Ascites IL-10 Promotes Ovarian Cancer Cell Migration

Abstract

Ovarian cancer (OC) ascites is an inflammatory and immunosuppressive tumor environment characterized by the presence of various cytokines, chemokines and growth factors. The presence of high concentrations of these cytokines/chemokines in ascites is associated with a more aggressive tumor phenotype. IL-10 is an immunosuppressive cytokine for which high expression has been associated with poor prognosis in some cancers. However, its role on OC tumor cells has not been explored. Therefore, the aim of the current study was to elucidate the role of ascites IL-10 on the proliferation, migration and survival of OC cell lines. Here, we show that IL-10 levels are markedly increased in patients with advanced serous OC ascites relative to serous stage I/II ascites and peritoneal effusions from women with benign conditions. Ascites and IL-10 dose-dependently enhanced the proliferation and migration of OC cell lines CaOV3 and OVCAR3 but had no effect on cell survival. IL-10 levels in ascites positively correlated with the ability of ascites to promote cell migration but not proliferation. Depletion of IL-10 from ascites markedly inhibited ascites-induced OC cell migration but was not crucial for ascites-mediated cell proliferation. Taken together, our findings establish an important role for IL-10, as a component of ascites, in the migration of tumor cells.

https://ift.tt/2uGE1o5

Efficacy of Osimertinib in EGFR -Mutated Non-Small Cell Lung Cancer with Leptomeningeal Metastases Pretreated with EGFR-Tyrosine Kinase Inhibitors

Abstract

Background

The prognosis of patients with non-small cell lung cancer (NSCLC) who develop leptomeningeal metastasis (LM) is poor.

Objective

To assess the clinical efficacy of osimertinib, a third-generation tyrosine-kinase inhibitor (TKI), in patients with epidermal growth-factor receptor (EGFR)-mutated NSCLCs and LM.

Patients and Methods

Retrospective study of NSCLC patients with osimertinib-treated EGFR-mutated NSCLC and LM.

Results

Twenty patients (mean age, 61.2 years; 70% women) with adenocarcinoma NSCLC were included in the study. EGFR mutations were reported in exons 18 (n = 2), 19 (n = 7), and 21 (n = 11). Before starting osimertinib, patients had received a mean of 2.3 treatment lines. When LM was diagnosed, all patients had clinical symptoms. Sixteen (80%) patients had a performance status ≥2. At osimertinib initiation, 13 (65%) patients harbored the EGFR-T790M–resistance mutation. Osimertinib was started at 80 (n = 17), 160 (n = 2), or 40 mg/day (n = 1). All 13 (100%) patients with the T790M mutation and 4 (57%) of those without it obtained clinical responses. Among the 11 radiologically assessable patients, 9 (82%) responded, with 5 responses reported within 15 days after treatment initiation. Median overall survival and progression-free survival were 18.0 and 17.2 months, respectively, from the start of osimertinib.

Conclusions

In this non-selected population, osimertinib had remarkable efficacy in NSCLC patients with LM irrespective of the presence of the EGFR-T790M–resistance mutation. Osimertinib efficacy was rapid in several patients, even some with poor performance status.

https://ift.tt/2JM6HAE

Supporting self-management in palliative care throughout the cancer care trajectory

Purpose of review Despite increased survivorship and the subsequent need for chronic management of cancer, the association of self-management and palliative care is still emerging within cancer care. Routine and timely use of self-management strategies in the palliative setting can help reduce self-management burden and maximize quality of life. In this review, we consider the complementary relationship of self-management and palliative care and how they support living with cancer as a chronic illness. Recent findings Recent studies provide evidence of support among patients, family caregivers and healthcare professionals for integration of self-management interventions into palliative cancer care. As a guiding framework, components of the revised Self and Family Management Framework correspond to the provision of palliative care across the care trajectory, including the phases of curative care, palliative care, end-of-life care and bereavement. Additional work among self-management partners facing cancer and other life-limiting illnesses, that is patients, family caregivers and healthcare professionals, would be useful in developing interventions that incorporate self-management and palliative care to improve health outcomes. Summary There is an increasing acceptance of the complementarity of self-management and palliative care in cancer care. Their integration can support patients with cancer and their family caregivers across the care trajectory. Correspondence to Dena Schulman-Green, Yale School of Nursing, P.O. Box 27399, West Haven, CT 06516, USA. Tel: +1 203 785 7623; e-mail: dena.schulman-green@yale.edu Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2Le3orq

Headache in an Uzbekistani Immigrant: A Startling Diagnosis

No abstract available

https://ift.tt/2LhYWb6

All in The Name of Vanity: An Unanticipated Outcome of Mycobacterium abscessus Infection

We report a case of refractory skin abscesses caused by Mycobacterium abscessus resulting from cosmetic surgery. A 25-year-old woman developed recurrent cutaneous infection caused by M. abscessus after multiple cosmetic surgeries in the Dominican Republic. Despite of the removal of infected implants, she failed a 20-month treatment with azithromycin, cefoxitin, and amikacin. The patient presented to our institution 28 months after the initial surgeries and approximately 5 months after initiation of her latest antimicrobial regimen of azithromycin, imipenem, and amikacin. Here, she was restarted on cefoxitin 2 g daily, amikacin 750 mg daily, and azithromycin 1000 mg daily. She completed an additional 4 months (a total of 9 months) of therapy with complete clinical resolution. In conclusion, clinical suspicion of M. abscessus infection is essential for the diagnosis. Patient compliance is integral to a successful outcome because the treatment involves prolonged duration, continuous intravenous antibiotics, and multiple potential adverse effects. Correspondence to: George M. Abraham, MD, MPH, FACP, FIDSA, Department of Medicine, Saint Vincent Hospital, University of Massachusetts Medical School, Worcester, MA. E-mail: george.abraham@stvincenthospital.com. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2LhYCJq

Long-Term Safety of Tedizolid in a Patient With Spondilodiscitis After Switch From Linezolid Due to Toxicity

The patient is a 57-year-old man with liver cirrhosis, Bricker anastomosis after a radical cystoprostatectomy and, a history of bacteremias caused by extended-spectrum β-lactamase–positive Escherichia coli, Enterococcus faecium, and Candida albicans. He presented with persistent low back pain and was diagnosed with vertebral osteomyelitis, for which he received ertapenem-linezolid treatment. However, after 20 days, linezolid had to be discontinued because of myelotoxicity and metabolic acidosis. The patient was switched to tedizolid, which, in combination with ertapenem, was successfully given for 114 days until biopsy showed no growth of gram-positive cocci. We conclude that tedizolid can be an alternative to linezolid in case of toxicity, especially in long-term treatments. Correspondence to: Rosa Maria Martínez Álvarez, MD, PhD, Infectious Diseases Unit, Antimicrobial Stewardship, Internal Medicine Department, Miguel Servet University Hospital, Avenida Isabel La Católica 1-3, 50009 Zaragoza, Spain. E-mail: rmartineza@salud.aragon.es. The authors have no conflicts of interest to disclose. Editorial assistance was provided by Content Ed Net, Madrid, Spain. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2JKwARs

Urban-Acquired Leptospirosis in Washington, DC: A Case Report and Review of the Literature

Leptospirosis is rarely reported in the United States. Although primarily considered a disease of the tropics or of resource limited areas, leptospirosis is being reported more frequently in industrialized urban areas. We report a case of severe leptospirosis in a man living in Washington, DC, with occupational exposure to rats. A review of the literature was conducted, with a focus on the urban form of the disease, using the MEDLINE database from inception to May 2018. Correspondence to: Andrea Lerner, MD, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Dr, Bldg 40, Room 3608B, Bethesda, MD 20892. E-mail: Andrea.Lerner@nih.gov. The authors have no funding and conflicts of interest to disclose. This article has been seen, reviewed, and approved by all contributing authors; has not been previously published; and is not under consideration for publication elsewhere. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2LeSdiv

Nocardia nova Tenosynovitis and Abscess After a Remote Gunshot Wound

Nocardia nova is a less commonly isolated Nocardia species that was formerly classified as belonging to the Nocardia asteroides complex. This organism is a rare cause of primary cutaneous nocardiosis. We report a case of N. nova flexor tenosynovitis and abscess involving the right forearm after a remote inoculation injury. Correspondence to: Kathleen A. Linder, MD, Infectious Diseases Section, VA Ann Arbor Healthcare System, 2215 Fuller Rd, Ann Arbor, MI 48105. E-mail: linderk@med.umich.edu. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2LCHTga

Neuroinvasive Seronegative West Nile Virus in the Setting of R-CHOP Chemotherapy for Diffuse Large B-Cell Lymphoma

West Nile virus (WNV) is a mosquito-borne infectious disease that can produce potentially life-threatening meningoencephalitis in immunocompromised individuals. In 2017, there were 536 human cases of WNV in California, with 43 fatalities reported to the California Department of Public Health. Peak mosquito transmission periods are in the late summer and early fall when mosquitoes are maximally viremic. In addition to risk factors such as advanced age, malignancy, or prior organ transplantation, the probability of progression to severe, neuroinvasive disease has been reported to be significantly higher in individuals suffering from lymphoma receiving rituximab in addition to other oncologic treatments. Here, we describe the case of a patient who recently received chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone for diffuse large B-cell lymphoma, complicated by meningoencephalitis due to seronegative neuroinvasive WNV infection, ultimately resulting in death. Correspondence to: Alexander D. Yuen, BA, BS, Department of Medicine, UCLA/VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd, Los Angeles, CA 90073. E-mail: adyuen@mednet.ucla.edu. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2LeLIfj

Disseminated Adenovirus Disease Presenting as Septic Shock in an Immunocompetent Pubertal Girl

Adenovirus is a common cause of respiratory illness in childhood and is associated with approximately 5% to 15% of upper and lower respiratory tract infections. Immunocompetent individuals usually have a mild and self-limited disease course, with syndromes typically including pharyngitis, bronchiolitis, keratoconjunctivitis, otitis media, and gastroenteritis. Neurologic manifestations in immunocompetent children are less common and include aseptic meningitis, myelitis, subacute focal encephalitis, seizures, paralysis, and Reye-like syndrome. Disseminated adenovirus disease is rare in immunocompetent children, occurring in approximately 1% to 1.5% of all cases of adenovirus infection compared with a 12.5% occurrence rate in immunocompromised children. Furthermore, to the best of our knowledge, disseminated adenovirus disease causing a severe sepsis–like picture in an immunocompetent child has only been described in 1 published report. Here, we present a case of a previously healthy pubertal girl who presented in severe hypotensive shock and who subsequently had adenovirus DNA detected from the cerebrospinal fluid and no other etiology identified. Correspondence to: Sofya Maslyanskaya, MD, Division of Adolescent Medicine, Children's Hospital at Montefiore and Albert Einstein College of Medicine, 3415 Bainbridge Ave, Bronx, NY 10467. E-mail: smaslyan@montefiore.org. The authors of this article have no sources of support to claim and have not received funding of any kind for this work. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2JMdwCt

Successful Daptomycin Therapy for Postsurgical Shoulder Arthritis With Propionibacterium acnes

No abstract available

https://ift.tt/2LhZ9eo

Hypertrophic Herpes Simplex—Pseudocarcinoma

Individuals with human immunodeficiency virus (HIV) are commonly coinfected with herpes simplex virus type 2 (HSV-2) and human papilloma virus (HPV). Herpes simplex virus type 2 in HIV-infected individuals can present as atypical hypertrophic lesions, and HPV-induced malignant lesions can present as atypical hyperkeratotic lesions. We report a case of an atypical hypertrophic HSV-2 lesion in a well-managed HIV-infected male with a history of nonmalignant Buschke-Lowenstein tumor (giant condyloma) of HPV and squamous cell carcinoma of the scrotum. Determining the definitive diagnosis of hypertrophic HSV-2 in this patient was confounded by the macroscopic clinical presentation of the proliferative lesion and by the patient's history of squamous cell carcinoma, in the same perineal region. Knowledge of hypertrophic HSV-2 is imperative when considering the etiologic agent of anogenital lesions in HIV-infected individuals. Correspondence to: Laura R. Parker, BA, Rutgers Robert Wood Johnson Medical School, 675 Hoes Lane W, Piscataway Township, NJ 08854. E-mail: lrp87@rwjms.rutgers.edu. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2LGlsGY

Acupuncture-Associated Mycobacterium goodii Infection of Prosthetic Knee Joint

Mycobacterium goodii is rarely associated with prosthetic joint infections. We report a case of M. goodii septic arthritis in an adult with a prosthetic knee–associated diagnosis subsequent to acupuncture. In patients with prosthetic joint replacements receiving acupuncture therapy, one should consider avoiding insertions near these joints. Correspondence to: Roshan J. Lewis, MD, 1415 Woodland Ave, Suite 140, Des Moines, IA 50309. E-mail: Roshan.Lewis@unitypoint.org; Hayden L. Smith, PhD, Medical Education, UnityPoint Health—Des Moines, Des Moines, IA 50309. E-mail: hayden.smith@unitypoint.org. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2LhZ1eU

A Clinical Amalgam: Fever of Unknown Origin, Intravascular Large B-Cell Lymphoma and Hemophagocytic Lymphohistiocytosis

Infectious disease specialists are frequently called to investigate fever of unknown origin, the etiology attributed to noninfectious causes more than half the time. This reports a fever of unknown origin case of intravascular large B-cell lymphoma and secondary hemophagocytic lymphohistoiocytosis despite a negative lymph node pathology result and a myriad of investigations. Correspondence to: Mark Lacy, MD, Infectious Diseases, Department of Internal Medicine, School of Medicine, Texas Tech University, 3601 4th St, Lubbock, TX 79430. E-mail: mark.lacy@ttuhsc.edu. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2JIqFMx

Back to Basics: Deciphering a Procalcitonin Picture in Clinical Practice

The procalcitonin assay is a popular tool among antimicrobial stewardship programs. There are procalcitonin algorithms and further guidance in the medical literature to aid clinicians in decision making regarding antibiotic therapy initiation and duration. Diagnostic utility of procalcitonin levels is a matter of debate and should be interpreted only in conjunction with the context of the patient's clinical picture. Researchers present a case of ambiguous procalcitonin findings along with a stepwise approach in reviewing the medical literature. Although not listed as a common cause of false-positive procalcitonin results, it was felt that advanced non–Hodgkin lymphoma coupled with worsening renal function was ultimately the cause of this patient's elevated procalcitonin levels. Correspondence to: Jennifer L. Cole, PharmD, BCPS, BCCCP, Department of Pharmacy, Veterans Healthcare System of the Ozarks, 1100 North College Ave, Fayetteville, AR 72703. E-mail: Jennifer.cole@va.gov. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2LFLMBd

Establishing and Utilizing Strategic Partnerships for Vaccine-Preventable Diseases: Best Practices in Haiti

On March 10 to 11, 2016, the Ministère de la Santé Publique et de la Population (Ministry of Health of Haiti) and the Global Health Initiative at Henry Ford Health System hosted their Second Annual Scientific Conference entitled, "Best Practices for Establishing and Utilizing Partnerships for Vaccine-Preventable Diseases in Haiti," at the National Laboratory in Port-au-Prince, Haiti. The conference brought together Ministry of Health officials, researchers, clinicians, academics, public health professionals, and other stakeholders to discuss vaccine programs and policies in Haiti. This forum provides a learning and discussion space to fuel strategies and public health research responding to priority areas identified by the Ministry of Health, and consequently, this forum serves as counsel for the Ministry of Health in its decision making on strategies to prevent and control infectious diseases in Haiti. The following article summarizes the presentations and conclusions of the March 2016 conference and covers a variety of important issues relating to vaccines and vaccine-preventable diseases in Haiti, including Haiti's Expanded Program on Immunization, surveillance, logistical and funding challenges, and community approaches, as well as case studies detailing introduction of the pentavalent, rotavirus, oral cholera, and human papillomavirus vaccines in Haiti. Most importantly, this article highlights a model for effective partnerships for vaccines, a model that can transcend response to specific diseases and apply to all global health partnerships. Correspondence to: Dana M. Parke, BA, 440 Burroughs, Ste 229, Detroit, MI 48202. E-mail: dparke1@hfhs.org. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2LhYQjK

Evaluation of Clostridium Bacteremia in the Cancer Population: A Case Series

Introduction Clostridium species are gram-positive or gram-variable anaerobic organisms that have been known to cause different kinds of infections of varying scope and severity. Clostridium species have been associated with high in-hospital mortality rates, particularly in immunocompromised patients with malignancies. Despite the potential severity of these infections in the oncologic population, primary literature on the topic is relatively scarce. Methods A retrospective chart review was performed to identify all patients older than 18 years with positive Clostridium species blood cultures at the H. Lee Moffitt Cancer Center and Research Institute from April 10, 2005, to September 30, 2016. Data were analyzed to identify underlying risk factors, clinical presentation, and treatment of Clostridium bacteremia in the cancer population. Results A total of 18 patients had bacteremia with Clostridium species. The patients' ages ranged from 26 to 79 years (median, 62.5 years), and 6 of the patients were female (33%). The predominant Clostridium species in our sample was Clostridium perfringens, which was found in 7 patients (38%), followed by Clostridium septicum found in 4 patients (22%). A gastrointestinal source was identified in 11 patients (66%). Three patients died of the infection (16%). Conclusions The potential severity of Clostridium infections in the oncologic population warrants a thorough evaluation in every patient with positive blood cultures, with focus on the gastrointestinal tract as a potential source of infection. Further studies about susceptibility testing would provide valuable information and may serve to reduce mortality rates among patients with Clostridium bacteremia. Correspondence to: John N. Greene, MD, FACP, H. Lee Moffitt Cancer Center, 12902 Magnolia Dr, FOB-3, Tampa, FL 33612. E-mail: John.Greene@moffitt.org. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2JRaNYs

A Fatal Case of Hemophagocytic Lymphohistiocytosis in a Patient With Ehrlichiosis

We present a case of Ehrlichia-induced hemophagocytic lymphohistiocytosis (HLH), which resulted in a fatal outcome. Hemophagocytic lymphohistiocytosis is a rare syndrome of abnormal activation of the cellular immune system, which can be potentially fatal. Infections are a common trigger of the secondary form of the syndrome. We review the literature for published reports of Ehrlichia-induced HLH, all of which have resulted in a favorable outcome. We try to analyze the reasons for the poor outcome in our case including the possibility of central nervous system involvement with HLH. Early recognition and treatment of HLH and its associated central nervous system involvement may improve outcome. Correspondence to: Jad A. Khoury, MD, 621 S New Ballas Rd, Suite 7018-B, St Louis. MO 63141. E-mail: jad.khoury@mercy.net. The authors have no funding or conflicts of interest to disclose. All authors have contributed equally to this article. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2LhYJok

Liposomal Amphotericin B–Associated Cardiac Arrest: Case Report and Literature Review

Liposomal amphotericin B (L-AmB) was developed with the intent to minimize the adverse effects associated with amphotericin B deoxycholate, especially nephrotoxicity. Although there has been a substantial decrease in adverse effects with L-AmB compared with its predecessor, there is a small body of evidence suggesting its association with cardiovascular adverse events. We report a case of L-AmB-associated cardiac arrest in a patient with preexisting cardiac-related disease states. In addition, we review currently available literature regarding cardiac-related adverse events associated with L-AmB. When the Naranjo Adverse Drug Reaction Probability Scale was applied to this case, the probability of association was determined as possible. This case adds to a small but important body of literature regarding L-AmB–associated cardiotoxicity. Moreover, a review of the available literature indicates that providers should be aware of the potential for cardiac adverse events with L-AmB. Correspondence to: Marcus Tad Autry, PharmD, BCPS, PGY2 Ambulatory Care Pharmacy Residency, College of Pharmacy, University of Oklahoma, 1122 NE 13th St, Suite 2301A, Oklahoma City, OK 73117. E-mail: Marcus-Autry@ouhsc.edu. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2JMMCtZ

Pseudomonas japonica: A Novel Cause of Bacteremia and Skin and Soft Tissue Infection

No abstract available

https://ift.tt/2LGgqKC

Candida parapsilosis Lumbar Spondylodiscitis as a Cause of Chronic Back Pain

Vertebral bone infections caused by Candida species are uncommon, but their reported frequency is increasing. Candida parapsilosis, a commensal of human skin, is currently an emerging human pathogen, with increasing prevalence and medical significance. We report the case of a Caucasian man who presented with C. parapsilosis spondylodiscitis, who was having a persistent low back pain for 3 months before diagnosis. He had no history of immunosuppression, fever, or elevation of inflammatory markers. The diagnosis was made by fine needle aspiration and culture. A combined medical and surgical intervention was necessary to achieve the best outcome in our case. Correspondence to: Teresa Khoo, MD, Department Infectious Diseases, Stony Brook University Hospital, Stony Brook, NY 11753. E-mail: Teresa.Khoo@stonybrookmedicine.edu. The authors have no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2LDFTnL

Zika Virus–Associated Guillain-Barré Syndrome in a Returning US Traveler

Zika virus (ZIKV) infection has been associated with Guillain-Barré syndrome (GBS). Roughly 60% of people in countries such as the United States live in areas at risk of seasonal spread of ZIKV. Zika virus belongs to a class of diseases that is not typically seen in hospital settings across the United States and Europe. We describe the case presentation, management, and treatment of ZIKV infection complicated by GBS. A 64-year-old woman with recent travel to the Dominican Republic presented with rash followed by an acute, ascending polyneuropathy consistent with GBS. She was confirmed to have an acute ZIKV infection by detection of ZIKV nucleic acid by reverse transcription–polymerase chain reaction. She met Brighton Collaboration criteria level 1 evidence for GBS. She received 2 courses of intravenous immunoglobulin and slowly improved, but still had weakness at discharge. More research is needed to identify the pathophysiology behind ZIKV-associated GBS and its optimal treatment. Prevention is fundamental to limiting infection and spread of ZIKV. Correspondence to: Anna Nolan, MD, MS, Division of Pulmonary, Critical Care and Sleep, New York University School of Medicine, New Bellevue, 7N Room 24, 462 1st Ave, New York, NY 10016. E-mail: anna.nolan@med.nyu.edu. All authors were involved in the data collection and analysis and review of the literature. All authors participated in writing and revision of the report and approval of the final version. Source(s) of Support: NIH/NHLBI R01HL119326. The authors have no conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2LenDFw

Plesiomonas shigelloides Gastroenteritis from Freshwater Ingestion in Western Pennsylvania

Plesiomonas shigelloides is a rare etiologic agent of bacterial gastroenteritis. Since the year 2000, there is only one published case report of P. shigelloides gastroenteritis. Presented here is a case reporting the typical presentation and successful oral antibiotic treatment of a rarely reported cause of gastroenteritis in the United States, after ingestion of freshwater from a stream in western Pennsylvania. Correspondence to: Vincent Peyko, PharmD, BCPS, St Elizabeth Hospital—Boardman, 8401 Market St, Boardman, OH 44512. E-mail: vpeyko@neomed.edu. The author has no funding or conflicts of interest to disclose. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2JLBbTi

Response to "Doctors share responsibility for damaging discourse" [Letters]

https://ift.tt/2JLFTka

Woodys last dance [Humanities]

https://ift.tt/2LiR0Xm

Doctors top list of worst drivers for fifth straight year [News]

https://ift.tt/2JLdmed

Self-determination and data control vital to Indigenous health research [News]

https://ift.tt/2LiczHB

Use physician-rating websites with caution [Letters]

https://ift.tt/2JIicZL

How medical school debt shapes the health workforce [News]

https://ift.tt/2LepFpc

The authors respond to "Fueling the culture of distrust in doctors" [Letters]

https://ift.tt/2JNGUYL

Vesiculobullous cutaneous larva migrans in a 29-year-old man, diagnosed using teledermatology [Practice]

https://ift.tt/2Li04vo

Metabolic cardiomyopathy from propionic acidemia precipitating cardiac arrest in a 25-year-old man [Practice]

https://ift.tt/2LEYfVG

Development and validation of a cardiovascular disease risk-prediction model using population health surveys: the Cardiovascular Disease Population Risk Tool (CVDPoRT) [Research]

BACKGROUND:

Routinely collected data from large population health surveys linked to chronic disease outcomes create an opportunity to develop more complex risk-prediction algorithms. We developed a predictive algorithm to estimate 5-year risk of incident cardiovascular disease in the community setting.

METHODS:

We derived the Cardiovascular Disease Population Risk Tool (CVDPoRT) using prospectively collected data from Ontario respondents of the Canadian Community Health Surveys, representing 98% of the Ontario population (survey years 2001 to 2007; follow-up from 2001 to 2012) linked to hospital admission and vital statistics databases. Predictors included body mass index, hypertension, diabetes, and multiple behavioural, demographic and general health risk factors. The primary outcome was the first major cardiovascular event resulting in hospital admission or death. Death from a noncardiovascular cause was considered a competing risk.

RESULTS:

We included 104 219 respondents aged 20 to 105 years. There were 3709 cardiovascular events and 818 478 person-years follow-up in the combined derivation and validation cohorts (5-year cumulative incidence function, men: 0.026, 95% confidence interval [CI] 0.025–0.028; women: 0.018, 95% 0.017–0.019). The final CVDPoRT algorithm contained 12 variables, was discriminating (men: C statistic 0.82, 95% CI 0.81–0.83; women: 0.86, 95% CI 0.85–0.87) and was well-calibrated in the overall population (5-year observed cumulative incidence function v. predicted risk, men: 0.28%; women: 0.38%) and in nearly all predefined policy-relevant subgroups (206 of 208 groups).

INTERPRETATION:

The CVDPoRT algorithm can accurately discriminate cardiovascular disease risk for a wide range of health profiles without the aid of clinical measures. Such algorithms hold potential to support precision medicine for individual or population uses. Study registration: ClinicalTrials.gov, no. NCT02267447

https://ift.tt/2LjorJe

A call to mandate patient access to personal primary care medical records across Canada [Commentary]

https://ift.tt/2LJRhys

Mendelian randomization with a binary exposure variable: interpretation and presentation of causal estimates

Abstract

Mendelian randomization uses genetic variants to make causal inferences about a modifiable exposure. Subject to a genetic variant satisfying the instrumental variable assumptions, an association between the variant and outcome implies a causal effect of the exposure on the outcome. Complications arise with a binary exposure that is a dichotomization of a continuous risk factor (for example, hypertension is a dichotomization of blood pressure). This can lead to violation of the exclusion restriction assumption: the genetic variant can influence the outcome via the continuous risk factor even if the binary exposure does not change. Provided the instrumental variable assumptions are satisfied for the underlying continuous risk factor, causal inferences for the binary exposure are valid for the continuous risk factor. Causal estimates for the binary exposure assume the causal effect is a stepwise function at the point of dichotomization. Even then, estimation requires further parametric assumptions. Under monotonicity, the causal estimate represents the average causal effect in 'compliers', individuals for whom the binary exposure would be present if they have the genetic variant and absent otherwise. Unlike in randomized trials, genetic compliers are unlikely to be a large or representative subgroup of the population. Under homogeneity, the causal effect of the exposure on the outcome is assumed constant in all individuals; rarely a plausible assumption. We here provide methods for causal estimation with a binary exposure (although subject to all the above caveats). Mendelian randomization investigations with a dichotomized binary exposure should be conceptualized in terms of an underlying continuous variable.

https://ift.tt/2uV6llO

Novel Therapeutic Options in Treatment of Idiopathic Inflammatory Myopathies

Abstract

Purpose of review

The purpose of this review is to update the audience on the recent progress in the treatment of idiopathic inflammatory myopathies, highlighting a myriad of treatment trials aimed at slowing down progression of muscle weakness and/or skin involvement in idiopathic inflammatory myopathies.

Recent findings

Myositis continues to be an active area of clinical and translational research. Through the work of a number of investigators, we now have a much better understanding of the pathogenesis underlying the various myositides. The role of T cells, B cells, and dendritic cells has been better defined in dermatomyositis and inclusion body myositis. The role of autoantibodies has been better elucidated, with the recognition that autoantibodies play an important role in not only establishing the diagnosis but also helping with prognostication and choosing treatment paradigms. A number of new treatment trials were designed to alter the pathogenic factors, including T cell activation, docking, and signaling, cytokines, B cell signaling, B cell depletion, as well as targeting Toll-like receptors (TLRs). Myostatin inhibitors have been developed and tried in inclusion body myositis (IBM) in hopes that they would stop muscle atrophy and improve muscle strength and function.

Summary

This review will outline the progress made to date in the treatment of idiopathic inflammatory myopathies.

https://ift.tt/2uZAYqu

Neural sensitivity to natural texture statistics in infancy

Developmental Psychobiology, EarlyView.


https://ift.tt/2uGSqRd

Triple-negative and HER2 positive ductal carcinoma in situ of the breast: characteristics, behavior, and biomarker profile

Abstract

We compared the characteristics, clinical behavior, and biomarker profile between HER2 positive (HER2+) and triple-negative (TN) ductal carcinoma in situ (DCIS) which are considered more aggressive than other DCIS subtypes. In addition, we explored the impact of these features on its potential of progression to invasive breast carcinomas. Cases of DCIS diagnosed at the Department of Pathology, Singapore General Hospital from 1994 to 2010 were identified. TN and HER2+ DCIS cases formed the study cohort. Immunohistochemistry (IHC) was performed for ER, PR, HER2, CK14, EGFR, and p53. Comparisons of clinicopathological features, IHC results, and clinical outcomes were performed between the two groups. We evaluated 145 HER2+ and 85 TN DCIS cases. HER2 positive DCIS had significantly higher nuclear grade (p < 0.001) and more frequent necrosis (p < 0.001) than TN DCIS. HER2 positive DCIS also harbored significantly higher rates of nuclear p53 immunoreactivity (p = 0.002) than TN DCIS. Younger patients (age < 40) with HER2+ and TN DCIS demonstrated statistically significant worse invasive DFS than older women (p < 0.001). Multivariate cox regression analysis (HR 15.08, 95% CI 12.79–81.45, p = 0.002) also confirmed these findings. In addition, younger patients (age < 40) with HER2+ DCIS experienced significantly poorer prognosis when p53 was also positive (p = 0.033). HER2+ DCIS had more aggressive pathological characteristics compared to TN DCIS; accumulation of mutant p53 could possibly be contributory. Age was an independent predictor of aggressive biological behavior of HER2+ and TN DCIS. We demonstrated that younger patients with p53 positive HER2+ DCIS had significantly adverse clinical outcome.

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25-hydroxyvitamin D serum levels in patients with high risk resected melanoma treated in an adjuvant bevacizumab trial

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Routine blood investigations have limited utility in surveillance of aggressive lymphoma in asymptomatic patients in complete remission

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A machine learning approach to radiogenomics of breast cancer: a study of 922 subjects and 529 DCE-MRI features

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Angiopoietin-like protein 3 blocks nuclear import of FAK and contributes to sorafenib response

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EMCrit Wee – The Great Beta-Blocker for Cocaine Toxicity Slugfest

Is it safe to use beta-blockers in cocaine toxicity and is that even the questions...

EMCrit Project by Scott Weingart.

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Tackling the quandary of the late-night call to increase retention

Our co-hosts discuss a recent article on the topic of late-night fatigue in EMS and how addressing those issues can lead to increased retention rates in the industry

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How to recover mentally and emotionally after an act of mass violence

For emergency responders, trauma from an act of mass violence can create a cyclical pattern of negative thinking

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Data: Behavioral emergencies are frequent, complex responses for EMS

EMS responses to psychiatric or behavioral emergencies are frequent, but violence, physical restraint and chemical restraint are rare

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AAA study sets a benchmark for turnover in the EMS industry

Voluntary turnover and involuntary turnover of part-time and full-time EMS providers was studied to determine the overall EMS turnover rate

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How to use tax incentives to boost EMS recruitment

Tax incentives are one way to incentivize volunteer EMS professionals for agencies struggling with EMS recruitment and retention

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5 tips for starting and sustaining a career in EMS

You may be surprised to treat more psych than critical patients, but protect the ABCs and you'll be off to a great start in a career in EMS

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What is vicarious trauma and how to prevent it in EMS

Moderating exposure to secondary trauma and practicing self-care can help EMTs and paramedics avoid PTSD

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Should nonviolent, convicted felons be accepted into the EMS field?

Our co-hosts discuss a recent article detailing possible legislation in California that would allow nonviolent, convicted felons to enter the EMS field

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Fix the late call conundrum to improve retention

Two Australian paramedics are under investigation for refusing a late call assignment because of fatigue

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Addressing leadership and caregiver bias in EMS

The EMS leader's task is to recognize and reduce negative impacts of bias as much as possible

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EMS From a Distance: Upgrading EMS

Changing a fragmented industry from the bottom up

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What is a system?

Featuring systems-level questions that help to identify high-functioning STEMI systems of care

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Understanding the mindset of a paramedic student

Our co-hosts talk with paramedic student Reagan DeLuca about the process of learning and how confident he feels in his knowledge

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Convicted felons as EMTs?

California legislation proposes former inmates as emergency medical technicians

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Training Day: Video laryngoscopes for increased intubation success

Ensure your EMS providers understand when to use video laryngoscopes and airway anatomy, and practice their intubation skills

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Did a canceled drug trial strain the relationship between police and EMS?

Our co-hosts discuss a recent article about a pulled drug trial in Minnesota and its implication for local emergency responders

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How EMS data is being used to measure value, improve patient care

Two agencies share innovative ways to use data to improve performance, as well as measure and report the value EMS providers offer to their patients, agencies and communities

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STEMI benchmarks in EMS care

EMS benchmarks can help drive STEMI care improvements through data-driven improvements and hospital collaboration

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A Video Surveillance System to Monitor Breeding Colonies of Common Terns (Sterna Hirundo)

This paper describes a protocol that uses a remote video monitoring surveillance system to continuously monitor breeding colonies of ground-nesting waterbirds. The system includes five cameras monitoring individual nests and one camera monitoring the colony as a whole, and is powered by car batteries that are recharged via solar panels.

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Axial Lumbar and Lumbosacral Interbody Fusion for Degenerative Spinal Conditions and Adult Deformity: Surgical Technique and Supporting Evidence

Publication date: Available online 22 July 2018

Source: Seminars in Spine Surgery

Author(s): Raj J. Gala, Peter G. Whang

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Protective Effects of Rhubarb in Rats with Acute Pancreatitis and the Role of Its Active Compound Rhein on Mitochondria of Exocrine Cells

Da-Cheng-Qi-Decoction (DCQD) has been used in the treatment of acute pancreatitis (AP) in China for many years. The aim of the current study was to examine the principal ingredient rhubarb of DCQD and its potential link to the pancreatic repair effects in rats with AP. The pancreatitis was induced in SD rats by intraperitoneal injections of cerulein. The results showed that rhubarb significantly increased blood perfusion of pancreatic tissue, reversed mitochondrial damage, and promoted pancreatic acinar and stellate cell proliferation. In addition, the rhein (from rhubarb) had high distribution in pancreas tissue and protected mitochondria in AR42J cells via the activation of PI3K/AKT/mTOR signaling pathway and activity inhibition of AMPK (P

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Blood Biochemical and Hematological Study after Subacute Intravenous Injection of Gold and Silver Nanoparticles and Coadministered Gold and Silver Nanoparticles of Similar Sizes

Background. To investigate the effect of subacute intravenous administration AgNP (silver nanoparticles, 10 nm) and AuNP (gold nanoparticles, 12.8 nm) and AgNP/AuNP mixture to blood biochemistry, hematology, and platelet coagulation, subacute toxicity study was conducted. Methods. AuNP and AgNP in which their size distribution was not statistically different, mixed or separate, were injected into the caudal vein of male Sprague-Dawley rats for 4 weeks. The rats were allowed to recover for a further 4 weeks in order to examine systemic toxicity expressed in the blood biochemistry and hematology. The dose groups (5 males per group for the administration and 3 males for the recovery) consisted of 7 divisions, i.e., control, AgNP (with a low dose of 10 μg/kg/day and a high dose of 100 μg/kg/day), AuNP (with a low dose of 10 μg/kg/day and a high dose of 100 μg/kg/day), and mixed AgNP/AuNP (with a low dose of 10/10 μg/kg/day and a high dose of 100/100 μg/kg/day). Results. There were no significant dose-related changes in the hematology and blood biochemical values for the rats. Coagulation time in terms of the active partial thromboplastin time (APTT) and prothrombin time (PT) did not show any significant changes, when compared to the control group. Conclusion. The subacute injection of AuNP and AgNP or their mixture did not induce any noticeable systemic toxicity.

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A Dendritic Cell-Targeted Adenoviral Vector Facilitates Adaptive Immune Response Against Human Glioma Antigen (CMV-IE) and Prolongs Survival in a Human Glioma Tumor Model.

Related Articles

A Dendritic Cell-Targeted Adenoviral Vector Facilitates Adaptive Immune Response Against Human Glioma Antigen (CMV-IE) and Prolongs Survival in a Human Glioma Tumor Model.

Neurotherapeutics. 2018 Jul 19;:

Authors: Kim JW, Kane JR, Panek WK, Young JS, Rashidi A, Yu D, Kanojia D, Hasan T, Miska J, Gómez-Lim MA, Ulasov IV, Balyasnikova IV, Ahmed AU, Wainwright DA, Lesniak MS

Abstract
Antitumor immunotherapeutic strategies represent an especially promising set of approaches with rapid translational potential considering the dismal clinical context of high-grade gliomas. Dendritic cells (DCs) are the body's most professional antigen-presenting cells, able to recruit and activate T cells to stimulate an adaptive immune response. In this regard, specific loading of tumor-specific antigen onto dendritic cells potentially represents one of the most advanced strategies to achieve effective antitumor immunization. In this study, we developed a DC-specific adenoviral (Ad) vector, named Ad5scFvDEC205FF, targeting the DC surface receptor, DEC205. In vitro analysis shows that 60% of DCs was infected by this vector while the infectivity of other control adenoviral vectors was less than 10%, demonstrating superior infectivity on DCs. Moreover, an average of 14% of DCs were infected by Ad5scFvDEC205FF-GFP, while less than 3% of non-DCs were infected following in vivo administration, demonstrating highly selective in vivo DC infection. Importantly, vaccination with this vehicle expressing human glioma-specific antigen, Ad5scFvDEC205FF-CMV-IE, shows a prolonged survival benefit in GL261CMV-IE-implanted murine glioma models (p < 0.0007). Furthermore, when rechallenged, cancerous cells were completely rejected. In conclusion, our novel, viral-mediated, DC-based immunization approach has the significant therapeutic potential for patients with high-grade gliomas.

PMID: 30027430 [PubMed - as supplied by publisher]

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Antitumor Effects of DC Vaccine With ALA-PDT-Induced Immunogenic Apoptotic Cells for Skin Squamous Cell Carcinoma in Mice.

Related Articles

Antitumor Effects of DC Vaccine With ALA-PDT-Induced Immunogenic Apoptotic Cells for Skin Squamous Cell Carcinoma in Mice.

Technol Cancer Res Treat. 2018 Jan 01;17:1533033818785275

Authors: Zhang H, Wang P, Wang X, Shi L, Fan Z, Zhang G, Yang D, Bahavar CF, Zhou F, Chen WR, Wang X

Abstract
Targeted immunotherapy using dendritic cell vaccine has been employed for the treatment of solid tumors. Topical 5-aminolevulinic acid-mediated photodynamic therapy, an established approach for topical cancers, can induce an effective antitumor immune response. We have previously shown that 5-aminolevulinic acid-mediated photodynamic therapy-induced tumor lysates could considerably enhance antigen-presenting capacity of ex vivo-generated dendritic cells. The current study further demonstrates that 5-aminolevulinic acid-mediated photodynamic therapy dendritic cell vaccine can induce immune responses against cancers. Dendritic cells pulsed by photodynamic therapy-treated skin squamous cell carcinoma cells inhibited squamous cell carcinoma to a greater extent than tumor lysates treated by photodynamic therapy alone or dendritic cells pulsed by freeze-thawed treated tumor cells. Immunohistochemistry showed that photodynamic therapy dendritic cell vaccine could increase the activity of CD4+ and CD8+ T cells in the tumor implantation sites. Flow cytometry assays showed that CD4+ and CD8+ T cells in the spleens of photodynamic therapy dendritic cell vaccine immunized mice increased significantly. Furthermore, we observed increased amounts of interleukin 12 and Interferon gamma (IFN-γ) and decreased amounts of interleukin 10 in the splenocytes and peripheral blood of photodynamic therapy dendritic cell vaccine immunized mice by enzyme linked immunosorbent assay (ELISA). Taken together, our findings suggest that photodynamic therapy dendritic cell vaccination is an effective prophylactic therapy for squamous cell carcinoma.

PMID: 30025490 [PubMed - in process]

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Upregulation of the Long Noncoding RNA SNHG3 Promotes Lung Adenocarcinoma Proliferation

Lung cancer is the leading cause of cancer-associated mortalities worldwide. Non-small-cell lung cancer (NSCLC) is the main reason for cancer-relevant death and constitutes 80% of lung cancer cases. Long noncoding RNAs (lncRNAs) have been found to be related to different kinds of cancer. Long noncoding RNAs played important roles in regulating the pathological and physiological processes of numerous cancers. To explore novel lung adenocarcinoma-associated lncRNAs, we analyzed the TCGA database and found that the lncRNA SNHG3 was significantly upregulated in lung adenocarcinoma. Bioinformatic analysis showed that SNHG3 may play key roles in regulating RNA splicing, tRNA processing, signal transduction, cell adhesion, transcription, and apoptosis. We also performed functional experiments to explore the roles of SNHG3 in lung adenocarcinoma cells. We found that SNHG3 promoted proliferation, cell cycle, and suppressed cell apoptosis of lung adenocarcinoma, suggesting that SNHG3 acted as an oncogene in lung adenocarcinoma. We believe that this study will provide a potential new therapeutic and prognostic target for lung adenocarcinoma.

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MiR-7 regulates the PI3K/AKT/VEGF pathway of retinal capillary endothelial cell and retinal pericytes in diabetic rat model through IRS-1 and inhibits cell proliferation

OBJECTIVE: To investigate the role of miR-7 in diabetic retinopathy and the underlying mechanism.

MATERIALS AND METHODS: The rat model of diabetic retinopathy (DR) was established. After that, the endothelial cell (EC) and retinal pericyte (RP) were isolated. QRT-PCR was used to detect the expression of miR-7 and insulin receptor substrate-1 (IRS-1) in ECs and RPs cells while the protein level of IRS1 was detected by Western blot. miR-7 mimic and miR-7 inhibitor were transfected to achieve miR-7 overexpression or knockdown. Cell viability was detected by Cell Counting Kit-8 (CCK-8) assay after miR-7 overexpression or knockdown. Besides, the expression levels of PI3K, AKT, and VEGF were detected by Western Blot. The luciferase reporter assay was performed to investigate whether miR-7 could be combined with IRS-1. Conversely, whether miR-7 could affect IRS-1 was also verified.

RESULTS: miR-7 expression was significantly decreased in ECs and RPs of the experimental group compared with the control group, while the mRNA and protein levels of IRS-1 were increased. The CCK-8 assay showed that overexpression of miR-7 decreased the cell activity in ECs and RPs. In contrast, knock-down of miR-7 could increase the cell viability. Besides, Western blot showed that after overexpression of miR-7, the expressions of PI3K, AKT, and VEGF in ECs and RPs cells were down-regulated. Meanwhile, miR-7 knockdown upregulated the protein levels of PI3K, AKT, and VEGF. The luciferase reporter assay suggested that the 3'UTR region of IRS-1 could be combined with miR-7, which may be the downstream target gene for miR-7. Moreover, knockdown of IRS-1 could reverse the effect of the miR-7 inhibitor on cell proliferation in the diabetic model.

CONCLUSIONS: MiR-7 was lowly expressed in ECs and RPs cells. Overexpression of miR-7 can down-regulate the expression levels of PI3K, AKT, and VEGF by down-regulating its downstream target gene IRS-1, and ultimately inhibit the proliferation of retinal cells.

L'articolo MiR-7 regulates the PI3K/AKT/VEGF pathway of retinal capillary endothelial cell and retinal pericytes in diabetic rat model through IRS-1 and inhibits cell proliferation sembra essere il primo su European Review.

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