Reply to: "Herpes zoster seven days after SARS-CoV-2 vaccination in a patient with ankylosing spondylitis under adalimumab" by Josef Finsterer.

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Erythema nodosum after COVID-19 vaccine.

The current coronavirus disease 2019 (COVID-19) pandemic is a global challenge with strong medical and socioeconomic implications. Hopes have been placed in the development of various vaccines. As the vaccination campaign is in progress, adverse effects need to be monitored closely. Possible side effects range from minor events to more serious manifestations. In this article, we describe two cases of erythema nodosum (EN) after COVID-19 vaccination in two previously healthy female patients of 59 and 51 years, respectively. Most of the usual etiologies of EN were excluded by laboratory testing. EN was successfully treated with corticosteroids. Remarkably, in the first case, a relapse occurred 48 hours after the second dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. In this case series, we describe two unusual occurrences of EN after vaccination with an mRNA COVID-19 vaccine and a viral vector vaccine, respectively, and we discuss the available related literature.

Herpes zoster infection following mRNA COVID-19 vaccine in a patient with ankylosing spondylitis.

Since the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) pandemic outbreak, vaccines gained a growing role. Possible vaccine-related side effects range from minor local events to more prominent systemic manifestations up to anaphylactic reactions. A heterogeneous spectrum of cutaneous reactions has been reported, ranging from local injection site reactions to urticarial and morbilliform eruptions, pernio/chilblains and zoster flares. Here, we describe a case of varicella zoster virus reactivation following mRNA coronavirus 2019 vaccine and discuss the available literature upon the topic published so far.

Risk factors, management, and survival of bladder cancer after kidney transplantation.

INTRODUCTION AND OBJECTIVES: Kidney transplantation is associated with an increased risk of bladder cancer; however guidelines have not been established on the management of bladder cancer after kidney transplantation. MATERIALS AND METHODS: A systematic literature review using PubMed was performed in accordance with the PRISMA statement to identify studies concerning the prevalence and survival of bladder cancer after kidney transplantation. The risk factors and management of bladder cancer after kidney transplantation were also reviewed and discussed. RESULTS: A total of 41 studies, published between 1996 and 2018, reporting primary data on bladder cancer after kidney transplantation were identified. Marked heterogeneity in bladder cancer prevalence, time to diagnosis, non-muscle invasive/muscle-invasive bladder cancer prevalence, and survival was noted. Four studies, published between 2003 and 2017, reporting primary data on bladder cancer treated with Bacillus Calmette-Guérin (BCG) after kidney transplantation were identified. Disease-free survival, cancer-specific survival, and overall survival were similar between BCG studies (75-100%). CONCLUSIONS: Carcinogen exposure that led to ESRD, BKV, HPV, immunosuppressive agents, and the immunosuppressed state likely contribute to the increased risk of bladder cancer after renal transplantation. Non-muscle invasive disease should be treated with transurethral resection. BCG can be safely used in transplant recipients and likely improves the disease course. Muscle-invasive disease should be treated with radical cystectomy, with special consideration to the dissection and urinary diversion choice. Chemotherapy and immune checkpoint inhibitors can be safely used in regionally advanced bladder cancer with potential benefit. mTOR inhibitors may reduce the risk of developing bladder cancer, and immunosuppression medications should be reduced if malignancy develops.

Radiotherapy in cancer and rheumathoid arthritis patients: cancer treatment or control of articular flares? We can achieve both.

OBJECTIVE: The study was aimed to investigate the role of radiotherapy (RT) as a risk factor for reactivation or worsening of symptoms in patients affected by rheumatoid arthritis (RA) PATIENTS AND METHODS: This is a single-center retrospective observational study on RA patients who developed cancer requiring RT during the course of the disease. The control group consisted of RA patients with cancer who did not undergo RT. In both groups, the disease activity was evaluated at baseline and at 6 and 12 months through the DAS28 index. A relapse was defined as an increase of >20% in DAS28. A radiotherapist evaluated total and daily doses and timing of radiation. Acute and late toxicity was defined as events occurring within 90 days from the start and more than 90 days after the completion of RT, respectively. RESULTS: Seventy-two RA patients (38F/34M; mean age: 70±9 years; mean disease duration: 13±9 years), 29 (40.2%) of whom received radiotherapy (mean age 72.9±9 years), were enrolled. The most frequent malignancies were breast (27.2%), thyroid (9.8%), and skin (7%). Between radio-treated and non-radio-treated patients, no significant differences in RA reactivation (6/29 vs. 17/43; p=0.12) or mean exacerbation time (6.7 ± 4.9 months compared to 6.4 ± 4.1 months; p=0.78) were found. Overall, RT was well tolerated with low rates of both acute and late toxicity. CONCLUSIONS: In RA patients, RT was well tolerated and not associated with an increased risk of articular flares. Properly designed prospective clinical studies with a larger number of patients should be performed to confirm these data.

Controversies in the diagnosis of renal cell carcinoma with tumor thrombus. / Controversias en el diagnóstico del carcinoma de células renales con trombosis venosa asociada.

Diagnosis and treatment of renal cell carcinoma with venous tumor thrombosis remains a challenge today, requiring multidisciplinary teams, mainly in tumor thrombus levels III-IV. Our objective is to present the various diagnostic techniques used and its controversies. A review of the most relevant related articles between January 2000 and August 2020 has been carried out in PubMed, EMBASE and Scielo. Continuous technological development has allowed progress in its detection, in the approximation of the histological subtype, and in the determination of tumor thrombus level. Regardless of the imaging technique used for its diagnosis (CT, MRI, TEE, ultrasound with contrast), the time elapsed until treatment is vitally important to reduce the risk of complications, some of them fatal, such as pulmonary thromboembolism.

Renal transplantation using vascular conduit reconstruction in deceased kidneys with multiple renal arteries and short renal veins. / Trasplante renal mediante reconstrucción de conducto vascular en riñones de donantes fallecidos con arterias renales múltiples y venas renales cortas.

BACKGROUND: Transplantation of kidneys with vascular anatomical variants remains a challenge. Due to its varying success in regard to graft function after transplantation, these organs have been frequently discarded assuming in advance an unaffordable rate of vascular complications. PATIENTS AND METHODS: We performed three kidney transplants using organs from deceased donors harboring vascular variants (multiple arteries and short veins), including an unsplittable horseshoe kidney. Different grafts harvested from the same donor aorta, common iliac artery, and inferior vena cava, were used to reconstruct the initial vascular configuration by creating single arterial and venous conduits aimed to simplify the vascular anastomoses in the recipient. RESULTS: No post-operative complications were recorded. Warm ischemia times remained comparable to single artery renal allografts. No delayed graft function was noted in any case, and every patient regained normal renal function after transplantation. CONCLUSIONS: Vascular reconstruction using arterial and venous grafts harvested from the same deceased donor may result a helpful tool to simplify vascular anastomoses during transplantation surgery, thus avoiding their discard in advance, minimizing perioperative complications, and enabling normal graft function rates in the long-term follow-up. The successful outcome obtained by using this approach would help to expand the donor criteria for the inclusion of organs containing vascular anatomical variants.

Hemoglobin-Based Oxygen Carrier Rescues Double-Transplant Patient From Life-Threatening Anemia.

This case describes a 46-year-old male recipient of a kidney-pancreas transplant who is Jehovah's Witness. Early in the postoperative period, he was found to have splenic vein thrombosis requiring heparin infusion. Two days later, he developed severe symptomatic anemia (hemoglobin <6 g/dL). Standard medical therapy for bloodless surgical patients with severe anemia was instituted. Nevertheless, the patient's hemoglobin concentration continued to decline to critical levels (2 g/dL). Because he was Jehovah's Witness, transfusion of allogeneic blood products was not an option, prompting use of a hemoglobin-based oxygen carrier (HBOC). After approval by the U.S. Food and Drug Administration and the local institutional review board, 12 U of HBOC-201 were transfused over a period of 8 days. Two weeks later, the patient's hemoglobin levels had increased to 6.8 g/dL. The patient's overall clinical condition improved, and he was discharged home. This case describes the first use of HBOC transfusion in a double solid organ transplant patient. HBOC may represent a viable option in patients with severe symptomatic anemia when allogeneic blood transfusion is not an option.

Pilot Randomized Trial of Tacrolimus/Everolimus vs Tacrolimus/Enteric-Coated Mycophenolate Sodium in Adult, Primary Kidney Transplant Recipients at a Single Center.

BACKGROUND: Recent studies suggest that the combination of tacrolimus (TAC) and everolimus (EVL) could become a viable option for use as standard maintenance immunosuppression in non-highly sensitized kidney transplant recipients. METHODS: We conducted a single-center, open-label, randomized pilot trial comparing two maintenance immunosuppression regimens in non-highly sensitized, adult, primary kidney transplant recipients: (TAC/EVL, Group A) vs our standard maintenance regimen of TAC plus enteric-coated mycophenolate mofetil (TAC/EC-MPS, Group B). In both treatment arms, dual induction therapy consisting of anti-thymocyte globulin (Thymoglobulin) and basiliximab was given. Early corticosteroid withdrawal (by 7-10 days posttransplantation) was also planned in both arms. There were 30 study participants, 15 per treatment arm. Results during the first 12 months posttransplantation are reported here. RESULTS: Between 1 month and 12 months posttransplantation, mean TAC trough levels ranged between 5 and 8 ng/mL in both arms. Mean trough EVL level in Group A ranged between 4 and 6 ng/mL, and mean EC-MPS dose in Group B ranged from 1440 mg at 1 month to 945 mg at 12 months. One patient in Group A vs three patients in Group B experienced a first biopsy-proven acute rejection during the first 12 months posttransplantation (P = .32). Four patients in each group experienced biopsy-proven chronic allograft injury (interstitial fibrosis/tubular atrophy) (P = .99). There was a slight trend toward more favorable renal function in Group A at months 1-3 posttransplantation (P = .06, .10, and .18 for estimated glomerular filtration rate, respectively). No graft failures or deaths were observed in either group during the first 12 months posttransplantation. Four patients in each group developed an infection during the first 12 months posttransplantation. Two patients in Group A developed new-onset diabetes after transplant during the 12-month follow-up period, vs no patients in Group B (P = .13). CONCLUSION: TAC/EVL may be a viable alternative to TAC/EC-MPS for use as standard maintenance immunosuppression in non-highly sensitized kidney transplant recipients and should be given further consideration.

Ancillary therapy of intranasal T-LysYal® for patients with allergic, non-allergic, and mixed rhinitis.

Allergic rhinitis (AR) is caused by an IgE-mediated inflammatory reaction. Non-allergic rhinitis (NAR) is characterized by a non-IgE-mediated pathogenesis. Frequently, patients have the two disorders associated: such as mixed rhinitis (MR). Hyaluronic acid (HA) is a fundamental component of the human connective tissue. HA may exert anti-inflammatory and immune-modulating activities. Recently, an intranasal HA formulation was proposed: a supramolecular system containing lysine hyaluronate, thymine and sodium chloride (T-LysYal®). This randomized study investigated whether intranasal T-LysYal® (rinoLysYal®, Farmigea, Italy) was able to reduce symptom severity, endoscopic features, and nasal cytology in 89 patients (48 males and 41 females, mean age 36.3±7.1 years) with AR, NAR, and MR. Patients were treated with intranasal T-LysYal® or isotonic saline solution as adjunctive therapy to nasal corticosteroid and oral antihistamine for 4 weeks. Patients were visited at baseline, after treatment and after 4-week follow-up. Intranasal T-LysYal® treatment significantly reduced the quote of patients with symptoms, endoscopic features, and inflammatory cells. In conclusion, the present study demonstrates that intranasal T-LysYal® is able, as ancillary therapy, to significantly improve patients with AR, NAR, and MR, and its effect is long lasting.

Pretransplant CD4 Count Influences Immune Reconstitution and Risk of Infectious Complications in Human Immunodeficiency Virus-Infected Kidney Allograft Recipients.

In current practice, human immunodeficiency virus-infected (HIV(+) ) candidates with CD4 >200 cells/mm(3) are eligible for kidney transplantation; however, the optimal pretransplant CD4 count above this threshold remains to be defined. We evaluated clinical outcomes in patients with baseline CD4 >350 and <350 cells/mm(3) among 38 anti-thymocyte globulin (ATG)-treated HIV-negative to HIV(+) kidney transplants performed at our center between 2006 and 2013. Median follow-up was 2.6 years. Rates of acute rejection and patient and graft survival were not different between groups. Occurrence of severe CD4 lymphopenia (<200 cells/mm(3) ), however, was more common among patients with a baseline CD4 count 200-349 cells/mm(3) compared with those transplanted at higher counts (75% vs. 30% at 4 weeks [p = 0.04] and 71% vs. 5% at 52 weeks [p = 0.001], respectively, after transplant). After adjusting for age, baseline CD4 count of 200-349 cells/mm(3) was an independent predictor of severe CD4 lymphopenia at 4 weeks (relative risk [RR] 2.6; 95% confidence interval [CI] 1.3-5.1) and 52 weeks (RR 14.3; 95% CI 2-100.4) after transplant. Patients with CD4 <200 cells/mm(3) at 4 weeks had higher probability of serious infections during first 6 months after transplant (19% vs. 50%; log-rank p = 0.05). These findings suggest that ATG must be used with caution in HIV(+) kidney allograft recipients with a pretransplant CD4 count <350 cells/mm(3) .

Risk Factors for Type 1 Diabetes Recurrence in Immunosuppressed Recipients of Simultaneous Pancreas-Kidney Transplants.

Patients with type 1 diabetes (T1D) who are recipients of pancreas transplants are believed to rarely develop T1D recurrence in the allograft if effectively immunosuppressed. We evaluated a cohort of 223 recipients of simultaneous pancreas-kidney allografts for T1D recurrence and its risk factors. With long-term follow-up, recurrence was observed in approximately 7% of patients. Comparing the therapeutic regimens employed in this cohort over time, lack of induction therapy was associated with recurrence, but this occurs even with the current regimen, which includes induction; there was no influence of maintenance regimens. Longitudinal testing for T1D-associated autoantibodies identified autoantibody positivity, number of autoantibodies, and autoantibody conversion after transplantation as critical risk factors. Autoantibodies to the zinc transporter 8 had the strongest and closest temporal association with recurrence, which was not explained by genetically encoded amino acid sequence donor-recipient mismatches for this autoantigen. Genetic risk factors included the presence of the T1D-predisposing HLA-DR3/DR4 genotype in the recipient and donor-recipient sharing of HLA-DR alleles, especially HLA-DR3. Thus, T1D recurrence is not uncommon and is developing in patients treated with current immunosuppression. The risk factors identified in this study can be assessed in the transplant clinic to identify recurrent T1D and may lead to therapeutic advances.

Ten-Year Follow-up of a Reused Kidney Graft for Transplant Using Sirolimus for Maintenance Immunosuppression.

Reused kidney grafts have been transplanted with successful outcomes, though not widely performed in the Unites States. We present the case of a reused kidney graft with 10-year follow-up. The first donation was from a patient who died from a cerebrovascular accident and whose organs were used for a simultaneous pancreas and kidney transplant. After 5 years, the patient died and kidney was considered for donation and reuse. The patient had a virtual crossmatch with the first donor and a complement-dependent and flow-dependent crossmatch with the second donor. Long-term immune suppression was kept with a calcineurin-inhibitor-free regimen with sirolimus to prevent further damage from the first recipient. Control kidney biopsy showed steady progression of previous CNI toxicity without further damage. We describe the immunological basis of reused graft, the technical aspects of procurement and transplantation, as well as the use of Mammalian target of rapamycin for maintenance immunosuppression with good long-term results. Reused kidney grafts can be a good source of kidney grafts when adequate selection between donor and recipients is made and immunosuppression protocol is tailored to the preexisting damage to the original graft.

Lessons From Pancreas Transplantation in Type 1 Diabetes: Recurrence of Islet Autoimmunity.

Type 1 diabetes recurrence (T1DR) affecting pancreas transplants was first reported in recipients of living-related pancreas grafts from twins or HLA identical siblings; given HLA identity, recipients received no or minimal immunosuppression. This observation provided critical evidence that type 1 diabetes (T1D) is an autoimmune disease. However, T1DR is traditionally considered very rare in immunosuppressed recipients of pancreas grafts from organ donors, representing the majority of recipients, and immunological graft failures are ascribed to chronic rejection. We have been performing simultaneous pancreas-kidney (SPK) transplants for over 25 years and find that 6-8 % of our recipients develop T1DR, with symptoms usually becoming manifest on extended follow-up. T1DR is typically characterized by (1) variable degree of insulitis and loss of insulin staining, on pancreas transplant biopsy (with most often absent), minimal to moderate and rarely severe pancreas, and/or kidney transplant rejection; (2) the conversion of T1D-associated autoantibodies (to the autoantigens GAD65, IA-2, and ZnT8), preceding hyperglycemia by a variable length of time; and (3) the presence of autoreactive T cells in the peripheral blood, pancreas transplant, and/or peripancreatic transplant lymph nodes. There is no therapeutic regimen that so far has controlled the progression of islet autoimmunity, even when additional immunosuppression was added to the ongoing chronic regimens; we hope that further studies and, in particular, in-depth analysis of pancreas transplant biopsies with recurrent diabetes will help identify more effective therapeutic approaches.

Caval thrombus in conjunction with renal tumors: indication for surgery and technical details.

Patients with locally advanced renal cell carcinoma require an aggressive surgical approach, as this strategy represents the only hope for curing the disease. Selection of the appropriate surgical technique to treat these cases is essential in order to achieve the best outcomes. This process usually entails a tailored approach centered on the individual disease features. This article reviews the indications and provides a technical description for each of the surgical steps commonly used to address the multiple possible scenarios in this context.

Kidney allograft survival of African American and Caucasian American recipients with lupus.

BACKGROUND: African Americans with lupus who receive kidney transplants have high prevalence of predictors of allograft failure, which can explain their poor outcomes. METHODS: Of 1223 African Americans and 1029 Caucasian Americans with lupus who received kidney transplants from deceased donors between 1987 and 2006 with complete records in the UNOS program, 741 pairs were matched in 16 predictors employing a predicted probability of group membership. The primary outcome was allograft failure. Main secondary outcomes were rejection, allograft failure due to rejection, and mortality. RESULTS: Matched pairs were predominantly women (82%) with a mean age of 39 years. Twenty-four percent of recipients received kidneys from expanded criteria donors. African Americans and Caucasian Americans matched well (p ≥ 0.05): donor age, gender and race; recipient age, gender, education and insurance; dialysis prior to transplant, kidneys from expanded criteria donors, cold ischemia time, history of prior kidney transplant, panel reactive antibodies, human leukocyte antigens mismatch, blood type compatibility, transplant Era, and follow-up time. Contrary to the unmatched cohort with significantly higher allograft failure rate (events per 100 patient-years) in African Americans compared to Caucasian Americans (10.49 vs 6.18, p<0.001), matched pairs had similar allograft failure rates (8.41 vs 7.81, p=0.418). Matched pairs also had similar rates of rejections (9.82 vs 9.39, p=0.602), allograft failure due to rejection (6.19 vs 5.71, p=0.453), and mortality (2.79 vs 3.52, p=0.097). CONCLUSION: In lupus recipients of kidney transplants from deceased donors, African American and Caucasian Americans have similar allograft failure rates when predictors are matched between groups.

Advantage of rapamycin over mycophenolate mofetil when used with tacrolimus for simultaneous pancreas kidney transplants: randomized, single-center trial at 10 years.

Simultaneous pancreas kidney transplantation (SPKT) is the treatment of choice for patients with type 1 diabetes and end-stage renal disease. Rapamycin and mycophenolate mofetil (MMF) have been used for maintenance immunosuppression with tacrolimus in SPKT; however, long-term outcomes are lacking. From September 2000 through December 2009, 170 SPKT recipients were enrolled in a randomized, prospective trial receiving Rapamycin (n = 84) or MMF (n = 86). All patients received dual induction therapy with thymoglobulin and daclizumab, and low-dose maintenance tacrolimus and corticosteroids. Compared to MMF, rates of freedom from first biopsy-proven acute kidney or pancreas rejection were superior for Rapamycin at year 1 (kidney: 100% vs. 88%; P = 0.001; pancreas: 99% vs. 92%; P = 0.04) and at year 10 (kidney: 88% vs. 71%, P = 0.01; pancreas: 99% vs. 89%, P = 0.01). The higher rates of rejection were associated with withholding MMF (vs. Rapamycin, p = 0.009), generally for gastrointestinal or bone marrow toxicity. There was no significant difference in creatinine, proteinuria, c-peptide, viral infections, lymphoproliferative disorders or posttransplant diabetes. HbA1C and lipid levels were normal in both groups, although higher in the Rapamycin arm. There were no significant differences in patient or allograft survival. In this 10-year SPKT study, Rapamycin in combination with tacrolimus was better tolerated and more effective than MMF. Overall, the patient and allograft survival were equivalent.