Organ procurement in forensic deaths: A retrospective analysis of the Italian context with a focus on the Puglia Region virtuous experience.

Organ transplantation is one the most important contributions of modern medicine to society since it provides a unique therapy for terminal organ failure. However, the development of this therapeutic approach is hindered by the limited organ supply. In Italy, organ procurement requires a multidisciplinary medical-surgical approach in which legal medical doctors (LMDs) are generally tasked with ascertaining the reality of death. Sometimes, a medico-legal report is required when the deceased's family deny their consent to the organs and tissues removal from a potential deceased donor. LMDs can also be appointed by law to carry out post-mortem examinations of potential deceased donors. In these cases, the public prosecutors' interest in preserving the corpse integrity for forensic purposes seems to conflict with the ethical-humanitarian interest in promoting, at most, the opportunity to donate; however, a LMD can act as a mediator and allow both goals. This paper aims to illustrate the Apulia Region experience in reconciling the justice interests with those of a culture promoting deceased organ and tissue donation. It has been pursued by analyzing the virtuous regional organ procurement trend in forensic deaths before and after a crucial 2015 initiative, comparing the results with the national ones, and contextualizing them in the relevant literature to show systemic strengths and weaknesses and inform future Italian policy development.

A Clinical Workflow for Cost-Saving High-Rate Diagnosis of Genetic Kidney Diseases.

SIGNIFICANCE STATEMENT: To optimize the diagnosis of genetic kidney disorders in a cost-effective manner, we developed a workflow based on referral criteria for in-person evaluation at a tertiary center, whole-exome sequencing, reverse phenotyping, and multidisciplinary board analysis. This workflow reached a diagnostic rate of 67%, with 48% confirming and 19% modifying the suspected clinical diagnosis. We obtained a genetic diagnosis in 64% of children and 70% of adults. A modeled cost analysis demonstrated that early genetic testing saves 20% of costs per patient. Real cost analysis on a representative sample of 66 patients demonstrated an actual cost reduction of 41%. This workflow demonstrates feasibility, performance, and economic effect for the diagnosis of genetic kidney diseases in a real-world setting. BACKGROUND: Whole-exome sequencing (WES) increases the diagnostic rate of genetic kidney disorders, but accessibility, interpretation of results, and costs limit use in daily practice. METHODS: Univariable analysis of a historical cohort of 392 patients who underwent WES for kidney diseases showed that resistance to treatments, familial history of kidney disease, extrarenal involvement, congenital abnormalities of the kidney and urinary tract and CKD stage ≥G2, two or more cysts per kidney on ultrasound, persistent hyperechoic kidneys or nephrocalcinosis on ultrasound, and persistent metabolic abnormalities were most predictive for genetic diagnosis. We prospectively applied these criteria to select patients in a network of nephrology centers, followed by centralized genetic diagnosis by WES, reverse phenotyping, and multidisciplinary board discussion. RESULTS: We applied this multistep workflow to 476 patients with eight clinical categories (podocytopathies, collagenopathies, CKD of unknown origin, tubulopathies, ciliopathies, congenital anomalies of the kidney and urinary tract, syndromic CKD, metabolic kidney disorders), obtaining genetic diagnosis for 319 of 476 patients (67.0%) (95% in 21 patients with disease onset during the fetal period or at birth, 64% in 298 pediatric patients, and 70% in 156 adult patients). The suspected clinical diagnosis was confirmed in 48% of the 476 patients and modified in 19%. A modeled cost analysis showed that application of this workflow saved 20% of costs per patient when performed at the beginning of the diagnostic process. Real cost analysis of 66 patients randomly selected from all categories showed actual cost reduction of 41%. CONCLUSIONS: A diagnostic workflow for genetic kidney diseases that includes WES is cost-saving, especially if implemented early, and is feasible in a real-world setting.

Ferric carboxymaltose vs. ferrous sulfate for the treatment of anemia in advanced chronic kidney disease: an observational retrospective study and cost analysis.

In non-dialysis-dependent chronic kidney disease (NDD-CKD), erythropoiesis-stimulating agents (ESAs) and iron supplementation are essential for anemia management. Ferric carboxymaltose (FCM) is a relatively novel intravenous iron formulation used in different clinical settings, although scarce data exist in NDD-CKD patients. Primary objective of this study was to retrospectively evaluate the efficacy of FCM compared with oral ferrous sulfate for the treatment of iron-deficiency anemia in a cohort of NDD-CKD patients, considering also the treatment costs. This was a monocentric, retrospective observational study reviewing 349 NDD-CKD patients attending an outpatient clinic between June 2013 and December 2016. Patients were treated by either FCM intravenous infusion or oral ferrous sulfate. We collected serum values of hemoglobin, ferritin and transferrin saturation (TSAT) and ESAs doses at 12 and 18 months. The costs related to both treatments were also analysed. 239 patients were treated with FCM intravenous infusion and 110 patients with oral ferrous sulfate. The two groups were not statistically different for age, BMI and eGFR values. At 18 months, hemoglobin, serum ferritin and TSAT values increased significantly from baseline in the FCM group, compared with the ferrous sulfate group. ESAs dose and rate of infusion decreased only in the FCM group. At 18 months, the treatment costs, analysed per week, was higher in the ferrous sulfate group, compared with the FCM group, and this was mostly due to a reduction in ESAs prescription in the FCM group. Routine intravenous FCM treatment in an outpatient clinic of NDD-CKD patients results in better correction of iron-deficiency anemia when compared to ferrous sulfate. In addition to this, treating NDD-CKD patients with FCM leads to a significant reduction of the treatment costs by reducing ESAs use.

The healthcare professionals' support towards organ donation. An analysis of current practices, predictors, and consent rates in Apulian hospitals.

INTRODUCTION: The paper investigates the critical care staff's support towards organ donation by analysing how their attitude, knowledge, confidence, engagement, and training can act as predictors of donation consent rates. Our study focused on hospitals in the Apulia Region, Italy. MATERIAL AND METHODS: The study employs a quantitative methodology based on a survey of healthcare professionals. The rate of consent to organ and tissue donation at the hospital level, given as a ratio of the permissions received to the proposals performed, was extracted from GEDON software related to the year 2019 report. For each Apulian participating hospital, we calculated a median score for each of the five predictors (namely, attitude, knowledge, confidence, engagement, and training) and investigated the association with hospital consent rates. RESULTS: The results highlight that the engagement of the intensive care units' healthcare personnel stands as the only influential predictor of the consent rate. DISCUSSION: In Italy's Apulia Region, efforts are needed to increase consent rates for organ donation. Strategies should concentrate on continuous support, as well as specific training of hospital staff involved in the donation process.

Diagnostic accuracy of anti-phospholipase A2 receptor (PLA2R) antibodies in idiopathic membranous nephropathy: an Italian experience.

BACKGROUND: Autoantibodies against-phospholipase A2 receptor (PLA2R) are specific markers of idiopathic membranous nephropathy (iMN). Enzyme-linked immunosorbent assay (ELISA) is becoming the preferred method in many laboratories for the determination of anti-PLA2R antibodies, because it provides quantitative results, and is not prone to subjective interpretation, as is the case with indirect immunofluorescence assay. METHODS: The purpose of our study was to determine the diagnostic performance of serum PLA2R antibodies detected by commercially available ELISA in a large Italian multicenter cohort of patients with biopsy-proven iMN and in patients with other renal diseases, with special focus on evaluating the optimal cut-off value to discriminate positive and negative results. A total of 495 consecutive patients were recruited. Renal biopsies were performed in all patients, and blood samples were taken before the initiation of immunosuppressive treatment. RESULTS: According to the clinical diagnosis and to kidney biopsy, 126 patients were diagnosed with iMN and 369 had other non-membranous nephropathies. Anti-PLA2R autoantibodies were detected using a commercial anti-PLA2R ELISA. At a cut-off value of 20 relative units (RU)/ml indicated by the manufacturer for positive classification, sensitivity was 61.1% and specificity 99.7%. At a cut-off value of 14 RU/ml indicated by the manufacturer for borderline results, sensitivity was 63.5% and specificity remained the same (99.7%). At a cut-off of 2.7 RU/ml, selected as the optimal cut-off on the basis of ROC curve analysis, sensitivity was 83.3% and specificity 95.1%. The best overall efficiency of the test was observed at 2.7 RU/ml; however, the highest positive likelihood ratio and diagnostic odds ratio were achieved at 14 RU/ml. A cut-off threshold higher than 14 RU/ml or lower than 2.7 RU/ml entailed worse test performance. CONCLUSION: Depending on the clinical use (early diagnosis or as a support to confirm clinical diagnosis), nephrologists may take advantage of this evidence by choosing the most convenient cut-off. However, renal biopsy remains mandatory for the definitive diagnosis of iMN and for the assessment of disease severity.

Depressive Symptoms in Dialysis: Prevalence and Relationship with Uremia-Related Biochemical Parameters.

BACKGROUND: Depression is the most common psychiatric disorder in long-term dialysis patients and a risk factor for morbidity and mortality. Although there is a relevance of the issue in the dialysis setting, we still know little about possible relationships between depression and uraemia-related biochemical abnormalities. Our aims were to evaluate (1) the prevalence of depression in our haemodialysis (HD) and peritoneal dialysis (PD) population using a validated and easy-to-implement screening tool and (2) the association between depression and the main uraemia-related clinical and biochemical parameter changes. METHODS: In this monocentric cross-sectional study, all patients of our centre with at least 3 months of dialysis were screened by Patient Health Questionnaire-9 (PHQ-9), a self-administered depression-screening questionnaire validated in dialysis setting. The impact of depressive symptoms on daily life was also assessed. We then analysed relationships between the PHQ-9-derived depressive score, functional impairment score, demographic, clinical and laboratory variables. RESULTS: In our cohort of 145 patients, depressive symptoms were found in 69 patients (46%). Stratifying for severity, mild, moderate and severe grade accounted for 31, 13 and 2% respectively. Depressive symptoms affected 36% of patients on PD versus 52% of patients on HD. Moreover, the PD patients had significantly less functional impairment derived from depressive symptoms than the HD patients. Simple and multiple regression analysis identified serum phosphorus as the only uraemia-related laboratory parameter that was high statistically associated with depressive score. CONCLUSIONS: Using a reliable, simple and fast tool, we found that depressive symptoms affect almost half of dialysis patients, particularly so the HD cohort. Severity of depressive symptoms seems related to serum levels of phosphorus possibly because depression affects compliance to therapy.

Drug-coated balloons reduce the risk of recurrent restenosis in arteriovenous fistulas and prosthetic grafts for hemodialysis.

BACKGROUND: Aim of this study was to evaluate the early and mid-term outcomes of drug-coated balloons (DCBs) in hemodialysis patients with recurrent stenosis of arteriovenous fistula and previously treated with plain balloon angioplasty (PBA). METHODS: Between July 2013 and June 2016 38 hemodialysis patients with recurrent stenosis of arteriovenous fistula underwent endovascular treatment with a DCB at our center. All patients were previously treated at the target lesion with a PBA. The intervals in months between the standard PBA and the procedure with DCB (time PBA-DCB) and between the procedure with DCB and the restenosis at the target lesion (time DCB-restenosis) were evaluated and compared with T-test. Estimated outcomes at 2 years in terms of patient survival, primary patency, primary assisted patency, secondary patency, and freedom from target lesion restenosis were assessed with Kaplan-Meier curves. RESULTS: Intraprocedural technical success was obtained in 97.4% of the cases. During the follow-up (mean duration 14.3 months, range 2-33) 19 patients (50%) developed a restenotic lesion at the target lesion with an estimated 2-year freedom from target lesion restenosis of 32.8%. Mean time PBA-DCB was 6.4 months, and the mean time DCB-restenosis was 7.9 months with a statistically significant difference at T-test (P<0.001). Estimated 2-year rates of primary patency, primary assisted patency, and secondary patency were 40.8%, 73.1%, and 82.5%, respectively. CONCLUSIONS: In our experience DCBs were safe and effective in the treatment of recurrent stenosis in patients with failing arteriovenous fistula. The time to restenosis at the target lesion was longer respect to that necessary to have a recurrent restenosis after PBA.

Low-dose RATG with or without basiliximab in renal transplantation: a matched-cohort observational study.

BACKGROUND/AIMS: In renal transplantation, peri-operative low-dose rabbit-antithymocyte-globulin (RATG) plus basiliximab induction prevented acute allograft rejection more effectively than post-operative RATG plus basiliximab induction. We investigated the specific antirejection contribution of basiliximab in this context. METHODS: This single-center, observational, matched-cohort study evaluated allograft rejections (primary outcome), steroid exposure and side effects, GFR (iohexol plasma clearance) and treatment costs in 16 deceased-donor renal transplant recipients induced with RATG (0.5 mg/kg/day) and 32 age-, gender- and treatment-matched reference-patients given RATG plus basiliximab (20 mg on days 0 and 4). RESULTS: Induction was well tolerated. At 18 months, 8 patients (50%) vs. 3 reference-patients (9.4%) rejected the graft [HR (95% CI): 6.53 (1.73-24.70), p = 0.006]. Difference was significant (p < 0.01) even after adjusting for recipient/donor age and gender, cold ischemia time and HLA mismatches. There were 1 antibody-mediated rejection and 2 moderate cellular rejections in patients vs. none in reference-patients (p = 0.032). The median (interquartile range) prednisone cumulative dose was remarkably higher in patients than reference-patients [4.78 (1.12-6.10) vs. 0.19 (0.18-3.81) grams, p = 0.002]. Three patients vs. 24 reference-patients were off-steroid at study end (p < 0.001). Three patients vs. no reference-patient developed new-onset diabetes (p = 0.003). Both inductions similarly depleted B-cells. Outcomes of AZA- vs. MMF-treated participants were similar. GFR was similar in all groups. Compared to MMF, AZA therapy saved ≈ EUR 2,500/year and by month 14.3 post-transplant compensated basiliximab costs. CONCLUSION: In renal transplantation, basiliximab plus peri-operative low-dose RATG more efficiently prevented allograft rejection than RATG monotherapy, and minimized steroid exposure and toxicity. AZA- vs MMF-based maintenance immunosuppression largely compensated the extra costs of basiliximab.