Efficacy of Belimumab for active lupus nephritis in a young Hispanic woman intolerant to standard treatment: a case report.

BACKGROUND: Lupus nephritis (LN) is a frequent severe complication of Systemic Lupus Erythematosus (SLE), especially in patients of non-Caucasian ethnicity. Induction treatment for LN consists in the combination of steroids plus a second agent (cyclophosphamide or mycophenolate mofetil) or, as a second-line, calcineurin inhibitors or Rituximab. Induction treatment for LN can be complicated by a series of side effects, the most severe being serious infections. Belimumab is a fully humanized monoclonal antibody that targets soluble B lymphocyte stimulator (BLyS), approved for treatment of serologically active SLE in addition to standard of care. CASE PRESENTATION: A young Hispanic woman was diagnosed with SLE at the age of 15. After several immunosuppressive treatments for arthritic symptoms (high-dose steroids, mycophenolate mofetil, Rituximab, cyclophosphamide) leading to serious complications and scarce clinical improvement, she developed severe LN. Induction treatment with a combination of intravenous high-dose methylprednisolone and cyclophosphamide was started but, after few days, the patient developed cryptococcal meningitis. After institution of appropriate antifungal therapy, treatment with Tacrolimus was attempted but poorly tolerated by the patient and withdrawn. Eventually, Belimumab was initiated off-label as a last resource to treat LN. Belimumab was well tolerated by the patient and resulted in a rapid and marked improvement in clinical symptoms and reduction in proteinuria, serum complement levels and anti-dsDNA titer; of note, the patient developed no infectious complications. CONCLUSIONS: We report the case of a severe LN in a young Hispanic woman who did not respond to conventional and second-line induction therapies, due both to intolerance and to the development of serious infectious complications. Eventually, Belimumab was successfully added to steroids and was well tolerated by the patient, resulting in a marked improvement in clinical and biochemical parameters. We suggest that Belimumab should be considered as a potentially efficacious treatment in patients with LN who cannot tolerate conventional therapies.

Methicillin-Resistant Staphylococcus aureus Peritonitis due to Hematogenous Dissemination from Central Venous Catheter in a Maintenance Dialysis Patient.

Staphylococcus aureus is a Gram-positive bacterium commonly associated with severe infections in hospitalized patients. S. aureus produces many virulence factors leading to local and distant pathological processes. Invasiveness of S. aureus generally induces metastatic infections such as bacteremia, infective endocarditis, osteomyelitis, arthritis, and endophthalmitis. Peritoneal localization from extra-abdominal infection can be a potential consequence of S. aureus infection. Two cases of metastatic peritonitis have been described in patients on peritoneal dialysis with concomitant peripheral vascular catheter-related bloodstream infection. We reported a case of peritoneal metastatic infection caused by methicillin-resistant Staphylococcus aureus (MRSA) in a patient on maintenance hemodialysis. A 37-year-old man was admitted with fever and chill due to jugular central vascular catheter (CVC)-related bloodstream infection caused by MRSA. CVC was placed after switching the patient from peritoneal dialysis to hemodialysis for scarce adherence to fluid restriction. Detection of MRSA on the peritoneal effluent combined with a total white blood cell count of 554 cells/mm3 prompted the diagnosis of satellite MRSA peritonitis. Antibiotic treatment with daptomycin and simultaneous CVC and peritoneal catheter removal resolved the infectious process. No further metastatic localizations were detected elsewhere. In conclusion, S. aureus can induce metastatic infections far from the site of primary infection. As reported in this case, peritonitis can be secondary to the hematogenous dissemination of S. aureus especially in hospitalized patients having a central line.

Kidney Transplantation From Circulatory Death Donors: Monocentric Experience.

BACKGROUND: Donation after circulatory death (DCD) is an accepted strategy to widen organ procurement worldwide. Authorized centers in Italy are spreading, increasing kidney transplantation (KTX) from DCD donors (40 in 2017 vs 24 in 2016). In this study, we describe DCD KTX activity at the University of Modena and Reggio Emilia (Modena, Italy) since its beginning in November 2017. METHODS: We retrospectively studied DCD KTX performed in our center from November 2017 to June 2018. We considered donor characteristics (age, sex, cause of death) and recipient clinical data (length of hospital stay, serum creatinine, estimated glomerular filtration rate, delayed graft function [DGF]), primary nonfunction [PNF], HLA match). All the grafts underwent in situ normothermic (ExtraCorporeal Membrane Oxygenation-ECMO) and ex situ hypothermic oxygenated perfusion (HOPE) with Kidney Assist machines. We monitored ex situ perfusion solution biochemical (lactate dehydrogenase [LDH] and lactate) and dynamic (resistance and flow) parameters. A kidney biopsy was performed for allocation strategy according to Karpinski score. RESULTS: We performed 6 kidney transplants (3 single and 3 double); the mean recipient (57.5 ± 4.9) and donor age (57.3 ± 7.5) were similar. Mean ECMO duration was 3 h 27 ± 57 min, HOPE was 4 h 47 min ± 119 min, lactate sample values (collected every 15 minutes from the beginning of perfusion) were always lower than1.6 mmol/L, and LDH maximum value was 400 UI/L. Median cold ischemia time was 11 h 18 min. Mean Karpinski score was 3.6; mean HLA match 1.7.We experienced 1 DGF (16.6%), no PNF, with a mean hospital stay of 14.6 days, mean creatinine at hospital discharge 2 ± 1.04 mg/dL), and mean eGFR 53.8 ±27.3 mL/min); at 1 month, mean creatinine and eGFR were 2 ± 1.34 mg/dL and 59.8 ± 24.5 mL/min, respectively. CONCLUSIONS: DCD is a promising resource for increasing organ donation. The Emilia Romagna regional organization allowed short ischemia times, with solid KTX outcomes, supporting further development of this program.

T-cell large granular lymphocyte leukemia in solid organ transplant recipients: case series and review of the literature.

T-cell large granular lymphocyte (T-LGL) leukemia is a rare clonal proliferation of cytotoxic lymphocytes rarely described in solid organ transplant (SOT). We reviewed records from 656 kidney transplant recipients in follow-up at our Center from January 1998 to July 2017. In addition, we researched, through PubMed, further reports of T-LGL leukemia in SOT from March 1981 to December 2017. We identified six cases of T-LGL leukemia in our cohort of patients and 10 in the literature. This lymphoproliferative disorder was detected in one combined liver-kidney, one liver and 14-kidney transplant recipients. Median age at presentation was 46.5 years (IQR 39.2-56.9). The disease developed after a median age of 10 years (IQR 4.9-12) from transplantation. Anemia was the most common presentation (62.5%) followed by lymphocytosis (43.7%) and thrombocytopenia (31.2%). Splenomegaly was reported in 43.7% of the patients. Eight patients (50%) who experienced severe symptoms were treated with non-specific immunosuppressive agents. Six of them (75%) had a good outcome, whereas two (25%) remained red blood cell transfusion dependent. No cases progressed to aggressive T-LGL leukemia or died of cancer at the end of follow-up. These results suggest that T-LGL leukemia is a rare but potentially disruptive hematological disorder in the post-transplant period.

[Screening Test of Fabry Disease in Patients with Renal Replacement Therapy in the City of Modena].

BACKGROUND: Fabry disease is a rare genetic lysosomal storage disease, inherited in an X-linked manner, characterized by lysosomal deposition of globotriaosylceramide due to deficient activity of the enzyme α-galactosidase A. Because the prevalence of this genetic disorder is unknown in the Emilia Romagna region, we conducted a screening study to assess the prevalence of Fabry disease in the city of Modena, Italy. MATERIAL AND METHODS: A screening study has been conducted in patients on renal replacement therapy at University Hospital of Modena. Screening tests have been performed using dried blood spot method. Alpha-galactosidase A activity and Lyso-Gb3 levels were evaluated in peripheral blood of all men. In women test based on genetic analysis; Lyso-Gb3 was measured only in patients with mutation of gene GLA. RESULTS: Screening tests have been performed on 388 subjects: 181 maintenance hemodialysis patients, 166 kidney transplant recipients and 41 peritoneal dialysis patients. About 40% of the patients did not had etiological diagnosis of renal disease. Lyso-Gb3 was more specific test than α- galactosidase A (100% vs. 82.5%) to diagnose Fabry disease. We found two different mutations: c.13 A >G p.(Asn5Asp), a variant likely benign and c.937 G >T p.(Asp313Tyr) a variant of uncertain significance. Both the patients carrying these genetic mutations had no symptoms or medical history compatible with Fabry disease. CONCLUSION: Identification of variant of uncertain significance such as c.937G >Tp.(Asp313Tyr) showed the limits of genetic analysis to diagnose an inherit disease. Further studies are need to assess the diagnostic value of Lyso-Gb3 for screening for Fabry disease.

Boceprevir is highly effective in treatment-experienced hepatitis C virus-positive genotype-1 menopausal women.

AIM: To investigate the safety/efficacy of Boceprevir-based triple therapy in hepatitis C virus (HCV)-G1 menopausal women who were historic relapsers, partial-responders and null-responders. METHODS: In this single-assignment, unblinded study, we treated fifty-six menopausal women with HCV-G1, 46% F3-F4, and previous PEG-α/RBV failure (7% null, 41% non-responder, and 52% relapser) with 4 wk lead-in with PEG-IFNα2b/RBV followed by PEG-IFNα2b/RBV+Boceprevir for 32 wk, with an additional 12 wk of PEG-IFN-α-2b/RBV if patients were HCV-RNA-positive by week 8. In previous null-responders, 44 wk of triple therapy was used. The primary objective of retreatment was to verify whether a sustained virological response (SVR) (HCV RNA undetectable at 24 wk of follow-up) rate of at least 20% could be obtained. The secondary objective was the evaluation of the percent of patients with negative HCV RNA at week 4 (RVR), 8 (RVR BOC), 12 (EVR), or at the end-of-treatment (ETR) that reached SVR. To assess the relationship between SVR and clinical and biochemical parameters, multiple logistic regression analysis was used. RESULTS: After lead-in, only two patients had RVR; HCV-RNA was unchanged in all but 62% who had ≤ 1 log10 decrease. After Boceprevir, HCV RNA became undetectable at week 8 in 32/56 (57.1%) and at week 12 in 41/56 (73.2%). Of these, 53.8% and 52.0%, respectively, achieved SVR. Overall, SVR was obtained in 25/56 (44.6%). SVR was achieved in 55% previous relapsers vs. 41% non-responders (P = 0.250), in 44% F0-F2 vs 54% F3-F4 (P = 0.488), and in 11/19 (57.9%) of patients with cirrhosis. At univariate analysis for baseline predictors of SVR, only previous response to antiviral therapy (OR = 2.662, 95%CI: 0.957-6.881, P = 0.043), was related with SVR. When considering "on treatment" factors, 1 log10 HCV RNA decline at week 4 (3.733, 95%CI: 1.676-12.658, P = 0.034) and achievement of RVR BOC (7.347, 95%CI: 2.156-25.035, P = 0.001) were significantly related with the SVR, although RVR BOC only (6.794, 95%CI: 1.596-21.644, P = 0.010) maintained significance at multivariate logistic regression analysis. Anemia and neutropenia were managed with Erythropoietin and Filgrastim supplementation, respectively. Only six patients discontinued therapy. CONCLUSION: Boceprevir obtained high SVR response independent of previous response, RVR or baseline fibrosis or cirrhosis. RVR BOC was the only independent predictor of SVR.