SYNGAP-1 Mutation And Catatonia: A Case Series and Systematic Review.

Hyperactive catatonia is often unrecognized in pediatric patients due to its clinical heterogeneity, though it is often seen in children with neurodevelopmental disabilities, especially autism spectrum disorder (ASD). Emerging evidence implicates hyperactive catatonia in more cases of self-injury and aggression in ASD than previously thought. The study seeks to describe cases of hyperactive catatonia in SYNGAP-1 mutation and examine existing literature for symptomatic overlap between previously-described clinical and behavioral phenotypes of individuals with SYNGAP-1 mutations and catatonia.

C-reactive protein gene polymorphisms influence susceptibility and outcomes of biopsy-proven giant cell arteritis in Italian patients.

Objectives: To investigate potential associations between the two functional C-reactive protein (CRP) gene polymorphisms at position 3872C>T (rs1205) and 4741G>C (rs3093068) and susceptibility, clinical expression, laboratory and pathological findings, and outcomes of giant cell arteritis (GCA) in a Nothern Italian population.

Methods: One hundred and seventy Italian patients with biopsy-proven GCA resident in Reggio Emilia area, Italy, and 200 healthy controls from the same geographic area were genotyped for rs1205 and rs3093068 CRP gene polymorphisms by molecular methods. The patients were subgrouped on the basis of the presence or absence of clinical manifestations, histological and laboratory findings, and outcomes.

Artificial Intelligence-Assisted Processing of Anterior Segment OCT Images in the Diagnosis of Vitreoretinal Lymphoma.

Anterior segment optical coherence tomography (AS-OCT) allows the explore not only the anterior chamber but also the front part of the vitreous cavity. Our cross-sectional single-centre study investigated whether AS-OCT can distinguish between vitreous involvement due to vitreoretinal lymphoma (VRL) and vitritis in uveitis. We studied AS-OCT images from 28 patients (11 with biopsy-proven VRL and 17 with differential diagnosis uveitis) using publicly available radiomics software written in MATLAB.

Medullary Thyroid Carcinomas Classified According to the International Medullary Carcinoma Grading System and a Surveillance, Epidemiology, and End Results-Based Metastatic Risk Score: A Correlation With Genetic Profile and Angioinvasion.

Due to the lack of a standardized tool for risk-based stratification, the International Medullary Carcinoma Grading System (IMTCGS) has been proposed for medullary thyroid carcinomas (MTCs) based on necrosis, mitosis, and Ki67. Similarly, a risk stratification study using the Surveillance, Epidemiology, and End Results (SEER) database highlighted significant differences in MTCs in terms of clinical-pathological variables. We aimed to validate both the IMTCGS and SEER-based risk table on 66 MTC cases, with special attention to angioinvasion and the genetic profile.

Mother-newborn ABO group discrepancy caused by a rare BW.17 variant.

Several ABO gene mutations are known to determine rare subgroups: these ABO variants are often responsible for weak or null phenotypes and may cause an incorrect determination of the serotype. Here we describe for the first time the phenotypic discrepancy of a rare B allele within the same Caucasian family that depends on the co-inheritance with A or H antigen. Blood samples from newborns, mothers, and grandmothers were analysed through routine serotype and genotype testing.

Posterolateral transpedicular approach for ventrally seated cervicothoracic spinal cord lesions: how I do it.

Background: Surgical exposure of lower cervical and upper thoracic intradural extramedullary lesions located along the ventral medulla are among the most complexes to address in spinal surgery, and their surgical removal carries a high risk.

Methods: We describe the surgical steps of a posterolateral transpedicular approach for resection of an intradural extramedullary lesion located anterolaterally at C7-T1 level.

Conclusions: A posterolateral transpedicular approach is a safe and efficient surgical corridor to explore the ventral spinal cord and to have a direct access to lower cervical-upper thoracic lesions without the extensive manipulation of the spinal cord and the spine instability.

Primary Vitreoretinal Lymphoma: Current Diagnostic Laboratory Tests and New Emerging Molecular Tools.

Primary vitreoretinal lymphoma (PVRL), a rare aggressive malignancy primarily involving the retina and/or the vitreous, is a major diagnostic challenge for clinicians (who commonly misdiagnose it as chronic uveitis) as well as for pathologists (for biological and technical reasons). Delays in diagnosis and treatment are responsible for visual impairments and life-threatening consequences, usually related to central nervous system involvement. The identification of lymphoma cells in vitreous fluid, obtained by vitrectomy, is required for diagnosis.

Therapeutic Outcomes and Clinical Features of Advanced Non-Small Cell Lung Cancer Carrying KRAS Mutations: A Multicenter Real-life Retrospective Study.

Introduction: Targeting Kirsten Rat Sarcoma (KRAS) has been deemed impossible for long time, but new drugs have recently demonstrated promising results. Evidence on the outcome of KRAS-mutant advanced-NSCLC treated with new standard regimens are still scarce. Thus, we aimed at assessing the incidence and clinical impact of KRAS mutations in a real-life population of advanced-NSCLC, exploring the prognostic significance of distinct alterations.

Percutaneous Cement-Augmented Screws Short Fixation for the Treatment of Severe Osteoporotic Vertebral Burst Fractures.

Objective: This study aims to evaluate the therapeutic reliability of posterior percutaneous cement-augmented screws short fixation (PASF) in patients with severe osteoporotic vertebral burst fractures (OVBFs).

Methods: Single-level OVBFs with an anterior vertebral body height reduction ≥60% were included. A Frailty Index was used for preoperative frailty assessment.

What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 5: Epigenetic Regulation of PD-L1.

Epigenetic alterations (including DNA methylation or miRNAs) influence oncogene/oncosuppressor gene expression without changing the DNA sequence. Prostate cancer (PC) displays a complex genetic and epigenetic regulation of cell-growth pathways and tumor progression. We performed a systematic literature review (following PRISMA guidelines) focused on the epigenetic regulation of PD-L1 expression in PC.

VEXAS Syndrome: A Case Series From a Single-Center Cohort of Italian Patients With Vasculitis.

Objective: To identify patients with VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic syndrome) from a single-center cohort of Italian patients with vasculitis, using a clinically oriented phenotype-first approach.

Methods: We retrospectively reviewed the clinical records of 147 consecutive male patients followed up in our vasculitis clinic from 2013 to date. All patients with a diagnosis of vasculitis and treatment-resistant manifestations of inflammation, persistently elevated inflammation markers, and hematologic abnormalities were identified.

Survival and Recurrence in Vitreoretinal Lymphoma Simulating Uveitis at Presentation: The Possible Role of Combined Chemotherapy.

Purpose: To investigate the role of combined systemic and local chemotherapy in improving the survival of patients with vitreoretinal lymphoma (VRL).

Methods: Patients with VRL consecutively seen from 2006 to 2020 were retrospectively reviewed; data on the presence and time of central nervous system (CNS) involvement and treatment regimen (systemic, local or combined chemotherapy) were collected. Overall survival (OS) and progression-free survival (PFS) were calculated for each group.

Adducted Thumb and Peripheral Polyneuropathy: Diagnostic Supports in Suspecting White-Sutton Syndrome: Case Report and Review of the Literature.

One of the recently described syndromes emerging from the massive study of cohorts of undiagnosed patients with autism spectrum disorders (ASD) and syndromic intellectual disability (ID) is White-Sutton syndrome (WHSUS) (MIM #616364), caused by variants in the gene (MIM *614787), located on the long arm of chromosome 1 (1q21.3). So far, more than 50 individuals have been reported worldwide, although phenotypic features and natural history have not been exhaustively characterized yet.

Clinical Manifestations in a Girl with NAA10-Related Syndrome and Genotype-Phenotype Correlation in Females.

Since 2011, eight males with an X-linked recessive disorder (Ogden syndrome, MIM #300855) associated with the same missense variant p.(Ser37Pro) in the gene have been described. After the advent of whole exome sequencing, many variants have been reported as causative of syndromic or non-syndromic intellectual disability in both males and females.

Case Report: Irreversible Watery Diarrhea, Severe Metabolic Acidosis, Hypokalemia and Achloridria Syndrome Related to Vasoactive Intestinal Peptide Secreting Malignant Pheochromocytoma.

Background: Pheochromocytoma (PHEO) clinical manifestations generally mirror excessive catecholamines secretion; rarely the clinical picture may reflect secretion of other hormones. Watery diarrhea, hypokalemia and achlorhydria (WDHA) is a rare syndrome related to excessive secretion of vasoactive intestinal peptide (VIP).

Clinical Case: A 73-year-old hypotensive man affected by adrenal PHEO presented with weight loss and watery diarrhea associated with hypokalemia, hyperchloremic metabolic acidosis (anion gap 15 mmol/l) and a negative urinary anion gap.

Expanding the phenotype of Wiedemann-Steiner syndrome: Craniovertebral junction anomalies.

Wiedemann-Steiner syndrome (WDSTS) is a rare autosomal dominant condition caused by heterozygous loss of function variants in the KMT2A (MLL) gene, encoding a lysine N-methyltransferase that mediates a histone methylation pattern specific for epigenetic transcriptional activation. WDSTS is characterized by a distinctive facial phenotype, hypertrichosis, short stature, developmental delay, intellectual disability, congenital malformations, and skeletal anomalies. Recently, a few patients have been reported having abnormal skeletal development of the cervical spine.

Acute Radiation Colitis after Preoperative Short-Course Radiotherapy for Rectal Cancer: A Morphological, Immunohistochemical and Genetic Study.

Preoperative radiotherapy is a widely accepted treatment procedure in rectal cancer. Radiation-induced changes in the tumor are well described, whereas less attention has been given to the non-neoplastic mucosa. Our aim is to provide a detailed analysis of the morphological features present in non-neoplastic mucosa that pathologists need to be familiar with, in order to avoid misdiagnosis, when evaluating rectal cancer specimens of patients preoperatively treated with radiotherapy, especially with short-course regimen.

The impact of the AMV on Eurasian summer hydrological cycle.

Impact studies of the Atlantic Multidecadal Variability (AMV) on the climate system are severely limited by the lack of sufficiently long observational records. Relying on a model-based approach is therefore mandatory to overcome this limitation. Here, a novel experimental setup, designed in the framework of the CMIP6-endorsed Decadal Climate Prediction Project, is applied to the CMCC climate model to analyse the remote climate impact of the AMV on the Northern Eurasian continent.

North Atlantic climate far more predictable than models imply.

Quantifying signals and uncertainties in climate models is essential for the detection, attribution, prediction and projection of climate change. Although inter-model agreement is high for large-scale temperature signals, dynamical changes in atmospheric circulation are very uncertain. This leads to low confidence in regional projections, especially for precipitation, over the coming decades.

Detection of EGFR-Activating and T790M Mutations Using Liquid Biopsy in Patients With EGFR-Mutated Non-Small-Cell Lung Cancer Whose Disease Has Progressed During Treatment With First- and Second-Generation Tyrosine Kinase Inhibitors: A Multicenter Real-Life Retrospective Study.

Background: In advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) patients whose disease has progressed during treatment with first- and second-generation tyrosine kinase inhibitors (TKIs), liquid biopsy (LB) is routinely used to evaluate the presence of EGFR T790M as an acquired resistance mechanism. The objective of this study was to assess a real-life picture of EGFR T790M detection in LB.

Materials And Methods: Liquid biopsies performed between June 2016 and October 2018 for advanced EGFR-mutated NSCLC at disease progression during treatment with first- and second-generation TKIs were retrospectively evaluated in 5 Italian centers.

Alazami syndrome: the first case of papillary thyroid carcinoma.

Alazami syndrome (MIM#615071) is a rare developmental disorder caused by biallelic variants in the LARP7 gene. Hallmark features include short stature, global developmental delay, and distinctive facial features. To date, 23 patients from 11 families have been reported in the literature.

Concurrent heterozygous Von-Hippel-Lindau and transmembrane-protein-127 gene mutation causing an erythropoietin-secreting pheochromocytoma in a normotensive patient with severe erythrocytosis.

Background: Mutations of genes related to Krebs cycle enzymes, kinases or to pseudohypoxic signaling pathways, including Von-Hippel-Lindau (VHL) and transmembrane-protein-127 predispose to pheochromocytoma and paraganglioma development. Homozygous loss of function mutation of VHL (VHL 598C>T) gene can associate with polycythemia because of an altered hypoxia sensing.

Patient: A 19-year-old normotensive man presented with headache, fatigue associated with severe erythrocytosis (hematocrit 76%), high hemoglobin (25.

The clinical relevance of multiple DPYD polymorphisms on patients candidate for fluoropyrimidine based-chemotherapy. An Italian case-control study.

Background: Deleterious polymorphisms in the gene encoding DPD (DPYD) may result in severe reduction of DPD enzymatic activity that causes life-threatening toxicities when the standard dose of fluorouracil is used. The best panel of single-nucleotide polymorphism (SNPs) of DPYD is not well defined.

Methods: In 2011, we began screening DPYD*2A in patients candidate for fluoropyrimidine-based chemotherapy.