Citations

During the Fifth Pediatric Anesthesia Neurodevelopmental Assessment Symposium, experts and stakeholders met to present and discuss recent advances made in the study of neurodevelopmental outcomes after exposure to anesthetic drugs in infants and children. This article summarizes the update of 5 ongoing clinical studies: General Anesthesia compared to Spinal Anesthesia, Toxicity of Remifentanil and Dexmedetomidine, Mayo Anesthesia Safety in Kids, the University of California San Francisco human cohort study, and Columbia University Medical Center Neonatal Magnetic Resonance Imaging study. The purpose of this summary is to discuss the contributions and limitations of these studies, how they fit into the published literature, and what questions remain to be answered.

On April 16 and 17, 2016, the Fifth biennial Pediatric Anesthesia & Neurodevelopment Assessment (PANDA) symposium was convened at the Morgan Stanley Children’s Hospital of New York at Columbia University Medical Center. During the symposium, experts in the fields of anesthesiology, neuropsychology, and epidemiology were convened in a small group session to determine the level of confidence in the current clinical evidence and the next steps in anesthetic neurotoxicity clinical research. Among the participants in the discussion, there remained a lack of consensus on whether anesthetic exposure causes long-term neurodevelopmental deficits in children based on the current evidence. This causal relationship between anesthesia exposure and neurodevelopmental deficit is difficult to establish using observational data, and current and future clinical trials are critical for answering this question. It was, however, recognized that the continuum of data that is seen in studies of other toxic environmental exposures, such as lead poisoning, has not been established in the anesthetic neurotoxicity literature, specifically regarding the timing of the exposure, the dose effects, contributing perioperative conditions, or vulnerable populations. As a result, these questions may need to be addressed in observational studies to guide future clinical trials.

Objectives The aim of this study was to determine whether intra-arterial administration of contrast material is associated with a higher risk of acute kidney injury (AKI) compared with that of intravenous (IV) administration in a cohort of patients that received both routes of administration. Materials and Methods All patients who received both a contrast-enhanced computed tomography (CT) and a diagnostic or interventional cardiac catheterization between 2000 and 2014 were identified. Patients who lacked sufficient preprocedure and postprocedure serum creatinine results, who were on preexisting renal dialysis, or who underwent additional contrast-enhanced procedures within 7 days of either procedure were excluded. The rate of AKI (serum creatinine ≥0.3 mg/dL or 50% above baseline) was compared after CT scan and cardiac catheterization using McNemar test. Results A total of 1969 patients met all study inclusion criteria. The rate of AKI after CT scan was similar to the rate after catheterization when examining all patients (9.9% CT vs 11% catheterization, P = 0.12). A similar rate of AKI after both procedures was observed regardless of procedure order, catheterization type, and patient baseline estimated glomerular filtration rate. Conclusions Intra-arterial administration of contrast material during cardiac catheterization had a similar risk of AKI as compared with that of CT scanning involving IV administration in a cohort of patients who underwent both procedures. These findings suggest that previously reported much higher rates of AKI after cardiac catheterization compared with that of IV contrast administration reflect higher baseline clinical risk factors for AKI in the former cohort compared with that in the latter.

Background In comparison to warfarin, non–vitamin K antagonist oral anticoagulants ( NOAC s) have the advantages of ease of dosing, fewer drug interactions, and lack of need for ongoing monitoring. We sought to evaluate whether these advantages translate to improved adherence and whether adherence is associated with improved outcomes in patients with atrial fibrillation. Methods and Results We performed a retrospective cohort analysis by using a large US commercial insurance database to identify 64 661 patients with atrial fibrillation who initiated warfarin, dabigatran, rivaroxaban, or apixaban treatment between November 1, 2010, and December 31, 2014. During a median of 1.1 y of follow‐up, 47.5% of NOAC patients had a proportion of days covered of ≥80%, compared with 40.2% in warfarin patients ( P <0.001). Patients with CHA 2 DS 2 ‐ VAS c (risk based on the presence of congestive heart failure, hypertension age 65–74 y, age ≥75 y, diabetes mellitus, prior stroke or transient ischemic attack, vascular disease, sex category) score ≥4 were at increased risk of stroke when they were not taking anticoagulation ≥1 month versus <1 week (1–3 months: hazard ratio [ HR ] 1.96, 3–6 months: HR 2.64, ≥6 months: HR 3.66; all P <0.001). Patients with CHA 2 DS 2 ‐ VAS c score 2 or 3 were at increased risk of stroke when they were not taking anticoagulation ≥6 months ( HR 2.73, P <0.001). In these patients with CHA 2 DS 2 ‐ VAS c score ≥2, nonadherence was not associated with intracranial hemorrhage. Among patients with CHA 2 DS 2 ‐ VAS c score 0 or 1, time not taking anticoagulation was not associated with stroke, but not taking anticoagulation ≥3 months was associated with a significant reduction of bleeding. Conclusions Adherence to anticoagulation is poor in practice and may be modestly improved with NOAC s. Adherence to therapy appears to be most important in patients with CHA 2 DS 2 ‐ VAS c score ≥2, whereas the benefits of anticoagulation may not outweigh the harms in patients with CHA 2 DS 2 ‐ VAS c score 0 or 1.

Abstract Background: Recent genome-wide association studies (GWAS) have identified 28 susceptibility loci for Lung cancer (LC), 32 loci for smoking behavior, 10 loci for chronic obstructive pulmonary disease (COPD), 63 loci for pulmonary function and related phenotypes, totaling 107 GWAS susceptibility loci (as of November 2014). Given the common variants that have been found to be associated with LC in GWAS, targeted-region exome sequencing provides a cost-effective approach for further investigation of high-priority regions of the genome and has the great potential to identify rare causal variants in GWAS loci. Patients and Methods: Using an extreme phenotype approach, we selected 48 sporadic LC patients reporting heavy smoking histories with the presence of severe COPD in whom environmental factors are considered overwhelming, and 54 familial LC cases from families with at least three first-degree relatives with LC who are likely enriched for genomic signal, to search for the disease-causing rare mutations within the target 107 GWAS loci using exome sequencing data. Results: By focusing on exome profiles of these target 107 loci, we identified two disease-causing rare mutations on 6p21.32 TNXB p. Arg504His and 10q25.1 CCDC147 p.Arg696Cys. The homozygous Arg504His mutation presented in four familial and one sporadic LC cases. Notably, the minor allele frequency (MAF) of this variant in Caucasians from 1000 Genomes is very rare (&lt;0.001). The heterozygous CCDC147 Arg696Cys variant were identified in two familial cases and one sporadic case. The MAF for this variant in the Caucasians from 1000 Genomes is 0.004. Both deleterious changes lead to truncation of the putative proteins, which disrupts the predicted domain and alters the cellular localization. We also observed several other suggestive rare mutations on G7C, TNS1, DBH1, and CHRNA5. Conclusion: Our target exome sequencing results demonstrate novel highly disruptive LC risk-conferring TNXB and CCDC147 mutations. Since the rare variants have appreciable effects on disease risk prediction, families and patients may warrant screening for mutations in TNXB and CCDC147 (if validated) to assess their potential LC risk. Citation Format: Yanhong Liu, Farrah Kheradmand, Michael Scheurer, Caleb Davis, David Wheeler, Edwin Silverman, Shete Sanjay, Spiridon Tsavachidis, Georgina Armstrong, Elena Kupert, Marshall Anderson, Yafang Li, Claudio Pikielny, Joan E. Bailey-Wilson, Ming You, Colette Gaba, Mariza DeAndrade, Diptasri Mandal, Claire Simpson, Susan Pinney, Christopher Amos, Margaret Spitz. Target exome sequencing for disease-causing rare mutations in familial and sporadic lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4600. doi:10.1158/1538-7445.AM2015-4600

ABSTRACT Purpose To present and discuss a case of herniation of subconjunctival orbital fat, a very rare but benign condition. Case Report An 84‐year‐old man presented to the eye clinic for a cataract surgery consultation but also had a secondary complaint about yellow lesions on the bulbar conjunctiva of both eyes. Examination with biomicroscopy revealed protruding orbital masses superotemporally in both eyes, with the right lesion being larger than the left. After thorough testing, these lesions were diagnosed as being subconjuntival herniated orbital fat (HOF), and the patient underwent surgical excision of the lesions. Conclusions In cases of HOF, appropriate and accurate testing is essential, as this condition can mimic several other neoplasms, all of which require specialized treatment strategies. If cosmesis is unacceptable to the patient or the lesion impedes normal ocular function, a subconjunctival excision of the excess fat may be performed with little concern of recurrence. This article discusses a case of HOF, with an explanation of testing and treatment options.

One commonly reported complication of pyrolytic carbon arthroplasty at the proximal interphalangeal (PIP) joint is an annoying, painless, squeaking postoperatively. This squeak has been anecdotally associated with implant loosening or impending dislocation. The purpose of this study was to investigate the etiology of this squeaking. Proximal and distal components of the pyrolytic carbon PIP implant were inserted into foam bones and mounted onto an oscillating test device. We evaluated the effect of 96 combinations of load, velocity, contact angle, implant size, lubrication, and displacement amplitude over a total of 300 cycles for each condition. Sound analysis was performed on squeaking conditions. Fourteen conditions resulted in squeaking, all with a sound pattern similar to that noted clinically. Unlubricated, “dry” joints did not squeak. Squeaking most commonly occurred with fetal bovine serum lubrication, at higher loads, and at 0 deg hyperextension. Hyaluronic acid viscosupplementation stopped the squeaking in all cases.