Prevalence and Clinical Profile of Human Salivirus in Children with Acute Gastroenteritis in Northern Italy, 2014–2015

Objective: Human Salivirus (SalV) has been associated with gastroenteritis on all continents. Methods: This paper presents the real-time RT-PCR assay for the detection of SalV in clinical fecal samples collected from 192 hospitalized children with acute gastroenteritis in Piedmont, Italy. Results: The most commonly detected virus was Norovirus genogroup II (GII) (33.8%), followed by Rotavirus (21.3%), Sapovirus (10.9%), Parechovirus (8%), Norovirus GI (6.7%), and Adenovirus (1%). PCR detected SalV in 1 (0.5%) subject. Conclusions: Our data show that the detection rate of SalV in diarrheal children (0.5%) is lower than that observed in other countries, where it is reported in diarrheal children in 8.6–1.2% of patients

Novel Insights into Molecular Mechanisms of Endometrial Diseases

Endometrial diseases are the most common gynecological pathologies in Western Countries [...]

Practice patterns and 90-day treatment-related morbidity in early-stage cervical cancer

To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) Trial on patterns of care and surgery-related morbidity in early-stage cervical cancer

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Endometrial Cancer and BRCA Mutations: A Systematic Review

This systematic review identifies, evaluates, and summarises the findings of all relevant individual studies on the prevalence of BRCA mutation (BRCAm) in endometrial cancer patients and the incidence of endometrial cancer in BRCAm women patients. Consequently, the benefits and limits of a prophylactic hysterectomy at the time of the risk-reducing salpingo-oophorectomy are analysed and discussed. A systematic literature search was performed in the databases of PubMed, Cochrane, and Web of Science until May 2022; 13 studies met the eligibility criteria. Overall, 1613 endometrial cancer patients from 11 cohorts were tested for BRCA1/2 mutation. BRCA1/2m were identified in 4.3% of women with endometrial cancer (70/1613). BRCA1m was the most represented (71.4%) pathogenic variant. Alongside, a total of 209 BRCAm carriers from 14 studies were diagnosed with endometrial cancer. Only 5 out of 14 studies found a correlation between BRCAm and an increased risk of endometrial cancer. Nevertheless, two studies found a statistical difference only for BRCA1m women. The present systematic review does not provide strong evidence in favour of performing routine hysterectomy at the time of risk-reducing salpingo-oophorectomy; however, it provides epidemiological data that can be useful for counselling patients in order to offer a tailored approach

Early-stage cervical cancer treatment – what’s new?

The gold standard of treatment for patients with early-stage cervical cancer is radical hysterectomy, in agreement with the entire scientific community. During the last decade, growing evidence has supported the minimally invasive approach. Several studies have suggested that the minimally invasive approach could improve surgical and perioperative outcomes. Because of these findings, ESCO/ESTRO/ESP guidelines state that a “minimally invasive approach is favoured” in comparison with open surgery, as a grade B recommendation. Because of the lack of a grade A recommendation, this randomized Laparoscopic Approach to Cervical Cancer trial evaluated open vs. minimally invasive approach in the early stage. It demonstrated an increase in mortality among patients treated with minimally invasive surgery, revolutionizing current thinking on the primary surgical approach to early cervical cancer. The aim of this study is to analyse which is the best treatment for early cervical cancer and which approach is the most effective at the moment. Further studies are needed to state with certainty the appropriateness of the treatments offered to patients with early cervical cancer

Therapeutic Approaches to Vulvar Cancer: A Review of Literature

Objective: Vulvar cancer is a rare gynecological cancer that mainly affects postmenopausal women. The aim of this review is to analyze the most recent data available in the literature on the clinical and therapeutic approach to vulvar carcinoma. Mechanism: Studies available in the literature on the therapeutic management of patients with vulvar carcinoma until November 2022 have been screened. A comprehensive search was performed in the PubMed (MEDLINE), EMBASE, SCOPUS and Web of Science databases. Findings in Brief: The approach to vulvar carcinoma has deeply evolved over the years. The management of early-stage vulvar carcinomas is well established and widely shared, while that of advanced and recurrent cancers is a subject of debate. The assessment of the nodal status has changed from the past with the passage from inguinal lymphadenectomy to the removal of only the sentinel node. Conclusions: The gold standard for the management of vulvar cancer is surgery, applicable in the first instance in early-stage tumors and after neoadjuvant therapy for larger tumors. Assessment of the nodal state is crucial and the method to be used depends on the degree of suspicious of positive lymph nodes. The prognosis is good if the treatment is applicable as soon as possible