Light and shade of multigene panel testing for hereditary cancer: Examples from the real world.

Background: MultiGene Panel Testing (MGPT) allows for simultaneous analysis of multiple cancer-related genes, enabling the identification of pathogenic variants in genes beyond those that would be analyzed based on a specific phenotype. However, a relevant fraction of variants so identified has little or no clinical utility, raising the need for guidance in selecting genes to include in panels and for interpretation of the results.

Methods: Taking advantage of seven real paradigmatic cases, we analyze some of the scenarios where MGPT constitutes a meaningful advantage for diagnosis, as well as situations where panel use increases the risk of misinterpretation or complicates result communication and management.

Hereditary breast and ovarian cancer genetic testing in unselected patients: example of private supplementation of public healthcare service.

In the Emilia-Romagna region (Northern Italy), the identification and management of women at familial/hereditary risk of breast and ovarian cancer is guided by a well-established regional protocol. Here we report the results of the experience of private supplementation of public healthcare service in offering the possibility to undergo BRCA1/2 testing and/or multigene panel testing (MGPT) within a well-defined pathway to women unfulfilling regional criteria. Out of 177 patients referred to our center who underwent BRCA1/2 testing, 175 tested negative while two (1.

Atypical cancer risk profile in carriers of Italian founder BRCA1 variant p.His1673del: Implications for classification and clinical management.

Background: BRCA1:c.5017_5019del (p.His1673del) is a founder variant relatively frequent in Northern Italy.

Multi-Gene Next-Generation Sequencing Panel for Analysis of / and Homologous Recombination Repair Genes Alterations Metastatic Castration-Resistant Prostate Cancer.

Despite significant therapeutic advances, metastatic CRPC (mCRPC) remains a lethal disease. Mutations in homologous recombination repair (HRR) genes are frequent in mCRPC, and tumors harboring these mutations are known to be sensitive to PARP inhibitors. The aim of this study was to verify the technical effectiveness of this panel in the analysis of mCRPC, the frequency and type of mutations in the / genes, as well as in the homologous recombination repair (HRR) genes.

Spatially explicit effective reproduction numbers from incidence and mobility data.

Current methods for near real-time estimation of effective reproduction numbers from surveillance data overlook mobility fluxes of infectors and susceptible individuals within a spatially connected network (the metapopulation). Exchanges of infections among different communities may thus be misrepresented unless explicitly measured and accounted for in the renewal equations. Here, we first derive the equations that include spatially explicit effective reproduction numbers, ℛ(), in an arbitrary community .

The Enigmatic Genetic Landscape of Hereditary Hearing Loss: A Multistep Diagnostic Strategy in the Italian Population.

Hearing loss is the most frequent sensorineural disorder, affecting approximately 1:1000 newborns. Hereditary forms (HHL) represent 50-60% of cases, highlighting the relevance of genetic testing in deaf patients. HHL is classified as non-syndromic (NSHL-70% of cases) or syndromic (SHL-30% of cases).

Characterization of BRCA Deficiency in Ovarian Cancer.

BRCA testing is recommended in all Ovarian Cancer (OC) patients, but the optimal approach is debated. The landscape of alterations was explored in 30 consecutive OC patients: 6 (20.0%) carried germline pathogenic variants, 1 (3.

Double Asymmetric Circular Incision, a New Skin-Sparing Mastectomy Technique: Results and Outcomes of the First 46 Procedures.

Summary: Skin-sparing mastectomy (SSM) is a surgical technique that preserves as much of the breast skin as possible. Double asymmetric circular incision (DACI) is a novel immediate breast reconstruction technique for immediate prepectoral implant placement using a titanium-coated polypropylene mesh. The aim of this technique is to optimize the cosmetic benefits of smaller incisions, preserve breast anatomy, avoid breast deformities, and reduce the negative psychological impact on the patient without increasing local recurrence risk.

Chromoendoscopy Is Not Superior to White Light Endoscopy in Improving Adenoma Detection in Lynch Syndrome Cohort Undergoing Surveillance with High-Resolution Colonoscopy: A Real-World Evidence Study.

Background: Endoscopic surveillance in patients with Lynch syndrome (LS) is crucial due to a genetically based high risk of colorectal cancer (CRC). We aimed to compare the adenoma detection rate (ADR) between high-resolution white light endoscopy (WLE) alone and WLE plus dye chromoendoscopy (CE) in a cohort of LS patients.

Methods: In a context of real-world data, we retrospectively enrolled 50 LS patients who had non-randomly undergone WLE versus CE surveillance examinations from 2007 to 2019.

Hamartoma Tumor Syndrome: Skin Manifestations and Insights Into Their Molecular Pathogenesis.

Germline pathogenic variants cause a spectrum of disorders collectively labeled Hamartoma Tumor Syndrome (PHTS) and featured by hamartomas, developmental anomalies and increased cancer risk. Studies on experimental models provided evidence that is a "haploinsufficient" tumor-suppressor gene, however, mechanisms involved in the pathogenesis of clinical manifestations in PHTS patients remain elusive. Beyond analyzing clinical and molecular features of a series of 20 Italian PHTS patients, we performed molecular investigations to explore the mechanisms involved in the pathogenesis of -associated manifestations, with special focus on mucocutaneous manifestations.

Local mortality estimates during the COVID-19 pandemic in Italy.

Unlabelled: Estimates of the real death toll of the COVID-19 pandemic have proven to be problematic in many countries, Italy being no exception. Mortality estimates at the local level are even more uncertain as they require stringent conditions, such as granularity and accuracy of the data at hand, which are rarely met. The "official" approach adopted by public institutions to estimate the "excess mortality" during the pandemic draws on a comparison between observed all-cause mortality data for 2020 and averages of mortality figures in the past years for the same period.

The epidemicity index of recurrent SARS-CoV-2 infections.

Several indices can predict the long-term fate of emerging infectious diseases and the effect of their containment measures, including a variety of reproduction numbers (e.g. [Formula: see text]).

Colorectal polyposis as a clue to the diagnosis of Cowden syndrome: Report of two cases and literature review.

Cowden Syndrome (CS) is an autosomal dominant disorder characterized by hamartomatous growth in several organs and by an increased risk of malignancies, which makes its recognition essential to undertake risk reduction measures. Although the involvement of gastrointestinal tract is extremely common, awareness of this entity among gastroenterologists appears limited. We report on two unrelated patients: a 46-year-old male and a 38-year-old woman, who were referred to the Genetic Clinic because of the endoscopic finding of multiple colorectal polyps.

Preferences of Italian patients for return of secondary findings from clinical genome/exome sequencing.

Exome/genome sequencing (ES/GS) is increasingly becoming routine in clinical genetic diagnosis, yet issues regarding how to disclose and manage secondary findings (SFs) remain to be addressed, and limited evidence is available on patients' preferences. We carried out semi-structured interviews with 307 individuals undergoing clinical genetic testing to explore their preferences for return of SFs in the hypothetical scenario that their test would be performed using ES/GS. Participants were 254 females (82.

The patient's pathway for breast cancer in the COVID-19 era: An Italian single-center experience.

COVID-19 has been declared a pandemic by the World Health Organization. As of April 1, 2020, Italy was the country with the second highest number of cases in the world. The spread of COVID-19 has required a rapid reorganization of health service delivery in face of the pandemic.

Clinical histopathological features and CDKN2A/CDK4/MITF mutational status of patients with multiple primary melanomas from Bologna: Italy is a fascinating but complex mosaic.

Background: The incidence of cutaneous melanoma (cM) has increased in the last decades. Germline mutations in the high-penetrance melanoma susceptibility gene CDKN2A (Cyclin-dependent kinase inhibitor 2A) are associated with a younger age at diagnosis and an increased risk to develop pancreatic cancer.

Methods: We retrospectively analyzed the data of patients with prior diagnosis of cM referring to our service from January 2005 to May 2017.

Dealing With BRCA1/2 Unclassified Variants in a Cancer Genetics Clinic: Does Cosegregation Analysis Help?

Detection of variants of uncertain significance (VUSs) in BRCA1 and BRCA2 genes poses relevant challenges for counseling and managing patients. VUS carriers should be managed similarly to probands with no BRCA1/2 variants detected, and predictive genetic testing in relatives is discouraged. However, miscomprehension of VUSs is common and can lead to inaccurate risk perception and biased decisions about prophylactic surgery.

miR-155 Is Downregulated in Familial Adenomatous Polyposis and Modulates WNT Signaling by Targeting AXIN1 and TCF4.

Adenomatous Polyposis Coli () gene mutations are responsible for the onset of familial adenomatous polyposis (FAP) and sporadic colorectal cancer and have been associated with miRNAs dysregulation. The capacity of miR-155, a cancer-related miRNA, to target components of the WNT/β-CATENIN pathway suggests that gene mutations, controlling miRNAs expression, may critically regulate WNT/β-CATENIN signaling. To this end, gene target sequencing was performed on colonic adenomatous polyps and paired normal mucosa clinical specimens from FAP patients ( = 9) to elucidate the role of miR-155-5p in -mutant setting.

[Errors in Medicine: perceptions of nursing students in Rome].

Introduction: The error in medicine has long been discussed in scientific debates. The purpose of this study is to evaluate the degree knowledge, attitude and behavior of students in Nursing for the failure in the health sector.

Methods: It was administered to 231 students of Nursing of the Sapienza University of Rome (171 females and 60 males), aged between 21 and 45 years, a structured questionnaire in three questions that explore the experiences and opinions about the errors found in medical practice, the causes underlying them and the mistakes that should never be committed.