Publications by authors named "Jeffrey Schiff"

61 Publications

Care processes and structures associated with higher medication adherence in adolescent and young adult transplant recipients.

Pediatr Transplant 2021 Aug 2:e14106. Epub 2021 Aug 2.

Research Institute of The McGill University Health Centre, Montreal, QC, Canada.

Background: We aimed to identify care processes and structures that were independently associated with higher medication adherence among young transplant recipients.

Methods: We conducted a prospective, observational cohort study of 270 prevalent kidney, liver, and heart transplant recipients 14-25 years old. Patients were ≥3 months post-transplant, ≥2 months post-discharge, and followed in one of 14 pediatric or 14 adult transplant programs in Canada. Patients were enrolled between June 2015 and March 2018 and followed for 6 months. Adherence was assessed at baseline, 3, and 6 months using the BAASIS self-report tool. Patients were classified as adherent if no doses were missed in the prior 4 weeks. Transplant program directors and nurses completed questionnaires regarding care organization and processes.

Results: Of the 270 participants, 99 were followed in pediatric programs and 171 in adult programs. Median age was 20.3 years, and median time since transplant was 5 years. At baseline, 71.5% were adherent. Multivariable mixed effects logistic regression models with program as a random effect identified two program-level factors as independently associated with better adherence: minimum number of prescribed blood draws per year for those >3 years post-transplant (per 1 additional) (OR 1.12 [95% CI 1.00, 1.26]; p = .047), and average time nurses spend with patients in clinic (per 5 additional minutes) (OR 1.15 [1.03, 1.29]; p = .017).

Conclusion: Program-level factors including protocols with a greater frequency of routine blood testing and more nurse time with patients were associated with better medication adherence. This suggests that interventions at the program level may support better adherence.
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http://dx.doi.org/10.1111/petr.14106DOI Listing
August 2021

Prospective Clinical, Virologic, and Immunologic Assessment of COVID-19 in Transplant Recipients.

Transplantation 2021 Jun 18. Epub 2021 Jun 18.

Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada. Department of Biochemistry, University Health Network, Toronto, ON, Canada.

Background: Several studies have described the clinical features of COVID-19 in solid organ transplant recipients. However, many have been retrospective or limited to more severe cases (hospitalized) and have not routinely included serial virologic sampling (especially in outpatients) and immunologic assessment.

Methods: Transplant patients diagnosed with COVID-19 based on a respiratory sample PCR were prospectively followed up to 90 days. Patients provided consent for convalescent serum samples and serial nasopharyngeal swabs for SARS-CoV-2 antibody (anti-nucleoprotein and anti-RBD) and viral load respectively.

Results: In the 161 SOT recipients diagnosed with COVID-19, the spectrum of disease ranged from asymptomatic infection (4.3%) to hospitalization (60.6%), supplemental oxygen requirement (43.1%), mechanical ventilation (22.7%) and death (15.6%). Increasing age (OR:1.031 95%CI 1.001-1.062, p=0.046) and >=2 comorbid conditions (OR:3.690 95%CI 1.418-9.615, p=0.007) were associated with need for supplemental oxygen. Allograft rejection was uncommon (3.7%) despite immunosuppression modification. Antibody response at >=14 days post-symptoms onset was present in 90% (anti-RBD) and 76.7% (anti-NP) with waning of anti-NP titers and stability of anti-RBD over time. Median duration of nasopharyngeal positivity was 10.0 days (IQR: 5.5-18.0) and shedding beyond 30 days was observed in 6.7% of patients. The development of antibody did not have an impact on viral shedding.

Conclusions: This study demonstrates the spectrum of COVID-19 illness in transplant patients. Risk factors for severe disease are identified. The majority form antibody by 2 weeks with differential stability over time. Prolonged viral shedding was observed in a minority of patients. Reduction of immunosuppression was a safe strategy.
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http://dx.doi.org/10.1097/TP.0000000000003860DOI Listing
June 2021

Evaluation of Recombinant Herpes Zoster Vaccine for Primary Immunization of Varicella-seronegative Transplant Recipients.

Transplantation 2021 01 19. Epub 2021 Jan 19.

1 Pediatric Infectious Diseases Unit, Geneva University Hospitals and Faculty of Medicine, 4 rue Gabrielle-Perret-Gentil, 1211 Geneva 4, Switzerland 2 Division of Infectious Diseases, Inselspital, Freiburgstrasse 18, 3010 Bern, Switzerland 3 Ajmera Transplant Centre, University Health Network, 585 University Avenue, Toronto, Ontario M5G 2N2, Canada 4 Centers for Disease Control and Prevention, Division of Viral Diseases, 1600 Clifton Road, Atlanta, GA 30333, USA.

Background: Immunization of VZV-seronegative solid organ transplant (SOT) patients using the live-attenuated varicella vaccine is generally contraindicated, leaving no widely applicable immunization option. The recombinant subunit herpes zoster vaccine (RZV) is indicated for VZV seropositive persons to prevent shingles but could potentially also protect VZV-seronegative persons against varicella. We performed a safety and immunogenicity evaluation of RZV in VZV-seronegative SOT recipients as an option for protection.

Methods: VZV-seronegative adult SOT patients with no history of varicella/shingles vaccine or disease were given 2 doses of RZV vaccine 2-6 months apart. Blood was drawn prevaccination (V1), prior to the second dose (V2) and 4 weeks after second dose (V3). Humoral (anti-gE) and cell-mediated immunity was evaluated, with polyfunctional cells defined as cells producing ≥2 cytokines.

Results: Among 31 eligible VZV-seronegative SOT patients screened, 23 were enrolled. Median age was 38 years and median time since transplant procedure was 38 years. The most frequent transplant types were liver (35%) and lung (30%). Median anti-gE levels significantly increased from V1 to V3 (p=0001) and V2 to V3 (p<0001), even though only 55% had a positive seroresponse. Median polyfunctional CD4 T-cells counts increased from V1 to V2 (54/10 vs 104/10 cells; p=0041), and from V2 to V3 (380/10; p=0002). Most adverse events were mild with no rejection episodes.

Conclusion: RZV was safe and elicited significant humoral and cellular responses in VZV-seronegative SOT patients, and has the potential to be considered as a preventive strategy against primary varicella.
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http://dx.doi.org/10.1097/TP.0000000000003621DOI Listing
January 2021

Angiogenesis Inhibitors as Anti-Cancer Therapy Following Renal Transplantation: A Case Report and Review of the Literature.

Curr Oncol 2021 01 22;28(1):661-670. Epub 2021 Jan 22.

Division of Medical Oncology & Hematology, Bras Family Drug Development Program, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON M5G2M9, Canada.

Solid organ transplant recipients on long-term immunosuppressive medication are at increased risk of developing malignancy, and treatment of advanced cancers with angiogenesis inhibitors in this context has not been widely studied. We present a case of recurrent high-grade serous ovarian carcinoma treated with paclitaxel and bevacizumab in the context of prior renal transplantation where the patient responded well to treatment with controlled toxicities, discussing the potential for increased rates of adverse events and drug interactions in this select population.
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http://dx.doi.org/10.3390/curroncol28010064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924357PMC
January 2021

Short-course, direct-acting antivirals and ezetimibe to prevent HCV infection in recipients of organs from HCV-infected donors: a phase 3, single-centre, open-label study.

Lancet Gastroenterol Hepatol 2020 07 6;5(7):649-657. Epub 2020 May 6.

Toronto General Hospital, University Health Network, University of Toronto, Toronto, ON, Canada; Soham and Shaila Ajmera Family Transplant Centre, University Health Network, University of Toronto, Toronto, ON, Canada.

Background: An increasing percentage of potential organ donors are infected with hepatitis C virus (HCV). After transplantation from an infected donor, establishment of HCV infection in uninfected recipients is near-universal, with the requirement for post-transplant antiviral treatment. The aim of this study was to determine if antiviral drugs combined with an HCV entry blocker given before and for 7 days after transplant would be safe and reduce the likelihood of HCV infection in recipients of organs from HCV-infected donors.

Methods: HCV-uninfected organ recipients without pre-existing liver disease were treated with ezetimibe (10 mg; an HCV entry inhibitor) and glecaprevir-pibrentasvir (300 mg/120 mg) before and after transplantation from HCV-infected donors aged younger than 70 years without co-infection with HIV, hepatitis B virus, or human T-cell leukaemia virus 1 or 2. Recipients received a single dose 6-12 h before transplant and once a day for 7 days after surgery (eight doses in total). HCV RNA was assessed once a day for 14 days and then once a week until 12 weeks post-transplant. The primary endpoint was prevention of chronic HCV infection, as evidenced by undetectable serum HCV RNA at 12 weeks after transplant, and assessed in the intention-to-treat population. Safety monitoring was according to routine post-transplant practice. 12-week data are reported for the first 30 patients. The trial is registered on ClinicalTrials.gov, NCT04017338. The trial is closed to recruitment but follow-up is ongoing.

Findings: 30 patients (23 men and seven women; median age 61 years (IQR 48-66) received transplants (13 lung, ten kidney, six heart, and one kidney-pancreas) from 18 HCV-infected donors. The median donor viral load was 5·11 logIU/mL (IQR 4·55-5·63) and at least three HCV genotypes were represented (nine [50%] donors with genotype 1, two [11%] with genotype 2, five [28%] with genotype 3, and two [11%] with unknown genotype). All 30 (100%) transplant recipients met the primary endpoint of undetectable HCV RNA at 12 weeks post-transplant, and were HCV RNA-negative at last follow-up (median 36 weeks post-transplant [IQR 25-47]). Low-level viraemia was transiently detectable in 21 (67%) of 30 recipients in the early post-transplant period but not after day 14. Treatment was well tolerated with no dose reductions or treatment discontinuations; 32 serious adverse events occurred in 20 (67%) recipients, with one grade 3 elevation in alanine aminotransferase (ALT) possibly related to treatment. Non-serious transient elevations in ALT and creatine kinase during the study dosing period resolved with treatment completion. Among the serious adverse events were two recipient deaths due to causes unrelated to study drug treatment (sepsis at 49 days and subarachnoid haemorrhage at 109 days post-transplant), with neither patient ever being viraemic for HCV.

Interpretation: Ezetimibe combined with glecaprevir-pibrentasvir given one dose before and for 7 days after transplant prevented the establishment of chronic HCV infection in recipients of different organs from HCV-infected donors. This study shows that an ultra-short course of direct-acting antivirals and ezetimibe can prevent the establishment of chronic HCV infection in the recipient, alleviating many of the concerns with transplanting organs from HCV-infected donors.

Funding: Canadian Institutes of Health Research; the Organ Transplant Program, University Health Network.
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http://dx.doi.org/10.1016/S2468-1253(20)30081-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391837PMC
July 2020

Clinical predictors of progression and clearance of low-level CMV DNAemia in solid organ transplant recipients.

Transpl Infect Dis 2020 Feb 19;22(1):e13207. Epub 2019 Nov 19.

Multi Organ Transplant Program, University Health Network, Toronto, ON, Canada.

Background: Low-level CMV DNAemia is common and in the absence of treatment may either progress to higher viral loads that require therapy, or may spontaneously resolve. The clinical predictors of progression and spontaneous viral clearance are not well defined.

Methods: We performed a retrospective cohort study of organ transplant recipients who had untreated low-level CMV DNAemia (<1000 IU/mL). Outcomes were evaluated for 8 weeks after initial viral detection, and progression to CMV high viral load was defined as CMV viral load ≥1000 IU/mL. CMV DNAemia doubling time was calculated for a subset of patients with sufficient viral load timepoints.

Results: Of the 297 patients analyzed, 118/297 (39.7%) patients progressed to a high viral load and the remaining cleared DNAemia spontaneously (46.8%) or remained at low level (13.4%). In multivariate analysis, progression was significantly more likely in lung transplant recipients (odds ratio 3.09) and less likely in those with an episode of previously treated CMV infection (odds ratio 0.081). In a subset of 27 patients with progression, the doubling time for CMV DNAemia was a median of 6.1 days (range 2.4-21.8).

Conclusion: We found that previous CMV infection significantly decreased the likelihood of low-level DNAemia progression suggesting that CMV immunity plays a role in progression vs spontaneous clearance.
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http://dx.doi.org/10.1111/tid.13207DOI Listing
February 2020

Pathologic measures of quality compare favorably in patients undergoing robot-assisted radical cystectomy to open cystectomy cohorts: a National Cancer Database analysis.

J Robot Surg 2020 Aug 3;14(4):609-614. Epub 2019 Oct 3.

Department of Urology, NYU-Winthrop Hospital, 1300 Franklin Ave, Garden City, Mineola, NY, 11530, USA.

This study aims to assess the impact of facility characteristics on measures of surgical quality (positive surgical margin rates and lymph-node yield) in patients undergoing robot-assisted (RARC) versus open (ORC) radical cystectomy using the National Cancer Database. Patients who received RC between the years of 2010-2013 were stratified according to surgery type (ORC vs. RARC), and corresponding patient and facility-level variables (facility type and volume) were assessed. Logistic regression models for procedure type, positive surgical margins (PSMs), and LN dissection (LND) rates were estimated. Radical cystectomies (ORC = 13,236, RARC = 3687) were performed more often in academic centers (58.3%) compared to community centers (31.6%). As facility volume increased, centers performed more LNDs during ORCs (p = 0.03) and the number of nodes retrieved increased in both ORC and RARC (ORC p < 0.001; RARC p < 0.0001). Increased facility volume also resulted in significantly fewer PSMs within the RARC cohort (p = 0.01). Comparison of ORC and RARC within each facility type cohort identified improved pathological metrics for RARC with fewer PSMs (p = 0.001) as well as increased LNDs (p < 0.0001) and median number of LNs retrieved (p < 0.0001), which suggests that RARC may facilitate comparative outcomes in community centers and academic centers. Overall, higher facility volume and robot-assisted surgery resulted in more favorable pathologic metrics compared to lower facility volume and ORC.
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http://dx.doi.org/10.1007/s11701-019-01031-zDOI Listing
August 2020

Cell-Mediated Immune Responses After Influenza Vaccination of Solid Organ Transplant Recipients: Secondary Outcomes Analyses of a Randomized Controlled Trial.

J Infect Dis 2020 01;221(1):53-62

Multi-Organ Transplant Program, University Health Network, Toronto, Canada.

Background: Despite annual immunization, solid organ transplant (SOT) patients remain at increased risk for severe influenza infection because of suboptimal vaccine immunogenicity. We aimed to compare the CD4+ and CD8+ T-cell responses of the high-dose (HD) and the standard-dose (SD) trivalent inactivated vaccine.

Methods: We collected peripheral blood mononuclear cells pre- and postimmunization from 60 patients enrolled in a randomized trial of HD versus SD vaccine (30 HD; 30 SD) during the 2016-2017 influenza season.

Results: The HD vaccine elicited significantly greater monofunctional and polyfunctional CD4+ and CD8+ T-cell responses against influenza A/H1N1, A/H3N2, and B. For example, median vaccine-elicited influenza-specific polyfunctional CD4+ T cells were higher in recipients of the HD than SD vaccine after stimulation with influenza A/H1N1 (1193 vs 0 per 106 CD4+ T cells; P = .003), A/H3N2 (1154 vs 51; P = .008), and B (1102 vs 0; P = .001). Likewise, vaccine-elicited influenza-specific polyfunctional CD8+ T cells were higher in recipients of the HD than SD vaccine after stimulation with influenza B (367 vs 0; P = .002).

Conclusions: Our study provides novel evidence that HD vaccine elicits greater cellular responses compared with the SD vaccine in SOT recipients, which provides support to preferentially consider use of HD vaccination in the SOT setting.
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http://dx.doi.org/10.1093/infdis/jiz471DOI Listing
January 2020

A Gap Analysis Assessing the Perceptions of Primary Care Physicians in the Management of Kidney Recipients After Transplantation.

Prog Transplant 2019 12 11;29(4):309-315. Epub 2019 Sep 11.

Division of Nephrology and the Kidney Transplant Program, University Health Network, Toronto, Ontario, Canada.

Objectives: To examine the practice patterns and perceptions of primary care physicians in the management of chronic diseases in kidney recipients, assess care provided to recipients, and identify barriers to the optimal delivery of primary care to recipients.

Methods: A self-administered questionnaire on the primary care of kidney recipients was developed and implemented. The survey investigated physician comfort and practice patterns in providing preventive and chronic care to recipients, patient self-management support, and physician perceptions on communication with transplant centers and barriers to ideal care.

Results: A total of 210 physicians completed the survey (response rate of 22%). Among the respondents, 73% indicated they were currently providing care to kidney recipients. The majority of physicians specified that they rarely (57%) or never (20%) communicate with transplant centers. Most physicians felt comfortable providing care to recipients for non-transplant-related issues (92.5%), vaccinations (85%), and periodic health examinations (94%). The majority (75.3%) of physicians felt uncomfortable managing the immunosuppressive medications of recipients. Physicians' most commonly stated barriers to delivering optimal care to recipients were insufficient guidelines provided by the transplant center (68.9%) and lack of knowledge in managing recipients (58.8%). Suggested resources by physicians to improve their comfort level in managing recipients included guidelines and continuing medical educational activities related to transplantation.

Conclusions: Our results suggest that there are barriers to delivering optimal primary care to kidney recipients. The approach to providing resources needed to bridge the knowledge gap for physicians in the management of recipients requires further exploration.
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http://dx.doi.org/10.1177/1526924819873911DOI Listing
December 2019

A Case of a Primary Intratesticular Leiomyosarcoma With Metastatic Disease.

Urology 2020 Feb 27;136:e45-e47. Epub 2019 Aug 27.

Department of Urology, NYU Winthrop Hospital, Mineola, NY.

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http://dx.doi.org/10.1016/j.urology.2019.08.023DOI Listing
February 2020

Measurement That Matters-Joy in the Village!

Psychiatr Serv 2019 05;70(5):357

Minnesota Department of Human Services, St. Paul, Minnesota (Schiff); Integrated Care Program, Boston Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston (Antonelli).

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http://dx.doi.org/10.1176/appi.ps.70503DOI Listing
May 2019

Systemic immunosuppression in limbal stem cell transplantation: best practices and future challenges.

Can J Ophthalmol 2018 08 20;53(4):314-323. Epub 2018 Jan 20.

Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Ont.; Toronto Transplant Institute, University Health Network, Toronto, Ont.. Electronic address:

The objective of this study was to evaluate systemic immunosuppression regimens used for patients undergoing ocular surface stem cell transplantation, including their benefits and adverse effects in the adjunctive management of limbal stem cell deficiency (LSCD). A systematic literature review was conducted using the MEDLINE and EMBASE databases (1980-2015). Data were collected on surgical intervention(s), type of immunosuppressive agent(s), duration of immunosuppression, percentage with stable ocular surface at last follow-up, mean follow-up time, and demographics. Data were also collected on adverse ocular and systemic outcomes. Sixteen reports met the inclusion criteria. There were no randomized controlled studies. Three studies were noncomparative prospective case series, whereas the majority were retrospective case series. Bilateral severe LSCD was the most common disease (50%), and keratolimbal allograft was the most common intervention (80%). Immunosuppressive regimens showed a progression from early studies using oral cyclosporine to later studies using combinations of mycophenolate mofetil and tacrolimus. Most studies included a course of high-dose systemic corticosteroids. For patients adherent to long-term systemic immunosuppression, stable ocular surface rates of 70%-80% at last follow-up were reported. Adverse effects included hypertension, diabetes mellitus, and biochemical abnormalities managed with pharmacotherapy or discontinuation of offending agents. There were no cases of mortality related to immunosuppression. However, the current literature does not elucidate which immunosuppressive regimen is most efficacious for different categories of LSCD or graft types. Evidence-based guidelines for systemic immunosuppression in limbal allograft therapy would benefit from randomized controlled and/or additional prospective studies. Long-term immunosuppression would benefit from close collaboration between ophthalmologists and transplant specialists to individualize treatments.
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http://dx.doi.org/10.1016/j.jcjo.2017.10.040DOI Listing
August 2018

Risk factors for surgical site infection after kidney and pancreas transplantation.

Infect Control Hosp Epidemiol 2018 09 13;39(9):1042-1048. Epub 2018 Jul 13.

Multi-Organ Transplant Program, University Health Network, University of Toronto, Toronto, Ontario, Canada.

Objective: To evaluate the incidence of surgical site infection (SSI) in a cohort of pancreas transplant recipients and assess predisposing risk factors for SSI DESIGN: Retrospective cohort study SETTING: Single transplant center in CanadaPatientsPatients who underwent any simultaneous pancreas and kidney (SPK) or pancreas after kidney (PAK) transplant procedures between January 2000 and December 2015 METHODS: In this retrospective cohort evaluation of SPK or PAK recipients, we assessed the incidence of SSI and risk factors associated with superficial, deep, and organ/space SSI. Multivariate logistic regression was used to identify independent risk factors for SSI in SPK and PAK recipients.

Results: In total, 445 adult transplant recipients were enrolled. The median age of these patients was 51 years (range, 19-71 years), and 64.9% were men. SSIs were documented in 108 patients (24.3%). Organ/space SSIs predominated (59 patients, 54.6%), followed by superficial SSIs (47 patients, 43.5%) and deep SSIs (3 patients, 2.8%). Factors predictive of SSIs in the multivariate analysis were cold pancreas ischemic time (odds ratio [OR], 1.002; P=.019) and SPK transplant (compared to PAK transplant recipients; OR, 2.38; P=.038). Patients with SSIs developed graft loss more frequently (OR, 16.99; P<.001).

Conclusions: Organ/space SSIs remain a serious and common complication after SPK and PAK. Prolonged cold ischemic time and SPK transplant were the risk factors predictive of SSIs. Appropriate perioperative prophylaxis in high-risk patients targeting the potential pathogens producing SSIs in kidney and/or pancreas transplant recipients and a reduction in cold ischemia may prove beneficial in reducing these SSIs.
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http://dx.doi.org/10.1017/ice.2018.148DOI Listing
September 2018

Cost-Effectiveness of a Community-Based Diabetes Prevention Program with Participation Incentives for Medicaid Beneficiaries.

Health Serv Res 2018 12 16;53(6):4704-4724. Epub 2018 May 16.

HealthPartners Institute, Bloomington, MN.

Objective: To examine the cost-effectiveness of a community-based Diabetes Prevention Program (DPP) for Medicaid beneficiaries from the perspective of the health care sector.

Data Sources/study Setting: A total of 847 Medicaid enrollees at high risk for type 2 diabetes participating in a community-based DPP.

Study Design: Pre- and post clinical outcome and cost data were used as inputs into a validated diabetes simulation model. The model was used to evaluate quality-adjusted life years (QALYs) and health care costs over a 40-year time horizon from the perspective of the health care sector.

Data Collection/extraction Methods: Clinical outcome and cost data were derived from a study examining the effect of financial incentives on weight loss.

Principal Findings: Study participants lost an average of 4.2 lb (p < .001) and increased high-density lipoprotein cholesterol by 1.75 mg/dl (p = .002). Intervention costs, which included financial incentives for participation and weight loss, were $915 per participant. The incremental cost-effectiveness ratio was estimated to be $14,011 per QALY but was sensitive to the time horizon studied.

Conclusions: Widespread adoption of community-based DPP has the potential to reduce diabetes and cardiovascular-related morbidity and mortality for low-income persons at high risk for diabetes and may be a cost-effective investment for Medicaid programs.
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http://dx.doi.org/10.1111/1475-6773.12973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232439PMC
December 2018

Effects of Focal vs Total Cryotherapy and Minimum Tumor Temperature on Patient-reported Quality of Life Compared With Active Surveillance in Patients With Prostate Cancer.

Urology 2018 03 23;113:110-118. Epub 2017 Dec 23.

Stony Brook University School of Medicine, Stony Brook, NY; Department of Urology, NYU-Winthrop Hospital, Mineola, NY.

Objective: To investigate the effects of focal (hemiablation) or total cryotherapy and minimum tumor temperature on patient-reported quality of life (QoL) in patients with prostate cancer.

Methods: An Institutional Review Board-approved database was reviewed for patients who underwent cryotherapy or active surveillance (AS). QoL questionnaire responses were collected and scores were analyzed for differences between focal and total cryotherapy and between very cold (<-76°C) and moderate-cold (≥-76°C) minimum tumor temperatures.

Results: A total of 197 patients responded to a total of 547 questionnaires. Focal and total cryotherapy patients had initially lower sexual function scores relative to AS (year 1 mean difference focal: -31.7, P <.001; total: -48.1, P <.001). Focal cryotherapy was associated with a more rapid improvement in sexual function. Both focal and total cryotherapy sexual function scores were not statistically significantly different from the AS cohort by postprocedural year 4. Very cold and moderate-cold temperatures led to initially lower sexual function scores relative to AS (year 1 very cold: -38.1, P <.001; moderate-cold: -30.7, P <.001). Moderate-cold temperature scores improved more rapidly than those of very cold temperature. Neither very cold nor moderate-cold temperatures had a statistically significant difference in sexual function scores relative to AS by postprocedural year 4. Urinary function and bowel habits were not significantly different between focal and total cryotherapy and between very cold and moderate-cold temperature groups.

Conclusion: Focal cryotherapy and moderate-cold (≥-76°C) temperature were associated with favorable sexual function relative to total cryotherapy and very cold temperature, respectively. No significant differences in urinary function or bowel habits were observed between groups.
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http://dx.doi.org/10.1016/j.urology.2017.10.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5866195PMC
March 2018

Randomized open-label crossover assessment of Prograf vs Advagraf on immunosuppressant pharmacokinetics and pharmacodynamics in simultaneous pancreas-kidney patients.

Clin Transplant 2018 02 29;32(2). Epub 2018 Jan 29.

Department of Surgery, Multi-organ Transplant Program, Western University, London, ON, Canada.

Introduction: We assessed the pharmacokinetic and pharmacodynamic impact of converting stable simultaneous pancreas-kidney (SPK) recipients from standard tacrolimus (Prograf) to long-acting tacrolimus (Advagraf).

Methods: In a randomized prospective crossover study, stable SPK recipients on Prograf were assigned to Prograf with 1:1 conversion to Advagraf or vice versa. Demographics, tacrolimus, mycophenolic acid levels, and Cylex CD4 + ATP levels were taken at specified intervals in addition to standard blood work.

Results: Twenty-one patients, who were a minimum of 1 year post-transplant, were entered into the study. No difference in tacrolimus or mycophenolic acid levels was noted between patients who were first assigned to Prograf or Advagraf. Additionally, Cylex levels as well as serum creatinine, lipase, and blood sugar levels were unchanged. There were no episodes of rejection during the 6-month study.

Conclusions: It is safe to convert between Prograf and Advagraf 1:1, without major impact on pharmacokinetics or pharmacodynamics in SPK recipients.
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http://dx.doi.org/10.1111/ctr.13180DOI Listing
February 2018

A Double-Blind, Randomized Trial of High-Dose vs Standard-Dose Influenza Vaccine in Adult Solid-Organ Transplant Recipients.

Clin Infect Dis 2018 05;66(11):1698-1704

Multi Organ Transplant Program, University Health Network, University of Toronto, Ontario, Canada.

Background: The annual standard-dose (SD) influenza vaccine has suboptimal immunogenicity in solid organ transplant recipients (SOTRs). Influenza vaccine that contains higher doses of antigens may lead to greater immunogenicity in this population.

Methods: We conducted a randomized, double-blind trial to compare the safety and immunogenicity of the 2016-2017 high-dose (HD; FluzoneHD, Sanofi) vs SD (Fluviral, GSK) influenza vaccine in adult SOTRs. Preimmunization and 4-week postimmunization sera underwent strain-specific hemagglutination inhibition assay.

Results: We enrolled 172 patients who received study vaccine, and 161 (84 HD; 77 SD) were eligible for analysis. Seroconversion to at least 1 of 3 vaccine antigens was present in 78.6% vs 55.8% in HD vs SD vaccine groups (P < .001), respectively. Seroconversions to A/ H1N1, A/H3N2, and B strains were 40.5% vs 20.5%, 57.1% vs 32.5%, and 58.3% vs 41.6% in HD vs SD vaccine groups (P = .006, P = .002, P = .028, respectively). Post-immunization geometric mean titers of A/H1N1, A/H3N2, and B strains were significantly higher in the HD group (P = .007, P = .002, P = .033). Independent factors associated with seroconversion to at least 1 vaccine strain were the use of HD vaccine (odds ratio [OR], 3.23; 95% confidence interval [CI], 1.56-6.67) and use of mycophenolate doses <2 g daily (OR, 2.76; 95% CI, 1.12-6.76).

Conclusions: HD vaccine demonstrated significantly better immunogenicity than SD vaccine in adult transplant recipients and may be the preferred influenza vaccine for this population.

Clinical Trials Registration: NCT03139565.
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http://dx.doi.org/10.1093/cid/cix1082DOI Listing
May 2018

Patient-reported quality of life progression in men with prostate cancer following primary cryotherapy, cyberknife, or active holistic surveillance.

Prostate Cancer Prostatic Dis 2018 09 7;21(3):355-363. Epub 2017 Dec 7.

Stony Brook University School of Medicine, Stony Brook, NY, 11794, USA.

Background: Technological advancements have led to the success of minimally invasive treatment modalities for prostate cancer such as CyberKnife and Cryotherapy. Here, we investigate patient-reported urinary function, bowel habits, and sexual function in patients following CyberKnife (CK) or Cryotherapy treatment, and compare them with active holistic surveillance (AHS) patients.

Methods: An IRB-approved institutional database was retrospectively reviewed for patients who underwent CK, Cryotherapy, or AHS. Quality of life (QoL) survey responses were collected every three months and the mean function scores were analyzed in yearly intervals over the 4 years post-treatment.

Results: 279 patients (767 survey sets) were included in the study. There was no difference among groups in urinary function scores. The CyberKnife group had significantly lower bowel habit scores in the early years following treatment (year 2 mean difference: -5.4, P < 0.01) but returned to AHS level scores by year 4. Cryotherapy patients exhibited initially lower, but not statistically significant, bowel function scores, which then improved and approached those of AHS. Both CyberKnife (year 1 mean difference: -26.7, P < 0.001) and Cryotherapy groups (-35.4, P < 0.001) had early lower sexual function scores relative to AHS, but then gradually improved and were not significantly different from AHS by the third year post-treatment. A history of hormonal therapy was associated with a lower sexual function scores relative to those patients who did not receive hormones in both CyberKnife (-18.45, P < 0.01) and Cryotherapy patients (-14.6, P < 0.05).

Conclusions: After initial lower bowel habits and sexual function scores, CyberKnife or Cryotherapy-treated patients had no significant difference in QoL relative to AHS patients. These results highlight the benefit of CyberKnife and Cryotherapy in the management of organ-confined prostate cancer.
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http://dx.doi.org/10.1038/s41391-017-0004-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991980PMC
September 2018

PSA kinetics following primary focal cryotherapy (hemiablation) in organ-confined prostate cancer patients.

World J Urol 2018 Feb 17;36(2):209-213. Epub 2017 Nov 17.

Department of Urology, NYU-Winthrop Hospital, 1300 Franklin Ave, Garden City, Mineola, NY, 11530, USA.

Purpose: We aim to evaluate prostate-specific antigen (PSA) trends in post-primary focal cryotherapy (PFC) patients.

Materials And Methods: This was an institutional review board-approved retrospective study of PFC patients from 2010 to 2015. Patients with at least one post-PFC PSA were included in the study. Biochemical recurrence (BCR) was determined using the Phoenix criteria. PSA bounce was also assessed. We analyzed rates of change of PSA over time of post-PFC between BCR and no BCR groups. PSA-derived variables were analyzed as potential predictors of BCR.

Results: A total of 104 PFC patients were included in our analysis. Median (range) age and follow-up time were 66 (48-82) years and 19 (6.3-38.6) months, respectively. Four (3.8%) patients experienced PSA bounce. The median percent drop in first post-PFC PSA of 80.0% was not associated with BCR (p = 0.256) and may indicate elimination of the index lesion. The rate of increase of PSA in BCR patients was significantly higher compared to patients who did not recur (median PSA velocity (PSAV): 0.15 vs 0.04 ng/ml/month, p = 0.001). Similar to PSAV (HR 9.570, 95% CI 3.725-24.592, p < 0.0001), PSA nadir ≥ 2 ng/ml [HR (hazard ratio) 1.251, 95% CI 1.100-1.422, p = 0.001] was independently associated with BCR.

Conclusion: A significant drop in post-PFC PSA may indicate elimination of the index lesion. Patients who are likely to recur biochemically have a significantly higher PSAV compared to those who do not recur. Nadir PSA of less than 2 ng/ml may be considered the new normal PSA in focal cryotherapy (hemiablation) follow-up.
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http://dx.doi.org/10.1007/s00345-017-2130-5DOI Listing
February 2018

Preserving the Pancreas Graft: Outcomes of Surgical Repair of Duodenal Leaks in Enterically Drained Pancreas Allografts.

Transplant Direct 2017 Jul 23;3(7):e179. Epub 2017 Jun 23.

Department of Surgery, University Health Network, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.

Background: Duodenal leak remains a major cause of morbidity and graft loss in pancreas transplant recipients. The role and efficacy of surgical and image-guided interventions to salvage enterically drained grafts with a duodenal leak has yet to be defined.

Methods: We investigated the incidence, treatment, and outcome of duodenal leak in 426 pancreas transplantation recipients from 2000 to 2015.

Results: Duodenal leak developed in 33 (7.8%) recipients after a median follow-up of 5.3 (range, 0.5-15.2) years. Most leaks occurred during the first year (n = 22; 67%), and most were located near the proximal and distal duodenal staple line. Graft pancreatectomy was performed in 8 patients as primary therapy because of unfavorable local and/or systemic conditions. Salvage was attempted in 25 patients using percutaneous drainage (n = 4), surgical drainage (n = 4), or surgical repair (n = 17). Percutaneous or surgical drainage failed to control the leak in 7 of these 8 patients, and all 7 ultimately required graft pancreatectomy for persistent leak and sepsis. Surgical repair salvaged 14 grafts, and 13 grafts continue to function after a median follow-up of 2.9 (range, 1.1-6.3) years after repair.

Conclusions: Our study shows that in selected patients a duodenal leak can be repaired successfully and safely in enterically drained grafts.
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http://dx.doi.org/10.1097/TXD.0000000000000698DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498020PMC
July 2017

Salvage focal cryosurgery may delay use of androgen deprivation therapy in cryotherapy and radiation recurrent prostate cancer patients.

Int J Hyperthermia 2017 11 29;33(7):810-813. Epub 2017 Mar 29.

a Department of Urology , Winthrop University Hospital , Garden City , NY , USA.

Introduction: Salvage treatment options for recurrent unilateral prostate cancer (PCa) after primary radiation are limited and associated with severe complications and poor quality of life measures. Salvage focal cryotherapy (SFC) has shown success in biochemical recurrence (BCR) free survival. We aim to determine if SFC can delay use of androgen deprivation therapy (ADT) in recurrent PCa with low morbidity.

Methods: A retrospective review of patients who underwent SFC at our institution from 2007 to 2015 was performed. Patients with <2 follow-up prostate-specific antigen (PSA) values, metastatic disease, and a history of radical prostatectomy were excluded. Age at treatment, prior treatment history, PSA nadir, complications, BCR status (nadir +2 ng/ml), and follow-up data were obtained/analysed. ADT was commenced if patient experienced BCR and had a PSA doubling time <6 months or positive confirmatory biopsy or positive imaging. Cox regression and survival analysis were used to assess confounding and time to BCR respectively.

Results: A total of 65 patients were included and followed for a median of 26.6 (8.0-99.0) months. Thirty-one (47.7%) patients did not experience BCR. An even higher number of patients (52/65, 80.0%) are yet to receive ADT. Of those who experienced BCR [median time to BCR, 17.1 [interquartile range (IQR):11.4-23.3] months], 22/34 (64.7%) are currently carefully monitored without ADT. Survival analysis showed a biochemical recurrence-free survival of 48.1 at 1- and 3-year follow up. No patient died/experienced major complications.

Conclusions: SFC may be used to delay the use of ADT. Further assessment of our findings with high-powered studies and longer follow-up is required.
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http://dx.doi.org/10.1080/02656736.2017.1306121DOI Listing
November 2017

Use of Canagliflozin in Kidney Transplant Recipients for the Treatment of Type 2 Diabetes: A Case Series.

Diabetes Care 2017 07 17;40(7):e75-e76. Epub 2017 Apr 17.

Division of Nephrology, Department of Medicine, University of Toronto, Toronto, Canada

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http://dx.doi.org/10.2337/dc17-0237DOI Listing
July 2017

Predictors of biochemical recurrence after primary focal cryosurgery (hemiablation) for localized prostate cancer: A multi-institutional analytic comparison of Phoenix and Stuttgart criteria.

Urol Oncol 2017 08 11;35(8):530.e15-530.e19. Epub 2017 Apr 11.

Department of Urology, Winthrop University Hospital, Mineola, NY.

Background: The Phoenix definition (PD) and Stuttgart definition (SD) designed to determine biochemical recurrence (BCR) in patients with postradiotherapy and high-intensity focused ultrasound organ-confined prostate cancer are being applied to follow patients after cryosurgery. We sought to identify predictors of BCR using the PD and SD criteria in patients who underwent primary focal cryosurgery (PFC).

Materials And Methods: We performed a retrospective review of patients who underwent PFC (hemiablation) at 2 referral centers from 2000 to 2014. Patients were followed up with serial prostate-specific antigen (PSA). PSA levels, pre- and post-PFC biopsy, Gleason scores, number of positive cores, and BCR (PD = [PSA nadir+2ng/ml]; SD = [PSA nadir+1.2ng/ml]) were recorded. Patients who experienced BCR were biopsied, monitored carefully or treated at the discretion of the treating urologist. Cox regression and survival analyses were performed to assess time to BCR using PD and SD.

Results: A total of 163 patients were included with a median follow-up of 36.6 (interquartile range: 18.9-56.4) months. In all, 64 (39.5%) and 98 (60.5%) experienced BCR based on PD and SD, respectively. On multivariable Cox regression, the number of positive pre-PFC biopsy cores was an independent predictor of both PD (hazard ratio [HR] = 1.4, P = 0.001) and SD (HR = 1.3, P = 0.006) BCRs. Post-PFC PSA nadir was an independent predictor of BCR using the PD (HR = 2.2, P = 0.024) but not SD (HR = 1.4, P = 0.181). Survival analysis demonstrated a 3-year BCR-free survival rate of 56% and 36% for PD and SD, respectively. Of those biopsied after BCR, 14/26 (53.8%) using the PD and 18/35 (51.4%) using the SD were found to have residual/recurrent cancer. Of those with prostate cancer on post-PFC biopsy, 57.1% of those with BCR by the PD and 66.7% of those with BCR by the SD were found to have a Gleason score ≥7.

Conclusion: Both the PD and the SD may be used to determine BCR in post-PFC patients. However, the ideal definition of BCR after PFC remains to be elucidated.
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http://dx.doi.org/10.1016/j.urolonc.2017.03.016DOI Listing
August 2017

Conservative Pancreas Graft Preservation at the Extreme.

Transplant Direct 2016 Jan 15;2(1):e50. Epub 2015 Dec 15.

Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.

Because of the value some patients place in remaining insulin-independent after pancreas transplantation, they may be reluctant to undergo graft pancreatectomy, even in the face of extreme complications, such as graft thrombosis and duodenal segment leak. Partly, for this reason, a variety of complex salvage techniques have been described to save the graft in such circumstances. We report a case of a series of extreme complications related to a leak from the duodenal segment after a simultaneous pancreas and kidney transplant. These included infected thrombosis of the inferior vena cava associated with a graft venous thrombosis and a retroperitoneal fistula. The patient retained graft function with insulin independence and repeatedly declined graft pancreatectomy against the advice of the transplant team. Conservative treatment with percutaneous drainage, antibiotics, and anticoagulation was eventually successful. This outcome is unique in our experience and may be instructive to teams caring for pancreas transplant recipients.
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http://dx.doi.org/10.1097/TXD.0000000000000558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946502PMC
January 2016

Gross Findings of Widespread Visceral Metastasis of Prostatic Adenocarcinoma With Neuroendocrine Features: A Case Report.

Urol Case Rep 2016 Sep 21;8:49-51. Epub 2016 Jul 21.

Department of Urology, Winthrop University Hospital, Mineola, New York, USA.

Although prostate cancer is common in the western world and is associated with favorable overall survival, neuroendocrine prostate cancer is difficult to detect and is known to aggressively metastasize throughout the body. This subset of disease thus has a poor prognosis, and early detection and treatment of neuroendocrine prostate cancer may increase overall survival. We present a case of a now deceased 63 year old male with extensive epicardial, respiratory, hepato-bilary, adrenal, genitourinary, and osseous tissue metastasis.
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http://dx.doi.org/10.1016/j.eucr.2016.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963249PMC
September 2016

The significance of pre-operative coronary interventions on outcome after pancreas transplantation.

Clin Transplant 2016 Mar 25;30(3):233-40. Epub 2016 Jan 25.

Department of Surgery, Toronto General Hospital, University of Toronto, Toronto, ON, Canada.

Pancreas transplant candidates are at very high risk of coronary vascular disease. We hypothesized that the requirement for pre-operative coronary intervention (PCI) may be associated with an adverse impact on short- and long-term outcomes. Retrospective analysis of 366 consecutive primary pancreas transplants was undertaken. Outcomes were compared between recipients who had undergone PCI (n = 48) and those who had not (n = 318). In 48% (23/48) of instances, the PCI was initiated by the transplant cardiology evaluation. The recipients undergoing PCI were older than those not undergoing PCI (47.6 yr vs. 41.9 yr, respectively, p < 0.0001). Although not statistically significant, there was a higher rate of post-operative major cardiovascular events (MCVE) in the PCI group (10.4%) compared with those not undergoing PCI (4.7%) (RR [95% CI]: 2.0 [0.90-4.5]; p = 0.17). In the long term, there were no differences in the rate of death with graft function (p = 0.77) or rejection (p = 0.17). There were no statistically significant differences between the groups with respect to patient (p = 0.54), kidney (p = 0.76), or pancreas (p = 0.63) graft survival. PCI is not a risk factor for short-term perioperative events, and long-term transplant outcomes are equivalent to patients not requiring PCI. PCI, by itself, should not be considered a contraindication for pancreas transplantation, but should raise awareness of perioperative risk.
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http://dx.doi.org/10.1111/ctr.12681DOI Listing
March 2016

Benefits of a transfer clinic in adolescent and young adult kidney transplant patients.

Can J Kidney Health Dis 2015 15;2:45. Epub 2015 Dec 15.

Division of Nephrology and Department of Medicine, University Health Network, Toronto, Ontario Canada ; Multi-Organ Transplant Program, University Health Network, Toronto, Ontario Canada ; Toronto General Hospital, 585 University Avenue, 11 PMB 185, Toronto, Ontario M5G 2N2 Canada.

Background: Adolescent and young adult kidney transplant recipients have worse graft outcomes than older and younger age groups. Difficulties in the process of transition, defined as the purposeful, planned movement of adolescents with chronic health conditions from child to adult-centered health care systems, may contribute to this. Improving the process of transition may improve adherence post-transfer to adult care services.

Objective: The purpose of this study is to investigate whether a kidney transplant transfer clinic for adolescent and young adult kidney transplant recipients transitioning from pediatric to adult care improves adherence post-transfer.

Methods: We developed a joint kidney transplant transfer clinic between a pediatric kidney transplant program, adult kidney transplant program, and adolescent medicine at two academic health centers. The transfer clinic facilitated communication between the adult and pediatric transplant teams, a face-to-face meeting of the patient with the adult team, and a meeting with the adolescent medicine physician. We compared the outcomes of 16 kidney transplant recipients transferred before the clinic was established with 16 patients who attended the clinic. The primary outcome was a composite measure of non-adherence. Non-adherence was defined as either self-reported medication non-adherence or displaying two of the following three characteristics: non-attendance at clinic, non-attendance for blood work appointments, or undetectable calcineurin inhibitor levels within 1 year post-transfer.

Results: The two groups were similar at baseline, with non-adherence identified in 43.75 % of patients. Non-adherent behavior in the year post-transfer, which included missing clinic visits, missing regular blood tests, and undetectable calcineurin inhibitor levels, was significantly lower in the cohort which attended the transfer clinic (18.8 versus 62.5 %, p = 0.03). The median change in estimated glomerular filtration rate (eGFR) in the year following transfer was smaller in the group that attended the transition clinic (-0.9 ± 13.2 ml/min/1.73 m(2)) compared to those who did not (-12.29 ± 14.9 ml/min/1.73 m(2)), p = 0.045.

Conclusions: Attendance at a single kidney transplant transfer clinic was associated with improved adherence and renal function in the year following transfer to adult care. If these changes are sustained, they may improve long-term graft outcomes for adolescent kidney transplant recipients.
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http://dx.doi.org/10.1186/s40697-015-0081-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678464PMC
December 2015

Canadian Forum on Combined Organ Transplantation.

Transplantation 2016 06;100(6):1339-48

1 Division of Nephrology, Department of Medicine, Multi-Organ Transplant Program, McGill University Health Center, Montréal, Québec, Canada. 2 Division of Pediatric Nephrology, University of British Columbia, Vancouver, British Columbia, Canada. 3 Division of Nephrology, Department of Medicine, St. Paul's Hospital, Vancouver, British Columbia, Canada. 4 Division of Nephrology, Department of Medicine, Multi-Organ Transplant Program, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. 5 Canadian Blood Services Donation and Transplantation, Edmonton, Alberta, Canada. 6 Division of Surgery, Multi-Organ-Transplant Program, Queen Elisabeth II, Health Sciences Centre, Dalhousie University, Halifax, Nova Scotia, Canada. 7 Division of Gastroenterology, Department of Medicine, Liver Transplant Program, University of Alberta Hospital, Edmonton, Alberta, Canada. 8 Department of Paediatrics, Labatt Family Heart Centre, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. 9 Division of Cardiology, Department of Medicine, Multi-Organ Transplant Program, Alberta Health Services, Calgary, Alberta, Canada. 10 Division of Pulmonary Medicine, Department of Medicine, Lung Transplant Program, University of Alberta Hospital, Edmonton, Alberta, Canada. 11 Division of Nephrology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada l2 Division of Nephrology, Department of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.

The Canadian Society of Transplantation and Canadian Blood Services conducted a consensus forum on combined renal/nonrenal transplants, as they are not part of Canadian organ-specific allocation models at present. The purpose of this initiative was to make recommendations, develop eligibility criteria, and a decision-making model on listing and allocation. Forty-two participants with expertise in combined transplantation participated in the consensus forum. The United States and Canadian data were reviewed. The consensus forum made recommendations regarding the following: (1) investigation of etiology, severity, duration, and level of renal dysfunction; (2) documentation of degree of nonreversible kidney injury; (3) eligibility for combined (either simultaneous or staged) transplantation; (4) research. Key recommendations were: (1) patients with end-stage nonrenal disease with estimated glomerular filtration rate less than 30 mL/min per 1.73 m for longer than 1 month or on dialysis less than 3 months, who fulfill criteria for nonreversibility of renal dysfunction (by level and duration of renal dysfunction, imaging, and pathology findings), would be eligible for combined renal/nonrenal transplantation; (2) patients on dialysis longer than 3 months would be eligible for combined renal/nonrenal transplantation; (3) staged renal after nonrenal transplantation with subsequent prioritized allocation of renal transplant was endorsed in selected cases. The validation and impact of these recommendations on allocation will require further studies.
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http://dx.doi.org/10.1097/TP.0000000000000963DOI Listing
June 2016

Intravenous immunoglobulin for antibody-mediated keratolimbal allograft rejection.

BMJ Case Rep 2015 Jun 25;2015. Epub 2015 Jun 25.

Department of Ophthalmology, University of Toronto, Toronto, Canada.

A 33-year-old woman with congenital aniridia presented with decreased vision in her right eye. Slit lamp examination revealed diffuse conjunctivalisation of the ocular surface with mild subepithelial fibrosis consistent with aniridic keratopathy secondary to limbal stem cell deficiency. She underwent limbal stem cell transplantation with cadaver donor tissue (keratolimbal allograft (KLAL) surgery) and received systemic immunosuppression. Despite optimal combination immunosuppressive therapy managed by a renal transplant specialist, 2 weeks after the KLAL, the patient developed intractable eye pain, conjunctival injection, dilation of the KLAL graft blood vessels and limbal haemorrhages. There were no epithelial defects noted. Donor-specific antibody testing was positive, and intravenous immunoglobulin therapy was initiated. There was immediate symptomatic and objective improvement. Fifteen months postoperatively, the patient's vision was 20/400 with a stable corneal epithelium and no evidence of inflammation.
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http://dx.doi.org/10.1136/bcr-2015-210733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4488636PMC
June 2015
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