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Objective: Vitamin D deficiency is a common public health issue worldwide. The purpose of this study was to investigate the vitamin D status and its potential determinants in children residing in Sardinia (40°N), Italy., Methods: Children were enrolled over a 12-month period. Serum 25(OH)D was measured by an immunochemiluminescence assay. A questionnaire was used to gather information on other variables, including passive smoke exposure., Results: A total of 182 children (males: 51.7%; median age: 9 years) were included. Mean±standard deviation serum 25(OH)D was 25.2±8.3 ng/mL for the whole group. The majority (n=123, 67.6%) had vitamin D sufficient values >20 ng/mL, while 32.4% (n=59) had vitamin D insufficient/deficient values (≤20 ng/mL). Among the variables investigated, passive smoke exposure was significantly associated with insufficient 25(OH)D levels (p<0.0001)., Conclusion: Our results confirm that hypovitaminosis D is common in Italian children. Furthermore, passive smoke exposure was identified as a significant risk factor for hypovitaminosis D., Competing Interests: Conflict of interest: None declared., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Kidney transplant (KT) recipients are known to be at risk of developing several cancer types; however, cancer mortality in this population is underinvestigated. Our study aimed to assess the risk of cancer death among Italian KT recipients compared to the corresponding general population. A cohort study was conducted among 7373 individuals who underwent KT between 2003 and 2020 in 17 Italian centers. Date and cause of death were retrieved until 31 December 2020. Indirect standardization was used to estimate standardized mortality ratios (SMRs) and corresponding 95% confidence intervals (CIs). Cancer was the most common cause of death among the 7373 KT recipients, constituting 32.4% of all deaths. A 1.8-fold excess mortality (95% CI: 1.59-2.09) was observed for all cancers combined. Lymphomas (SMR = 6.17, 95% CI: 3.81-9.25), kidney cancer (SMR = 5.44, 95% CI: 2.97-8.88) and skin melanoma (SMR = 3.19, 95% CI: 1.03-6.98) showed the highest excess death risks. In addition, SMRs were increased about 1.6 to 3.0 times for cancers of lung, breast, bladder and other hematopoietic and lymphoid tissues. As compared to the general population, relative cancer mortality risk remained significantly elevated in all age groups though it decreased with increasing age. A linear temporal increase in SMR over time was documented for all cancers combined (P < .01). Our study documented significantly higher risks of cancer death in KT recipients than in the corresponding general population. Such results support further investigation into the prevention and early detection of cancer in KT recipients., (© 2023 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Individuals who suffer from end-stage renal disease are at a higher risk of developing certain types of tumors. This risk increases as kidney function deteriorates further. Dialysis patients often witness a surge in the incidence of such malignancies. Interestingly, after the initial period following a kidney transplant, there is a dip in the number of deaths related to neoplasms. However, a long-term view reveals a progressive increase in the risk of developing tumors. The evaluation process for transplant candidacy is thorough, taking into account several factors, including the individual's history of neoplasms and the implications of immunosuppressive therapy. Immunosuppressive therapy is a double-edged tool in managing post-transplant complications, as it can foster environments conducive to neoplasm growth. It is essential to reevaluate, with the aid of an oncological opinion, the waiting time between cancer recovery and the listing for kidney transplantation, based on clinical data and follow-up. Independent of the type of tumor, the requirement to treat and achieve remission delays the listing process, consequently extending the time spent with end-stage renal disease and undergoing dialysis. These factors correlate with increased mortality, heightened risk of cardiovascular disease, and graft loss., (Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.)

Human serum paraoxonase-1 (PON-1) is a critical antioxidant defence system against lipid oxidation. Decreased PON-1 activity has been associated with systemic oxidative stress in several disease states. We conducted a systematic review and meta-analysis of plasma/serum concentrations of PON-1 in asthma, a chronic inflammatory airway disease. The electronic databases PubMed, Web of Science, Scopus and Google Scholar were searched from inception to February 2022. In total, 8 studies in 355 asthmatic patients and 289 healthy controls were included in the meta-analysis. Serum PON-1 concentrations were significantly lower in asthmatic patients (SMD = -1.58, 95% CI -2.53 to -0.63; p = 0.001). The pooled SMD values were not substantially altered in sensitivity analysis. There was no publication bias. There were non-significant differences in PON-1 concentrations in patients with severe vs. mild-to-moderate asthma (SMD =  - 0.39, 95% CI - 1.00 to 0.22, p = 0.21). Our meta-analysis has shown that serum PON-1 concentrations are significantly lower in patients with asthma, suggesting the presence of an impaired antioxidant defense in this group., (© 2022. The Author(s).)

A meeting entitled Renal BIopsy for Kidney Transplantation Therapy (ReBIrth) took place on May 31 st , 2022 in Bologna, Italy. The meeting drew together nephrologists, surgeons, and pathologists and recognized as experts in the field of kidney transplantation in Italy. In this paper, we present our experience working with kidney transplants in the current era of immunosuppression therapy. The primary aim is to report the histopathological characteristics of failed kidney allografts after a consensus of experts reviewed the cases on a wholeslide imaging digital platform. Regardless of the cases discussed, digital pathology was reliable in identifying all the morphological and immunohistochemical features required to improve the correct use of immunosuppressive therapy to prevent graft failure and optimize patient management., (Copyright © 2023 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Human serum paraoxonase-1 (PON-1) is a critical antioxidant defense system against lipid oxidation. Decreased PON-1 activity has been associated with systemic oxidative stress in several disease states. We conducted a systematic review and meta-analysis of plasma/serum concentrations of PON-1 paraoxonase and arylesterase activity in psoriasis, a chronic immune-mediated and inflammatory skin disease. The electronic databases PubMed, Web of Science, and Scopus were searched from inception to November 2021. In total, 14 studies in 691 psoriatic patients and 724 healthy controls were included in the meta-analysis. Serum paraoxonase activity was significantly lower in psoriatic patients (SMD = - 2.30, 95% CI - 3.17 to - 1.42; p < 0.001); however, no significant between-group differences were observed in serum arylesterase activity (SMD = - 0.34, 95% CI - 0.11 to 0.80; p = 0.14). The pooled SMD values were not substantially altered in sensitivity analysis. There was no publication bias. In conclusion, our meta-analysis has shown that serum paraoxonase, but not arylesterase, activity is significantly lower in psoriasis, suggesting an impaired antioxidant defense in these patients., (© 2022. The Author(s).)

This cohort study examined 25-year variations in cancer incidence among 11,418 Italian recipients of kidney transplantation (KT) from 17 Italian centers. Cancer incidence was examined over three periods (1997-2004; 2005-2012; and 2013-2021) by internal (Incidence rate ratio-IRR) and external (standardized incidence ratios-SIR) comparisons. Poisson regression was used to assess trends. Overall, 1646 post-transplant cancers were diagnosed, with incidence rates/1000 person-years ranging from 15.5 in 1997-2004 to 21.0 in 2013-2021. Adjusted IRRs showed a significant reduction in incidence rates across periods for all cancers combined after exclusion of nonmelanoma skin cancers (IRR = 0.90, 95% confidence interval-CI: 0.76-1.07 in 2005-2012; IRR = 0.72, 95% CI: 0.60-0.87 in 2013-2021 vs. 1997-2004; P trend < 0.01). In site-specific analyses, however, significant changes in incidence rates were observed only for Kaposi's sarcoma (KS; IRR = 0.37, 95% CI: 0.24-0.57 in 2005-2012; IRR = 0.09, 95% CI: 0.04-0.18 in 2013-2021; P trend < 0.01). As compared to the general population, the overall post-transplant cancer risk in KT recipients was elevated, with a decreasing magnitude over time (SIR = 2.54, 95% CI: 2.26-2.85 in 1997-2004; SIR = 1.99, 95% CI: 1.83-2.16 in 2013-2021; P trend < 0.01). A decline in SIRs was observed specifically for non-Hodgkin lymphoma and KS, though only the KS trend retained statistical significance after adjustment. In conclusion, apart from KS, no changes in the incidence of other cancers over time were observed among Italian KT recipients.

This study assessed the impact of cancer on the risk of death with a functioning graft of kidney transplant (KT) recipients, as compared to corresponding recipients without cancer. A matched cohort study was conducted using data from a cohort of 13 245 individuals who had undergone KT in 17 Italian centers (1997-2017). Cases were defined as subjects diagnosed with any cancer after KT. For each case, two controls matched by gender, age, and year at KT were randomly selected from cohort members who were cancer-free at the time of diagnosis of the index case. Overall, 292 (20.5%) deaths with a functioning graft were recorded among 1425 cases and 238 (8.4%) among 2850 controls. KT recipients with cancer had a greater risk of death with a functioning graft (hazard ratio, HR = 3.31) than their respective controls. This pattern was consistent over a broad range of cancer types, including non-Hodgkin lymphoma (HR = 33.09), lung (HR = 20.51), breast (HR = 8.80), colon-rectum (HR = 3.51), and kidney (HR = 2.38). The survival gap was observed throughout the entire follow-up period, though the effect was more marked within 1 year from cancer diagnosis. These results call for close posttransplant surveillance to detect cancers at earlier stages when treatments are more effective in improving survival., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The presence of an interatrial block (IAB) on surface ECG should be considered as a hallmark of atrial electrical remodelling. This is often accompanied by morphological abnormalities. We aimed to investigate the frequency of IAB and its relationship with the echocardiographic indices of left atrial (LA) remodelling in patients hospitalised with acute HF. Ninety-four consecutive HF patients underwent 12-lead ECG, transthoracic echocardiogram including a detailed study of the LA, and blood tests (including NT-proBNP) on the same day. Thirty-six patients were excluded from the analysis because of atrial fibrillation or rhythms other than sinus. Twenty-eight over 58 (48%) were males. Median age was 72 (IQR 60-82) years. The majority of patients (72%) were diagnosed as having an HF with reduced ejection fraction. Overall, 27 (46%) patients presented with an advanced III or IV NYHA functional class. Median plasma NT-proBNP was 3046 (IQR 1066-5460) pg/ml. Nearly, all the enrolled patients (90%) showed LA dilation. Nineteen patients (33%) presented with advanced IAB. There was a trend toward a more advanced age in patients with advanced IAB (median age 79 vs 68, p = 0.051). Moreover, they were more frequently treated with anticoagulants (42% vs 13%, p = 0.01), and they exhibited greater LA structural and functional remodelling documented by larger area (28 vs 26 cm 2 , p = 0.04) and greater minimum LA volume index-LAVi (43 ± 16 vs 36 ± 10, p = 0.04). Advanced IAB resulted to be an independent determinant of LA area (Beta 3.49 (0.37-6.60), p = 0.03) and minimum LAVi (Beta 7.22 (0.15-14.30), p = 0.045), and vice versa. LA electrical and structural remodelling is highly prevalent in a non-selected cohort of patients with acute HF. Advanced IAB on surface ECG is present in a high percentage of cases. Patients with advanced IAB tend to be older, and they exhibit higher degrees of LA structural and functional remodelling., (© 2021. Springer Japan KK, part of Springer Nature.)

Background: The prevalence of parvovirus B19 infection in renal transplantation ranges from 2% to 30%. The age and immune status of the patient influence the severity of the clinical picture. A diagnosis is made by taking as evidence the giant proerythroblasts on a bone marrow sample and the parvovirus B19 viral replication with a polymerase chain reaction (PCR) technique at the blood level. Clinically, parvovirus B19 may appear with fever and severe anemia, which can be followed by pancytopenia and thrombotic microangiopathy in some cases. The literature reports a graft dysfunction rate ranging from 10% to 36%. An infection relapse may happen in 30% of cases., Case Presentation: We report the case of a 33-year-old patient who underwent a kidney transplant in January of 2018. After transplantation, he reached a creatinine value of 1.1 mg/dL and a hemoglobin (Hb) level of 14 g/dL. In April 2019, he developed mycoplasma pneumonia, with signs of hemolytic anemia on bone marrow aspiration. Eventually, he was admitted because of fever, arthralgia, and anemia, with serologic and bone marrow biopsy evidence of red cell aplasia secondary to parvovirus B19 infection. He was treated with 400 mg/kg intravenous immunoglobulin (IVIg) for 10 days; 18 days after the end of treatment, he reached a creatinine value of 1.15 mg/dL, an Hb of 12.5 g/dL, and a reduction of the viral load from 25,000,000 copies/mL to 1,600,000 copies/mL., Conclusions: Anemia with both an aplasic and hemolytic component was successfully treated using immunoglobulin therapy, with a significant fall in the parvovirus B19 viral load., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by an excessive immune activation. HLH can be triggered by a variety of events that disrupt immune homeostasis, such as infections and immunosuppression. HLH presents with heterogeneous clinical symptoms and laboratory findings such as pancytopenia, elevated liver enzymes, impaired renal function, and hyperferritinemia., Case Presentations: Case 1. A 58-year-old man was admitted because of a high fever and diarrhea. Laboratory findings showed acute renal impairment, pancytopenia, Epstein-Barr virus (EBV) DNA seropositivity with a replication index of 2 million copies/mL, and hyperferritinemia. A diagnosis of HLH was confirmed by bone marrow aspiration. He was treated with etoposide, steroids, and rituximab with initial good response and good kidney function restoration. He was discharged after 31 days but eventually died after 44 days after a disease relapse. Case 2. A 51-year-old kidney transplant recipient was admitted because of a fever of unknown origin. A worsening renal function, pancytopenia, EBV DNA of 4,356,222 copies/mL on blood, D-Dimer 7505 ng/mL, ferritinemia 9180.9 ug/L, and triglycerides 1273 mg/dL were found. Bone marrow aspiration was negative for HLH; a few days later, a diagnosis of HLH was made after a positive bone marrow biopsy. Continuous renal replacement therapy was started in the intensive care unit because of severe lactic acidosis due to sepsis. She died few days later., Conclusion: EBV infection could be a trigger for HLH in a renal transplant patient. Hyperferritinemia is useful for differential diagnosis in a septic patient. The outcome is very poor even with prompt treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Kidney transplantation is a life-saving treatment for patients with end-stage renal disease. However, despite progress in surgical techniques and patient management, immunological rejection continues to have a negative impact on graft function and overall survival. Incompatibility between donors and recipients for human leukocyte antigens (HLA) of the major histocompatibility complex (MHC) generates a series of complex cellular and humoral immune response mechanisms that are largely responsible for rejection and loss of graft function. Within this context, a growing amount of evidence shows that alloreactive natural killer (NK) cells play a critical role in the immune response mechanisms elicited by the allograft. Killer immunoglobulin-like receptors (KIRs) are prominent mediators of NK cell alloreactivity., Methods and Findings: A cohort of 174 first cadaveric kidney allograft recipients and their donors were selected from a total cohort of 657 transplanted patients for retrospective immunogenetic analyses. Patients with HLA Class II mismatches were excluded. HLA Class I allele frequencies were compared among patients with chronic rejection, patients with stable graft function and a group of 2388 healthy controls. Activating and inhibitory KIR gene frequencies, KIR haplotypes, KIR-HLA ligand matches/mismatches and combinations of recipient KIRs and donor HLA Class I ligands were compared among patients with and without chronic rejection and a group of 221 healthy controls. Patients transplanted from donors homozygous for HLA-C1 antigens had a significantly higher risk for chronic rejection than patients transplanted from donors homozygous or heterozygous for HLA-C2 antigens or with epitopes belonging to the HLA-Bw4 ligand group. The Kaplan-Meier curves obtained by dividing the patients into 3 groups according to the presence or absence of one or both of the combinations of recipient KIRs and donor HLA ligands (rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4) showed a significantly higher cumulative incidence of chronic rejection in the group of patients completely lacking these functional units. These patients showed a progressively stronger decline in modification of diet in renal disease-estimated glomerular filtration rate., Conclusions: KIR genotyping should be performed at the time of enrolment of patients on the waiting list for organ transplantation. In our study, a significantly higher risk of chronic rejection after kidney transplantation was observed when recipient (r) and donor (d) pairs completely lacked the two functional rKIR-dHLA ligand combinations rKIR2DL1/dHLA-C2 and rKIR3DL1/dHLA-Bw4. This immunogenetic profile corresponds to low levels of NK cell inhibition. Therefore, patients with this high risk profile could benefit from immunosuppressive therapy aimed at reducing NK-cell cytotoxicity.

Objectives: Several studies have investigated the cytokine profile of patients with systemic lupus erythematosus (SLE); however, their role is still controversial, mostly because SLE has a heterogeneous disease manifestation. We measured 4 of the most important cytokines in patients with SLE after dividing them in uniform groups according to disease activity and organ involvement., Materials and Methods: Eighty-two adult female patients with SLE were divided into 3 groups according to disease activity and organ involvement: Group A (SLE activity index [SLEDAI] score, 7 ± 0.4) included subjects with newly diagnosed, active SLE, investigated before starting therapy. Group B (SLEDAI score, < 6) included patients without renal involvement, treated with prednisone and azathioprine or hydroxychloroquine. Group C (SLEDAI score, < 6) included patients with lupus nephritis, treated with methylprednisolone and cyclophosphamide, reaching complete remission. Fourteen healthy females served as controls., Results: Interleukin-1 levels were 1.0, 0.8, 0.7, and 0.25 pg/mL in groups A, B, C, and D, respectively. Interleukin-6 levels were 3.2, 3.6, 4.0, and 1.4 pg/mL in groups A, B, C, and D, respectively; Il-10 levels, 3.05, 1.1, 1.5, and 1.65; tumor necrosis factor-α levels, 8.75, 5.8, 5.4, and 3.6. Interleukin 1, IL-6, and tumor necrosis factor-α were significantly higher in the patients with SLE than in the healthy controls; IL-1 was significantly higher in group A than in group C. Interleukin 10 showed positive correlation with C-reactive protein, whereas it showed negative correlation with C3., Conclusions: Data from our cohort, one of the largest so far reported, add to the evidence that proinflammatory cytokines such as Interleukin-1, Interleukin-6, Interleukin-10 and tumor necrosis factor-α are important in SLE pathogenesis.