Objective Acute lower extremity ischemia secondary to arterial thromboembolism is a common problem. Contemporary data regarding this problem are sparse. This report examines a 10-year single-center ...experience and describes the surgical management and outcomes observed. Methods Procedural codes were used to identify consecutive patients treated surgically for acute lower extremity embolization from January 2002 to September 2012. Patients presenting >7 days after onset of symptoms, occlusion of grafts/stents, and cases secondary to trauma or iatrogenic injury were excluded. Data collected included demographics, medical comorbidities, presenting clinical characteristics, procedural specifics, and postoperative outcomes. Results were evaluated using descriptive statistics, product-limit survival analysis, and logistic regression multivariable modeling. Results The study sample included 170 patients (47% female). Mean age was 69.1 ± 16.0 years. Of these, 82 patients (49%) had a previous history of atrial fibrillation, and four (2%) were therapeutically anticoagulated (international normalized ratio ≥2.0) at presentation. Presentation for 83% was >6 hours after symptom onset, and 9% presented with a concurrent acute stroke. Femoral artery exploration with embolectomy was the most common procedural management and was used for aortic, iliac, and infrainguinal occlusion. Ten patients (6%) required bypass for limb salvage during the initial operation. Local instillation of thrombolytic agents as an adjunct to embolectomy was used in 16%, fasciotomies were performed in 39%, and unexpected return to the operating room occurred in 24%. Ninety-day amputation above or below the knee was required during the index hospitalization in 26 patients (15%). In-hospital or 30-day mortality was 18%. Median (interquartile range) length of stay was 8 days (4, 16 days), and 36% of patients were discharged to a nursing facility. Recurrent extremity embolization occurred in 23 patients (14%) at a median interval of 1.6 months. The 5-year amputation freedom and survival estimates were 80% and 41%, respectively. Predictors of 90-day amputation included prior vascular surgery, gangrene, and fasciotomy. Predictors of 30-day mortality included age, history of coronary artery disease, prior vascular surgery, and concurrent stroke. Conclusions Despite advances in contemporary medical care, lower extremity arterial embolization remains a condition that is associated with significant morbidity and mortality. Furthermore, the condition is resource-intensive to treat and is likely preventable (initially or in recurrence) in a substantial subset of patients.
Objective Renal artery aneurysms (RAAs) are uncommon, and rates of growth and rupture are unknown. Limited evidence therefore exists to guide clinical management of RAAs, particularly small aneurysms ...that are asymptomatic. To further characterize the natural history of RAAs, we studied anatomic characteristics and changes in diameter during imaging surveillance. Methods Patients evaluated for native RAAs at a single institution during a 5-year period (July 2008 to July 2013) were identified and analyzed retrospectively. Patients with two or more cross-sectional imaging studies (computed tomography or magnetic resonance imaging) more than 1 month apart were included. Demographic and clinical data were collected from medical records, and anatomic data (including aneurysm diameter, calcification, and location) were obtained from electronic images. Changes in RAA diameters over time were evaluated by plots and Wilcoxon signed rank tests. Results Sixty-eight RAAs in 55 patients were analyzed. Median follow-up was 19.4 months (interquartile range, 11.2-49.0 months). Mean age at presentation was 61.8 ± 9.8 years, and 73% of patients were women. Hypertension was prevalent among 73% of patients. Multiple RAAs were present in 18% of patients, and 24% also had arterial aneurysms of other splanchnic or iliac vessels. The majority of RAAs were calcified and located at the main renal artery bifurcation. Mean initial aneurysm diameter was 16.0 ± 6.4 mm. Median annualized growth rate was 0.06 mm (interquartile range, −0.07 to 0.33 mm; P = .11). No RAA ruptures or acute symptoms occurred during surveillance, and 10.3% of RAAs were repaired electively. Conclusions Risk of short-term RAA growth or rupture was low. These findings suggest that annual (or less frequent) imaging surveillance is safe in the majority of patients and do not support pre-emptive repair of asymptomatic, small-diameter RAAs.
Abstract
Introduction
Laws regulating substance use in pregnancy are changing and may have unintended consequences on scientific efforts to address the opioid epidemic. Yet, how these laws affect ...care and research is poorly understood.
Methods
We conducted semi-structured qualitative interviews using purposive and snowball sampling of researchers who have engaged pregnant people experiencing substance use. We explored views on laws governing substance use in pregnancy and legal reform possibilities. Interviews were double coded. Data were examined using thematic analysis.
Results
We interviewed 22 researchers (response rate: 71 per cent) and identified four themes: (i) harms of punitive laws, (ii) negative legal impacts on research, (iii) proposals for legal reform, and (iv) activism over time.
Discussion
Researchers view laws penalizing substance use during pregnancy as failing to treat addiction as a disease and harming pregnant people and families. Respondents routinely made scientific compromises to protect participants. While some have successfully advocated for legal reform, ongoing advocacy is needed.
Conclusion
Adverse impacts from criminalizing substance use during pregnancy extend to research on this common and stigmatized problem. Rather than penalizing substance use in pregnancy, laws should approach addiction as a medical issue and support scientific efforts to improve outcomes for affected families.
The International Crocodilian Genomes Working Group (ICGWG) will sequence and assemble the American alligator (Alligator mississippiensis), saltwater crocodile (Crocodylus porosus) and Indian gharial ...(Gavialis gangeticus) genomes. The status of these projects and our planned analyses are described.
Historic DNA data have the potential to identify phenotypic information otherwise invisible in the historical, archaeological and palaeontological record. In order to determine whether a single ...nucleotide polymorphism typing protocol based on single based extension (SNaPshot™) could produce reliable phenotypic data from historic samples, we genotyped three coat colour markers for a sample of historic Thoroughbred horses for which both phenotypic and correct genotypic information were known from pedigree information in the General Stud Book. Experimental results were consistent with the pedigrees in all cases. Thus we demonstrate that historic DNA techniques can produce reliable phenotypic information from museum specimens.
IGF binding protein (IGFBP)-3 can induce apoptosis in human prostate cancer cells directly without sequestering IGF-I and -II. The molecular mechanisms responsible for the IGF-independent actions of ...IGFBP-3 remain unclear. IGFBP-3, a secreted protein, can be internalized and translocate to the nucleus. It binds to the nuclear retinoid X receptor (RXR)-α. Binding to RXR-α has been proposed to be required for IGFBP-3 to induce apoptosis. The present study tests this hypothesis in the PC-3 human prostate cancer cell line. PC-3 cells express RXR-α, and apoptosis is induced by incubation with RXR-specific ligand. A COOH-terminal region in IGFBP-3 (residues 215–232) contains a nuclear localization signal, and binding domains for RXR-α and heparin (HBD). Different combinations of the 11 amino acids in this region that differ from IGFBP-1, a related IGFBP, which does not localize to the nucleus or bind RXR-α, were mutated to the IGFBP-1 sequence. By confocal imaging, mutation of residues 228-KGRKR-232 in nonsecreted IGFBP-3 diminished its nuclear localization. IGFBP-3 binding to glutathione S-transferase-RXR-α only was lost when all 11 sites were mutated (HBD-11m-IGFBP-3). Expressed nuclear RXR-α did not transport cytoplasmic IGFBP-3 nuclear localization signal mutants that can bind RXR-α to the nucleus even after treatment with RXR ligand. Expressed HBD-11m-IGFBP-3 still induced apoptosis in PC-3 cells in an IGF-independent manner as determined by flow cytometric analysis of Annexin V staining. We conclude that in PC-3 cells, RXR-α is not required for the nuclear translocation of IGFBP-3 and that IGFBP-3 can induce apoptosis in human prostate cancer cells without binding RXR-α.
Glutamatergic neurotransmission requires vesicular glutamate transporters (VGLUTs) to sequester glutamate into synaptic vesicles. Generally, VGLUT1 and VGLUT2 isoforms show complementary expression ...in the CNS and retina. However, little is known about whether isoform-specific expression serves distinct pathways and physiological functions. Here, by examining visual functions in VGLUT1-null mice, we demonstrate that visual signaling from photoreceptors to retinal output neurons requires VGLUT1. However, photoentrainment and pupillary light responses are preserved. We provide evidence that melanopsin-containing, intrinsically photosensitive retinal ganglion cells (RGCs), signaling via VGLUT2 pathways, support these non-image-forming functions. We conclude that VGLUT1 is essential for transmitting visual signals from photoreceptors to second- and third-order neurons, but VGLUT1 is not necessary for intrinsic visual functions. Furthermore, melanopsin and VGLUT2 expression in a subset of RGCs immediately after birth strongly supports the idea that intrinsic vision can function well before rod- and cone-mediated signaling has matured.
Mitral valve (MV) repair is performed with less frequency than MV replacement in older persons, with referral often delayed until symptoms are severe. Surgical practice in this population remains ...inconsistent in the absence of national MV repair outcomes. The goal of this study was to assess durability and longitudinal outcomes after isolated primary MV repair in patients aged 65 years or more.
We linked clinical data from The Society of Thoracic Surgeons adult cardiac surgery database (STS) to longitudinal claims data from the Centers for Medicare and Medicaid Services (CMS). Between January 1991 and December 2007, we identified 14,604 isolated nonemergent primary MV repair operations in STS-CMS data. These were longitudinally examined for mortality, mitral reoperation, and readmissions for heart failure, bleeding, and stroke. Predictors of 5-year death after MV repair were identified using Cox proportional hazard modeling.
The study cohort had a mean age of 73.3±5.5 years, ejection fraction 54.0%±12.9%; 55.8% (8,148 of 14,604) were female; and 8.4% (1,233 of 14,604) were non-Caucasian. Operative mortality was 2.59% (378 of 14,604). Mean follow-up was 5.9±3.9 years (range, 1.0 to 18.0). Survival during follow-up was 74.9% (10,934 of 14,604). The number of observed events for mitral reoperation, heart failure, bleeding, and stroke were 552 of 14,604 (3.7%), 2,681 of 14,604 (18.4%), 1,051 of 14,604 (7.2%), and 1,131 of 14,604 (7.7%), respectively. The 10-year Kaplan-Meier event rates for mitral reoperation, heart failure, bleeding, and stroke were 6.2%, 30.1%, 15.3%, and 16.4%, respectively. The 10-year actuarial survival of 57.4% was equivalent to the matched US population.
Utilizing linked STS and CMS databases, we demonstrate that MV repair is a safe and durable long-term option for older patients. Survival restored to the normal population suggests repair may suppress the longitudinal impact of mitral regurgitation in the elderly and that the practice of delayed referral should be reevaluated. These data provide a contemporary longitudinal benchmark of MV repair outcomes.
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