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Article: Proteomic Profiling of Cerebrospinal Fluid and Its Extracellular Vesicles from Extraventricular Drainage in Pediatric Pilocytic Astrocytoma, towards Precision Oncology.

Spinelli, Sonia / Kajana, Xhuliana / Garbarino, Andrea / Bartolucci, Martina / Petretto, Andrea / Pavanello, Marco / Verrina, Enrico / Candiano, Giovanni / Panfoli, Isabella / Bruschi, Maurizio

Cancers

2024 Volume 16, Issue 6

Abstract: Pediatric pilocytic astrocytoma (PA) is the most common brain tumor in children. Complete resection provides a favorable prognosis, except for unresectable PA forms. There is an incomplete understanding of the molecular and cellular pathogenesis of PA. ... ...

Abstract	Pediatric pilocytic astrocytoma (PA) is the most common brain tumor in children. Complete resection provides a favorable prognosis, except for unresectable PA forms. There is an incomplete understanding of the molecular and cellular pathogenesis of PA. Potential biomarkers for PA patients, especially the non-BRAF-mutated ones are needed. Cerebrospinal fluid (CSF) is a valuable source of brain tumor biomarkers. Extracellular vesicles (EVs), circulating in CSF, express valuable disease targets. These can be isolated from CSF from waste extraventricular drainage (EVD). We analyzed the proteome of EVD CSF from PA, congenital hydrocephalus (CH, non-tumor control), or medulloblastoma (MB, unrelated tumoral control) patients. A total of 3072 proteins were identified, 47.1%, 65.6%, and 86.2% of which were expressed in the unprocessed total and in its large-EV (LEV), and small-EV (SEV) fractions. Bioinformatics identified 50 statistically significant proteins in the comparison between PA and HC, and PA and MB patients, in the same fractions. Kinase enrichment analysis predicted five enriched kinases involved in signaling. Among these, only Cyclin-dependent kinase 2 (CDK2) kinase was overexpressed in PA samples. PLS-DA highlighted the inactive carboxypeptidase-like protein X2 (CPXM2) and aquaporin-4 (AQP4) as statistically significant in all the comparisons, with CPXM2 being overexpressed (validated by ELISA and Western blot) and AQP4 downregulated in PA. These proteins were considered the most promising potential biomarkers for discriminating among pilocytic astrocytoma and unrelated tumoral (MB) or non-tumoral conditions in all the fractions examined, and are proposed to be prospectively validated in the plasma for translational medicine applications.
Language	English
Publishing date	2024-03-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16061223
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Article ; Online: Vaccines and nephrotic syndrome: efficacy and safety.

Angeletti, Andrea / Lugani, Francesca / La Porta, Edoardo / Verrina, Enrico / Caridi, Gianluca / Ghiggeri, Gian Marco

Pediatric nephrology (Berlin, Germany)

2022 Volume 38, Issue 9, Page(s) 2915–2928

Abstract: Vaccines represent the most important medical evolution in the last two centuries allowing prevention and formally eradication of a wide number of infectious diseases. Safety and effectiveness are main issues that still require an open discussion. A few ... ...

Abstract	Vaccines represent the most important medical evolution in the last two centuries allowing prevention and formally eradication of a wide number of infectious diseases. Safety and effectiveness are main issues that still require an open discussion. A few clinical reports described a critical temporal relationship between vaccination and acute nephrotic syndrome, indirectly suggesting an association. For this review, the literature was reviewed to identify articles reporting associations of nephrotic syndrome with vaccines against a vast array of infectious diseases (including bacteria, virus and Sars-Cov-2). As specific aims, we evaluated effectiveness and safety in terms of occurrence of either "de novo" nephrotic syndrome in health subjects or "relapse" in those already affected by the disease. In total, 377 articles were found; 166 duplicates and 71 non-full text, animal studies or non-English language were removed. After excluding another 50 articles not containing relevant data on generic side effects or on relapses or new onset nephrotic syndrome, 90 articles met the search criteria. Overall, studies reported the effect of vaccines in 1015 patients, plus 4 nationwide epidemiologic investigations. Limited experience on vaccination of NS patients with measles, mumps, and rubella live attenuated vaccines does not allow any definitive conclusion on their safeness. VZV has been administered more frequently without side effects. Vaccines utilizing virus inactivated, recombinant, and toxoid can be utilized without risks in NS. Vaccines for influenza reduce the risk of infections during the pandemic and are associated with reduced risk of relapse of NS typically induced by the infection. Vaccines for SARS-CoV-2 (all kinds) offer a concrete approach to reduce the pandemic. "De novo" NS or recurrence are very rare and respond to common therapies.
MeSH term(s)	Animals ; Humans ; Communicable Diseases ; COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Nephrotic Syndrome/prevention & control ; Nephrotic Syndrome/drug therapy ; SARS-CoV-2
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2022-12-13
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-022-05835-4
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Article ; Online: Biologics in steroid resistant nephrotic syndrome in childhood: review and new hypothesis-driven treatment.

Angeletti, Andrea / Bruschi, Maurizio / Kajana, Xhuliana / La Porta, Edoardo / Spinelli, Sonia / Caridi, Gianluca / Lugani, Francesca / Verrina, Enrico Eugenio / Ghiggeri, Gian Marco

Frontiers in immunology

2023 Volume 14, Page(s) 1213203

Abstract: Nephrotic syndrome affects about 2-7 per 100,000 children yearly and accounts for less than 15% of end stage kidney disease. Steroids still represent the cornerstone of therapy achieving remission in 75-90% of the cases The remaining part result as ... ...

Abstract	Nephrotic syndrome affects about 2-7 per 100,000 children yearly and accounts for less than 15% of end stage kidney disease. Steroids still represent the cornerstone of therapy achieving remission in 75-90% of the cases The remaining part result as steroid resistant nephrotic syndrome, characterized by the elevated risk of developing end stage kidney disease and frequently presenting disease recurrence in case of kidney transplant. The pathogenesis of nephrotic syndrome is still far to be elucidated, however, efficacy of immune treatments provided the basis to suggest the involvement of the immune system in the pathogenesis of the disease. Based on these substrates, more immune drugs, further than steroids, were administered in steroid resistant nephrotic syndrome, such as antiproliferative and alkylating agents or calcineurin inhibitors. However, such treatments failed in inducing a sustained remission. In last two decades, the developments of monoclonal antibodies, including the anti-CD20 rituximab and inhibitor of B7-1 abatacept, represented a valid opportunity of treatment. However, also the effectiveness of biologics resulted limited. We here propose a new hypothesis-driven treatment based on the combining administration of rituximab with the anti-CD38 monoclonal antibody daratumumab (NCT05704400), sustained by the hypothesis to target the entire B-cells subtypes pool, including the long-lived plasmacells.
MeSH term(s)	Child ; Humans ; Biological Products ; Nephrotic Syndrome/drug therapy ; Rituximab/therapeutic use ; Abatacept ; Kidney Failure, Chronic
Chemical Substances	Biological Products ; Rituximab (4F4X42SYQ6) ; Abatacept (7D0YB67S97)
Language	English
Publishing date	2023-08-29
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1213203
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Article ; Online: Co-Occurrence of Nephronophthisis Type 1 and Alström Syndrome: A Case Report.

Rossoni, Lisa / Lugani, Francesca / Orsi, Silvia Maria / Verrina, Enrico Eugenio / Ghiggeri, Gian Marco / Angeletti, Andrea / Caridi, Gianluca / La Porta, Edoardo

Nephron

2023 Volume 148, Issue 5, Page(s) 345–348

Abstract: We describe the unique case of a patient in whom two ciliopathies with autosomal recessive transmission were clinically and molecularly diagnosed: nephronophthisis type 1 (NPHP1) and Alström syndrome (AS). NPHP1 is one of the main genetic causes of ... ...

Abstract	We describe the unique case of a patient in whom two ciliopathies with autosomal recessive transmission were clinically and molecularly diagnosed: nephronophthisis type 1 (NPHP1) and Alström syndrome (AS). NPHP1 is one of the main genetic causes of terminal kidney failure in childhood. AS is an ultra-rare multi-systemic disease, characterized by progressive kidney disease, hepatic failure, dystrophy of the rods and cones to blindness, slowly progressive neuro-sensory deafness, dilated cardiomyopathy, obesity, insulin resistance/type 2 diabetes mellitus. The coexistence in the same patient of two rare syndromes with overlapping clinical manifestations but genetically different is an eventuality to be considered. This case report would describe the onset and progression of the multi-organ manifestations of both syndromes to highlight that ciliopathies present a strong phenotype overlap but also specific peculiarities. Therefore, to make a correct diagnosis that is essential to achieve the best clinical management could be challenging.
MeSH term(s)	Humans ; Alstrom Syndrome/genetics ; Alstrom Syndrome/complications ; Kidney Diseases, Cystic/genetics ; Kidney Diseases, Cystic/complications ; Male ; Female ; Membrane Proteins/genetics ; Adaptor Proteins, Signal Transducing/genetics ; Cytoskeletal Proteins
Chemical Substances	NPHP1 protein, human ; Membrane Proteins ; Adaptor Proteins, Signal Transducing ; Cytoskeletal Proteins
Language	English
Publishing date	2023-02-06
Publishing country	Switzerland
Document type	Case Reports ; Journal Article
ZDB-ID	207121-6
ISSN	2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
ISSN (online)	2235-3186 ; 1423-0186
ISSN	1660-8151 ; 0028-2766
DOI	10.1159/000529473
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Article ; Online: Corrigendum: Case report: Multisystem inflammatory syndrome in children with associated proximal tubular injury.

Orsi, Silvia Maria / Pepino, Carlotta / Rossoni, Lisa / Serafino, Margherita / Caorsi, Roberta / Volpi, Stefano / Palmeri, Serena / Faragli, Alessandro / Lugani, Francesca / Bigatti, Carolina / Ghiggeri, Gian Marco / Verrina, Enrico Eugenio / La Porta, Edoardo / Angeletti, Andrea

Frontiers in nephrology

2024 Volume 4, Page(s) 1374200

Abstract: This corrects the article DOI: 10.3389/fneph.2023.1194989.]. ...

Abstract	[This corrects the article DOI: 10.3389/fneph.2023.1194989.].
Language	English
Publishing date	2024-02-26
Publishing country	Switzerland
Document type	Published Erratum
ISSN	2813-0626
ISSN (online)	2813-0626
DOI	10.3389/fneph.2024.1374200
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Article: Biologics and Non-Biologics Immunosuppressive Treatments for IgA Nephropathy in Both Adults and Children.

Chiarenza, Decimo Silvio / Verrina, Enrico Eugenio / La Porta, Edoardo / Caridi, Gianluca / Ghiggeri, Gian Marco / Mortari, Gabriele / Lugani, Francesca / Angeletti, Andrea / Bigatti, Carolina

Journal of clinical medicine

2024 Volume 13, Issue 9

Abstract: Immunoglobulin A nephropathy represents the most prevalent cause of glomerulonephritis worldwide and may lead to renal failure in a relevant number of cases in both paediatric and adult subjects. Although their pathogenesis is still largely unclear, ... ...

Abstract	Immunoglobulin A nephropathy represents the most prevalent cause of glomerulonephritis worldwide and may lead to renal failure in a relevant number of cases in both paediatric and adult subjects. Although their pathogenesis is still largely unclear, evidence of immune abnormalities provides the background for the use of immunosuppressive drugs, such as corticosteroids, calcineurin inhibitors, and antiproliferative and alkylating agents. Unfortunately, these treatments fail to achieve a sustained remission in a significant percentage of affected patients and are burdened by significant toxicities. Recent developments of new biologics, including anti-BAFF/APRIL inhibitors and molecules targeting complement components, offered the opportunity to selectively target immune cell subsets or activation pathways, leading to more effective and safer hypothesis-driven treatments. However, studies testing new biologic agents in IgAN should also consider paediatric populations to address the unique needs of children and close the therapeutic gap between adult and paediatric care.
Language	English
Publishing date	2024-04-23
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm13092465
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Article ; Online: Brain and spine malformations and neurodevelopmental disorders in a cohort of children with CAKUT.

Boeri, Silvia / Bodria, Monica / Ammendola, Rosa Maria / Giacomini, Thea / Tortora, Domenico / Nobili, Lino / Malacarne, Michela / Rossi, Andrea / Verrina, Enrico / Piaggio, Giorgio / Mancardi, Maria Margherita / Severino, Mariasavina

Pediatric nephrology (Berlin, Germany)

2024

Abstract: Background: Congenital anomalies of the kidney and urinary tract (CAKUT) represent 20-30% of all birth defects and are often associated with extra-renal malformations. We investigated the frequency of brain/spine malformations and neurological features ... ...

Abstract	Background: Congenital anomalies of the kidney and urinary tract (CAKUT) represent 20-30% of all birth defects and are often associated with extra-renal malformations. We investigated the frequency of brain/spine malformations and neurological features in children with CAKUT. Methods: We reviewed the clinico-radiological and genetic data of 199 out of 1,165 children with CAKUT evaluated from 2006 to 2023 (99 males, mean age at MRI 6.4 years) who underwent brain and/or spine MRI. Patients were grouped according to the type of CAKUT (CAKUT-K involving the kidney and CAKUT-H involving the inferior urinary tract). Group comparisons were performed using χ Results: Brain/spine malformations were observed in 101/199 subjects (50.7%), 8.6% (101/1165) of our CAKUT population, including midbrain-hindbrain anomalies (40/158, 25.3%), commissural malformations (36/158, 22.7%), malformation of cortical development (23/158, 14.5%), Chiari I anomaly (12/199, 6%), cranio-cervical junction malformations (12/199, 6%), vertebral defects (46/94, 48.9%), caudal regression syndrome (29/94, 30.8%), and other spinal dysraphisms (13/94, 13.8%). Brain/spine malformations were more frequent in the CAKUT-K group (62.4%, p < 0.001). Sixty-two subjects (62/199, 31.2%) had developmental delay/intellectual disability. Neurological examination was abnormal in 40/199 (20.1%). Seizures and/or electroencephalographic anomalies were reported in 28/199 (14%) and behavior problems in 19/199 subjects (9%). Developmental delay/intellectual disability was more frequent in kidney dysplasia (65.2%) and agenesis (40.7%) (p = 0.001). Conclusions: We report a relative high frequency of brain/spine malformations and neurodevelopmental disorders in children with CAKUT who underwent MRI examinations in a tertiary referral center, widening the spectrum of anomalies associated with this condition.
Language	English
Publishing date	2024-02-20
Publishing country	Germany
Document type	Journal Article
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-024-06289-6
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Article ; Online: Acute pancreatitis in children on chronic maintenance dialysis.

Vidal, Enrico / Alberici, Irene / Verrina, Enrico

Pediatric nephrology (Berlin, Germany)

2018 Volume 34, Issue 9, Page(s) 1501–1512

Abstract: Patients on dialysis are exposed to a series of factors that are known to be associated with risk of acute pancreatitis (AP), including medications, hyperparathyroidism, hypercalcemia, and hypertriglyceridemia; the role of the dialysis modality itself is ...

Abstract	Patients on dialysis are exposed to a series of factors that are known to be associated with risk of acute pancreatitis (AP), including medications, hyperparathyroidism, hypercalcemia, and hypertriglyceridemia; the role of the dialysis modality itself is still debated. Data regarding AP in children on chronic dialysis are scarce. Data from the Italian Registry of Pediatric Chronic Dialysis (IRPCD) confirm that children on dialysis have a significant increased relative risk (RR) for AP as compared with the general pediatric population (RR 60.4; 95% CI 3.2-214). Diagnosis of AP in patients on dialysis may be troublesome, because it can mimic other acute intraabdominal conditions and the role of serum pancreatic enzyme assays may be confounding. In this setting, instrumental imaging is mandatory. Conservative management such as fluid, bowel rest, and antibiotics is the mainstay of AP management, as necrotizing forms are rare. Mortality in the series of 12 patients from the IRPCD was high (25%), but deaths were not directly related to AP. Adult case series confirm that mortality among patients on dialysis who develop AP is highly variable (8-58%), but higher as compared to 10% mortality from AP in non-renal failure patients.
MeSH term(s)	Adolescent ; Anti-Bacterial Agents/therapeutic use ; Child ; Child, Preschool ; Diagnosis, Differential ; Female ; Fluid Therapy/methods ; Humans ; Incidence ; Italy/epidemiology ; Kidney Failure, Chronic/mortality ; Kidney Failure, Chronic/therapy ; Male ; Pancreas/diagnostic imaging ; Pancreas/pathology ; Pancreatitis/diagnosis ; Pancreatitis/epidemiology ; Pancreatitis/etiology ; Pancreatitis/therapy ; Registries/statistics & numerical data ; Renal Dialysis/adverse effects ; Risk Factors ; Tomography, X-Ray Computed
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2018-08-23
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-018-4043-y
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Article ; Online: An update on COVID-19 in paediatric and young adults with nephrotic syndrome, receiving chronic immunosuppression during the Omicron pandemic.

Angeletti, Andrea / Bruschi, Maurizio / Bigatti, Carolina / Palmeri, Serena / Lugani, Francesca / Verrina, Enrico / Ghiggeri, Gian Marco

Journal of nephrology

2022 Volume 35, Issue 6, Page(s) 1775–1776

MeSH term(s)	COVID-19 ; Child ; Graft vs Host Disease ; Humans ; Immunosuppression Therapy ; Immunosuppressive Agents/adverse effects ; Nephrotic Syndrome/diagnosis ; Nephrotic Syndrome/drug therapy ; Pandemics ; Young Adult
Chemical Substances	Immunosuppressive Agents
Language	English
Publishing date	2022-04-09
Publishing country	Italy
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	1093991-x
ISSN	1724-6059 ; 1120-3625 ; 1121-8428
ISSN (online)	1724-6059
ISSN	1120-3625 ; 1121-8428
DOI	10.1007/s40620-022-01319-8
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Article: Renal involvement and Strømme syndrome.

Caridi, Gianluca / Lugani, Francesca / Lerone, Margherita / Divizia, Maria Teresa / Ghiggeri, Gian Marco / Verrina, Enrico

Clinical kidney journal

2020 Volume 14, Issue 1, Page(s) 439–441

Abstract: Strømme syndrome is a rare autosomal recessive congenital disorder involving multiple systems. Centromeric protein F ( ...

Abstract	Strømme syndrome is a rare autosomal recessive congenital disorder involving multiple systems. Centromeric protein F (
Language	English
Publishing date	2020-01-25
Publishing country	England
Document type	Case Reports
ZDB-ID	2655800-2
ISSN	2048-8513 ; 2048-8505
ISSN (online)	2048-8513
ISSN	2048-8505
DOI	10.1093/ckj/sfz189
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