Showing papers by "University of Medicine and Dentistry of New Jersey published in 2017"

Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As a Graft Source for T-Cell–Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide

Abstract: PurposeT-cell–replete HLA-haploidentical donor hematopoietic transplantation using post-transplant cyclophosphamide was originally described using bone marrow (BM). With increasing use of mobilized peripheral blood (PB), we compared transplant outcomes after PB and BM transplants.Patients and MethodsA total of 681 patients with hematologic malignancy who underwent transplantation in the United States between 2009 and 2014 received BM (n = 481) or PB (n = 190) grafts. Cox regression models were built to examine differences in transplant outcomes by graft type, adjusting for patient, disease, and transplant characteristics.ResultsHematopoietic recovery was similar after transplantation of BM and PB (28-day neutrophil recovery, 88% v 93%, P = .07; 100-day platelet recovery, 88% v 85%, P = .33). Risks of grade 2 to 4 acute (hazard ratio [HR], 0.45; P < .001) and chronic (HR, 0.35; P < .001) graft-versus-host disease were lower with transplantation of BM compared with PB. There were no significant differences ...

Extreme Drug Tolerance of Mycobacterium tuberculosis in Caseum.

Abstract: Tuberculosis (TB) recently became the leading infectious cause of death in adults, while attempts to shorten therapy have largely failed. Dormancy, persistence, and drug tolerance are among the factors driving the long therapy duration. Assays to measure in situ drug susceptibility of Mycobacterium tuberculosis bacteria in pulmonary lesions are needed if we are to discover new fast-acting regimens and address the global TB threat. Here we take a first step toward this goal and describe an ex vivo assay developed to measure the cidal activity of anti-TB drugs against M. tuberculosis bacilli present in cavity caseum obtained from rabbits with active TB. We show that caseum M. tuberculosis bacilli are largely nonreplicating, maintain viability over the course of the assay, and exhibit extreme tolerance to many first- and second-line TB drugs. Among the drugs tested, only the rifamycins fully sterilized caseum. A similar trend of phenotypic drug resistance was observed in the hypoxia- and starvation-induced nonreplicating models, but with notable qualitative and quantitative differences: (i) caseum M. tuberculosis exhibits higher drug tolerance than nonreplicating M. tuberculosis in the Wayne and Loebel models, and (ii) pyrazinamide is cidal in caseum but has no detectable activity in these classic nonreplicating assays. Thus, ex vivo caseum constitutes a unique tool to evaluate drug potency against slowly replicating or nonreplicating bacilli in their native caseous environment. Intracaseum cidal concentrations can now be related to the concentrations achieved in the necrotic foci of granulomas and cavities to establish correlations between clinical outcome and lesion-centered pharmacokinetics-pharmacodynamics (PK-PD) parameters.

Initial hospital management of patients with emergent large vessel occlusion (ELVO): report of the standards and guidelines committee of the Society of NeuroInterventional Surgery

Abstract: Objective To summarize the current literature regarding the initial hospital management of patients with acute ischemic stroke (AIS) secondary to emergent large vessel occlusion (ELVO), and to offer recommendations designed to decrease the time to endovascular treatment (EVT) for appropriately selected patients with stroke. Methods Using guidelines for evidenced-based medicine proposed by the Stroke Council of the American Heart Association, a critical review of all available medical literature supporting best initial medical management of patients with AIS secondary to ELVO was performed. The purpose was to identify processes of care that most expeditiously determine the eligibility of a patient with an acute stroke for interventions including intravenous fibrinolysis with recombinant tissue plasminogen activator (IV tPA) and EVT using mechanical embolectomy. Results This review identifies four elements that are required to achieve timely revascularization in ELVO. (1) In addition to non-contrast CT (NCCT) brain scan, CT angiography should be performed in all patients who meet an institutional threshold for clinical stroke severity. The use of any advanced imaging beyond NCCT should not delay the administration of IV tPA in eligible patients. (2) Activation of the neurointerventional team should occur as soon as possible, based on either confirmation of large vessel occlusion or a prespecified clinical severity threshold. (3) Additional imaging techniques, particularly those intended to physiologically select patients for EVT (CT perfusion and diffusion–perfusion mismatch imaging), may provide additional value, but should not delay EVT. (4) Routine use of general anesthesia during EVT procedures, should be avoided if possible. These workflow recommendations apply to both primary and comprehensive stroke centers and should be tailored to meet the needs of individual institutions. Conclusions Patients with ELVO are at risk for severe neurologic morbidity and mortality. To achieve the best possible clinical outcomes stroke centers must optimize their triage strategies. Strategies that provide patients with ELVO with the fastest access to reperfusion depend upon detail-oriented process improvement.

Mortality after emergent trauma laparotomy: A multicenter, retrospective study

Abstract: BACKGROUNDTwo decades ago, hypotensive trauma patients requiring emergent laparotomy had a 40% mortality. In the interim, multiple interventions to decrease hemorrhage-related mortality have been implemented but few have any documented evidence of change in outcomes for patients requiring emergent l

HIV-infected macrophages and microglia that survive acute infection become viral reservoirs by a mechanism involving Bim.

Abstract: While HIV kills most of the cells it infects, a small number of infected cells survive and become latent viral reservoirs, posing a significant barrier to HIV eradication. However, the mechanism by which immune cells resist HIV-induced apoptosis is still incompletely understood. Here, we demonstrate that while acute HIV infection of human microglia/macrophages results in massive apoptosis, a small population of HIV-infected cells survive infection, silence viral replication, and can reactivate viral production upon specific treatments. We also found that HIV fusion inhibitors intended for use as antiretroviral therapies extended the survival of HIV-infected macrophages. Analysis of the pro- and anti-apoptotic pathways indicated no significant changes in Bcl-2, Mcl-1, Bak, Bax or caspase activation, suggesting that HIV blocks a very early step of apoptosis. Interestingly, Bim, a highly pro-apoptotic negative regulator of Bcl-2, was upregulated and recruited into the mitochondria in latently HIV-infected macrophages both in vitro and in vivo. Together, these results demonstrate that macrophages/microglia act as HIV reservoirs and utilize a novel mechanism to prevent HIV-induced apoptosis. Furthermore, they also suggest that Bim recruitment to mitochondria could be used as a biomarker of viral reservoirs in vivo.

ASCCP Colposcopy Standards: Role of Colposcopy, Benefits, Potential Harms, and Terminology for Colposcopic Practice.

Abstract: ObjectivesThe American Society for Colposcopy and Cervical Pathology Colposcopy Standards address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. Working Group 1 was tasked with defining the role of colposcopy, describing benefits and potential

Evidence-Based Consensus Recommendations for Colposcopy Practice for Cervical Cancer Prevention in the United States.

Abstract: The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of colposcopy and directed biopsy for cervical cancer prevention in the United States (US). The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. An extensive literature review was conducted and supplemented by a systematic review and meta-analysis of unpublished data. In addition, a survey of practicing colposcopists was conducted to assess current colposcopy practice in the US. Recommendations were approved by the working group members, and the final revisions were made based on comments received from the public. The recommendations cover terminology, risk-based colposcopy, colposcopy procedures, and colposcopy adjuncts. The ASCCP Colposcopy Standards recommendations are an important step toward raising the standard of colposcopy services delivered to women in the US. Because cervical cancer screening programs are currently undergoing important changes that may affect colposcopy performance, updates to some of the current recommendations may be necessary in the future.

Tunneling nanotubes (TNT) mediate long-range gap junctional communication: Implications for HIV cell to cell spread.

Abstract: Cell-to-cell communication is essen for the development of multicellular systems and is coordinated by soluble factors, exosomes, gap junction (GJ) channels, and the recently described tunneling nanotubes (TNTs). We and others have demonstrated that TNT-like structures are mostly present during pathogenic conditions, including HIV infection. However, the nature, function, and communication properties of TNTs are still poorly understood. In this manuscript, we demonstrate that TNTs induced by HIV infection have functional GJs at the ends of their membrane extensions and that TNTs mediate long-range GJ communication during HIV infection. Blocking or reducing GJ communication during HIV infection resulted in aberrant TNT cell-to-cell contact, compromising HIV spread and replication. Thus, TNTs and associated GJs are required for the efficient cell-to-cell communication and viral spread. Our data indicate that targeting TNTs/GJs may provide new therapeutic opportunities for the treatment of HIV.

Childhood Arthritis and Rheumatology Research Alliance Consensus Clinical Treatment Plans for Juvenile Dermatomyositis with Persistent Skin Rash

Abstract: Objective. Juvenile dermatomyositis (JDM) is the most common form of idiopathic inflammatory myopathy in children. While outcomes are generally thought to be good, persistence of skin rash is a common problem. The goal of this study was to describe the development of clinical treatment plans (CTP) for children with JDM characterized by persistent skin rash despite complete resolution of muscle involvement. Methods. The Childhood Arthritis and Rheumatology Research Alliance, a North American consortium of pediatric rheumatologists and other healthcare providers, used a combination of Delphi surveys and nominal group consensus meetings to develop CTP that reflected consensus on typical treatments for patients with JDM with persistent skin rash. Results. Consensus was reached on patient characteristics and outcome assessment. Patients should have previously received corticosteroids and methotrexate (MTX). Three consensus treatment plans were developed. Plan A added intravenous immunoglobulin (IVIG) if it was not already being used. Plan B added mycophenolate mofetil, while Plan C added cyclosporine. Continuation of previous treatments, including corticosteroids, MTX, and IVIG, was permitted in plans B and C. Conclusion. Three consensus CTP were developed for use in children with JDM and persistent skin rash despite complete resolution of muscle disease. These CTP reflect typical treatment approaches and are not to be considered treatment recommendations or standard of care. Using prospective data collection and statistical methods to account for nonrandom treatment assignment, it is expected that these CTP will be used to allow treatment comparisons, and ultimately determine the best treatment for these patients.

What is the Risk of Developing Proximal Junctional Kyphosis During Growth Friendly Treatments for Early-onset Scoliosis?

Abstract: Background Rib-based and spine-based systems are commonly used distraction-based growth friendly treatments for early-onset scoliosis (EOS). Our primary purpose was to determine the risk of developing postoperative proximal junctional kyphosis (PJK) during distraction-based growth friendly surgery. Methods A multicenter, retrospective, radiographic comparison was performed for a group of 40 children with EOS who were treated with posterior distraction-based implants. PJK was defined as proximal junction sagittal angle (PJA)≥10 degrees and PJA at least 10 degrees greater than preoperative. Results Eight subjects (20%) at immediate postoperative follow-up and 11 subjects (27.5%) at minimum 2-year follow-up had developed PJK. The risk of developing PJK between rib-based and spine-based growing systems was not significantly different at immediate postoperative (17% vs. 25%) or at final (25% vs. 31%) follow-ups.Further analysis combining both treatment groups demonstrated that PJK subjects were significantly older at time of initial surgery (7.1 y PJK vs. 5.0 y no PJK). Radiographic comparisons between PJK versus no PJK: Preoperative scoliosis (69.9 vs. 76.0 degrees), thoracic kyphosis (45.1 vs. 28.7 degrees), lumbar lordosis (53.1 vs. 44.0 degrees), PJA (2.2 vs. 2.8 degrees), sagittal vertical axis (1.5 vs. 2.6 cm), pelvic incidence (52.8 vs. 47.4 degrees), pelvic tilt (14.3 vs. 8.7 degrees), and sacral slope (37.7 vs. 35.9 degrees). At both initial postoperative and at final follow-up visits, a significant difference was found for cervical lordosis 32.2 versus 14.0 degrees and 42.0 versus 16.6 degrees, respectively. Risk ratio for developing PJK at final follow-up was 2.8 for subjects with preoperative thoracic hyperkyphosis and was 3.1 for subjects with high pelvic incidence (P Conclusions The risk of developing PJK during distraction-based growth friendly treatment for EOS was 20% immediately after implantation and 28% at minimum 2-year follow-up, with no difference observed between rib-based and spine-based treatment groups. As this study identifies a significant risk of developing PJK during the treatment of EOS, it allows clinicians to preoperatively council patients and their families about this possible complication. In addition, several potential risk factors for the development of postoperative PJK were identified, but should be investigated further in future studies. Level of evidence Level III-therapeutic study (retrospective, comparative).

New Therapeutic Approaches in Obesity and Metabolic Syndrome Associated with Polycystic Ovary Syndrome.

Abstract: Polycystic ovary syndrome (PCOS) is a pathophysiological disorder affecting reproductive and metabolic indices. PCOS is commonly associated with a high prevalence of insulin resistance and obesity; this association carries an increased risk of developing metabolic syndrome, type 2 diabetes mellitus (T2DM), and cardiovascular disease. Guidelines recommend lifestyle modification, metformin, hormonal contraceptives (HCs), and bariatric surgery as the main treatment options in obese patients with PCOS. Studies are being conducted to test the efficacy of existing treatment options as well as to discover new therapies. This review focuses on the most recent advances in this regard and highlights new hypotheses and emerging studies to give a picture of the latest therapeutic trends in the treatment of obese patients with PCOS. In this respect, much attention is given to the role of inositols, the mediators of insulin action. A deficiency of d-chiro-inositol containing inositol-phospho-glycans may be the basis of insulin resistance frequently seen in PCOS patients. Moreover, evidence suggests the use of statins in obese women with PCOS, but guidelines call for further research. Adiponectin, quercetin, vitamin D, and anti-obesity drugs have also been studied and seem to have a useful role in the treatment of obesity and metabolic syndrome in PCOS. Many trials have been conducted on the use of non-pharmacological therapies. Therapies including resveratrol, acupuncture, and berberine have favorable effects in overweight PCOS patients. However, more research is needed to reveal the clinical complexity of PCOS and develop more effective treatment options.

Guidelines and parameters: percutaneous sclerotherapy for the treatment of head and neck venous and lymphatic malformations

Abstract: Vascular anomalies are classified broadly into vascular tumors and vascular malformations.1 Vascular malformations are further subdivided based on the histology of the lesion and whether the lesion is ‘high flow’ or ‘low flow’.1–3 The ‘low flow’ vascular anomalies are the focus of this article, and this category is broadly comprised of venous malformations (VM) and lymphatic malformations (LM). VM and LM are congenital anomalies thought to occur secondary to developmental errors in venous or lymphatic patterning, respectively.3–6 These lesions most commonly affect the head and neck, and have a prevalence of approximately 1%.3 ,5 ,7 Lesions involving the aerodigestive tract may result in airway obstruction, impaired food intake, and prevent normal speech. Similarly, lesions that involve the orbit may compromise visual acuity or ocular mobility. Vascular malformations may become quite large and demonstrate contiguous extension from the neck into the chest, pleura, cervical spine, or thoracic spine with associated pleural effusions and osteolysis. The vast majority of VM and LM are sporadic, although an increased prevalence of these anomalies has been described in multiple syndromes and with inherited gene mutations.8–13 It is important to recognize the categorization of LM into macrocystic or microcystic subtypes when contemplating treatment of these lesions. Macrocystic LM are comprised of larger cysts (≥2 cm in diameter) and respond well to percutaneous sclerotherapy and surgery with good to excellent outcomes in 76–95% of patients.3 ,8 ,14–17 By contrast, microcystic LM are comprised of innumerable small cysts (<2 cm in size) and tend to respond poorly to percutaneous sclerotherapy or surgery.3 ,8 ,18–20 Emerging data regarding the medical treatment of microcystic LM with sildenafil and the mTOR inhibitor sirolimus are promising, but these studies are still in an investigational stage.21 Effective treatment of superficial microcystic …

Who Gets Testosterone? Patient Characteristics Associated with Testosterone Prescribing in the Veteran Affairs System: A Cross-Sectional Study.

Abstract: There has been concern about the growing off-label use of testosterone. Understanding the context within which testosterone is prescribed may contribute to interventions to improve prescribing. To evaluate patient characteristics associated with receipt of testosterone. Cross-sectional. A national cohort of male patients, who had received at least one outpatient prescription within the Veterans Affairs (VA) system during Fiscal Year 2008– Fiscal Year 2012. The study sample consisted of 682,915 non-HIV male patients, of whom 132,764 had received testosterone and a random 10% sample, 550,151, had not. Conditions and medications associated with testosterone prescription. Only 6.3% of men who received testosterone from the VA during the study period had a disorder of the testis, pituitary or hypothalamus associated with male hypogonadism. Among patients without a diagnosed disorder of hypogonadism, the use of opioids and obesity were the strongest predictors of testosterone prescription. Patients receiving >100 mg/equivalents of oral morphine daily (adjusted odds ratio = 5.75, p 40 kg/m2 (adjusted odds ratio = 3.01, p < 0.001) were more likely to receive testosterone than non-opioid users and men with BMI <25 kg/m2. Certain demographics (age 40–54, White race), comorbid conditions (sleep apnea, depression, and diabetes), and medications (antidepressants, systemic corticosteroids) also predicted a higher likelihood of testosterone receipt, all with an adjusted odds ratio less than 2 (p < 0.001). In the VA, 93.7% of men receiving testosterone did not have a diagnosed condition of the testes, pituitary, or hypothalamus. The strongest predictors of testosterone receipt (e.g., obesity, receipt of opioids), which though are associated with unapproved, off-label use, may be valid reasons for therapy. Interventions should aim to increase the proportion of testosterone recipients who have a valid indication.

The Crucial Role of Biofilms in Cryptococcus neoformans Survival within Macrophages and Colonization of the Central Nervous System.

Abstract: Cryptococcus neoformans is an encapsulated yeast-like fungus capable of causing life threatening meningoencephalitis in patients with impaired immunity. This microbe primarily infects the host via inhalation but has the ability to disseminate to the central nervous system (CNS) either as a single cell or inside of macrophages. Upon traversing the blood brain barrier, C. neoformans has the capacity to form biofilm-like structures known as cryptococcomas. Hence, we will discuss the C. neoformans elements contributing to biofilm formation including the fungus’ ability to survive in the acidic environment of a macrophage phagosome and inside of the CNS. The purpose of this mini-review is to instill fresh interest in understanding the importance of biofilms on fungal pathogenesis.

Use of a controlled subdermal radio frequency thermistor for treating the aging neck: Consensus recommendations

Abstract: Introduction: A new temperature-controlled device has been used as a percutaneous radio frequency probe to treat lax submental and other facial areas. It has significant advantages over other esthetic devices as it provides the dual benefit of fat lipolysis and skin tightening. Our goal here is to present consensus recommendations for treating the aging neck. Methods: A panel of 11 expert physicians convened in Dallas, Texas, on October 15, 2016 to arrive at a consensus on the best current practice for submental skin tightening and contour improvement. Prior to the meeting, a comprehensive review of the literature was performed and a survey was sent to esthetic dermatologists and plastic surgeons who were queried about various aspects of neck rejuvenation. Results: The literature search revealed 10 different technologies for neck rejuvenation evaluated in double-blind (n = 2) and single-blind (n = 1) clinical trials and other clinical evaluations (n = 21). The survey was sent via an email to 1248 ...

History of hypertension, heart disease, and diabetes and ovarian cancer patient survival: evidence from the ovarian cancer association consortium.

Abstract: Purpose Survival following ovarian cancer diagnosis is generally low; understanding factors related to prognosis could be important to optimize treatment. The role of previously diagnosed comorbidities and use of medications for those conditions in relation to prognosis for ovarian cancer patients has not been studied extensively, particularly according to histological subtype.

Transgender Associations and Possible Etiology: A Literature Review.

Abstract: Transgender or gender dysphoria has been defined in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), as distress resulting from the incongruence between one’s experienced gender and one’s assigned gender, along with a persistent and strong desire to be of another gender, and accompanied by clinically significant distress. Adolescents referred for evaluation often want hormonal therapy and several among them also express a desire for gender reassignment surgery. Furthermore, evidence shows that adolescents and adults with gender dysphoria without a sex development disorder, before gender reassignments, are at increased risk for suicide. For this review, a search of the English language scientific literature was conducted using the PubMed database. This summary discusses the associations and comorbidities of gender dysphoria and reiterates the evidence that its etiology is multifactorial. Transsexualism involves prenatal neuroanatomical changes, has a psychiatric association, and is found to be more prevalent in conjunction with schizophrenia and autism spectrum disorders. Childhood adversities and neglect are also linked to having a transgender identity. Moreover, the evidence favors a genetic predisposition. Likewise, there seems to be a growing concern with regards to the relationship between endocrine disruptors and transsexuals as well as other gender minority populations. More research needs to be done to understand the exact pathways.

Decreased maternal behavior and anxiety in ephrin-A5 -/- mice.

Abstract: During development of the nervous system, molecular signals mediating cell-cell interactions play critical roles in the guidance of axonal growth and establishment of synaptic functions. The Eph family of tyrosine kinase receptors and their ephrin ligands has been shown to mediate neuronal interactions in the development of topographic axon projection maps in several brain regions, and the loss of Eph activities result in defects in select axonal pathways. However, effects of deficiencies of the Eph signals on animal behavior have not been well documented. In this study, we showed that inactivation of a ligand of the Eph receptors, ephrin-A5, resulted in defects in maternal behavior and alterations in anxiety. Female ephrin-A5-/- mice show significant defects in nest building and pup retrieval. In addition, lower levels of anxiety were observed in both male and female null mice. These changes were not due to deficiencies in estradiol, progesterone, or corticosterone levels. Our observations suggest that ephrin-A5 plays a key role in the development and/or function of neural pathways mediating mouse maternal care and anxiety.

Connexin43 containing gap junction channels facilitate HIV bystander toxicity: Implications in neuroHIV

Abstract: Human immunodeficiency virus-1 (HIV-1) infection compromises the central nervous system (CNS) in a significant number of infected individuals, resulting in neurological dysfunction that ranges from minor cognitive deficits to frank dementia. While macrophages/microglia are the predominant CNS cells infected by HIV, our laboratory and others have shown that HIV-infected astrocytes, although present in relatively low numbers with minimal to undetectable viral replication, play key role in NeuroAIDS pathogenesis. Our laboratory has identified that HIV "hijacks" connexin (Cx) containing channels, such as gap junctions (GJs) and hemichannels (HCs), to spread toxicity and apoptosis to uninfected cells even in the absence of active viral replication. In this study, using a murine model with an astrocyte-directed deletion of Cx43 gene (hGFAP-cre Cx43fl/fl) and control Cx43fl/fl mice, we examined whether few HIV-infected human astrocytoma cells (U87-CD4-CCR5), microinjected into the mouse cortex, can spread toxicity and apoptosis through GJ-mediated mechanisms, into the mouse cells, which are resistant to HIV infection. In the control Cx43fl/fl mice, microinjection of HIV-infected U87-CD4-CCR5 cells led to apoptosis in 84.28 ± 6.38% of mouse brain cells around the site of microinjection, whereas hGFAP-cre Cx43fl/fl mice exhibited minimal apoptosis (2.78 ± 1.55%). However, simultaneous injection of GJ blocker, 18α-glycyrrhetinic acid, and Cx43 blocking peptide along with microinjection of HIV-infected cells prevented apoptosis in Cx43fl/fl mice, demonstrating the Cx43 is essential for HIV-induced bystander toxicity. In conclusion, our findings demonstrate that Cx43 expression, and formation of GJs is essential for bystander apoptosis during HIV infection. These findings reveal novel potential therapeutic targets to reduce astrocyte-mediated bystander toxicity in HIV-infected individuals because despite low to undetectable viral replication in the CNS, Cx channels hijacked by HIV amplify viral neuropathogenesis.

History of thyroid disease and survival of ovarian cancer patients: results from the Ovarian Cancer Association Consortium, a brief report

Abstract: Findings from in vitro studies suggest that increased exposure to thyroid hormones can influence progression of ovarian tumours. However, epidemiologic evidence on this topic is limited. We pooled data from 11 studies from the Ovarian Cancer Association Consortium. Using multivariate Cox proportional hazards models, we estimated associations between hyper- and hypothyroidism and medications prescribed for these conditions with 5-year all-cause survival among women diagnosed with invasive ovarian cancer. Overall, there was a nonsignificant association with history of hyperthyroidism (n=160 cases) and mortality (HR=1.22; 95% CI=0.97–1.53). Furthermore, diagnosis of hyperthyroidism within the 5 years before ovarian cancer diagnosis was associated with an increased risk of death (HR=1.94; 95% CI=1.19–3.18). A more modest association was observed with history of hypothyroidism (n=624 cases) and mortality (HR=1.16; 95% CI=1.03–1.31). Neither duration of hypothyroidism nor use of thyroid medications was associated with survival. In this large study of women with ovarian cancer, we found that recent history of hyperthyroidism and overall history of hypothyroidism were associated with worse 5-year survival.

Recruitment methods in a clinical trial of provoked vulvodynia: Predictors of enrollment.

Abstract: Background:Successful recruitment in clinical trials for chronic pain conditions is challenging, especially in women with provoked vulvodynia due to reluctance in discussing pain associated with sexual intercourse. The most successful recruitment methods and the characteristics of women reached with these methods are unknown.Objective:To compare the effectiveness and efficiency of four recruitment methods and to determine socioeconomic predictors for successful enrollment in a National Institutes of Health–sponsored multicenter clinical trial evaluating a gabapentin intervention in women with provoked vulvodynia.Methods:Recruitment methods utilized mass mailing, media, clinician referrals and community outreach. Effectiveness (number of participants enrolled) and efficiency (proportion screened who enrolled) were determined. Socioeconomic variables including race, educational level, annual household income, relationship status, age, menopausal status and employment status were also evaluated regarding whi...

Risk of Acute Liver Injury After Statin Initiation by Human Immunodeficiency Virus and Chronic Hepatitis C Virus Infection Status.

Abstract: Author(s): Byrne, Dana D; Tate, Janet P; Forde, Kimberly A; Lim, Joseph K; Goetz, Matthew Bidwell; Rimland, David; Rodriguez-Barradas, Maria C; Butt, Adeel A; Gibert, Cynthia L; Brown, Sheldon T; Bedimo, Roger; Freiberg, Matthew S; Justice, Amy C; Kostman, Jay R; Roy, Jason A; Lo Re, Vincent | Abstract: BackgroundPatients with human immunodeficiency virus (HIV) and/or chronic hepatitis C virus (HCV) infection may be prescribed statins as treatment for metabolic/cardiovascular disease, but it remains unclear if the risk of acute liver injury (ALI) is increased for statin initiators compared to nonusers in groups classified by HIV/HCV status.MethodsWe conducted a cohort study to compare rates of ALI in statin initiators vs nonusers among 7686 HIV/HCV-coinfected, 8155 HCV-monoinfected, 17739 HIV-monoinfected, and 36604 uninfected persons in the Veterans Aging Cohort Study (2000-2012). We determined development of (1) liver aminotransferases g200 U/L, (2) severe ALI (coagulopathy with hyperbilirubinemia), and (3) death, all within 18 months. Cox regression was used to determine propensity score-adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of outcomes in statin initiators compared to nonusers across the groups.ResultsAmong HIV/HCV-coinfected patients, statin initiators had lower risks of aminotransferase levels g200 U/L (HR, 0.66 [95% CI, .53-.83]), severe ALI (HR, 0.23 [95% CI, .12-.46]), and death (HR, 0.36 [95% CI, .28-.46]) compared with statin nonusers. In the setting of chronic HCV alone, statin initiators had reduced risks of aminotransferase elevations (HR, 0.57 [95% CI, .45-.72]), severe ALI (HR, 0.15 [95% CI, .06-.37]), and death (HR, 0.42 [95% CI, .32-.54]) than nonusers. Among HIV-monoinfected patients, statin initiators had lower risks of aminotransferase increases (HR, 0.52 [95% CI, .40-.66]), severe ALI (HR, 0.26 [95% CI, .13-.55]), and death (HR, 0.19 [95% CI, .16-.23]) compared with nonusers. Results were similar among uninfected persons.ConclusionsRegardless of HIV and/or chronic HCV status, statin initiators had a lower risk of ALI and death within 18 months compared with statin nonusers.

History of Comorbidities and Survival of Ovarian Cancer Patients, Results from the Ovarian Cancer Association Consortium.

Abstract: Background: Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients.Methods: Among patients diagnosed with invasive ovarian carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival. Using Cox proportional hazards regression models adjusted for age at diagnosis, stage of disease, histology, and study site, we estimated pooled HRs and 95% confidence intervals to assess associations between each comorbidity and ovarian cancer outcomes.Results: None of the comorbidities were associated with ovarian cancer outcome in the overall sample nor in strata defined by histologic subtype, weight status, age at diagnosis, or stage of disease (local/regional vs. advanced).Conclusions: Histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, or neurologic diseases were not associated with ovarian cancer overall or progression-free survival.Impact: These previously diagnosed chronic diseases do not appear to affect ovarian cancer prognosis. Cancer Epidemiol Biomarkers Prev; 26(9); 1470-3. ©2017 AACR.

Effect of Early Everolimus-Facilitated Reduction of Tacrolimus on Efficacy and Renal Function in De Novo Liver Transplant Recipients: 24-Month Results for the North American Subpopulation.

Abstract: BackgroundA recent randomized phase III study of 719 de novo liver transplant recipients showed that early everolimus plus reduced-dose tacrolimus (EVR + rTAC) led to significantly better kidney function than standard TAC (TAC-C), without compromising efficacy. In that study, patients from North Ame

Relentless placoid chorioretinitis: successful long-term treatment with intravitreal triamcinolone.

Abstract: Purpose To report a case of relentless placoid chorioretinitis (ampiginous choroiditis) treated with intravitreal triamcinolone acetonide (IVTA). Methods Interventional case report. Results A 34-year-old pregnant woman with a history of poor visual acuity in her left eye, secondary to an undetermined cause, developed an acute painless central scotoma and blurred vision in the right eye. The examination revealed decreased visual acuity, active inflammatory placoid choroidal lesions in the posterior pole, and mid-periphery with sharp disk margins and normal-appearing vasculature. A diagnosis of relentless placoid chorioretinitis was made, and the patient was treated biannually with 4 mg IVTA for 3 years with visual improvement to 20/25. Although she experienced a relapse at 12 months, the episode was adequately controlled with repeat IVTA. After the sixth IVTA treatment occurring at 30 months, the decision was made to stop IVTA, ultimately facilitating the preservation of 20/25 in the right eye at 63-month follow-up. The disease course was complicated by cataract progression that was successfully treated with a cataract extraction and episodic increases in intraocular pressure which were successfully treated with timolol ophthalmic solution. Conclusion Intravitreal triamcinolone acetonide therapy represents an important alternative in the treatment of relentless placoid chorioretinitis. By avoiding the potentially significant side effects of long-term systemic corticosteroid and immunosuppressive therapies, IVTA can be an important alternative in the long-term management of this uncommon and complicated entity.

Targeted deletion of Kcne3 impairs skeletal muscle function in mice.

Abstract: KCNE3 (MiRP2) forms heteromeric voltage-gated K+ channels with the skeletal muscle-expressed KCNC4 (Kv3.4) α subunit. KCNE3 was the first reported skeletal muscle K+ channel disease gene, but the requirement for KCNE3 in skeletal muscle has been questioned. Here, we confirmed KCNE3 transcript and protein expression in mouse skeletal muscle using Kcne3-/- tissue as a negative control. Whole-transcript microarray analysis (770,317 probes, interrogating 28,853 transcripts) findings were consistent with Kcne3 deletion increasing gastrocnemius oxidative metabolic gene expression and the proportion of type IIa fast-twitch oxidative muscle fibers, which was verified using immunofluorescence. The down-regulated transcript set overlapped with muscle unloading gene expression profiles (≥1.5-fold change; P < 0.05). Gastrocnemius K+ channel α subunit remodeling arising from Kcne3 deletion was highly specific, involving just 3 of 69 α subunit genes probed: known KCNE3 partners KCNC4 and KCNH2 (mERG) were down-regulated, and KCNK4 (TRAAK) was up-regulated (P < 0.05). Functionally, Kcne3-/- mice exhibited abnormal hind-limb clasping upon tail suspension (63% of Kcne3-/- mice ≥10-mo-old vs. 0% age-matched Kcne3+/+ littermates). Whereas 5 of 5 Kcne3+/+ mice exhibited the typical biphasic decline in contractile force with repetitive stimuli of hind-limb muscle, both in vivo and in vitro, this was absent in 6 of 6 Kcne3-/- mice tested. Finally, myoblasts isolated from Kcne3-/- mice exhibit faster-inactivating and smaller sustained outward currents than those from Kcne3+/+ mice. Thus, Kcne3 deletion impairs skeletal muscle function in mice.-King, E. C., Patel, V., Anand, M., Zhao, X., Crump, S. M., Hu, Z., Weisleder, N., Abbott, G. W. Targeted deletion of Kcne3 impairs skeletal muscle function in mice.