TP53 germline testing and hereditary cancer: how somatic events and clinical criteria affect variant detection rate.

Background: Germline heterozygous pathogenic variants (PVs) in TP53 cause Li-Fraumeni syndrome (LFS), a condition associated with increased risk of multiple tumor types. As the associated cancer risks were refined over time, clinical criteria also evolved to optimize diagnostic yield. The implementation of multi-gene panel germline testing in different clinical settings has led to the identification of TP53 PV carriers outside the classic LFS-associated cancer phenotypes, leading to a broader cancer phenotypic redefinition and to the renaming of the condition as "heritable TP53-related cancer syndrome" (hTP53rc).

vaRHC: an R package for semi-automation of variant classification in hereditary cancer genes according to ACMG/AMP and gene-specific ClinGen guidelines.

Motivation: Germline variant classification allows accurate genetic diagnosis and risk assessment. However, it is a tedious iterative process integrating information from several sources and types of evidence. It should follow gene-specific (if available) or general updated international guidelines.

Clinical and Radiological Outcome in a Series of Patients Treated by Anterior Cervical Discectomy and Fusion: Retrospective Controlled Study With 2 Different Stand-Alone Cages.

Background: Cervical spine balance and alignment targets after cervical spine surgery are poorly established in patients with cervical spine degenerative disease surgically treated by anterior cervical discectomy and fusion (ACDF). The objective of the study is to determine the correlation between radiological and clinical outcomes in patients surgically treated by ACDF with 2 different stand-alone cervical cages.

Methods: Clinical outcomes were evaluated using visual analog scale (VAS), Neck Disability Index (NDI), Nurick Scale, and Japanese Orthopedic Association score for myelopathy.

Can the intra-operative measurement of the diameter of the femoral head help surgeons to choose the best size of the acetabular cup?

Purpose: We hypothesized that the intra-operative measurement of the femoral head may increase the accuracy of the acetabular cup size optimal selection in total hip arthroplasty (THA). The purpose of this clinical research was to analyze the correlation between the estimated cup size from intra-operative measurement of the femoral head and the pre-operative templated cup size.

Methods: A prospective observational single-center study was conducted from June 2019 to January 2020 including primary THA (n = 100).

Usefulness of serum D-dimer and platelet count to mean platelet volume ratio to rule out chronic periprosthetic joint infection.

: Diagnosing periprosthetic joint infection (PJI) is challenging and usually requires the evaluation of several biomarkers. Our main aim was to evaluate the usefulness of D-dimer levels as well as the platelet count (PC) to mean platelet volume (MPV) ratio serum as biomarkers to rule out chronic knee and hip infection. : The study enrolled a prospective cohort of 93 patients undergoing hip or knee revision.

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Introduction: Total knee arthroplasty (TKA) is a surgery that aims to restore function and relieve pain in advanced osteoarthritis. The Educational Workshop (EW) for TKA is given to patients in the pre-surgery period to inform them and facilitating their participation in their health process (empowerment). The aim of this study was developing and validating a self-administered questionnaire to evaluate the acquired knowledge after the EW by the patients who will undergo the TKA procedure.

Dynamic Fixation Techniques for the Prevention of Adjacent Segment Disease: A Retrospective Controlled Study.

Study Design: Retrospective, controlled study.

Purpose: Dynamic fixation (topping-off technique) adjacent to a transforaminal lumbar interbody fusion (TLIF) level was developed to reduce the risk of adjacent segment disease (ASDi). This study was designed to compare the clinical and radiological outcomes between patients who underwent circumferential lumbar fusion (CLF) without the topping-off technique, CLF with dynamic rod constructs (DRC), and CLF with interspinous device (ISD).

Improving Genetic Testing in Hereditary Cancer by RNA Analysis: Tools to Prioritize Splicing Studies and Challenges in Applying American College of Medical Genetics and Genomics Guidelines.

RNA analyses are a potent tool to identify spliceogenic effects of DNA variants, although they are time-consuming and cannot always be performed. We present splicing assays of 20 variants that represent a variety of mutation types in 10 hereditary cancer genes and attempt to incorporate these results into American College of Medical Genetics and Genomics (ACMG) classification guidelines. Sixteen single-nucleotide variants, 3 exon duplications, and 1 single-exon deletion were selected and prioritized by in silico algorithms.

Comprehensive analysis and ACMG-based classification of CHEK2 variants in hereditary cancer patients.

CHEK2 variants are associated with intermediate breast cancer risk, among other cancers. We aimed to comprehensively describe CHEK2 variants in a Spanish hereditary cancer (HC) cohort and adjust the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines for their classification. First, three CHEK2 frequent variants were screened in a retrospective Hereditary Breast and Ovarian Cancer cohort of 516 patients.

Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification.

The multifactorial likelihood analysis method has demonstrated utility for quantitative assessment of variant pathogenicity for multiple cancer syndrome genes. Independent data types currently incorporated in the model for assessing BRCA1 and BRCA2 variants include clinically calibrated prior probability of pathogenicity based on variant location and bioinformatic prediction of variant effect, co-segregation, family cancer history profile, co-occurrence with a pathogenic variant in the same gene, breast tumor pathology, and case-control information. Research and clinical data for multifactorial likelihood analysis were collated for 1,395 BRCA1/2 predominantly intronic and missense variants, enabling classification based on posterior probability of pathogenicity for 734 variants: 447 variants were classified as (likely) benign, and 94 as (likely) pathogenic; and 248 classifications were new or considerably altered relative to ClinVar submissions.

Intraoperative Transfusion of Red Blood Cell Units Stored >14 Days is Associated with an Increased Risk of Prosthetic Joint Infection.

The aim of the present study was to evaluate the association between prosthetic joint infection (PJI) after joint arthroplasty and the length of red blood cell (RBC) storage, timing of RBC transfusion, and the number of RBC units transfused. All patients who underwent a primary or revision joint artrhoplasty between January 2000 and December 2012 were retrospectively reviewed. For this study, only patients who received RBC transfusions during the day of the surgery (early transfusion group) or within the first 4 days after surgery (late transfusion group) were included.

Knee Arthritis in Children: When Can It Be Safely Treated With Needle Joint Aspiration? A Large Children's Tertiary Hospital Study.

Background: Early joint decompression associated to antibiotic therapy is the most important procedure to reduce joint damage in septic knee arthritis in children. Several joint decompression methods have been described such as arthrotomy with open debriding, arthroscopic drainage or needle joint aspiration. The aim of the present study was to determinate which patients with acute septic knee arthritis could be safely treated with needle joint aspiration.

Does multilocus inherited neoplasia alleles syndrome have severe clinical expression?

Importance: Genetic testing of hereditary cancer using comprehensive gene panels can identify patients with more than one pathogenic mutation in high and/or moderate-risk-associated cancer genes. This phenomenon is known as multilocus inherited neoplasia alleles syndrome (MINAS), which has been potentially linked to more severe clinical manifestations.

Objective: To determine the prevalence and clinical features of MINAS in a large cohort of adult patients with hereditary cancer homogeneously tested with the same gene panel.

Predicting Failure in Early Acute Prosthetic Joint Infection Treated With Debridement, Antibiotics, and Implant Retention: External Validation of the KLIC Score.

Background: Debridement, antibiotics, and implant retention (DAIR) is a widely used treatment modality for early acute prosthetic joint infection (PJI). A preoperative risk score was previously designed for predicting DAIR failure, consisting of chronic renal failure (K), liver cirrhosis (L), index surgery (I), cemented prosthesis (C), and C-reactive protein >115 mg/L (KLIC). The aim of this study was to validate the KLIC score in an external cohort.

Tumor xenograft modeling identifies an association between TCF4 loss and breast cancer chemoresistance.

Understanding the mechanisms of cancer therapeutic resistance is fundamental to improving cancer care. There is clear benefit from chemotherapy in different breast cancer settings; however, knowledge of the mutations and genes that mediate resistance is incomplete. In this study, by modeling chemoresistance in patient-derived xenografts (PDXs), we show that adaptation to therapy is genetically complex and identify that loss of transcription factor 4 (TCF4; also known as ITF2) is associated with this process.

Correction to: Altruistic Behavior among Twins : Willingness to Fight and Self-Sacrifice for Their Closest Relatives.

The original version of this article unfortunately contained a mistake. The presentation of the article title and subtitle was incorrect.

Altruistic Behavior among Twins : Willingness to Fight and Self-Sacrifice for Their Closest Relatives.

According to kin selection theory, indirect reproductive advantages may induce individuals to care for others with whom they share genes by common descent, and the amount of care, including self-sacrifice, will increase with the proportion of genes shared. Twins represent a natural situation in which this hypothesis can be tested. Twin pairs experience the same early environment because they were born and raised at the same time and in the same family but their genetic relatedness differs depending on zygosity.

Moxifloxacin plus rifampin as an alternative for levofloxacin plus rifampin in the treatment of a prosthetic joint infection with Staphylococcus aureus.

Objectives: The combination of a fluoroquinolone with rifampin is one of the cornerstones in the treatment of prosthetic joint infections (PJI) caused by staphylococci. Moxifloxacin is highly active against methicillin-susceptible Staphylococcus aureus (MSSA) and, therefore, is an attractive agent to use. However, several studies reported a lowering in serum moxifloxacin levels when combined with rifampin.

Withholding Preoperative Antibiotic Prophylaxis in Knee Prosthesis Revision: A Retrospective Analysis on Culture Results and Risk of Infection.

Background: A significant amount of patients undergoing revision surgery of a prosthetic joint turn out to have an infection. Withholding preoperative antibiotic prophylaxis in these patients to optimize culture yield during revision surgery remains a matter of debate. The aim of our study was to determine (1) the rate of positive intraoperative cultures with or without preoperative antibiotic prophylaxis and (2) the incidence of a prosthetic joint infection (PJI) during the follow-up in the 2 groups.

A comprehensive custom panel design for routine hereditary cancer testing: preserving control, improving diagnostics and revealing a complex variation landscape.

We wanted to implement an NGS strategy to globally analyze hereditary cancer with diagnostic quality while retaining the same degree of understanding and control we had in pre-NGS strategies. To do this, we developed the I2HCP panel, a custom bait library covering 122 hereditary cancer genes. We improved bait design, tested different NGS platforms and created a clinically driven custom data analysis pipeline.

Benchmarking of Whole Exome Sequencing and Ad Hoc Designed Panels for Genetic Testing of Hereditary Cancer.

Next generation sequencing panels have been developed for hereditary cancer, although there is some debate about their cost-effectiveness compared to exome sequencing. The performance of two panels is compared to exome sequencing. Twenty-four patients were selected: ten with identified mutations (control set) and fourteen suspicious of hereditary cancer but with no mutation (discovery set).

Postoperative hyperglycaemia control reduces postoperative complications in patients subject to total knee arthroplasty.

Background: The aim of our study was the early detection and treatment of patients with unknown alterations of the hydrocarbon metabolism subject to total knee arthroplasty in order to reduce the incidence of postoperative complications.

Methods: Patients were classified as non-diabetic patients (group 1), diabetic patients (group 2) and patients with stress hyperglycaemia (group 3). The last two groups were recommended assessment by a primary care physician (PCP).