Citations

AbstractAimThis study aimed to determine the incidence and risk factors of acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR).MethodsWe included all adult patients undergoing TAVR for aortic stenosis from 1 January 2008 to 30 June 2014 at a tertiary referral hospital. AKI was defined based on Kidney Disease: Improving Global Outcomes criteria. We performed a multivariate logistic regression to identify factors associated with post‐procedural AKI occurrence.ResultsThree hundred eighty‐six patients met the inclusion criteria, of which 106 (28%) developed AKI. In multivariate analysis, AKI development was independently associated with a transapical approach (odds ratio (OR), 2.81; 95% confidence interval (CI), 1.72–4.65 compared with transfemoral approach) and the need for an intra‐aortic balloon pump (OR, 9.11; 95% CI, 1.77–68.29). Higher baseline renal function (OR, 0.78 per 10 mL/min per 1.73 m2 increment in glomerular filtration rate; 95% CI, 0.68–0.87) was significantly associated with a decreased risk of AKI. After adjustment for the Society of Thoracic Surgeons' risk score, post‐procedural AKI development remained significantly associated with an increased in‐hospital (OR, 4.74; 95% CI, 1.39–18.48) and 6‐month mortality (OR, 4.66; 95% CI, 2.32–9.63).ConclusionIn a cohort of patients undergoing TAVR for aortic stenosis, AKI commonly occurred and was significantly associated with increased mortality. Baseline renal function, procedure approach and the need for circulatory support were important predictive factors for post‐procedural AKI occurrence.

Study Design. Laboratory/animal-based proof of principle study. Objective. To validate the accuracy of a magnetic resonance imaging (MRI)-guided stereotactic system for intraspinal electrode targeting and demonstrate the feasibility of such a system for controlling implantation of intraspinal electrodes. Summary of Background Data. Intraspinal microstimulation (ISMS) is an emerging preclinical therapy, which has shown promise for the restoration of motor function following spinal cord injury. However, targeting inaccuracy associated with existing electrode implantation techniques remains a major barrier preventing clinical translation of ISMS. Methods. System accuracy was evaluated using a test phantom comprised of nine target locations. Targeting accuracy was determined by calculating the root mean square error between MRI-generated coordinates and actual frame coordinates required to reach the target positions. System performance was further validated in an anesthetized pig model by performing MRI-guided intraspinal electrode implantation and stimulation followed by computed tomography of electrode location. Finally, system compatibility with a commercially available microelectrode array was demonstrated by implanting the array and applying a selection of stimulation amplitudes that evoked hind limb responses. Results. The root mean square error between actual frame coordinates and software coordinates, both acquired using the test phantom, was 1.09 ± 0.20 mm. Postoperative computed tomography in the anesthetized pig confirmed spatially accurate electrode placement relative to preoperative MRI. Additionally, MRI-guided delivery of a microwire electrode followed by ISMS evoked repeatable electromyography responses in the biceps femoris muscle. Finally, delivery of a microelectrode array produced repeatable and graded hind limb evoked movements. Conclusion. We present a novel frame-based stereotactic system for targeting and delivery of intraspinal instrumentation. This system utilizes MRI guidance to account for variations in anatomy between subjects, thereby improving upon existing ISMS electrode implantation techniques. Level of Evidence: N/A

Abstract Background Treatment guidelines for stage II and III rectal cancer include neoadjuvant chemoradiotherapy, surgery and postoperative adjuvant chemotherapy. Although data support this recommendation in younger patients, it is unclear whether this benefit can be extrapolated to elderly patients (aged 75 years or older). Methods This was a retrospective review of patients aged at least 75 years with stage II or III rectal cancer who underwent surgery with curative intent from 1996 to 2013 at the Mayo Clinic. Kaplan–Meier analysis and log rank test were used to compare overall survival between therapy groups. Cox proportional hazards model was used to estimate the independent effect of treatment group on survival. Results A total of 160 elderly patients (median age 80 years) with stage II (66) and stage III (94) rectal cancer underwent surgical resection. Only 30·0 and 33·8 per cent received neoadjuvant or adjuvant therapy respectively. Among patients with stage II disease, there was no significant difference in 60-month survival between patients who received any additional therapy and those who had surgery alone (55 versus 38 per cent respectively; P = 0·184), whereas additional therapy improved survival in patients with stage III tumours (58 versus 30 per cent respectively; P = 0·007). Multivariable analysis found a survival benefit for additional therapy in elderly patients with stage III disease (hazard ratio 0·58, 95 per cent c.i. 0·34 to 0·98). Conclusion A multimodal approach in elderly patients with stage III rectal cancer improved oncological outcomes.

Recent applications of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system have greatly improved the efficiency of genome editing in pigs. However, in some cases, genetically modified pig models need an additional modification to improve their application. The objective of this experiment was to determine whether a combination of somatic cell NT (SCNT) by using a previously modified donor cell line and subsequent zygote injection with CRISPR/Cas9 guide RNA to target a second gene would result in embryos and offspring successfully containing both modifications. Fibroblast cell lines were collected from fumarylacetoacetate hydrolase deficient (FAH–/–) fetuses and used as the donor cell line. Somatic cell NT was performed by standard technique. A CRISPR guide RNA specific for recombination activating gene 2 (RAG2) was designed and in vitro transcribed from a synthesised gBlock (IDT) containing a T7 promoter sequence, the CRISPR Guide RNA (20 bp), and 85 bp of tracer RNA. The gBlock was PCR amplified with Q5 polymerase (NEB, Ipswich, MA, USA) and in vitro transcribed with the MEGAshortscript™ T7 Transcription Kit (Life Technologies, Grand Island, NY, USA). Guide RNA (20 ng µL–1) and polyadenylated Cas9 (20 ng µL–1, Sigma, St. Louis, MO, USA) were co-injected into the cytoplasm of SCNT zygotes at 14 to 16 h after fusion and activation. Injected SCNT were then cultured in vitro in PZM3 + 1.69 mM arginine medium (MU1) to Day 5. Three embryo transfers were performed surgically into recipient gilts on Day 4 or 5 of oestrus (50, 62, or 70 embryos per pig) to evaluate in vivo development. The remaining embryos were cultured in MU1 to Day 7 and analysed for the presence of modifications to the RAG2 gene. Embryos were classified as modified if they contained an INDEL as measured by both gel electrophoresis and DNA sequencing of PCR amplicons spanning the targeted exon. The RAG2 modification rate was 83.3% (n = 6), of which 50% (n = 3) of the embryos contained biallelic modifications. All control embryos contained a wild-type RAG2 gene (n = 5). Embryo transfer resulted in a 33.3% pregnancy rate (1/3). The combination of SCNT and CRISPR/Cas9 zygote injection can be a highly efficient tool to successfully create pig embryos with an additional modification. This additional technique further improves the usefulness of already created genetically modified pig models. This study was funded by the National Institutes of Health via U42 OD011140.

Recent publications in the dermatologic surgery literature have sparked a re‐emergence of interest in anatomy relevant for the Mohs surgeon necessitating a re‐visit of under‐appreciated concepts, regarding the topography of the face and its visceral contents from a surgically relevant perspective. This paper presents a pre‐operative review and a conceptual framework for intra‐operative planning for Mohs micrographic surgery and reconstruction. The key concepts presented are based on a series of (1) reviews regarding clinically significant points aimed at improving outcomes for reconstructive surgery, (2) anatomical dissections of fresh frozen cadavers, and (3) surgical experience of the authors. Basic anatomical concepts have been assimilated, surgically evaluated and re‐directed toward the dermatologic surgeon in the hope that improved anatomic competence will reduce surgical hesitance. Clin. Anat. 29:237–246, 2016. © 2015 Wiley Periodicals, Inc.