Citations

Background— Limited penetration into the caval wall is an important securing mechanism for inferior vena cava (IVC) filters; however, caval penetration can also cause unintentional complications. The aim of this study was to assess the incidence, severity, clinical consequences, and management of filter penetration across a range of commercially available IVC filters. Methods and Results— The MEDLINE database was searched for all studies (1970–2014) related to IVC filters. A total of 88 clinical studies and 112 case reports qualified for analysis; these studies included 9002 patients and 15 types of IVC filters. Overall, penetration was reported in 19% of patients (1699 of 9002), and 19% of those penetrations (322 of 1699) showed evidence of organ/structure involvement. Among patients with penetration, 8% were symptomatic, 45% were asymptomatic, and 47% had unknown symptomatology. The most frequently reported symptom was pain (77%, 108 of 140). Major complications were reported in 83 patients (5%). These complications required interventions including surgical removal of the IVC filter (n=63), endovascular stent placement or embolization (n=11), endovascular retrieval of the permanent filter (n=4), and percutaneous nephrostomy or ureteral stent placement (n=3). Complications led to death in 2 patients. A total of 87% of patients (127 of 146) underwent premature filter retrieval or interventions for underlying symptoms or penetration-related complications. Conclusions— Caval penetration is a frequent but clinically underrecognized complication of IVC filter placement. Symptomatic patients accounted for nearly 1/10th of all penetrations; most of these cases had organ/structure involvement. Interventions with endovascular retrieval and surgery were required in most of these symptomatic patients.

Background and Purpose— The majority of genome-wide association studies (GWAS) of stroke have focused on European-ancestry populations; however, none has been conducted in African Americans, despite the disproportionately high burden of stroke in this population. The Consortium of Minority Population Genome-Wide Association Studies of Stroke (COMPASS) was established to identify stroke susceptibility loci in minority populations. Methods— Using METAL, we conducted meta-analyses of GWAS in 14 746 African Americans (1365 ischemic and 1592 total stroke cases) from COMPASS, and tested genetic variants with P <10 −6 for validation in METASTROKE, a consortium of ischemic stroke genetic studies in European-ancestry populations. We also evaluated stroke loci previously identified in European-ancestry populations. Results— The 15q21.3 locus linked with lipid levels and hypertension was associated with total stroke (rs4471613; P =3.9×10 −8 ) in African Americans. Nominal associations ( P <10 −6 ) for total or ischemic stroke were observed for 18 variants in or near genes implicated in cell cycle/mRNA presplicing ( PTPRG , CDC5L ), platelet function ( HPS4 ), blood–brain barrier permeability ( CLDN17 ), immune response ( ELTD1, WDFY4 , and IL1F10-IL1RN ), and histone modification ( HDAC9 ). Two of these loci achieved nominal significance in METASTROKE: 5q35.2 ( P =0.03), and 1p31.1 ( P =0.018). Four of 7 previously reported ischemic stroke loci ( PITX2, HDAC9, CDKN2A/CDKN2B , and ZFHX3 ) were nominally associated ( P <0.05) with stroke in COMPASS. Conclusions— We identified a novel genetic variant associated with total stroke in African Americans and found that ischemic stroke loci identified in European-ancestry populations may also be relevant for African Americans. Our findings support investigation of diverse populations to identify and characterize genetic risk factors, and the importance of shared genetic risk across populations.

Preexposure prophylaxis (PrEP) of HIV infection with tenofovir-containing regimens is effective, but plagued by poor adherence in some studies. Options for safe, effective, and acceptable PrEP products, especially for men and women at risk of HIV via receptive anal intercourse (RAI), are needed. We performed a randomized, partially blinded, first-in-human evaluation of four candidate rectal microbicide vehicles—aqueous gel, aqueous fluid, lipid gel, and lipid fluid—to select a prototype for further clinical development. Eight seronegative participants received three doses of each product with each dose separated by at least 2 weeks: one dose was given alone without simulated RAI in clinic, another dose was followed by simulated RAI in clinic, and another dose was self-administered at home in the context of RAI with a partner. Assessments included safety, acceptability, colon histology, ex vivo HIV infectivity of colon tissue explants, and colonic luminal distribution of vehicle and HIV surrogates. Adverse events were all mild and mainly sigmoidoscopy associated. There were minor differences in colon distribution of products and little effect of RAI. Vehicle distribution covered 95% (±7% standard deviation) of the distribution of an HIV surrogate in the colonic lumen. The lipid fluid vehicle increased HIV colon tissue infectability 5-fold [log 10 p24 0.68 (95% confidence interval 0.08, 1.28)] and aqueous gel provided 6-fold protection [log 10 p24 0.80 (95% confidence interval 0.20, 1.41)] compared to no product baseline. Colon permeability of lipid vehicles was more than 10-fold greater than aqueous vehicles. All products received similar acceptability ratings, though trends favored the gel products. Intensive simultaneous assessment of safety and toxicity, luminal and tissue distribution, ex vivo HIV infectivity, and product acceptability in relevant sexual contexts provided clear differentiation among candidate gels very early in product development. We selected the aqueous gel for further development as a rectal microbicide vehicle.

Abstract Background: Excess adiposity has been associated with lymphomagenesis, possibly mediated by increased cytokine production causing a chronic inflammatory state. The relationship between obesity, cytokine polymorphisms, and selected mature B-cell neoplasms is reported. Method: Data on 4,979 cases and 4,752 controls from nine American/European studies from the InterLymph consortium (1988–2008) were pooled. For diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), joint associations of body mass index (from self-reported height and weight) and 12 polymorphisms in cytokines IL1A (rs1800587), IL1B (rs16944, rs1143627), IL1RN (rs454078), IL2 (rs2069762), IL6 (rs1800795, rs1800797), IL10 (rs1800890, rs1800896), TNF (rs1800629), LTA (rs909253), and CARD15 (rs2066847) were investigated using unconditional logistic regression. BMI-polymorphism interaction effects were estimated using the relative excess risk due to interaction (RERI). Results: Obesity (BMI ≥ 30 kg/m2) was associated with DLBCL risk [OR = 1.33; 95% confidence interval (CI), 1.02–1.73], as was TNF-308GA+AA (OR = 1.24; 95% CI, 1.07–1.44). Together, being obese and TNF-308GA+AA increased DLBCL risk almost 2-fold relative to those of normal weight and TNF-308GG (OR = 1.93; 95% CI, 1.27–2.94), with a RERI of 0.41 (95% CI, −0.05–0.84; Pinteraction = 0.13). For FL and CLL/SLL, no associations with obesity or TNF-308GA+AA, either singly or jointly, were observed. No evidence of interactions between obesity and the other polymorphisms were detected. Conclusions: Our results suggest that cytokine polymorphisms do not generally interact with BMI to increase lymphoma risk but obesity and TNF-308GA+AA may interact to increase DLBCL risk. Impact: Studies using better measures of adiposity are needed to further investigate the interactions between obesity and TNF-308G&gt;A in the pathogenesis of lymphoma. Cancer Epidemiol Biomarkers Prev; 24(7); 1061–70. ©2015 AACR.

Objectives/HypothesisInverting papillomas (IPs) are benign locally invasive tumors that most commonly present within the sinonasal cavity. Temporal bone involvement is exceedingly rare, with fewer than 30 cases reported within the English literature to date.Study DesignCase series and systematic review of the literature.MethodsFour consecutive subjects with temporal bone inverting papilloma (TBIP) were treated, and an additional 28 previously published cases were identified in the literature. Main outcome measures were disease presentation, diagnostic evaluation, management strategy, and outcome.ResultsA total of 32 cases were analyzed. The median age at diagnosis was 54 years (mean 54.1; range 19–81 years). Nineteen (59%) patients had synchronous or metachronous sinonasal IP, whereas 13 (41%) had isolated temporal bone disease without sinus involvement. Over half of the patients undergoing microsurgical resection experienced at least one recurrence. Compared to patients with a history of sinus IP, subjects with primary TBIP were younger at time of presentation (44 vs. 58 years; P = 0.012); were more commonly female (62% vs. 32%; P = 0.15); and were less likely to have intracranial spread (8% vs. 26%; P = 0.36), cranial neuropathy (8% vs. 26%; P = 0.36), human papillomavirus positivity (11% vs. 57%; P = 0.11), or associated carcinoma (0% vs. 47%; P = 0.004).ConclusionsInverting papilloma of the lateral skull base is rare and can pose a significant therapeutic challenge. Primary lesions of the temporal bone appear to follow a less aggressive clinical course when compared to those arising in association with sinonasal disease. Gross total resection is the preferred method of treatment, when feasible, given the high rate of recurrence with subtotal resection and risk of associated malignancy.Level of Evidence4. Laryngoscope, 125:2576–2583, 2015

ABSTRACT The epithelium is a highly organized type of animal tissue. Except for blood and lymph vessels, epithelial cells cover the body, line its cavities in single or stratified layers and support exchange between compartments. In addition, epithelia offer to the body a barrier to pathogen invasion. To transit through or to replicate in epithelia, viruses have to face several obstacles, starting from cilia and glycocalyx where they can be neutralized by secreted immunoglobulins. Tight junctions and adherens junctions also prevent viruses to cross the epithelial barrier. However, viruses have developed multiple strategies to blaze their path through the epithelium by utilizing components of cell–cell adhesion structures as receptors. In this Commentary, we discuss how viruses take advantage of the apical junction complex to spread. Whereas some viruses quickly disrupt epithelium integrity, others carefully preserve it and use cell adhesion proteins and their cytoskeletal connections to rapidly spread laterally. This is exemplified by the hidden transmission of enveloped viruses that use nectins as receptors. Finally, several viruses that replicate preferentially in cancer cells are currently used as experimental cancer therapeutics. Remarkably, these viruses use cell adhesion molecules as receptors, probably because – to reach tumors and metastases – oncolytic viruses must efficiently traverse or break epithelia.

The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain‐only donations and currently has banked more than 1600 brains. More than 430 whole‐body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed at subjects with Alzheimer's disease, Parkinson's disease and cancer. The median age at death is 82. Subjects receive standardized general medical, neurological, neuropsychological and movement disorders assessments during life and more than 90% receive full pathological examinations by medically licensed pathologists after death. The Program has been funded through a combination of internal, federal and state of Arizona grants as well as user fees and pharmaceutical industry collaborations. Subsets of the Program are utilized by the US National Institute on Aging Arizona Alzheimer's Disease Core Center and the US National Institute of Neurological Disorders and Stroke National Brain and Tissue Resource for Parkinson's Disease and Related Disorders. Substantial funding has also been received from the Michael J. Fox Foundation for Parkinson's Research. The Program has made rapid autopsy a priority, with a 3.0‐hour median post‐mortem interval for the entire collection. The median RNA Integrity Number (RIN) for frozen brain and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have been served and currently about 200 are served annually. These requests have been made by more than 400 investigators located in 32 US states and 15 countries. Tissue from the BBDP has contributed to more than 350 publications and more than 200 grant‐funded projects.

There is no standard of care for catheter size or post-procedure supine time in cerebral angiography. Catheter sizes range from 4-Fr to 6-Fr with supine times ranging from two to over six hours. The objective of our study was to establish the efficacy, safety, and cost savings of two-hour supine time after 4-Fr elective cerebral angiography. A prospective, single arm study was performed on 107 patients undergoing elective cerebral angiography. All cerebral angiograms were performed with a 4-Fr sheath-based system without closure devices. Ten minutes of manual compression was applied to the femoral access site, with further compression held as clinically indicated. Patients were then monitored in a nursing unit for two hours supine and subsequently mobilized. Nursing discretion was allowed for earlier mobilization. Patients were called the next day to assess delayed hematoma and bleeding. Estimates of cost savings and productivity increases are provided. All patients ambulated in two hours or less. There were no strokes or vessel dissections. Five patients (4.7%) experienced a palpable hematoma, three patients (2.8%) experienced bleeding immediately following the procedure requiring further compression, and one patient (0.9%) experienced minor groin oozing at home. No patient required transfusion, thrombin injection, or endovascular/surgical management of a groin complication. A two-hour post-procedure supine time resulted in cost savings of $952 per angiogram and a total of $101,864. 4-Fr sheath based cerebral angiography with two-hour post-procedure supine time is safe and effective, and allows for a considerable increase in patient satisfaction, cost savings and productivity.

The resection of large pelvic tumors is challenging due to their infiltrative nature into multiple structures and organ systems. In this report, we describe the use of multiple vascularized and nonvascularized spare parts to reconstruct a pelvic defect in a patient with a uniquely large pelvic sarcoma invading the spinal canal. A 39‐year‐old Caucasian female who presented with a large retroperitoneal sarcoma where the tumor encased the left ureter, kidney, colon, and external iliac vessels and invaded the L3‐S1 vertebral bodies. An extensive hemipelvectomy and reconstruction was performed over two days. A free thigh and leg fillet flap together with ipsilateral fibula flap, based on the superficial femoral artery and venae comitantes, was used for spinal reinforcement as well as abdominal and pelvic wall reconstruction. The postoperative course was uneventful without complications, no flap compromise or wound healing problems. After a follow‐up period of 4 months, the patient had no complications and returned to activities of daily living with mild limitations. The success of this flap procedure shows the practicality and usefulness of using the full spectrum of tissue transfer for the purposes of a large pelvic reconstruction. © 2014 Wiley Periodicals, Inc. Microsurgery 35:320–323, 2015.

BackgroundPatent foramen ovale (PFO) is common and may predispose to paradoxical embolism. Transcatheter device closure of PFO can be challenging in certain cases of “long‐tunnel” PFO morphology. We report our experience with device closure of long‐tunnel PFO using transseptal puncture.MethodsWe retrospectively reviewed all cases of PFO device closure using transseptal puncture at the Mayo Clinic from January 1, 2010 to September 30, 2013. We arbitrarily defined a PFO tunnel configuration as a tunnel length ≥ 12 mm as observed in intracardiac echocardiography (ICE) at the time of device closure.ResultsTwelve patients (mean age 40.8 [range 15–67] years; 7 males [58%]) underwent PFO device closure with transseptal puncture. The most common indication for PFO closure was previous stroke (n = 7, 58%). Median tunnel length measured by ICE was 15 mm (12–20 mm). GORE® HELEX® Septal Occluder was used for closure in all but one patient. The only significant procedural complication was a minor perforation of the left atrial wall during attempted septal puncture, which resulted in a trivial pericardial effusion that resolved without intervention. At latest follow‐up (mean 543 days, [range 170–1162]) one patient had a residual shunt and subsequently died due to complications during surgical PFO closure. No recurrent strokes or TIAs were reported.ConclusionThough not without risk, transseptal puncture can be a valuable tool for facilitating device closure of long‐tunnel type PFOs. GORE® HELEX® Septal Occluder may be an effective option for facilitating device closure for patients with long‐tunnel type PFO. © 2014 Wiley Periodicals, Inc.