Consensus of the Italian Primary Immunodeficiency Network on the use and interpretation of genetic testing for the diagnosis of inborn errors of immunity (IEI).

Background: Inborn errors of immunity (IEIs) are more than 500 different rare congenital disorders of the immune system characterized by susceptibility to infections and immune dysregulation. The significant overlap of the clinical features among the different forms may lead to diagnostic delay. High throughput sequencing techniques may allow a timely genetic definition.

Predictors for choosing doravirine-based versus INSTI-based regimen in ART-naïve and ART-experienced people with HIV in real-world setting: Data from the Icona cohort.

Rationale: Doravirine (DOR) is an attractive new option both for ART-naïve people with HIV (PWH) and those with suppressed HIV-RNA who seek treatment simplification. We used real-world data to examine the pattern of use of DOR-containing regimens in these settings.

Methods: All PWH enrolled in the Icona cohort after January 2020 who initiated a three-drug regimen (3-DR) with DOR or an integrase inhibitor (INSTI)-based regimen as first antiretroviral therapy (ART) or when switching ART, with HIV-RNA ≤50 copies/mL, were included.

Visual supports and informative material not to forget counselling on reproductive health in dialysis: a point of view.

Contraception, pregnancy and fertility are seldom discussed with women receiving dialysis and the medical staff of dialysis centres. Since the majority of women on dialysis are past childbearing age, these themes are not always given proper consideration and this category of patients may be missing important information. Young women of childbearing age who are on dialysis frequently experience sexual dysfunction and hormonal disorders of the hypothalamic-pituitary-gonadal axis.

Pulsed Radiofrequency Electromagnetic Fields as Modulators of Inflammation and Wound Healing in Primary Dermal Fibroblasts of Ulcers.

Venous leg ulcers are one of the most common nonhealing conditions and represent an important clinical problem. The application of pulsed radiofrequency electromagnetic fields (PRF-EMFs), already applied for pain, inflammation, and new tissue formation, can represent a promising approach for venous leg ulcer amelioration. This study aims to evaluate the effect of PRF-EMF exposure on the inflammatory, antioxidant, cell proliferation, and wound healing characteristics of human primary dermal fibroblasts collected from venous leg ulcer patients.

Mesothelioma among seamen: a systematic review and meta-analysis.

Objectives: Navy personnel and seafarers live and work 24 h per day in the shipboard environment and they are exposed to asbestos fibers released into the confined spaces aboard ships. We conducted a systematic review and meta-analysis to quantify the mesothelioma risk of seamen working aboard ships, either commercial or naval vessels, as compared to that of the general population.

Methods: We carried out a literature search in MEDLINE through PubMed and EMBASE, from inception to 31 December 2021, of all studies on seamen working aboard ships, either commercial or naval vessels, characterized by exposure to asbestos and providing mesothelioma risk estimates.

The Changing Landscape of Neonatal Diabetes Mellitus in Italy Between 2003 and 2022.

Context: In the last decade the Sanger method of DNA sequencing has been replaced by next-generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal diabetes mellitus (NDM).

Objective: To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.

Monoallelic pathogenic variants are a common cause of autosomal dominant polycystic kidney disease-spectrum phenotype.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disorder, characterized by development and enlargement of kidney cysts, eventually leading to end-stage kidney disease (ESKD). Pathogenic variants in the and genes are the major cause of ADPKD; additional rare variants in the and genes have been found in a minority of ADPKD patients. More recently, a significant number of ADPKD families have been linked to monoallelic variants in the gene.

Infections with long latency in international refugees, immigrants, and migrants seen at GeoSentinel sites, 2016-2018.

Background: The continued increase in global migration compels clinicians to be aware of specific health problems faced by refugees, immigrants, and migrants (RIM). This analysis aimed to characterize RIM evaluated at GeoSentinel sites, their migration history, and infectious diseases detected through screening and diagnostic workups.

Methods: A case report form was used to collect data on demographics, migration route, infectious diseases screened, test results, and primary infectious disease diagnosis for RIM patients seen at GeoSentinel sites.

Monogenic forms of common variable immunodeficiency and implications on target therapeutic approaches.

Purpose Of Review: Common variable immunodeficiency (CVID) is the most common symptomatic inborn error of immunity. The disorder is characterized by variable clinical and immunological manifestations, and, in a small minority of patients, a monogenic cause may be identified. In this review, we focalized on three different monogenic forms of CVID-like disease.

Rituximab Monotherapy Is Effective as First-Line Treatment for Granulomatous Lymphocytic Interstitial Lung Disease (GLILD) in CVID Patients.

Granulomatous lymphocytic interstitial lung disease (GLILD) represents a fatal immune dysregulatory complication in common variable immunodeficiency (CVID). Evidence-based diagnostic guidelines are lacking, and GLILD treatment consists in immunosuppressive drugs; nonetheless, therapeutical strategies are heterogeneous and essentially based on experts' opinions and data from small case series or case reports.We aimed to evaluate the efficacy and safety of first-line Rituximab monotherapy for CVID-related GLILD, by assessing symptoms and quality of life alterations, immunological parameters, pulmonary function tests, and lung computed tomography.

Scalable GMP-compliant gene correction of CD4+ T cells with IDLV template functionally validated and .

Hyper-IgM1 is a rare X-linked combined immunodeficiency caused by mutations in the CD40 ligand () gene with a median survival of 25 years, potentially treatable with CD4+ T cell gene editing with Cas9 and a one-size-fits-most corrective donor template. Here, starting from our research-grade editing protocol, we pursued the development of a good manufacturing practice (GMP)-compliant, scalable process that allows for correction, selection and expansion of edited cells, using an integrase defective lentiviral vector as donor template. After systematic optimization of reagents and conditions we proved maintenance of stem and central memory phenotypes and expression and function of in edited healthy donor and patient cells recapitulating the physiological regulation.

Strongyloides stercoralis infection: an underlying cause of invasive bacterial infections of enteric origin. Results from a prospective cross-sectional study of a northern Italian tertiary hospital.

Purpose Of The Study: We assessed the prevalence of S. stercoralis in a cohort of inpatients with invasive bacterial infections of enteric origin to investigate whether the parasite may facilitate these bacterial infections even in the absence of larval hyperproliferation.

Methods: We performed a prospective cross-sectional study in a hospital in northern Italy.

Temporomandibular joint involvement in patients with Juvenile Idiopathic Arthritis: comparison of ultrasonography and magnetic resonance imaging in assessing the periarticular space width.

Objectives: This study aimed to compare the performance of Ultrasonography (US) and Magnetic Resonance Imaging (MRI) in assessing the Lateral Periarticular Space (LPAS) of Temporomandibular Joints (TMJs) in patients with Juvenile Idiopathic Arthritis (JIA).

Methods: The LPAS width was evaluated in two different patient groups. In the JIA group, including 29 children (13 ± 2.

Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity.

Background: Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking.

Objectives: This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS.

Leader peptide or pro-segment mutants of renin are misrouted to mitochondria in autosomal dominant tubulointerstitial kidney disease.

Autosomal dominant tubulointerstitial kidney disease (ADTKD), a rare genetic disorder characterised by progressive chronic kidney disease, is caused by mutations in different genes, including REN, encoding renin. Renin is a secreted protease composed of three domains: the leader peptide that allows insertion in the endoplasmic reticulum (ER), a pro-segment regulating its activity, and the mature part of the protein. Mutations in mature renin lead to ER retention of the mutant protein and to late-onset disease, whereas mutations in the leader peptide, associated with defective ER translocation, and mutations in the pro-segment, leading to accumulation in the ER-to-Golgi compartment, lead to a more severe, early-onset disease.

COVID-19 Pneumonia with Migratory Pattern in Agammaglobulinemic Patients: A Report of Two Cases and Review of Literature.

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in serum immunoglobulins and early-onset infections. Coronavirus Disease-2019 (COVID-19) pneumonia in immunocompromised patients presents clinical and radiological peculiarities which have not yet been completely understood. Very few cases of agammaglobulinemic patients with COVID-19 have been reported since the beginning of the pandemic in February 2020.

Impact, healthcare utilization and costs of travel-associated mosquito-borne diseases in international travellers: a prospective study.

Background: International travellers frequently acquire infectious diseases whilst travelling, yet relatively little is known about the impact and economic burden of these illnesses on travellers. We conducted a prospective exploratory costing study on adult returning travellers with falciparum malaria, dengue, chikungunya or Zika virus.

Methods: Patients were recruited in eight Travel and Tropical Medicine clinics between June 2016 and March 2020 upon travellers' first contact with the health system in their country of residence.

Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome.

Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown.

Screening for Tuberculosis Infection among Migrants: A Cost-Effectiveness Analysis in the Italian Context.

Background: Screening of tuberculosis infection (TBI) among migrants from high-incidence countries is a cornerstone of tuberculosis control in low-incidence countries. However, the optimal screening strategy has not been defined yet.

Methods: A quasi-experimental study involving migrants residing in the province of Brescia was carried out that aimed at assessing the completion rate, time to completion, preventive treatment initiation rate, and cost-effectiveness of two strategies for TBI screening.

Identification of bi-allelic LFNG variants in three patients and further clinical and molecular refinement of spondylocostal dysostosis 3.

Spondylocostal dysostosis (SCD), a condition characterized by multiple segmentation defects of the vertebrae and rib malformations, is caused by bi-allelic variants in one of the genes involved in the Notch signaling pathway that tunes the "segmentation clock" of somitogenesis: DLL3, HES7, LFNG, MESP2, RIPPLY2, and TBX6. To date, seven individuals with LFNG variants have been reported in the literature. In this study we describe two newborns and one fetus with SCD, who were found by trio-based exome sequencing (trio-ES) to carry homozygous (c.

Rare Single Nucleotide and Copy Number Variants and the Etiology of Congenital Obstructive Uropathy: Implications for Genetic Diagnosis.

Significance Statement: Congenital obstructive uropathy (COU) is a prevalent human developmental defect with highly heterogeneous clinical presentations and outcomes. Genetics may refine diagnosis, prognosis, and treatment, but the genomic architecture of COU is largely unknown. Comprehensive genomic screening study of 733 cases with three distinct COU subphenotypes revealed disease etiology in 10.