Viral specific T cell therapy in kidney transplant recipients - A single-center experience.

BACKGROUND: Viral infections such as adenovirus (ADV), BK virus (BKV), and cytomegalovirus (CMV) after kidney transplantation negatively impact outcomes in transplant recipients despite advancements in screening and antiviral therapy. We describe our experience of using the virus-specific T cell therapy (VSTs) in kidney transplant recipients (KTR) at our transplant center. METHODS: This is a retrospective, single center review of KTR with ADV, BKV and CMV infections between June 2021 and December 2022. These patients received third party VSTs as part of the management of infections. The immunosuppression, details of infection and outcome data were obtained from electronic medical records. RESULTS: Two cases of ADV infection resolved after one infusion of VSTs. The response rate of BKV and CMV infection was not as robust with close to 50% reduction in median viral load after VSTs. Out of 23 patients, two patients developed chronic allograft nephropathy from membranoproliferative glomerulonephritis and acute rejection. CONCLUSION: Patients that are resistant to antivirals or who have worsening viremia despite conventional management may benefit from VSTs therapy to treat underlying viral infection. Additional studies are needed to ascertain efficacy and short- and long-term risks secondary to VSTs.

Allogeneic Ocular Surface Stem Cell Transplantation Outcomes With Decreased or No Systemic Immunosuppression in the Elderly.

PURPOSE: The aim of this study was to report outcomes after allogeneic ocular surface stem cell transplantation (OSST) for limbal stem cell deficiency in the setting of decreased or no systemic immunosuppression (SI) in the elderly. METHODS: A retrospective chart review was performed of all eyes that underwent OSST for limbal stem cell deficiency between 2005 and 2020 at CVP Physicians. Inclusion criteria included patients who were (1) at least 70 years at the time of (2) allogeneic OSST. Postoperative SI regimens were assessed. Outcome measures included improvement in visual acuity, ocular surface stability, and adverse effects. RESULTS: There were 14 eyes of 14 patients that met the inclusion criteria with mean follow-up of 3.0 (range 0.4-7.0) years. SI was run at a lower level for 6 patients, and 8 patients did not receive any SI. Nine eyes underwent keratolimbal allograft, 1 had a living-related conjunctival limbal allograft, and 4 had combined OSST. Most eyes (85.7%) attained improvement in visual acuity during their follow-up. At the last follow-up, 57.1% maintained a stable ocular surface. Six eyes developed acute rejection or late failure. Minimal adverse events were noted. CONCLUSIONS: Elderly patients administered less or no SI exhibit overall favorable outcomes after allogeneic OSST. Although not significantly different, surface stability and duration of improved vision was greater with low SI. No SI may be an option that still achieves improved vision in a high proportion for at least part of their follow-up. Decreasing SI after OSST in this population can improve quality of life while minimizing adverse effects.

Presence of Panel-reactive Antibodies after Penetrating Keratoplasty.

PURPOSE: To evaluate the relationship between penetrating keratoplasty (PK) and postoperative PRA level and number of unacceptable antigens. METHODS: A cross-sectionalstudy was performed on patients with history of PK. Patients with prior solid organ transplantation, pregnancy, or blood transfusion were excluded. These findings were combined with a retrospective review. Patients were grouped by single or multiple PKs. The primary outcome was postoperative PRA level. RESULTS: Incidence of postoperative PRA elevation and mean peak PRA was higher in the multiple PK group (p = .08 and p = .010, respectively). Mean number of unacceptable antigens was elevated in the multiple PK group (p = .024). There was a moderately positive correlation between number of PK grafts and PRA level (r = 0.629, p = .0002). CONCLUSIONS: PRA level may be influenced by PKs, with higher PRA associated with increased prior PKs. Further studies are necessary to determine the potential prognostic value.Abbreviations: PK: penetrating keratoplasty; PRA: panel reactive antibodies; OSST: ocular surface stem cell transplantation; LSCD: limbal stem cell deficiency.

Forty-Year Survival of Simultaneous Kidney and Duct-Injected Segmental Pancreas Transplants in a Recipient Maintained on Low-Dose Azathioprine and Prednisone.

Here, we report on the remarkable survival of a simultaneous kidney-pancreas transplant recipient who has received minimal immunosuppression, has had normal kidney function, and has been insulin-free for 40 years since her transplant surgery.

Acute Corneal Epithelial Rejection of LR-CLAL After SARS-CoV-2 Vaccination.

PURPOSE: The purpose of this study was to report a case of acute corneal epithelial rejection of living-related conjunctival limbal allograft (LR-CLAL) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. OBSERVATIONS: A 27-year-old woman developed acute epithelial rejection of LR-CLAL 2 weeks after receiving the SARS-CoV-2 vaccine. She received the LR-CLAL transplant 4 years and 7 months previously and had a stable clinical course with no history of rejection. She had an ABO blood group and human leukocyte antigen compatible donor, no systemic comorbidities, and no rejection risk factors. CONCLUSIONS: The novel SARS-CoV-2 vaccine upregulates the immune system to produce an adaptive immune response. The SARS-CoV-2 vaccine may potentially be associated with increased risk of rejection in those with ocular surface transplants.

Expanding the Donor Pool: First Use of Hepatitis B Virus Nat Positive Solid Organ Allografts Into Seronegative Recipients.

OBJECTIVES: The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients. SUMMARY BACKGROUND DATA: Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated. METHODS: From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival. RESULTS: With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT- with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT- recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P < 0.01). CONCLUSIONS: This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage.

Clinical Outcomes of Allogeneic Ocular Surface Stem Cell Transplantation in Pediatric Patients.

PURPOSE: To describe the outcomes of allograft ocular surface stem cell transplantation (OSST) and the complication profile of systemic immunosuppression (SI) in pediatric patients with limbal stem cell deficiency. METHODS: This was a retrospective interventional case series from a single tertiary referral institution of 20 eyes from 13 patients who 1) underwent allograft OSST surgery, 2) were 18 years or less at time of OSST, and 3) received SI with 4) a minimum of 12-months follow-up. The main outcome measures were ocular surface stability, visual acuity, and SI adverse events. RESULTS: The mean age of patients was 15.1 ± 3.2 years (range 9-18 years). The mean follow-up was 5.6 ± 5.0 years after OSST. At the last follow-up, 15 eyes (75%) had a stable ocular surface, 1 eye (5%) developed partial failure, and 4 eyes (20%) developed total surface failure. Preoperative mean logarithm of the minimum angle of resolution visual acuity 1.5 improved to 1.1 at the last follow-up (P = 0.1); when 4 eyes of 3 nonadherent patients were excluded, the results were more pronounced and statistically significant (1.5 improved to 1.0, P = 0.002). SI was tolerated well by all patients with minimal adverse events. CONCLUSIONS: OSST provides a stable ocular surface and is a successful treatment option for pediatric patients with limbal stem cell deficiency. SI is well-tolerated with a minimal complication profile.

Use of Panel-Reactive Antibody Testing in the Planning and Management of Ocular Surface Stem Cell Transplantation.

PURPOSE: Panel-reactive antibody (PRA) testing has been widely adopted in solid organ transplantation for risk assessment in potential allograft recipients but has not been studied in the context of ophthalmic transplantation. The purpose of this study is to evaluate outcomes in patients undergoing ocular surface stem cell transplantation (OSST) for limbal stem cell deficiency (LSCD) relative to preoperative PRA level. METHODS: This is retrospective chart review of all eyes with documented PRA level that underwent OSST for LSCD between May 2000 and March 2019 at a single institution. Eyes with stable ocular surface but <1 year of follow-up and eyes without updated PRA before repeat OSST were excluded. Eyes were grouped by PRA <80% and ≥80%. The primary outcome was ocular surface failure, whereas the secondary outcome was clinical allograft rejection. RESULTS: Sixty-nine surgeries met inclusion criteria, consisting of 54 living-related conjunctival limbal allografts, 5 keratolimbal allografts, and 10 combined living-related conjunctival limbal allografts/keratolimbal allografts (Cincinnati procedure). The most common etiologies for LSCD were aniridia (33%), chemical/thermal injury (28%), and contact lens associated (14%). Surface failure occurred in 5 of 12 eyes (58%) with PRA ≥80% versus 12 of 57 eyes (21%) with PRA <80% (P = 0.01). The relative risk for surface failure with PRA ≥80% was 2.8 [confidence interval (CI), 1.38-5.55]. There was no significant difference in acute rejection (P = 1). CONCLUSIONS: Pretransplant PRA level is an important prognostic factor for ocular surface stability in eyes undergoing OSST for LSCD, with implications for donor selection, perioperative management, and systemic immunosuppression.

Treatment Options for Coronavirus Disease 2019 in Patients With Reduced or Absent Kidney Function.

Coronavirus disease 2019, the disease caused by the severe acute respiratory syndrome coronavirus 2 virus, was first identified in the Hubei Province of China in late 2019. Currently, the only role for therapy is treatment of the disease, as opposed to postexposure prophylaxis, however multiple clinical trials are currently ongoing for both treatment and prophylaxis. Treating coronavirus disease 2019 relies on two components; the first is inhibition of the viral entrance and replication within the body and the second is inhibition of an exacerbated immune response which can be seen in patients with severe disease. Many drugs have shown in vitro antiviral activity; however, clinical trials have not been as promising. This review summarizes the current data for the most commonly used drugs for coronavirus disease 2019 and will cover the unique factors that may affect the dosing of these medications in patients with CKD. While clinical trials are ongoing, most are in patients with normal kidney function. During a pandemic, when patients with CKD are at higher risk of both infection and death, it is imperative to include patients these patients in the clinical trials.

Long-term Outcomes of Living-Related Conjunctival Limbal Allograft Compared With Keratolimbal Allograft in Patients With Limbal Stem Cell Deficiency.

PURPOSE: To compare the long-term outcomes of living-related conjunctival limbal allograft (lr-CLAL) with keratolimbal allograft (KLAL) in patients with limbal stem cell deficiency. METHODS: A retrospective, comparative, interventional cohort of patients with bilateral total limbal stem cell deficiency who underwent surgical treatment with a KLAL or lr-CLAL procedure alone (not combined with any other ocular surface stem cell transplantation procedures) with a minimum follow-up of 1 year and who received systemic immunosuppression. Ocular surface stability, best-corrected visual acuity (BCVA), and postoperative complications at the last follow-up were the main outcome measures. RESULTS: There were 224 eyes that underwent KLAL alone and 63 eyes that underwent lr-CLAL alone, with a mean follow-up time for all eyes of 7.2 years (range 1.0-16.0 years). For lr-CLAL eyes, 82.5% maintained a stable ocular surface compared with 64.7% of KLAL eyes at the last follow-up. Only 6.3% of lr-CLAL eyes demonstrated a failed ocular surface compared with 15.6% of KLAL eyes. The mean BCVA was 20/158 for KLAL eyes compared with 20/100 for lr-CLAL eyes at the last follow-up. A smaller proportion of lr-CLAL eyes (30.2% compared with 43.3%) developed an episode of acute rejection, and a higher proportion of these episodes resolved with treatment in the lr-CLAL group (79.0% compared with 53.6%). CONCLUSIONS: lr-CLAL demonstrates lower rejection rates, improved graft survival, and better BCVA compared with KLAL. Both careful preoperative donor selection and triple-agent systemic immunosuppression (including tapered systemic corticosteroids) are critical to optimizing the ocular surface stem cell transplantation outcomes.

Long-term outcomes in patients with obesity and renal disease after sleeve gastrectomy.

Morbid obesity is a barrier to kidney transplant in patients with end-stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (SG) is an increasingly considered intervention, but the safety and long-term outcomes are uncertain. We reviewed prospectively collected data on patients with ESRD and chronic kidney disease (CKD) undergoing SG from 2011 to 2018. There were 198 patients with ESRD and 45 patients with CKD (stages 1-4) who met National Institutes of Health guidelines for bariatric surgery and underwent SG; 72% and 48% achieved a body mass index of ≤ 40 and ≤ 35 kg/m2 , respectively. The mean percentages of total weight loss and excess weight loss were 18.9 ± 10.8% and 38.2 ± 20.3%, respectively. SG reduced hypertension (85.8% vs 52.1%), decreased antihypertensive medication use (1.6 vs 1.0) (P < .01 each), and reduced incidence of diabetes (59.6% vs 32.5%, P < .01). Of the 71 patients with ESRD who achieved a body mass index of ≤ 40 kg/m2 , 45 were waitlisted and received a kidney transplant, whereas 10 remain on the waitlist. Mortality rate after SG was 1.8 per 100 patient-years, compared with 7.3 for non-SG. Patients with stage 3a or 3b CKD exhibited improved glomerular filtration rate (43.5 vs 58.4 mL/min, P = .01). In conclusion, SG safely improves transplant candidacy while providing significant, sustainable effects on weight loss, reducing medical comorbidities, and possibly improving renal function in stage 3 patients.

Ocular Surface Stem Cell Transplantation for Treatment of Keratitis-Ichthyosis-Deafness Syndrome.

PURPOSE: To report our surgical experience with ocular surface stem cell transplantation (OSST) for limbal stem cell deficiency (LSCD) in the setting of keratitis-ichthyosis-deafness (KID) syndrome. METHODS: Retrospective interventional case series. RESULTS: We present 5 eyes of 3 patients with KID syndrome that developed LSCD and underwent OSST. Mean follow-up after OSST was 8.3 ± 4.3 years (range 3.4-11.4 years). Two eyes underwent living-related conjunctival limbal allograft (lr-CLAL), and 3 eyes were treated with keratolimbal allograft (KLAL). Four of the 5 eyes underwent subsequent keratoplasty. Both lr-CLAL eyes maintained a stable ocular surface at final follow-up. Conversely, all KLAL eyes developed a failed surface requiring repeat KLAL surgery. Because of multiple failed KLALs, 1 eye underwent placement of a keratoprosthesis. CONCLUSIONS: KID syndrome is a rare cause of LSCD. Although OSST can stabilize the surface, long-term treatment of KID syndrome can be challenging. An lr-CLAL may offer further benefit over a KLAL in these eyes because it is HLA- and ABO-matched tissue; it also helps to treat keratoconjunctivitis sicca, often a prominent feature of KID syndrome.

Infectious Keratitis After Ocular Surface Stem Cell Transplantation.

PURPOSE: To describe the rate, clinical/microbiological characteristics, and outcomes of infectious keratitis in eyes with limbal stem cell deficiency after ocular surface stem cell transplantation (OSST). METHODS: In this retrospective chart review of 278 eyes that underwent OSST between January 2006 and December 2016, eyes treated for previous infectious keratitis (bacterial, fungal, or viral) were included. Demographics, risk factors, course, microbiological characteristics, and outcomes were assessed. RESULTS: A total of 52 eyes (18.7%) of 48 patients (28 men and 20 women) developed 75 episodes (culture-proven or presumed) of infectious keratitis (range 1-4 episodes) with mean follow-up of 5.3 ± 3.6 years after OSST. The most common limbal stem cell deficiency etiologies included chemical/thermal (27 episodes), Stevens-Johnson syndrome (19 episodes), aniridia (8 episodes), and mucous membrane pemphigoid (8 episodes). There were 44 (58.7%) bacterial keratitis episodes, 24 (32%) fungal keratitis episodes, and 7 (9.3%) HSV keratitis episodes. Gram-positive bacteria (79%) and Candida species (73%) were the most common bacterial and fungal pathogens. Before infection, 33% had an epithelial defect, 69% had a bandage contact lens, 91% were on systemic immunosuppression, and 25% recently had undergone ocular surgery (<3 months). Although 75% resolved with antimicrobial treatment, 25% required a therapeutic keratoplasty (TPK; 2 cases needed multiple TPK). CONCLUSIONS: Despite successful OSST surgery, infectious keratitis is relatively common, and aggressive medical/surgical therapy is warranted. Prophylactic topical antibiotics and a cicatrizing conjunctivitis diagnosis may account for the high proportion of fungal keratitis in this population.

Cincinnati Protocol for Preoperative Screening and Donor Selection for Ocular Surface Stem Cell Transplantation.

PURPOSE: To describe our process for preoperative screening and donor selection for ocular surface stem cell transplantation (OSST). METHODS: A 7-year retrospective chart review was performed on limbal stem cell deficiency patients. The inclusion criterion was all patients who underwent an OSST procedure. The exclusion criterion was eyes with unilateral disease in which an autograft was performed. Data for human leukocyte antigen (HLA) typing, virtual crossmatching, donor-specific antibody, and panel reactive antibody level were obtained. RESULTS: Of the included 142 eyes (104 patients), 19 patients had no recorded living donor availability data, and HLA typing was not performed on 16 patients. A total of 94 donors (mean 1.4 donors/patient, range 1-6) were tested for 67 recipients. For 2 patients with graft-versus-host disease, no further HLA typing was needed, as the donors were known HLA-identical donors. For 47 patients, only 1 donor was tested, whereas multiple donors underwent HLA typing for 20 patients. There were 73 ABO (blood group)-compatible matches for the 61 tested recipients, and only 1 recipient did not have any ABO-compatible donor. For the virtual crossmatch, there were 5 patients who did not have a compatible donor (positive virtual crossmatch). The best available donor match was a sibling for 41 recipients (65%), a parent for 19 recipients (30%), and an offspring for 3 recipients (5%). CONCLUSIONS: Our protocol for OSST preoperative screening and donor selection minimizes the antigenic burden for transplanted tissue by selecting the best available donor match.

Surgical management of severe ocular surface injury due to Roman candle explosion accidents.

PURPOSE: To report the clinical features, management, and outcomes of patients with ocular surface damage secondary to Roman candle explosion accidents. METHODS: Retrospective, noncomparative, interventional case series of 11 patients with Roman candle explosion-related ocular surface injuries referred to the Cincinnati Eye Institute between 2007 and 2016. RESULTS: Eleven patients (10 male, 1 female, mean age 22.4 years) sustained unilateral ocular surface injuries with presenting visual acuity ranging from count fingers to light perception. All patients had severe limbal stem cell deficiency with total ocular surface failure. Eight eyes received a conjunctival-limbal autograft (CLAU) with a keratolimbal allograft (KLAL), 1 eye received a living related-conjunctival limbal allograft (lr-CLAL) with a KLAL, and 2 eyes received a CLAU with lr-CLAL. Nine eyes underwent subsequent penetrating keratoplasty, and 7 eyes had reconstructive eyelid surgery. Nine eyes demonstrated improved visual acuity at last follow-up; seven eyes demonstrated a stable ocular surface at last follow-up. Nonadherence was noted in 7 patients, either with poor adherence with post-operative treatment or poor follow-up; this portended a worse visual result. CONCLUSIONS: Roman candle-related accidents can lead to severe ocular surface injury. Despite total ocular surface failure, these eyes can achieve good postoperative visual results following limbal stem cell transplantation and subsequent keratoplasty with appropriate compliance.

Severe BK polyomavirus-induced hemorrhagic cystitis in a kidney transplant recipient with the absence of renal allograft involvement.

BK polyomavirus mostly manifests as polyomavirus-associated nephropathy (PyVAN) in kidney transplant patients and polyoma virus-associated hemorrhagic cystitis (PyVHC) in bone marrow transplant patients. PyVHC in kidney transplant patients is only reported in four cases in the literature. Our patient had severe hemorrhagic cystitis without renal involvement. We postulate that our patient's exposure to ifosfamide and radiation 8 years prior transplantation might predispose him to this disease.

Combined Conjunctival Limbal Autografts and Living-Related Conjunctival Limbal Allografts for Severe Unilateral Ocular Surface Failure.

PURPOSE: To describe the technique and present 2 cases of a combined conjunctival limbal autograft (CLAU) and living-related conjunctival limbal allograft (lr-CLAL) procedure for treatment of severe unilateral ocular surface failure. METHODS: Interventional case series of 2 eyes of 2 patients sustaining severe thermal/chemical injuries from firework explosions. They both underwent the combined CLAU/lr-CLAL procedure followed by penetrating keratoplasty. Systemic immunosuppression consisted of oral tacrolimus and mycophenolate mofetil. RESULTS: Preoperative vision was counting fingers for both patients, whereas visual acuity at last follow-up ranged between 20/40 and 20/50. Both patients maintained a stable surface at last follow-up without any episodes of rejection. Patients tolerated systemic immunosuppression well without any persistent adverse reactions. CONCLUSIONS: Certain etiologies of limbal stem cell deficiency also lead to significant conjunctival (and goblet cell) deficiency. Combined CLAU and lr-CLAL procedures maximize the amount of healthy limbal stem cells with conjunctiva while also minimizing the antigenic burden as all transplanted tissue potentially can be a complete (or near-complete), compatible HLA and crossmatch.

Long-term Outcomes of Ocular Surface Stem Cell Allograft Transplantation.

PURPOSE: To investigate the long-term outcomes of ocular surface stem cell allograft transplantation (OSST) in patients with total limbal stem cell deficiency (LSCD) owing to various etiologies with a follow-up ≥ 5 years. DESIGN: Retrospective interventional cohort. METHODS: Setting: Single tertiary referral hospital. STUDY POPULATION: Patients who had (1) presence of total LSCD, (2) surgical treatment with at least 1 allograft OSST procedure, and (3) minimum follow-up ≥ 5 years after OSST. INTERVENTION: All patients underwent allograft OSST from March 1998 to June 2009. All patients received systemic immunosuppression. MAIN OUTCOME MEASURES: Ocular surface stability, best-corrected visual acuity (BCVA). RESULTS: A total of 165 eyes of 110 patients fulfilled the inclusion criteria with a mean follow-up period of 109.22 ± 35.7 months or approximately 9.1 years (range 5.2-17.7 years). Ocular surface stability was achieved in 72.7% (120/165) of eyes at last follow-up, while 15.2% (25/165) maintained an improved ocular surface and 12.1% (20/165) developed total surface failure. Additional OSST surgery was necessary in 30.9% (51/165 eyes) to maintain a stable ocular surface. There was ≥ 2 lines BCVA improvement in 62.1%, no change in 7.7%, and a worsened BCVA in 18.6% at last follow-up. CONCLUSIONS: With proper immunosuppression and repeat procedure in case of failure, allograft OSST can provide true long-term ocular surface stability and successful visual outcomes.

Acute Kidney Injury in Transplant Setting: Differential Diagnosis and Impact on Health and Health Care.

Acute kidney injury (AKI) is common in kidney transplant recipients. In addition to the usual causes of AKI in native kidneys, certain features and risk factors are unique to kidney allografts. In this article, we will present an overview of the common transplant-specific AKI etiologies that include increased susceptibility to hemodynamic-mediated AKI, acute rejection, medication-induced AKI, recurrence of native kidney disease, infections, urinary tract obstruction, vascular thrombosis and post-transplant lymphoproliferative disorder. AKI is independently associated with allograft loss and patient mortality. It is, therefore, prudent for transplant centers to address it as a major quality measure.