Search

Conditioned media harvested from stem cell culturing have the potential to be innovative therapeutic tools against various diseases, due to their high content of growth, trophic and protective factors. The evaluation in vivo of the effects and biosafety of these products is essential, and zebrafish provides an ideal platform for high-throughput toxicological analysis, concurrently allowing the minimization of the use of mammalian models without losing reliability. In this study, we assessed the biological effects elicited by the exposure of zebrafish embryos to a conditioned medium derived from Wharton's jelly mesenchymal stem cells. By a multiparametric investigation combining molecular, embryological, behavioural and in vivo imaging techniques, we found that exposure to a conditioned medium at a non-toxic/non-lethal dosage triggers antioxidant, anti-apoptotic and pro-regenerative effects, by upregulation of a set of genes involved in antioxidant defence ( nrf2 , brg1 , sirt1 , sirt6 , foxO3a , sod2 and cat ), glycolysis ( ldha ) and cell survival ( bcl2l1 , mcl1a and bim ), coupled to downregulation of pro-apoptotic markers ( baxa , caspase-3a and caspase-8 ). To our knowledge, this is the first study comprehensively addressing the effects of a conditioned medium on a whole organism from a developmental, molecular and behavioural perspective, and we are fairly confident that it will pave the way for future therapeutic application.

Purpose: To report outcomes of keratolimbal allograft (KLAL) compatible for both human leukocyte (HLA) and/or blood type using oral prednisone, mycophenolate, and tacrolimus, with basiliximab if panel reactive antibodies (PRA) are present. Intravenous immunoglobulin (IVIG) was used post-operatively if donor-specific anti-HLA antibodies (DSA) were present., Methods: Retrospective interventional series of consecutive patients with KLAL for limbal stem cell deficiency (LSCD) from HLA and/or blood type compatible deceased donors with a minimum follow-up time of 12 months. Main outcome measures were ocular surface stability, visual acuity and systemic immunosuppression (SI) adverse events., Results: Eight eyes of eight patients with mean age of 48.6 ± 10.1 years (range 34-65 years) were included. Mean follow-up time was 37.3 ± 22.7 months (range 12-71 months) following KLAL; four (50%) had combined LR-CLAL surgery. The etiologies of LSCD were Stevens-Johnson Syndrome (n = 4/8), aniridia (n = 2/8), chemical injury (n = 1/8) and atopic eye disease (n = 1/8). All patients had PRA present and received basiliximab infusions. 5/8 patients received IVIG based on DSA identified pre-operatively. At last follow-up, 7 eyes (87.5%) had a stable ocular surface; 1 eye (12.5%) developed failure and had keratoprosthesis implantation. There was a significant improvement in visual acuity from 1.65 ± 0.48 to 0.68 ± 0.34 logMAR (p = 0.01). SI was tolerated well with minimal adverse events., Conclusions: Preliminary outcomes of KLAL with ABO compatible tissue using the Cincinnati protocol, preoperative basiliximab (when PRA present) and post-operative IVIG (when DSA present) are encouraging. This protocol may allow for utilization of deceased donor tissue with results approximating those of living donor tissue transplanted for severe bilateral LSCD., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Participation in sports is known to have positive effects on people's health and psychosocial well-being. Recently, physical activity implications for people with disabilities have been explored, showing promising results on quality of life and self-concept. However, few studies have specifically investigated the effects of participation in adaptive sports on quality of life in patients with neuromuscular disease., Objective: To evaluate differences in psychosocial well-being between people affected by a neuromuscular disease who play wheelchair hockey and those who do not. Individuals playing an adaptive sport would report better quality of life, higher physical self-efficacy scores, and more effective coping strategies, as assessed by self-reported measures., Design: Cross-sectional study., Setting: Data were collected during clinical follow-ups at the NEMO Clinical Center in Milan (Italy)., Participants: A total of 25 patients affected by neuromuscular diseases, ages 18 to 40 years, participated in the study., Interventions: Not applicable., Main Outcome Measures: The primary outcome was to compare quality of life between groups. Secondary outcomes were the comparisons of physical self-efficacy and coping strategies through self-reported measures., Results: Wheelchair hockey players scored significantly higher on the Quality of Life Index (specifically on the health/functioning and psychological/spiritual sub-scales) and reported better physical self-efficacy and perceived physical ability compared to the control group (i.e., patients who do not participate in any adaptive sport), controlling for age and pathology. On the contrary, no difference was found in coping strategies between the two groups., Conclusions: This study identified a significant association between participation in wheelchair hockey and improved physical and psychological well-being of people affected by neuromuscular diseases compared to those who are not involved in adaptive sports., (© 2021 American Academy of Physical Medicine and Rehabilitation.)

Background: Obesity affects nearly half of adults in the United States and is contributing substantially to a pandemic of obesity-associated chronic conditions such as type 2 diabetes, hypertension, and arthritis. The obesity-associated chronic condition pandemic is particularly severe in low-income, medically underserved, predominantly African-American areas in the southern United States. Little is known regarding the impact of geographic, income, and racial disparities in continuity of care on major health outcomes for patients with obesity-associated chronic conditions., Objective: The aim of this study is to assess, among patients with obesity-associated chronic conditions, and within this group, patients with type 2 diabetes, (1) whether continuity of care is associated with lower overall and potentially preventable emergency department and hospital utilization, (2) the effect of geographic, income, and racial disparities on continuity of care and on health care utilization, (3) whether continuity of care particularly protects individuals at risk for disparities from adverse health outcomes, and (4) whether characteristics of health systems are associated with higher continuity of care and better outcomes., Methods: Using 2015-2018 data from 4 practice-based research networks participating in the Southern Obesity and Diabetes Coalition, we will conduct a retrospective cohort analysis and distributed meta-analysis. Patients with obesity-associated chronic conditions and with type 2 diabetes will be assessed within each health system, following a standardized study protocol. The primary study outcomes are overall and preventable emergency department visits and hospitalizations. Continuity of care will be calculated at the facility level using a modified version of the Bice-Boxerman continuity of care index. Race will be assessed using electronic medical record data. Residence in a low-income area or a health professional shortage area respectively will be assessed by linking patient residence ZIP codes to the Centers for Medicare & Medicaid Services database., Results: In 4 regional health systems across Tennessee, Mississippi, Louisiana, and Arkansas, a total of 53 adult hospitals were included in the study. A total of 147,889 patients with obesity-associated chronic conditions who met study criteria were identified in these health systems, of which 45,453 patients met the type 2 diabetes criteria for inclusion. Results are expected by the end of 2020., Conclusions: This study should reveal whether health system efforts to increase continuity of care for patients with obesity and diabetes have potential to improve outcomes and reduce costs. Analyzing disparities in continuity of care and their effect on major health outcomes can help demonstrate how to improve care and use of health care resources for vulnerable patients with obesity-associated chronic conditions, and within this group, patients with type 2 diabetes. Better understanding of the association between continuity and health care utilization for these vulnerable populations will contribute to the development of higher-value health systems in the southern United States., International Registered Report Identifier (irrid): DERR1-10.2196/20788., (©Yilu Lin, James E Bailey, Satya Surbhi, Sohul A Shuvo, Christopher D Jackson, Ming Chen, Eboni G Price-Haywood, Joshua Mann, Daniel Fort, Jeffrey Burton, Ramona Sandlin, Alexandra Castillo, Hao Mei, Patti Smith, Cardella Leak, Phi Le, Alisha M Monnette, Lizheng Shi. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 09.09.2020.)

Objectives: To describe an innovative health information technology (HIT) model for supporting community-wide health improvement through multiprovider collaboration in a regional population health registry and practice-based research network (PBRN)., Study Design: Case study., Methods: We describe the HIT data structure and governance of the Diabetes Wellness and Prevention Coalition (DWPC) Registry and PBRN based in Memphis, Tennessee. The population served and their characteristics were assessed for all adult patients with at least 1 encounter in a participating health care delivery system from January 1, 2013, to March 31, 2019. Disparities in access and health care utilization were assessed by residential zip code., Results: The DWPC Registry is a chronic disease and population health data warehouse designed to facilitate chronic disease surveillance and tracking of processes and outcomes of care in medically underserved areas of the mid-South. The Registry primarily focuses on obesity-associated chronic conditions such as diabetes, hypertension, hyperlipidemia, and chronic kidney disease. It combines patient data from 7 regional health systems, which include 6 adult hospitals and more than 50 outpatient practices, covering 462,223 adults with 2,032,425 clinic visits and 602,679 hospitalizations and/or emergency department visits from January 1, 2013, to March 31, 2019. The most prevalent chronic conditions include obesity (37.2%), hypertension (34.4%), overweight (26.4%), hyperlipidemia (18.0%), and type 2 diabetes (14.0%). The Registry provides quarterly practice improvement reports to participating clinics, facilitates surveillance of and outreach to patients with unmet health needs, and supports a pragmatic clinical trial and multiple cohort studies., Conclusions: Regional registries and PBRNs are powerful tools that can support real-world quality improvement and population health efforts to reduce disparities and improve equity in chronic disease care in medically underserved communities across the United States.

Background: The Patient Centered Outcomes Research Institute (PCORI) established Clinical Data Research Networks (CDRNs) to support pragmatic research. The objective was to electronically identify, recruit, and survey coronary heart disease (CHD) patients and describe their characteristics, health status, and willingness to participate in future research., Methods: We developed a computable phenotype and assembled CHD patients 30 years or older and had visits or hospitalizations between 2009 and 2015. A sample of patients was surveyed between August 2014 and September 2015. Survey administration included the following methods: face-to-face, telephone, paper or web portal. Survey items covered broad domains including: health literacy and numeracy, and socio-demographics, physical and mental health, health behaviors, access to medical care, and willingness to participate in future research., Results: Of 5517 approached patients, 2605 completed the survey. Participants were mostly white (∼88%), male (68%) and had a median age of 69 years (interquartile range [IQR] 61-76 years). Most respondents' health literacy and numeracy were adequate (83.2% and 84.3%, respectively). Only 4% of respondents reported that their overall health or physical health was excellent. The majority (∼58%) reported that their health was good or very good, while 40% reported that their general and physical health were fair or poor. The majority reported that their quality of life was good to excellent (81%). Limitations in physical health and function were common, including often/always having fatigue (25%), pain (38.7%), or sleep difficulty (19.7%). A patient sample (n = 1936) was provided with a trial summary which would randomize their aspirin dose; and 63% reported that they would consider participating., Conclusion: Many patients with CHD had limitations in physical health. However, the majority reported a good or excellent quality of life.

Purpose: The objective of this study was to report survey response rates and demographic characteristics of eight recruitment approaches to determine acceptability and effectiveness of large-scale patient recruitment among various populations., Methods: We conducted a cross sectional analysis of survey data from two large cohorts. Patients were recruited from the Mid-South Clinical Data Research Network using clinic-based recruitment, research registries, and mail, phone, and email approaches. Response rates are reported as patients who consented for the survey divided by the number of eligible patients approached., Results: We contacted more than 90,000 patients and 13,197 patients completed surveys. Median age was 56.3years (IQR 40.9, 67.4). Racial/ethnic distribution was 84.1% White, non-Hispanic; 9.9% Black, non-Hispanic; 1.8% Hispanic; and 4.0% other, non-Hispanic. Face-to-face recruitment had the highest response rate of 94.3%, followed by participants who "opted-in" to a registry (76%). The lowest response rate was for unsolicited emails from the clinic (6.1%). Face-to-face recruitment enrolled a higher percentage of participants who self-identified as Black, non-Hispanic compared to other approaches (18.6% face-to-face vs. 8.4% for email)., Conclusions: Technology-enabled recruitment approaches such as registries and emails are effective for recruiting but may yield less racial/ethnic diversity compared to traditional, more time-intensive approaches., (Copyright © 2017. Published by Elsevier Inc.)

Previous research has not examined the effect of health literacy on research subjects' completion of scheduled research follow-up. This article evaluates patient factors associated with incomplete research follow-up at three time points after enrollment in a large, hospital-based prospective cohort study. Predictor variables included health literacy, age, race, gender, education, employment status, difficulty paying bills, hospital diagnosis, length of stay, self-reported global health status, depression, perceived health competence, medication adherence, and health care system distrust. In a sample of 2,042 patients, multivariable models demonstrated that lower health literacy and younger age were significantly associated with a lower likelihood of completing research follow-up interviews at 2-3 days, 30 days, and 90 days after hospital discharge. In addition, patients who had less education, were currently employed, and had moderate financial stress were less likely to complete 90-day follow-up. This study is the first to demonstrate that lower health literacy is a significant predictor of incomplete research follow-up.

Background: The occupational exposure to urban pollution may induce adverse effects on the human health., Methods: Plasma levels of thyrotropin stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) of 50 outdoor workers and 50 indoor workers were compared., Results: In the outdoor workers the TSH levels were significantly higher than in the control subjects (p =0.02) while the average of FT3 and FT4 values, was not significantly different compared to the controls (p > 0.05)., Conclusions: The differences found for TSH levels between outdoor and indoor workers, though not high, suggest that, due to greater exposure to environmental pollutants, the outdoor workers are more susceptible to the development of function abnormalities of the thyroid gland compared to indoor workers.

Purpose: Renal cell carcinoma develops in renal transplant recipients 30 or more times more commonly than in the general population. We assessed the prevalence, histology and outcome of renal cell carcinoma in a large, single center recipient population., Materials and Methods: We examined outcomes in patients who underwent renal transplantation at our center to determine the prevalence, histology and outcome of those in whom renal cell carcinoma developed., Results: A total of 3,568 patients received a renal allograft at our institution between 1966 and 2009. A total of 45 renal cell carcinomas were diagnosed in the native kidney of 39 patients (1.1%) and in 8 (0.2%) renal cell carcinoma developed in the allograft kidney. Mean age at diagnosis was 51.6 and 48.2 years in patients with native kidney and allograft tumors, respectively. The mean interval between transplantation and the native or allograft renal cell carcinoma diagnosis was 10.6 and 12.1 years, respectively. Clear cell renal cell carcinoma was the most common tumor histology in native kidneys, diagnosed in 21 cases, while papillary renal cell carcinoma was diagnosed in 20. Five allograft tumors were papillary renal cell carcinoma and 3 were clear cell renal cell carcinoma. Native kidney tumors were managed by radical nephrectomy in 44 or by observation after biopsy. Allograft tumors were managed by transplant nephrectomy in 3 cases, radio frequency ablation in 3 and partial nephrectomy in 2. At a mean 6.6-year followup 32 patients with native kidney renal cell carcinoma were alive while 7 with allograft tumors were alive at a mean 3.6-year followup., Conclusions: Renal cell carcinoma is more prevalent in patients with renal transplantation than the general population, although the subtype distribution differs. Excellent survival is seen at more than 6 years after treatment., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

This guideline for the use of immunoglobulin (IG) for sensitized patients undergoing solid organ transplantation (SOT) is an initiative of the Canadian Blood Services and the National Advisory Committee on Blood and Blood Products of Canada to (1) provide guidance for Canadian practitioners involved in the care of patients undergoing SOT and transfusion medicine specialists on the use of IG and (2) standardize care, limit adverse events, and optimize patient care. A systematic expert and bibliography literature search up to July 2008 was conducted, with 791 literature citations and 45 reports reviewed. To validate the recommendations, the guideline was sent to physicians involved in SOT in Canada and a patient representative. The recommendations identify (1) sensitized patients undergoing SOT that would have a better survival and decreased morbidity by receiving IG preoperatively, postoperatively, and for the treatment of organ rejection; (2) patients who may not have any benefit from receiving IG; and (3) potential adversities to IG.

Objective: Spinal sarcomas pose unique treatment dilemmas because of the difficulty of achieving adequate surgical margins and/or delivering curative radiation doses (65 Gy) in close proximity to the spinal cord. This study used hypofractionated stereotactic radiosurgery (SRS) to deliver higher biologically effective doses to treat primary spinal sarcomas and spinal sarcoma metastases., Methods: Twenty-four patients with spinal or paraspinal sarcomas entered an Institutional Review Board-approved registry trial to evaluate SRS efficacy. They were assessed at regular intervals for pain control, disease progression, and complications for a minimum of 12 months or until death., Results: The median treatment dose for the spinal sarcoma lesions was 30 Gy at the 80% isodose in 3 fractions, with some variation based on tumor size, shape, and dose to adjacent critical structures. Seven patients were treated definitively; all had excellent pain relief and are alive with a mean follow-up period of 33 months. Two patients had complete tumor regression, 3 had partial regression, and 2 experienced recurrences and have been re-treated. Seven patients underwent resection and adjuvant SRS. One of 3 patients treated preoperatively had complete tumor regression, and none of the 4 patients treated postoperatively had a local recurrence with a mean follow-up period of 43.5 months. All 10 patients with sarcoma metastases to the spine (16 lesions) died, with a mean survival of 11.1 months from first spinal metastasis treatment. Complete pain relief was achieved in 8 patients, partial relief in 7 patients, and none in 1 patient. No patient developed radiation myelitis., Conclusion: These preliminary results suggest that SRS may have a role in the definitive treatment of patients with primary spinal sarcomas who are deemed unresectable and as adjuvant treatment in those undergoing surgery and for palliation of sarcoma metastases.

Background: Chronic allograft nephropathy is the most frequent cause of long-term kidney allograft loss. Studies are desperately needed to improve long-term survival. Tacrolimus has been associated with less rejection and better kidney function compared with cyclosporine in clinical trials. This study tested the hypothesis that conversion from cyclosporine to tacrolimus might improve long-term outcomes in patients with chronic allograft damage., Methods: In this multicenter Canadian clinical trial, cyclosporine-treated patients with biopsy-proven chronic allograft nephropathy and impaired renal function were randomly assigned (2:1) to convert to tacrolimus or continue on cyclosporine therapy. A total of 106 (70 tacrolimus and 36 cyclosporine treated) patients were followed-up for up to 5 years. The primary outcome was graft survival., Results: In an intention to treat analysis, subsequent graft (73% vs. 81%, P=0.2835, log-rank test) and patient survival (91% vs. 92%, P=0.8668, log-rank test) were not different between the tacrolimus and cyclosporine groups, respectively. Changes in Chronic Allograft Damage Index scores on protocol biopsies from baseline to 3 years were not different (+0.4+/-1.8 vs. +1.3+/-3.2, P=0.5910, cyclosporine vs. tacrolimus, respectively). There were no significant differences in biopsy-proven acute rejection (6 [8.6%] vs. 2 [5.6%], tacrolimus vs. cyclosporine, respectively, P=0.5906)., Conclusions: In this study, patients with chronic allograft damage converted from cyclosporine to tacrolimus demonstrated no apparent benefit.

Background: Cardiovascular (CV) disease is the foremost cause of mortality and an important cause of morbidity in renal transplant recipients. The disease burden is likely to increase as older patients are accepted for transplantation. The outcome of these high-CV risk patients after renal transplantation, especially with known pre-transplant coronary artery disease (CAD), has not been studied. Hence, we looked at the CV outcome in patients with known pre-transplant CAD., Methods: All renal transplants performed between 1998 and 2002 at our center, followed up to 2005, were divided into high- and low-risk groups, based on the presence of one or more of the following: pre-transplant angina, myocardial infarction, and positive coronary angiogram. The two groups were compared for post-transplant cardiac events and patient and graft survival. The factors predictive of post-transplant cardiac events were also determined by Cox-regression multivariate analysis., Results: Forty-five patients (10.5%), out of 429, had post-transplant cardiac events; 31.3% in the high risk, and 6.5% in the low-risk group (p = 0.001). Five-yr patient survival was lower in the high-risk group (82.8% vs. 93.1%, p = 0.004), while five-yr overall graft survival and death censored graft survival were statistically not different (74.8% vs. 84.1%, p = 0.08 and 87.3% vs. 90%, p = 0.25). Forty-one percent of patients who were treated with angioplasty plus stenting or bypass graft prior to transplantation had post-transplant cardiac events, as compared with 28% of those without intervention in the high-risk group and 6.5% of patients in the low-risk group (p = 0.001). Age, pre-transplant cardiac disease, arrhythmias, and low-ejection fraction (< or = 40%) were significant independent predictors of post-transplant cardiac events., Conclusion: Post-transplant survival of high-CV risk patients (with known CAD) is lower than that of low-risk recipients but remains acceptable. Cardiac interventions may reduce perioperative risk but do not reduce the probability of post-transplant cardiac events to that of low-risk group.

The aim of the study is to evaluate if the occupational exposure to urban pollutants could cause alterations on 17-alfa-hydroxy-progesterone plasma levels and related diseases in male traffic policemen. 17-alpha-OH-P is synthesized in Leydig cells and in adrenals; it influences spermiogenesis, acrosoma reaction, testosterone biosynthesis, blocking of gonadotropin secretion; it regulates learning, memory and sleep. After excluding principal confounding factors, i.e., rotating or night shifts, exposure to solvents, paints and pesticides during time-off and smoking, traffic policemen were matched with controls by age, working life and drinking habit. Finally, 112 traffic policemen and 112 controls were included in the study. In traffic policemen 17-alpha-OH-P mean values were significantly higher vs. controls. The distribution of 17-alpha-OH-P values in both groups was significant. An increased frequency of fertility disorders referred to the questionnaire items were found in traffic policemen vs. controls, but the difference was not significant. The occupational exposure to low doses of chemical urban stressor, interacting with and adding to the psychosocial ones, could alter plasma 17-alpha-OH-P concentrations in traffic policemen vs. controls. 17-alpha-OH-P could be used as an early biological marker, even before the onset of the reproductive and mental health diseases.

There are few studies in literature about exposure to urban pollutants and effects on female reproductive health. The aim of the study was to evaluate if the occupational exposure to chemical urban stressor could cause luteinizing hormone (LH) plasma levels alterations in female traffic police compared to a control group. One hundred and eighty subjects were included in the study, subdivided into three different groups according to the day of the menstrual cycle (7th, 14th, 21st) in which a blood sample was taken. In follicular and lutheal phase of ovarian cycle, the LH mean levels were significantly higher in traffic police vs. controls. The distribution of LH values in traffic police and controls was significant in follicular, and lutheal phase. In ovulatory phase, LH mean levels were lower but not significant in traffic police compared to controls. An increase was found concerning mental health disorders referred to the questionnaire items in traffic police vs. controls, although the difference was not significant. Our results suggest that occupational exposure to urban stressor in female traffic police, may alter LH plasma concentrations. LH may be used in occupational set as an early biomarker of exposure to urban stressor.

Pathologies due to repetitive activity of the upper limb, well known in scientific literature as WMSDs (Work Related Musculoskeletal Disorders), are considerably increased in the last years. At the moment, there are no validated methods for the assessment of the work-related risk. This study compares two different methods proposed in literature for the assessment of the work-related risk, combining objective and subjective measures.

Background: Cyclosporine monitoring using the 2-hr postdose sample, C2, has been shown to have advantages in monitoring de novo renal transplant recipients. The purpose of this study was to assess cyclosporine exposure, using C2, in stable renal transplant patients previously monitored by C0 to determine the effect of dose reduction on patients with C2 more than 10% above target and the course of those with C2 at and more than 10% below target, whose dose was not modified., Methods: One hundred and seventy-five patients, three or more months after transplantation, had C2 assessed. The relationship of C2 to C0 and of both to renal function was analyzed by linear regression. Blood pressure, serum creatinine level, and lipids were followed for a mean of 15+/-2.6 months., Results: Eighty-five patients had values more than 10% above target, 42 were within 10% of target, and 48 were more than 10% below target. Cyclosporine dose was reduced in all patients above target. In this group, serum creatinine level was stable overall, but fell significantly in 46 (54%) of 85 from 153+/-55 to 132+/-49 microM. Blood pressure also fell in that group from 135/82 to 131/77. Serum creatinine level was stable in the remaining two groups of patients., Conclusions: These data suggest that dose reduction in many overexposed patients leads to improvements in renal function and blood pressure. Further study is required to confirm the long-term benefits of this strategy.

Objectives: Our institutional experience with 73 pediatric patients undergoing cardiac transplantation between January 1, 1990, and December 31, 1999, was reviewed to determine the impact of unconventional donor and recipient management protocols implemented to extend the availability of this therapy., Methods and Results: The introduction of donor blood cardioplegic solution with added insulin was associated with a significant improvement in patient and graft survival (hazard ratio [Cox] = 0.25, P =.08), despite significantly longer ischemic times with this protocol compared with the use of crystalloid-based donor procurement techniques (P <.01). Eleven patients underwent intentional transplantation of ABO-incompatible donor hearts with the aid of a protocol of plasma exchange on bypass. In this subgroup, there were 2 early deaths caused by nonspecific graft failure (n = 1) and respiratory complications with mild vascular rejection (n = 1), and there was 1 late death caused by lymphoma. ABO-incompatible transplantation was not a risk factor for death by multivariate analysis. The postoperative course in these patients suggests minimal reactivity directed against incompatible grafts on the basis of low anti-donor blood group antibody production, in association with a favorable rejection profile. Ten of 13 patients requiring preoperative support with an extracorporeal membrane oxygenator survived transplantation; there were 3 additional late deaths in this subgroup (hazard ratio = 2.88, P =.05)., Conclusions: The results with pediatric cardiac transplantation continue to improve as a result of changes in both surgical and medical protocols permitting successful treatment of patients conventionally considered at high risk or unsuitable for transplantation.

Background: Transplantation of hearts from ABO-incompatible donors is contraindicated because of the risk of hyperacute rejection mediated by preformed antibodies in the recipient to blood-group antigens of the donor. This contraindication may not apply to newborn infants, who do not yet produce antibodies to T-cell-independent antigens, including the major blood-group antigens., Methods: We studied 10 infants 4 hours to 14 months old (median, 2 months) who had congenital heart disease or cardiomyopathy and who received heart transplants from donors of incompatible blood type between 1996 and 2000. Serum isohemagglutinin titers were measured before and after transplantation. Plasma exchange was performed during cardiopulmonary bypass; no other procedures for the removal of antibodies were used. Standard immunosuppressive therapy was given, and rejection was monitored by means of endomyocardial biopsy. The results were compared with those in 10 infants who received heart transplants from ABO-compatible donors., Results: The overall survival rate among the 10 recipients with ABO-incompatible donors was 80 percent, with 2 early deaths due to causes presumed to be unrelated to ABO incompatibility. The duration of follow-up ranged from 11 months to 4.6 years. Two infants had serum antibodies to antigens of the donor's blood group before transplantation. No hyperacute rejection occurred; mild humoral rejection was noted at autopsy in one of the infants with antibodies. No morbidity attributable to ABO incompatibility has been observed. Despite the eventual development of antibodies to antigens of the donor's blood group in two infants, no damage to the graft has occurred. Because of the use of ABO-incompatible donors, the mortality rate among infants on the waiting list declined from 58 percent to 7 percent., Conclusions: ABO-incompatible heart transplantation can be performed safely during infancy before the onset of isohemagglutinin production; this technique thus contributes to a marked reduction in mortality among infants on the waiting list.

Method: Despite the need to expand the donor pool, it is unclear what parameters should be used. The value of donor renal pathology and calculated creatinine clearance (CrCl) in determining recipient outcome was assessed in 57 kidney transplants from 34 donors in whom pretransplant renal biopsies were performed because of age > or =60, hypertension, and/or vascular disease. We retrospectively compared clinical outcomes in these recipients and 57 control recipients selected to have the same baseline demographics but receiving transplants from low risk donors who were significantly younger (32+/-13.9 vs. 61+/-7.3 years) and lighter weight (71+/-18.1 vs. 84+/-20.2 kg) than the high-risk donors (P<.001 for both)., Results: Recipients of high-risk kidneys had a higher incidence of delayed graft function, defined by a <10% fall in serum creatinine (Cr) in the first 24 hr, (56% vs. 30%, P<.01), a higher incidence of rejection (60% vs. 37%, P = .02) and a higher Cr level (197+/-64 vs. 144+/-54 micromol/L at 18 months, P<.005). Graft and patient survival were similar; 12% and 5% vs. 91% and 9% in high-risk vs. control groups, respectively (P = NS). Donor renal pathology was scored 0-3 (none to severe disease) in four areas: glomerulosclerosis, interstitial fibrosis, tubular atrophy, and vascular disease. A donor vessel score of 3/3 was associated with a 100% incidence of delayed graft function and a mean 1-year Cr level of 275+106 micromol/L (compared with 43% and 192+54 micromol/L in those with lower vessel scores, P<.05). Calculated donor CrCl <100 ml/min was associated with higher recipient Cr levels at 1 year, 240+/-95 micromol/L vs. 180+/-54 micromol/L in recipients of kidneys from donors with CrCl levels >100 ml/min (P<.05). The mean 1-year Cr level was 320+/-102 micromol/L in recipients with both a vascular score of 3/3 and a donor CrCl <100 ml/min and 184+/-63 micromol/L in those with neither factor (P = .001)., Conclusion: Calculated donor CrCl and donor vascular pathology predict recipient graft function and may be helpful in selecting high-risk donors for single kidney transplantation.

Objective: To develop a set of comprehensive, standardized, evidence-based guidelines for the use of antiviral therapy to prevent cytomegalovirus disease in adult patients having undergone renal transplantation., Options: The use of medication, at the time of induction therapy or at the earliest sign of viremia. Treatments were evaluated by patient and donor serologic groups and the induction regimen used., Outcomes: The control of symptoms and features of cytomegalovirus disease over the first 6 mo to 1 yr after transplantation., Evidence: Articles, compiled using a MEDLINE search from 1976 to July 1997, were reviewed by representatives of nephrology, microbiology, pharmacy, and epidemiology. Additional information was obtained from recent review articles and conference abstracts, and from experts in the field., Values: The evidence-based methods and values of the Canadian Task Force on the Periodic Health Examinations were used. High value was placed on studies with a randomized controlled design and blinded outcome observers. Study quality was classified as poor when cointervention was present (especially with regard to immunosuppressive regimens), when more than 20% of patients were lost to follow-up, and when intention to treat analysis was not performed. Recommendations were made with a graded system (grades A and B: Use of the intervention advised, based on high or fair quality evidence, respectively; grades D and E: Use of the intervention not advised, based on high or fair quality evidence, respectively: grade C: No recommendation made because of insufficient or conflicting evidence)., Recommendations: (1) Seropositive recipient; donor seropositive or seronegative; immunosuppression with antilymphocyte products. Prophylaxis with antiviral therapy recommended (grade A recommendation). (2) Seronegative recipient; seropositive donor; immunosuppression with antilymphocyte products. Prophylaxis with antiviral therapy recommended (grade A recommendation) (3) Seronegative recipient; seropositive donor; conventional immunosuppression. Prophylaxis with antiviral therapy recommended (grade B recommendation). (4) Seronegative recipient; seronegative donor; any immunosuppressive regimen. No prophylaxis with antiviral therapy required (grade D/E recommendation). (5) Seropositive recipient: donor seropositive or seronegative; conventional immunosuppression. Prophylaxis left to the discrimination of the physician in charge (grade C recommendation).

1. The 5-year actuarial graft, patient and functional graft survival rates were analyzed in 743 consecutive primary cadaveric kidney transplants from The Toronto Hospital between January 1985-December 1997. 2. Recipient age > or = 55 years, male recipient sex, recipient diabetes mellitus, CIT > 36 hours and delayed graft function were found to significantly decrease patient survival. 3. Recipient age > or = 55 years, sensitization to HLA antigens (peak PRA > 50%), donor/recipient HLA antigen mismatches, CIT > 36 hours, delayed graft, function and 6-month SCr > 200 mumol/L were found to significantly decrease graft survival. 4. Acute rejection episodes had no significant impact on overall 5-year patient or graft survival. 5. The observation that serum creatinine > 200 mumol/L had a major adverse influence on long-term outcome reflects the importance of functional renal mass on graft survival.