Long-term results of pediatric liver transplantation: an analysis of 569 transplants.

OBJECTIVE: To analyze a single center's 13-year experience with 569 pediatric orthotopic liver transplants for end-stage liver disease. SUMMARY BACKGROUND DATA: Despite advances in medical therapy, liver replacement continues to be the only definitive mode of therapy for children with end-stage liver disease. Innovative surgical techniques and improved immunosuppression have broadened the application of liver replacement for affected children. However, liver transplantation in the child remains challenging because of the scarcity of donor organs, complex surgical technical demands, and the necessity to prevent long-term complications. METHODS: The medical records of 440 consecutive patients younger than 18 years of age undergoing orthotopic liver transplantation for end-stage liver disease from March 20, 1984, to November 15, 1997, were reviewed. Results were analyzed using Cox multivariate regression analysis to determine the statistical strength of independent associations between pretransplant covariates and patient and graft survival. Actuarial patient and graft survival rates were determined at 1, 3, 5, and 10 years. The type and incidence of posttransplant complications were determined, as was the quality of long-term allograft function. The median follow-up period was 4.1 years. RESULTS: Biliary atresia was the most common cause (50.4%) of endstage liver disease in this patient population. The median recipient age was 2.4 years; 239 patients (54%) were younger than 3 years of age and 1 11 patients (25%) were younger than 1 year of age. There were 471 whole organs, 29 were ex vivo reduced size, 33 were living-related donor, and 36 were in situ split-liver allografts. Three hundred forty-three (78%) patients underwent a single allograft, whereas 97 patients required retransplantation; hepatic artery thrombosis was the most common indication for retransplantation (55 patients). The 1-, 3-, 5-, and 10-year actuarial patient survival rates were 82%, 80%, 78%, and 76%, respectively; allograft survival rates were 68%, 63%, 60%, and 54%. Long-term liver function remains excellent: current median follow-up values for total bilirubin and aspartate aminotransferase were 0.5 mg/dl and 54 IU/L, respectively. Cox multivariate regression analysis demonstrated that pretransplant patient age, the era of transplantation, and the number of allografts performed significantly and independently predicted patient survival rates, whereas allograft type and pretransplant diagnosis did not. CONCLUSIONS: Liver transplantation in the pediatric patient is a durable procedure that provides excellent long-term survival. Although there have been overall improvements in patient outcome with increased experience, the effect is most pronounced for patients younger than 1 year of age. Retransplantation, although effective in a meaningful number of patients, continues to carry a progressive decrement in survival with the number of allografts performed. Use of living-related and in situ split-liver allografts has dramatically reduced waiting times for small children and has improved patient survival.     

The impairment of true glomerular filtration rate in long-term cyclosporine-treated pediatric allograft recipients

We performed indium-111-DTPA plasma clearance studies in 61 pediatric kidney and liver recipients treated with cyclosporine to compare true glomerular filtration rate with calculated GFR (cGFR). The mean true GFR of 61.9 +/- 36.6 ml/min/1.73 m2 indicated renal impairment. The mean cGFR of 85.2 +/- 22.4 ml/min/1.73 m2 was significantly higher (P less than 0.001), and overestimated GFR by 38%. cGFR alone did not accurately reflect the degree of renal dysfunction. A group of 48 pediatric orthotopic liver transplant recipients was studied in more detail: 73% of these patients had a true GFR less than 70 ml/min/1.73 m2, while 85% had a true GFR below 90 ml/min/1.73 m2, the lower limit for normal GFR in children. The mean true GFR for patients treated more than 24 months with CsA was lower (P = 0.02) than patients treated with CsA for 12 to 24 months. OLT patients with normal true GFR (greater than 90 ml/min/1.73 m2) had significantly lower plasma CsA levels, and 50% of patients with a true GFR less than or equal to 50 ml/min/1.73 m2 had hypertension. There was no effect on true GFR of age, liver function, azathioprine use, or peritransplant treatment with other nephrotoxic drugs. We conclude that true GFR is significantly impaired in long-term CsA-treated allograft pediatric recipients. Calculations of GFR underestimate the degree of renal dysfunction. As patients treated greater than 24 months had the lowest true GFRs, the fall in GFR may be progressive.     

One thousand liver transplants. The lessons learned.

OBJECTIVE: To evaluate the first 1000 liver transplants performed at UCLA Medical Center to determine factors responsible for improved results. SUMMARY BACKGROUND DATA: Liver transplant has evolved impressively since the first case was performed in 1963. The 1980s have highlighted this progress with the development of better organ preservation, standardization of operative procedure, improved immunosuppressive agents, and better understanding of patient selection. METHODS: The first 100 consecutive liver transplants (group 1) performed from February 1984 through October 1986 were compared with the last 200 (group 2) performed between September 1991 and June 1992. An analysis was made of donor use; changes in patient candidacy; patient care variables; morbidity and mortality; survival data; and hospital resource use. RESULTS: In group 1, 31% of donors were refused because of medical unsuitability compared with 4% in group 2 (p < 0.0001). In group 1, alcoholic patients comprised 1% of liver transplant candidates compared with 20% group 2 (p < 0.0001). High-risk patients (United Network for Organ Sharing criteria 4) only comprised 11% of patients in group 1 compared with 37% in group 2 (p < 0.0001). Operative time (7.6 hours compared with 5.4 hours), packed cell replacement (17 units compared with 9.5 units), intensive care unit stay (10 days compared with 5 days), and hospital stay (50 days compared with 31 days) were all significantly improved (p < 0.05). In group 1, the 1-year survival rate was 73% and improved to 88% in group 2 (p < 0.0001). CONCLUSIONS: Despite unfavorable donor characteristics (obesity, cause of death, age, hypotension), most organs function well and should not be refused based on history alone. The older and high-risk patient (renal failure, ventilator dependence, portal vein pathology, and so on) is routinely transplanted with good success. Despite liberalization of both donor and recipient criteria, patient survival after liver transplant is improved, use of hospital resources is maximized, and cost reduction is achieved.     

Preconception Brief: Occupational/Environmental Exposures

In the last decade, more than half of U.S. children were born to working mothers and 65% of working men and women were of reproductive age. In 2004 more than 28 million women age 18–44 were employed full time. This implies the need for clinicians to possess an awareness about the impact of work on the health of their patients and their future offspring. Most chemicals in the workplace have not been evaluated for reproductive toxicity, and where exposure limits do exist, they were generally not designed to mitigate reproductive risk. Therefore, many toxicants with unambiguous reproductive and developmental effects are still in regular commercial or therapeutic use and thus present exposure potential to workers. Examples of these include heavy metals, (lead, cadmium), organic solvents (glycol ethers, percholoroethylene), pesticides and herbicides (ethylene dibromide) and sterilants, anesthetic gases and anti-cancer drugs used in healthcare. Surprisingly, many of these reproductive toxicants are well represented in traditional employment sectors of women, such as healthcare and cosmetology. Environmental exposures also figure prominently in evaluating a woman’s health risk and that to a pregnancy. Food and water quality and pesticide and solvent usage are increasingly topics raised by women and men contemplating pregnancy. The microenvironment of a woman, such as her choices of hobbies and leisure time activities also come into play. Caregivers must be aware of their patients’ potential environmental and workplace exposures and weigh any risk of exposure in the context of the time-dependent window of reproductive susceptibility. This will allow informed decision-making about the need for changes in behavior, diet, hobbies or the need for added protections on the job or alternative duty assignment. Examples of such environmental and occupational history elements will be presented together with counseling strategies for the clinician.     

A comparison of treatments with exogenous FSH to promote folliculogenesis in patients with quiescent ovaries due to the continued administration of an LHRH agonist

The circulating levels of plasma follicle-stimulating hormone(FSH), luteinizing hormone (LH) and oestradlol (E₂) have beendetermined in three groups of three subjects during the continuous,subcutaneous administration of an LH-RH agonist (250 µg/day)and after the intramuscular injection of urinary FSH (groupI, 150 IU daily for 8 days, total 1200 IU; group II, 300 IUon alternate days for four injections, total 1200 IU; and groupIII, 150 IU on alternate days for four injections, total 600IU). The level of circulating FSH in group I rose steadily froma geometric mean of 1.11 (preinjection) to 8.76 U/I (at day8), while the corresponding levels in groups II and III fluctuatedaccording to the time and dose of the injected material. Twenty-fourhours after the injection the mean level of FSH in group IIwas significantly higher (7.31 U/I) than the corresponding valuefor group I (2.79 U/I) or group III (3.48 U/I). Only those subjectsin group II showed a resumption of folliculogenesis (leading,mean maximum follicular diameters of 16, 13 and 14 mm, respectively)and a corresponding Increase in the concentration of plasmaE₂ (from 22, 43 and 103 to 906, 1477 and 2362 pmol/l, respectively).     

Electronic FRAIL score may predict treatment outcomes in older adults with myeloma

IntroductionFrailty is a known risk factor for older patients with myeloma. Here we present realworld data using a computer-generated frailty assessment score (FRAIL score), based on 5 clinically derived parameters, in predicting patient outcomes.MethodsOlder patients with newly diagnosed multiple myeloma who received frontline treatment with cyclophosphamide-bortezomib-dexamethasone had their FRAIL score retrospectively assessed. Treatment outcomes were assessed using standard IMWG criteria, and event free survival and overall survival determined.Results155 patients were analysed. Compared to those who were assessed as non-frail (FRAIL score 0–1) likely-frail patients (score ≥ 2) were less likely to complete the full course of treatment (24.3% vs 53.4%, p = 0.002), and more likely to terminate treatment due to toxicities (35.1% vs 22.0%, p = 0.109), as well as having a greater number of patients stop treatment early for reasons other than toxicity or progression (27.0% vs 10.2%, p = 0.010). After a median follow up of 42.5 months, likely-frail patients were found to have a trend for shorter event-free survival (median EFS, 8.7 vs 17.9 months, p = 0.064) and statistically inferior overall survival (median OS, 30.2 vs 49.8 months, p < 0.001). After adjusting for age, stage, and Charlson comorbidity index, FRAIL score was prognostic for OS (HR = 3.47, 95% CI 1.88–6.4), but not EFS (HR = 1.28, 95%CI 0.79–2.06).ConclusionThe FRAIL score is independently predictive of overall survival in older patients with myeloma receiving bortezomib-based induction chemotherapy and can help identify those patients more likely to experience treatment toxicity.     

Attitudes towards mental health,mental health research and digital interventions by young adults with type 1 diabetes: A qualitative analysis

Background

Young people with type 1 diabetes are at increased risk of mental disorders. Whereas treatment need is high, difficulty recruiting young people with type 1 diabetes into psychosocial studies complicates development, testing and dissemination of these interventions.

Objective

Interviews with young adults with type 1 diabetes were conducted to examine attitudes towards mental health and mental health research, including barriers and motivators to participation in mental health studies and preferred sources of mental health support. The interviews were audio‐taped, transcribed and evaluated via thematic analysis.

Setting and participants

Young adults with type 1 diabetes were recruited via social media channels of 3 advocacy organizations. A total of 31 young adults (26 females and 5 males) with an average age of 22 years were interviewed between October 2015 and January 2016.

Results

Participants were largely unaware of their increased vulnerability to common mental health problems and knew little about mental health research. Major barriers to participation included perceived stigma and lifestyle issues and low levels of trust in researchers. Opportunities to connect with peers and help others were described as key motivators. Psychological distress was considered normal within the context of diabetes. A need for some level of human contact in receiving psychosocial support was expressed.

Discussion and conclusion

Findings provide valuable insights into the complex dynamics of engaging young adults with type 1 diabetes in mental health studies. Interviewees provided practical suggestions to assist investigation and delivery of psychosocial interventions for this vulnerable group.     

Rehabilitation Outcomes of Stroke Patients With and Without Diabetes

Objective

To investigate the relation of diabetes comorbidity and the rehabilitation outcomes of patients with stroke.

Design

Secondary data analysis.

Setting

Inpatient rehabilitation facilities.

Participants

Patients with stroke (N=35,243) who received inpatient rehabilitation in 2004 through 2008.

Interventions

None.

Main Outcome Measures

FIM, length of stay, and discharge destination.

Results

Mean age ± SD of the sample was 71.0±13.2 years. The percent of the sample of Medicare beneficiaries was 53.8%, whereas 46.2% had other sources of funding. Of the patients in the sample, 34.5% had a comorbidity of diabetes, with 17.2% classified as tier-eligible and 82.8% as nontier eligible. Findings included that patients in this sample with diabetes were admitted for rehabilitation services at a younger age than those without diabetes and support previous studies in which tier-eligible diabetes comorbidities moderated by patient age were found to be significant predictors of stroke rehabilitation outcomes. Furthermore, similar findings remained regardless of payer source.

Conclusions

This study provides additional evidence that diabetes as a comorbidity is significantly related to stroke rehabilitation outcome, but the relation is moderated by patient age.