at 3 months after TPIAT in the etanercept-treated group (p ≤ 0.02), but no differences in other efficacy measures. The groups did not differ overall at 1 year but when adjusted by sex, there was a trend towards a sex-specific treatment effect in females (AIRglu p = 0.05, ACRglu p = 0.06), with insulin secretion measures highest in A1AT-treated females. CONCLUSION: Our randomized trial supports a potential role for etanercept in optimizing early islet engraftment but it is unclear whether this benefit is sustained. Further studies are needed to evaluate possible sex-specific responses to either treatment. CLINICAL TRIAL NOTATION: This study was performed under an Investigational New Drug Application (IND #119828) from the Food and Drug Administration and was registered on clinicaltrials.gov (NCT#02713997).


Asunto(s)
Diabetes Mellitus , Trasplante de Islotes Pancreáticos , Pancreatitis Crónica , Femenino , Humanos , Masculino , Diabetes Mellitus/cirugía , Etanercept/farmacología , Etanercept/uso terapéutico , Glucosa , Insulina/uso terapéutico , Pancreatectomía , Pancreatitis Crónica/cirugía , Proyectos Piloto , Trasplante Autólogo , Resultado del Tratamiento , Timalfasina
4.
Cryobiology ; 110: 1-7, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36640932

RESUMEN

Transplantation has substituted dysfunctional organs with healthy organs from donors to significantly lower morbidity and mortality associated with end-stage organ disease. Since the advent of transplantation, the promise of functional replacement has attracted an exponential mismatch between organ supply and demand. Theoretical proposals to counter the increasing needs have either been to create a source through genetic engineering of porcine donors for xenotransplantation (with more potent immunosuppression protocols) or recreate one's organ in a pig using interspecies blastocyst complementation for exogenic organ transplantation (without immunosuppression). Another promising avenue has been organ banking through cryopreservation for transplantation. Although ice free preservation and acceptable early function following rewarming is critical for success in transplantation, the immunological response that predominantly defines short- and long-term graft survival has failed to captivate attention to date. It is well sorted that thermal and metabolic stress incurred at 4 °C during recovery and reperfusion of organs for clinical transplantation has varying impact on graft survival. Considering the magnitude of cellular imbalance and injury at sub-zero/ultralow temperatures in addition to the chemical toxicity of cryoprotective agents (CPA), it is essential to assess and address the immunological response associated following transplantation to maximize the success of cryopreservation.


Asunto(s)
Criopreservación , Riñón , Animales , Porcinos , Criopreservación/métodos , Trasplante Heterólogo , Temperatura , Crioprotectores
5.
Ann Surg ; 276(3): 441-449, 2022 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-35762611

RESUMEN

OBJECTIVE: To determine if islet autotransplantation (IAT) independently improves the quality of life (QoL) in patients after total pancreatectomy and islet autotransplantation (TP-IAT). BACKGROUND: TP-IAT is increasingly being used for intractable chronic pancreatitis. However, the impact of IAT on long-term islet function and QoL is unclear. METHODS: TP-IAT patients at our center >1 year after TP-IAT with ≥1 Short Form-36 QoL measure were included. Patients were classified as insulin-independent or insulin-dependent, and as having islet graft function or failure by C-peptide. The associations of insulin use and islet graft function with QoL measures were analyzed by using a linear mixed model, accounting for time since transplant and within-person correlation. RESULTS: Among 817 islet autograft recipients, 564 patients [median (interquartile range) age: 34 (20, 45) years, 71% female] and 2161 total QoL surveys were included. QoL data were available for >5 years after TP-IAT for 42.7% and for >10 years for 17.3%. Insulin-independent patients exhibited higher QoL in 7 of 8 subscale domains and for Physical Component Summary and Mental Component Summary scores ( P <0.05 for all). Physical Component Summary was 2.91 (SE=0.57) higher in insulin-independent patients ( P <0.001). No differences in QoL were observed between those with and without graft function, but islet graft failure was rare (15% of patients). However, glycosylated hemoglobin was much higher with islet graft failure. CONCLUSIONS: QoL is significantly improved when insulin independence is present, and glycosylated hemoglobin is lower with a functioning islet graft. These data support offering IAT, rather than just performing total pancreatectomy and treating with exogenous insulin.


Asunto(s)
Trasplante de Islotes Pancreáticos , Pancreatitis Crónica , Adulto , Femenino , Hemoglobina Glucada , Humanos , Insulina , Masculino , Pancreatectomía , Pancreatitis Crónica/complicaciones , Pancreatitis Crónica/cirugía , Calidad de Vida , Trasplante Autólogo , Resultado del Tratamiento
6.
Pancreatology ; 22(1): 1-8, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34620552

RESUMEN

BACKGROUND: Total pancreatectomy with islet autotransplantation (TPIAT) is a viable option for treating debilitating recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) in adults and children. No data is currently available regarding variation in approach to operation. METHODS: We evaluated surgical techniques, islet isolation and infusion approaches, and outcomes and complications, comparing children (n = 84) with adults (n = 195) enrolled between January 2017 and April 2020 by 11 centers in the United States in the Prospective Observational Study of TPIAT (POST), which was launched in 2017 to collect standard history and outcomes data from patients undergoing TPIAT for RAP or CP. RESULTS: Children more commonly underwent splenectomy (100% versus 91%, p = 0.002), pylorus preservation (93% versus 67%; p < 0.0001), Roux-en-Y duodenojejunostomy reconstruction (92% versus 35%; p < 0.0001), and enteral feeding tube placement (93% versus 63%; p < 0.0001). Median islet equivalents/kg transplanted was higher in children (4577; IQR 2816-6517) than adults (2909; IQR 1555-4479; p < 0.0001), with COBE purification less common in children (4% versus 15%; p = 0.0068). Median length of hospital stay was higher in children (15 days; IQR 14-22 versus 11 days; IQR 8-14; p < 0.0001), but 30-day readmissions were lower in children (13% versus 26%, p = 0.018). Rate of portal vein thrombosis was significantly lower in children than in adults (2% versus 10%, p = 0.028). There were no mortalities in the first 90 days post-TPIAT. CONCLUSIONS: Pancreatectomy techniques differ between children and adults, with islet yields higher in children. The rates of portal vein thrombosis and early readmission are lower in children.


Asunto(s)
Trasplante de Islotes Pancreáticos , Laparoscopía , Pancreatectomía , Pancreatitis Crónica/cirugía , Enfermedad Aguda , Adulto , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Prospectivos , Trasplante Autólogo , Resultado del Tratamiento
7.
Am J Transplant ; 21(10): 3411-3420, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33754431

RESUMEN

In this single-center, retrospective cohort study, we aimed to elucidate simple metabolic markers or surrogate indices of ß-cell function that best predict long-term insulin independence and goal glycemic HbA1c control (HbA1c ≤ 6.5%) after total pancreatectomy with islet autotransplantation (TP-IAT). Patients who underwent TP-IAT (n = 371) were reviewed for metabolic measures before TP-IAT and for insulin independence and glycemic control at 1, 3, and 5 years after TP-IAT. Insulin independence and goal glycemic control were achieved in 33% and 68% at 1 year, respectively. Although the groups who were insulin independent and dependent overlap substantially on baseline measures, an individual who has abnormal glycemia (prediabetes HbA1c or fasting glucose) or estimated IEQs/kg < 2500 has a very high likelihood of remaining insulin dependent after surgery. In multivariate logistic regression modelling, metabolic measures correctly predicted insulin independence in about 70% of patients at 1, 3, and 5 years after TP-IAT. In conclusion, metabolic testing measures before surgery are highly associated with diabetes outcomes after TP-IAT at a population level and correctly predict outcomes in approximately two out of three patients. These findings may aid in prognostic counseling for chronic pancreatitis patients who are likely to eventually need TP-IAT.


Asunto(s)
Diabetes Mellitus , Trasplante de Islotes Pancreáticos , Pancreatitis Crónica , Humanos , Pancreatectomía , Pancreatitis Crónica/cirugía , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento
8.
Pancreatology ; 21(8): 1491-1497, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34538580

RESUMEN

BACKGROUND/OBJECTIVES: The effect of total pancreatectomy with islet autotransplantation (TPIAT) on bone mineral density (BMD) in patients with CP is unknown. We aimed to assess bone health in patients with CP after TPIAT. METHODS: We measured BMD, BMD Z-score, and bone mineral content (BMC) for total body, lumbar spine, right and left hip in 78 patients before and after TPIAT using dual-energy X-ray absorptiometry (DXA, n = 78 pre-TPIAT, n = 65 paired pre- and 12 months post-TPIAT, n = 33 paired 12 and 18 months post-TPIAT), and tested for association with clinical history including age, smoking status, and medications using paired and two-sample t-tests, linear regression, and Fisher's exact test. Laboratory measures related to bone health were also assessed. RESULTS: In the patients with pre-TPIAT DXA, 12% had low BMD (Z-score ≤ -2). BMD, BMD Z-score, and BMC all decreased from pre-to 12 months post-TPIAT. BMD declined by 1.7%-4.1% with the greatest change at the hips. Adjusted for change in lean and fat body mass, DXA changes remained significant for total body and hip. Serum carboxy-terminal collagen crosslinks telopeptide and alkaline phosphatase increased at 12 months post-TPIAT, suggesting possible increased bone remodeling. BMD, BMD Z-score, and BMC did not change between 12 months and 18 months in any of the four regions (p > 0.6). CONCLUSIONS: TPIAT is associated with decreases in BMD in the body, lumbar, and hip regions of patients with CP in the first year after TPIAT but these appear to stabilize between 12 and 18 months after TPIAT.


Asunto(s)
Densidad Ósea , Pancreatectomía , Humanos , Trasplante Autólogo
9.
Pancreatology ; 21(1): 275-281, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33323311

RESUMEN

BACKGROUND AND AIMS: Many patients undergoing total pancreatectomy with islet autotransplant (TPIAT) for severe, refractory chronic pancreatitis or recurrent acute pancreatitis have a history of endoscopic retrograde cholangiopancreatography (ERCP). Using data from the multicenter POST (Prospective Observational Study of TPIAT) cohort, we aimed to determine clinical characteristics associated with ERCP and the effect of ERCP on islet yield. METHODS: Using data from 230 participants (11 centers), demographics, pancreatitis history, and imaging features were tested for association with ERCP procedures. Logistic and linear regression were used to assess association of islet yield measures with having any pre-operative ERCPs and with the number of ERCPs, adjusting for confounders. RESULTS: 175 (76%) underwent ERCPs [median number of ERCPs (IQR) 2 (1-4). ERCP was more common in those with obstructed pancreatic duct (p = 0.0009), pancreas divisum (p = 0.0009), prior pancreatic surgery (p = 0.005), and longer disease duration (p = 0.004). A greater number of ERCPs was associated with disease duration (p < 0.0001), obstructed pancreatic duct (p = 0.006), and prior pancreatic surgery (p = 0.006) and increased risk for positive islet culture (p < 0.0001). Mean total IEQ/kg with vs. without prior ERCP were 4145 (95% CI 3621-4669) vs. 3476 (95% CI 2521-4431) respectively (p = 0.23). Adjusting for confounders, islet yield was not significantly associated with prior ERCP, number of ERCPs, biliary or pancreatic sphincterotomy or stent placement. CONCLUSIONS: ERCP did not appear to adversely impact islet yield. When indicated, ERCP need not be withheld to optimize islet yield but the risk-benefit ratio of ERCP should be considered given its potential harms, including risk for excessive delay in TPIAT.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica/métodos , Trasplante de Islotes Pancreáticos/métodos , Islotes Pancreáticos/diagnóstico por imagen , Pancreatectomía/métodos , Adolescente , Adulto , Anciano , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Pancreáticas/cirugía , Pancreatitis/cirugía , Estudios Prospectivos , Recurrencia , Adulto Joven
10.
Clin Transplant ; 35(11): e14444, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34318522

RESUMEN

BACKGROUND: The Kidney Allocation System (KAS) includes a scoring system to match transplant candidate life expectancy with expected longevity of the donor kidney, and a backdating policy that gives waitlist time credit to patients waitlisted after starting dialysis treatment (post-dialysis). We estimated the effect of the KAS on employment among patient subgroups targeted by the policy. METHODS: We used a sample selection model to compare employment after transplant before and after KAS implementation among patients on the kidney-only transplant waitlist between December 4, 2011 and December 31, 2017. RESULTS: Post-dialysis transplant recipients aged 18-49 were significantly more likely to be employed 1-year post transplant in the post-KAS era compared to the pre-KAS era. Transplant recipients aged 35-64 with no dialysis treatment were significantly less likely to be employed 1 year after transplant in the post-KAS era compared to the pre-KAS era. CONCLUSIONS: This study provides the first assessment of employment after DDKT under the KAS and provides important information about both the methods used to measure employment after transplant and the outcome under the KAS. Changes in employment after DDKT among various patient subgroups have important implications for assessing long-term patient and societal effects of the KAS and organ allocation policy.


Asunto(s)
Trasplante de Riñón , Obtención de Tejidos y Órganos , Humanos , Riñón , Reinserción al Trabajo , Donantes de Tejidos , Receptores de Trasplantes
11.
Transpl Int ; 34(1): 87-96, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33020957

RESUMEN

The Igls criteria assess islet function after islet allotransplant, based on C-peptide, insulin use, hemoglobin A1c, and severe hypoglycemia. However, these criteria as currently defined cannot be applied to total pancreatectomy islet autotransplant (TPIAT) patients. We tested modified criteria for assessing islet function in a large cohort of TPIAT patients (n = 379). Metabolic outcomes were assessed. We assigned Auto-Igls class to each patient as able and evaluated the utility, validity, and perioperative risk factors of Auto-Igls at 1-year post-IAT. We tested the association of Auto-Igls with independent measures of islet graft function, specifically continuous glucose monitoring (CGM) data or acute C-peptide response to glucose (ACRglu) from intravenous glucose tolerance tests. An Auto-Igls class was assigned to 264 patients (69%). Among patients who could not be classified, most were missing exact insulin dose. Seventy-three percent of TPIAT recipients were classified as optimal or good at 1 year. The only significant predictor of Auto-Igls class was islet mass transplanted (P < 0.0001). Auto-Igls class was associated with percent time in range (70-140 mg/dl) on CGM (P = 0.02) and ACRglu (P < 0.0001). Modified Igls classification for IAT permits simple, comprehensive assessment of metabolic outcomes after TPIAT and is associated with other islet functional measures.


Asunto(s)
Trasplante de Islotes Pancreáticos , Pancreatectomía , Autoinjertos , Glucemia , Automonitorización de la Glucosa Sanguínea , Humanos , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento
12.
Transpl Int ; 34(5): 872-881, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33660330

RESUMEN

Hepatic steatosis (HS) beyond a certain degree can jeopardize living donor (LD) safety, particularly in right lobe (RL) donors, making it a major obstacle for donor pool expansion in adult-to-adult living donor liver transplantation (ALDLT). From July 2004 to June 2016, 58 LDs donated their RLs despite having moderate HS (30%-50% steatosis) determined by intraoperative biopsy at a single center. We performed greedy matching to compare the outcomes of the donors and recipients of this group with those of LDs with no HS. The mean left lobe (LL) HS value in the 58 cases was 20.9 ± 12.4%, which was significantly lower than the mean RL HS value (38.8 ± 6.7%, P < 0.001). The mean ratio of the remnant LL to the total liver volume was 37.8 ± 2.2. No differences were observed in the postoperative liver function and donor and recipient morbidity and mortality rates. The liver regeneration rates in recipients and donors at 1 month, 6 months, and 1 year postoperatively did not differ significantly. The patient and graft survival rates of the recipients showed no differences. The use of well-selected RL grafts with moderate steatosis does not impair graft function, recipient outcomes, or donor safety.


Asunto(s)
Hígado Graso , Trasplante de Hígado , Adulto , Hepatectomía/efectos adversos , Humanos , Hígado , Donadores Vivos , Estudios Retrospectivos
13.
Am J Transplant ; 20(7): 1768-1772, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32090448
14.
Ann Surg ; 272(3): 458-466, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32740239

RESUMEN

OBJECTIVE: To identify factors that accurately predict 1-year survival for liver transplant recipients with a MELD score ≥40. BACKGROUND: Although transplant is beneficial for patients with the highest acuity (MELD ≥40), mortality in this group is high. Predicting which patients are likely to survive for >1 year would be medically and economically helpful. METHODS: The Scientific Registry of Transplant Recipients database was reviewed to identify adult liver transplant recipients from 2002 through 2016 with MELD score ≥40 at transplant. The relationships between 44 recipient and donor factors and 1-year patient survival were examined using random survival forests methods. Variable importance measures were used to identify the factors with the strongest influence on survival, and partial dependence plots were used to determine the dependence of survival on the target variable while adjusting for all other variables. RESULTS: We identified 5309 liver transplants that met our criteria. The overall 1-year survival of high-acuity patients improved from 69% in 2001 to 87% in 2016. The strongest predictors of death within 1 year of transplant were patient on mechanical ventilator before transplantation, prior liver transplant, older recipient age, older donor age, donation after cardiac death, and longer cold ischemia. CONCLUSIONS: Liver transplant outcomes continue to improve even for patients with high medical acuity. Applying ensemble learning methods to recipient and donor factors available before transplant can predict survival probabilities for future transplant cases. This information can be used to facilitate donor/recipient matching and to improve informed consent.


Asunto(s)
Isquemia Fría/métodos , Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado/mortalidad , Donantes de Tejidos , Obtención de Tejidos y Órganos/métodos , Receptores de Trasplantes , Femenino , Estudios de Seguimiento , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiología
15.
Pancreatology ; 20(8): 1648-1655, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33097431

RESUMEN

BACKGROUND: The identification of genetic risk factors for chronic pancreatitis, such as PRSS1, CFTR and SPINK1, provides the opportunity to define key pathologic hallmarks and etiologic-specific changes. For example, pancreata from PRSS1 and CFTR patients exhibit progressive lipomatous atrophy without significant fibrosis. Considering the pathology of SPINK1-associated pancreatitis is ill-defined, we examined the pancreata of SPINK1 patients with chronic pancreatitis. METHODS: Histologic sections after total pancreatectomy with islet autotransplantation and associated clinicopathologic data were collected from 28 patients with SPINK1 germline alterations. Clinical findings, germline data, anatomic anomalies and pathologic findings were descriptively evaluated. RESULTS: Patients ranged in age from 5 to 48 years (median, 21.6 years) with abdominal pain between 2 and 25 years (median, 5.8 years). Most patients were SPINK1 heterozygous and 14 (50%) had co-occurring CFTR (n = 12) and CTRC (n = 2) mutations. Other pancreatitis risk factors included anatomic anomalies (n = 9) and tobacco use (n = 1). Overall, 24 (86%) patients had additional pancreatitis-associated germline alterations, SPINK1 homozygosity, anatomic anomalies or environmental factors. Examination of pancreata revealed a sequential pattern of exocrine parenchymal loss and replacement by prominent fibrosis, dependent on the duration of abdominal pain. No malignancies were identified, but low-grade pancreatic intraepithelial neoplasia was present for 2 cases. CONCLUSIONS: Within this descriptive study, SPINK1-associated pancreatitis is characterized by parenchymal fibrosis and suggests divergent pathophysiologic mechanisms from PRSS1 and CFTR-associated pancreatitis. Moreover, SPINK1 patients frequently had additional etiologic factors that did not impact the development of pancreatic fibrosis and may implicate SPINK1 as a disease modifier gene.


Asunto(s)
Mutación , Pancreatitis Crónica , Inhibidor de Tripsina Pancreática de Kazal , Dolor Abdominal , Adolescente , Adulto , Niño , Preescolar , Predisposición Genética a la Enfermedad , Humanos , Persona de Mediana Edad , Pancreatitis Crónica/genética , Inhibidor de Tripsina Pancreática de Kazal/genética , Adulto Joven
16.
Clin Transplant ; 34(8): e14008, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32530540

RESUMEN

Islet yield is an important predictor of acceptable glucose control after total pancreatectomy with islet autotransplantation (TP-IAT). We assessed if pancreas volume calculated with preoperative MRI could assess islet yield and postoperative outcomes. We reviewed dynamic MRI studies from 154 adult TP-IAT patients (2009-2016), and associations between calculated volumes and digest islet equivalents (IEQs) were tested. In multivariate regression analysis, pancreas volume (P < .001) and preoperative HbA1c levels (P = .009) were independently associated with digest IEQs. The IEQ prediction formula was calculated according to each preoperative HbA1c level, (a) pancreas volume × 5800 for HbA1c ≥ 6.5, (b) pancreas volume × 10 000 for HbA1c ≥5.7/<6.5 and (iii) pancreas volume × 11 400 for HbA1c < 5.7. The formula was internally validated with 28 TP-IAT patients between 2017 and 2018 (r2  = .657 and r2  = .710 when restricted to 24 patients without prior pancreatectomy). An estimated IEQs/Body Weight (kg) ≥3700 predicted HbA1c ≤6.5 and insulin independence at 1 year after TP-IAT with 77% and 88% sensitivity and 55% and 43% specificity, respectively. The combination of pancreas volume and preoperative HbA1c levels may be useful to estimate islet yield. Estimated IEQs were reasonably sensitive to predict acceptable glucose control at 1 year.


Asunto(s)
Trasplante de Islotes Pancreáticos , Pancreatitis Crónica , Adulto , Hemoglobina Glucada , Humanos , Páncreas/diagnóstico por imagen , Páncreas/cirugía , Pancreatectomía , Pancreatitis Crónica/cirugía , Trasplante Autólogo , Resultado del Tratamiento
17.
Am J Transplant ; 19(8): 2219-2231, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30748093

RESUMEN

Single-center studies have demonstrated regional organ procurement collaboration to reduce travel redundancy and improve procurement efficiency. We studied deceased donor kidney, liver, and pancreas transplants performed in the United States between 2002 and 2014 using the Scientific Registry of Transplant Recipients (SRTR). We compared graft failure (GF), death-censored graft failure (DCGF), and patient death (PD) between organs procured by surgeons from the recipient's center (transplant procurement team [TPT]) versus surgeons from a different center (NTPT). Primary nonfunction (PNF) was assessed for liver and kidney and delayed graft function (DGF) for kidney using mixed-effects logistic modeling. There were 64 906 liver (61.6% TPT), 118 152 kidney (26.1% TPT), 10 832 simultaneous pancreas kidney (SPK; 56.6% TPT), and 4378 solitary pancreas (SP; 34.0% TPT) transplants. When compared to NTPT, DCGF for organs procured by TPT was significantly less for liver (adjusted HR: 0.93; 95% CI: 0.88-0.98) and marginally significant for kidney (0.97; 0.93-1.00) and SPK (0.90; 0.82-1.00), and not significant for SP (0.98; 0.86 -1.11). DGF for TPT kidney was significantly lower (adjusted OR 0.91; 0.87-0.95). Albeit modest, our findings demonstrate a difference between locally procured organs and those procured by the implanting team. Elucidating the etiology of these differences will enhance regional organ procurement collaboration.


Asunto(s)
Trasplante de Órganos/mortalidad , Cirujanos/normas , Donantes de Tejidos/provisión & distribución , Obtención de Tejidos y Órganos/métodos , Obtención de Tejidos y Órganos/normas , Receptores de Trasplantes/estadística & datos numéricos , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Trasplante de Órganos/estadística & datos numéricos , Trasplante de Órganos/tendencias , Pronóstico
18.
Am J Transplant ; 19(7): 1888-1895, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31012525

RESUMEN

In accordance with the National Organ Transplant Act and Department of Health and Human Services' Final Rule, the Scientific Registry of Transplant Recipients (SRTR) publicly releases biannual program-specific reports that include analyses of transplant centers' risk-adjusted waitlist mortality, organ acceptance ratios, transplant rates, and graft and patient survival. Since the inception of these center metrics, 1-year posttransplant graft and patient survival have improved, and center variation has decreased, casting uncertainty on their clinical relevance. The SRTR has recently modified center evaluations by ranking centers into 5 tiers rather than 3 tiers in an attempt to discriminate between programs performing within a tight range, further exacerbating this uncertainty. The American Society of Transplantation/American Society of Transplant Surgeons convened an expert taskforce to examine both the utility and unintended consequences of transplant center metrics. Estimates of center variation in outcomes in adjacent tiers are imprecise and fleeting, but can result in consequential changes in clinician and center behavior. The taskforce has concerns that current metrics, based principally on 1-year graft and patient survival, provide minimal if any benefit in informing patient choice and access to transplantation, with the untoward effect of decreased utilization of organs and restriction of research and innovation.


Asunto(s)
Trasplante , Humanos , Garantía de la Calidad de Atención de Salud , Sistema de Registros , Obtención de Tejidos y Órganos , Listas de Espera
19.
Am J Kidney Dis ; 74(3): 382-389, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31027881

RESUMEN

Quality metrics have a long history in the field of kidney transplantation. These metrics are highly visible, with significant ramifications to transplantation centers based on their use in regulatory review and other stakeholders. In this perspective, we review the history of quality metrics in this field, discuss the perceptions and empirical evidence evaluating the impact of metrics on care delivery, and summarize the current landscape of quality oversight. Based on the research findings and opinions of the transplantation community, we suggest that significant reforms are needed for the evaluation of quality in the field based on more appropriately aligning metrics with optimizing patient outcomes. Moreover, there are vast potential uses of the current data that should be emphasized in a learning environment rather than a highly punitive system. In our view, these reforms would enhance care delivery, improve patient care, and better align incentives for providers of care that treat transplantation patients.


Asunto(s)
Benchmarking , Trasplante de Riñón/normas , Benchmarking/métodos , Humanos , Mejoramiento de la Calidad
20.
Clin Transplant ; 33(5): e13539, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30882949

RESUMEN

Kidney transplantation entails well-coordinated complex care delivery. Patient-provider cultural and linguistic discordance can lead to healthcare disparities. We analyzed kidney transplantation outcomes among our institution's Hmong recipients using a retrospective cohort study. From 1995 to 2015, 2164 adult (age ≥18) recipients underwent kidney transplantation at our institution; 78 self-identified as Hmong. Survival rates were analyzed and compared to Caucasian recipients (n = 2086). Fifty (64.1%) Hmong recipients consistently requested interpreters. Mean follow-up was 9.8 years for both groups. Hmong recipients (N = 78) were on average younger at transplant (45.7 vs 49.7 years; P = 0.02), more likely to be female (56% vs 38%; P = 0.001), and had higher gravidity (5.0 vs 1.9 births; P < 0.001). There were 13 (16.7%) Hmong living donor recipients, who were younger (32.8 vs 42.9 years; P = 0.006) at transplant compared to Caucasians (1429, 68.5%). Hmong 1- and 5-year patient survival was 100%; Caucasians, 97.1% and 88% (P < 0.001). Hmong 1- and 5-year graft survival was 98.7% and 84.9%; Caucasians 94.8% and 80.9% (P = 0.013). One- and 5-year rejection-free survival showed no difference (88.9% vs 82.4%; 86.7% vs 83.4%, P = 0.996). Despite cultural and linguistic differences between Hmong recipients and providers, we found no evidence of inferiority in KT outcomes in the Hmong population.


Asunto(s)
Atención a la Salud , Etnicidad/estadística & datos numéricos , Rechazo de Injerto/mortalidad , Disparidades en Atención de Salud/estadística & datos numéricos , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/mortalidad , Complicaciones Posoperatorias , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Disparidades en Atención de Salud/tendencias , Humanos , Incidencia , Fallo Renal Crónico/etnología , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Receptores de Trasplantes , Adulto Joven
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