Top advances of the year: Precision oncology

The advent of precision medicine has changed the landscape of oncologic biomarkers, drug discovery, drug development, and, more importantly, outcomes for patients with cancer. Precision oncology entails the genomic profiling of tumors to detect actionable aberrations. The advances in clinical next-generation sequencing from both tumor tissue and liquid biopsy and availability of targeted therapies has rapidly entered mainstream clinical practice. In this review, recent major developments in precision oncology that have affected outcomes for patients with cancer are discussed. Rapid clinical development was seen of targeted agents across various mutational profiles such as KRASG12C (which was considered “undruggable” for almost 4 decades), Exon 20 insertions, and RET mutations. Approaches to precision chemotherapy delivery by the introduction of antibody drug conjugates in the armamentarium against lung cancer has been appreciated.     

Myocardial Infarction Risk in Arthroplasty vs Arthroscopy: How Much Does Procedure Type Matter?

Background

This study aimed at assessing short-term risk of serious cardiac events after elective total joint arthroplasty (TJA) as compared to a less-invasive procedure, knee arthroscopy (KA).

CAPN1 mutations: Expanding the CAPN1-related phenotype: From hereditary spastic paraparesis to spastic ataxia

Aims and objectiveTo characterize the phenotype of CAPN1 (SPG76) mutations in patients diagnosed with hereditary spastic paraplegia (HSP).BackgroundThe CAPN1 gene, located on chromosome 11q13.1, is a protein-coding gene involved in neuronal plasticity, migration, microtubular regulation and cerebellar development. Several families with CAPN1 mutations have recently been reported to present with autosomal recessive (AR) HSP and/or ataxia.MethodPatients with HSP were identified through neurological and genetic clinics with detailed phenotyping. Whole exome sequencing revealed novel pathogenic CAPN1 mutations in four patients from 3 families.ResultsAffected families were of Turkish, Japanese, and Punjabi descent and all were consanguineous. Onset of spastic paraplegia in the four patients was between 20 and 37 years. Two also had mild ataxia. Three different novel, homozygous mutations in CAPN1 were found: c.2118+1G > T, c.397C > T, c.843+1G > C. The patient with the earliest onset also manifested profound muscle weakness, likely related to a second homozygous mutation in DYSF (dysferlinopathy).ConclusionsThe phenotype of AR CAPN1 mutations appears to be spastic paraplegia with or without ataxia; onset is most commonly in adulthood. Eye movement abnormalities, skeletal defects, peripheral neuropathy and amyotrophy can sometimes be seen. Occasionally, patients can present with ataxia, illustrating the genotypic and phenotypic overlap between HSP and spastic ataxia. With the advent of exome sequencing, mutations in more than one gene can be identified, which may contribute to the phenotypic variation, even within a family.     

Synthesis of 2-(aryl)-5-(arylidene)-4-thiazolidinone derivatives with potential analgesic and anti-inflammatory activity

A series of novel N-[5-(arylidene)-2-(aryl)-4-oxo-thiazolidin-3-yl]-4-biphenylcarboxamide derivatives was synthesized and evaluated for analgesic and anti-inflammatory activity. In this study, biphenyl-4-carboxylic acid hydrazide was converted to the corresponding aryl hydrazones using aryl aldehydes in the presence of catalytic amount of glacial acetic acid. The aryl hydrazones on reaction with thioglycolic acid in the presence of anhydrous zinc chloride yielded N-[2-(aryl)-4-oxo-thiazolidin-3-yl]-4-biphenylcarboxamide which further on reaction with aromatic aldehydes in the presence of anhydrous sodium acetate and glacial acetic acid furnished the title compounds. All compound exhibited anti-inflammatory activity at the dose 10?mg/kg. The structures of all these newly synthesized compounds were confirmed by their elemental analyses (C, H, N) and spectral data (IR and ¹H NMR).     

Effectiveness of seatbelts in mitigating traumatic brain injury severity

INTRODUCTION Over the past few decades,traumatic brain injuries(TBIs)have become one of the leading causes of death and the leading cause of injury-related death in the USA.[1,2]It is estimated that 1.70 million people are subject to TBIs each year.[2]Males are more likely to sustain TBIs(59%);the most common age groups are 0–5 years,15–19 years,and>65 years.[2]Approximately 1.36 million people present to the emergency department(ED),275,000 are admitted to the hospital,and 52,000 people die from TBIs.[2]The leading causes of TBIs are falling(35.2%),motor vehicle collisions(MVCs,17.3%),struck by/against an object(16.5%),and assault(10.0%).[2]These statistics combine to make TBIs the leading cause of injury-related death in the USA at 30.5%.[2]It has been estimated that,with specifi c guidelines from the Brain Trauma Foundation,up to 50.0%of the 52,000 TBIrelated deaths may be prevented.[3]     

Safety and Efficacy of Segmental Yttrium-90 Radioembolization for Hepatocellular Carcinoma after Transjugular Intrahepatic Portosystemic Shunt Creation

PurposeTo evaluate safety and efficacy of segmental yttrium-90 (Y90) radioembolization for hepatocellular carcinoma (HCC) after transjugular intrahepatic portosystemic shunt (TIPS) placement. The hypothesis was liver sparing segmental Y90 for HCC after TIPS would provide high antitumor response with a tolerable safety profile.Materials and MethodsThis single-arm retrospective study included 39 patients (16 women, 23 men) with ages 49–81 years old who were treated with Y90. Child-Pugh A/B liver dysfunction was present in 72% (28/39) with a median Model for End-stage Liver Disease score of 18 (95% confidence interval, 16.4–19.4). Primary outcomes were clinical and biochemical toxicities and antitumor imaging response by World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria. Secondary outcomes were orthotopic liver transplantation (OLT), time to progression (TTP), and overall survival (OS) estimates by the Kaplan-Meier method.ResultsThe 30-day mortality was 0%. Grade 3+ clinical adverse events and grade 3+ hyperbilirubinemia occurred in 5% (2/39) and 0% (0/39), respectively. Imaging response was achieved in 58% (22/38, WHO criteria) and 74% (28/38, EASL criteria), respectively. Median TTP was 16.1 months for any cause and 27.5 months for primary index lesions. OLT was completed in 88% (21/24) of listed patients at a median time of 6.1 months (range, 0.9–11.7 months). Median OS was 31.6 months and 62.9 months censored and uncensored to OLT, respectively.ConclusionsSegmental Y90 for HCC appears safe and efficacious in patients after TIPS. Preserved transplant eligibility suggests that Y90 is a useful tool for bridging these patients to liver transplantation.