Medscape Medical News Following a Mediterranean diet was associated with lower risk for incident cardiovascular disease and mortality, a prospective cohort study showed. Better adherence was tied to greater benefit.
Medscape Medical News Patients with clinically isolated syndrome and low vitamin D or high cotinine levels had twice the risk for disease severity as nonsmokers or those with normal vitamin D, a new study shows.
Medscape Medical News Sending a multidisciplinary team to visit homebound patients with advanced PD can improve quality of life for these patients.
Medscape Medical News A fungus in the gut could be a key factor in the development of Crohn's disease, according to an investigation by an international team of researchers.
WebMD Health News Krista Calderon first bought Wen hair products more than a year ago, believing that using something billed as “natural” would be better for her hair.
WebMD Health News Advances in technology and increases in the accessibility of hardware has allowed virtual reality to move from the realm of gaming into the field of medicine.
Medscape Medical News Clinton wants to modify the Affordable Care Act (ACA), while Trump wants it repealed. The candidates agree drug prices are prohibitive but diverge on how to make healthcare more affordable.
Medscape Medical News The lumacaftor/ivacaftor combination drug is now approved for children aged 6 to 11 years with two copies of the F508del mutation in the CTFR gene.
FDA Approvals Dr Anthony Fauci talks about progress made toward finding a vaccine against the Zika virus and outlines a comprehensive strategy for fighting antimicrobial resistance.
Medscape Public Health With the two antisense oligonucleotide agents, "we can get Lp(a) levels to normal in just about everybody who wants to," claim researchers, based on their early research.
Heartwire from Medscape Physicians who want to avoid getting locked out of their data or being silenced about software defects can find their answers in this government primer.
Medscape Medical News There's never been a study of cancer patients who die during radiation therapy. Until now.
Medscape Medical News A new study showed that weekly structured yoga classes have the same effect on chronic low back pain as does conventional physical therapy.
Medscape Medical News The promise of personalized cancer medicine is questioned, as few patients to date have benefited to any real extent from any agent targeted to tumor mutations.
Medscape Medical News The Congress of Delegates also voted last week in favor of allowing Medicare to negotiate drug prices, but opposed taking a neutral stance on physician-assisted death.
Medscape Medical News Patient expectations appear to be at odds with reality when it comes to participation in phase 1 clinical trials.
Medscape Medical News Although still in its infancy, precision medicine may someday transform healthcare.
Medscape Reader Polls Pooled analysis of 4000 patients with ductal carcinoma in situ shows that a radiation boost reduces local recurrence.
Medscape Medical News New results from a meta-analysis of the five published trials of thrombectomy also drum home the advantages of earlier treatment, researchers say.
Medscape Medical News
Pruritus since childhood.
J Fam Pract. 2016 Sep;65(9):E1-4
Authors: Richardson A, Usatine RP
The itchy rash had been previously diagnosed as psoriasis. But treatment provided minimal relief. So what was causing the itch?
PMID: 27672693 [PubMed - in process]
Do autologous blood and PRP injections effectively treat tennis elbow?
J Fam Pract. 2016 Sep;65(9):635
Authors: Widstrom L, Slattengren A
Both approaches reduce pain, but the improvement with platelet-rich plasma (PRP) is not clinically meaningful. Autologous blood injections (ABIs) are more effective than corticosteroid injections for reducing pain and disability in patients with tennis elbow in both the short and long term.
PMID: 27672692 [PubMed - in process]
Which SSRIs most effectively treat depression in adolescents?
J Fam Pract. 2016 Sep;65(9):632-4
Authors: DeLucia V, Kelsberg G, Safranek S
We don't know which selective serotonin reuptake inhibitors (SSRIs) are the most effective and safe because no studies have compared these antidepressants with each other. Three SSRI antidepressant medications--fluoxetine, sertraline, and escitalopram--produce modest improvements (about 5% to 10%) in standardized depression scores without a significant increase in the risk of suicide-related outcomes (suicidal behavior or ideation) in adolescent patients with major depression of moderate severity.
PMID: 27672691 [PubMed - in process]
Pruritic, lightly-scaled patches on wrists.
J Fam Pract. 2016 Sep;65(9):627-9
Authors: Brodell AP, Helms SE
A rash first appeared on this patient's left wrist and then spread to his right. Was his chrome-colored watch to blame--or was there a different cause?
PMID: 27672690 [PubMed - in process]
PURLs: Yeast infection in pregnancy? Think twice about fluconazole.
J Fam Pract. 2016 Sep;65(9):624-6
Authors: Barzin A, Mounsey A
This study's findings regarding the risk of miscarriage may mean it's time to forego fluconazole in favor of topical azoles as first-line treatment.
PMID: 27672689 [PubMed - in process]
Depigmented patches, mild scaling on newborn · Dx?
J Fam Pract. 2016 Sep;65(9):620-2
Authors: Dasarathy J, Tandra S, Chaudhry L, Alexander C
Depigmented patches covering approximately 15% of newborn's body, surrounded by areas of thickened skin. Mild scaling and hyperpigmentation.
PMID: 27672688 [PubMed - in process]
Practice Alert: Need-to-know information for the 2016-2017 flu season.
J Fam Pract. 2016 Sep;65(9):613-27
Authors: Campos-Outcalt D
ACIP now advises against using the LAIV nasal spray. In addition, 2 new vaccines are available and 2 more may soon be approved.
PMID: 27672687 [PubMed - in process]
Bone disease in patients with kidney disease: A tricky interplay.
J Fam Pract. 2016 Sep;65(9):606-12
Authors: Nyman H, Pippitt K, Hansen A, Gunning K
Managing bone disease in patients with kidney disease involves frequent lab testing and careful evaluation of therapeutic options. This review provides guidance.
PMID: 27672686 [PubMed - in process]
A new paradigm for pain?
J Fam Pract. 2016 Sep;65(9):598-605
Authors: Davis B, Vanderah TW
A new way of thinking about pain that occurs in the absence of a pathophysiologic process or injury may alter our approach to conditions like fibromyalgia.
PMID: 27672685 [PubMed - in process]
Is an SGLT2 inhibitor right for your patient with type 2 diabetes?
J Fam Pract. 2016 Sep;65(9):587-93
Authors: Lisenby KM, Meyer A, Slater NA
Metformin isn't quite doing the job or is contraindicated? Here's a look at the patients who may benefit from these agents and the monitoring required.
PMID: 27672684 [PubMed - in process]
Maybe it is all in your head.
J Fam Pract. 2016 Sep;65(9):586
Authors: Hickner J
Recent research provides strong evidence that in some cases of intractable chronic pain, the origin of the pain signal is in the brain--rather than the body.
PMID: 27672683 [PubMed - in process]
Correction to: 2016 ACC/AHA/HFSA Focused Update on New Pharmacological Therapy for Heart Failure: An Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America.
Circulation. 2016 Sep 27;134(13):e298
PMID: 27672202 [PubMed - in process]
Letter by Melgari et al Regarding Article, "Ivabradine: Role in the Chronic Heart Failure Armamentarium".
Circulation. 2016 Sep 27;134(13):e296-7
Authors: Melgari D, Ng GA, Hancox JC
PMID: 27672201 [PubMed - in process]
Letter by Koh Regarding Article, "Long-Term Effectiveness and Safety of Pravastatin in Patients With Coronary Heart Disease: 16 Years of Follow-Up of the LIPID Study".
Circulation. 2016 Sep 27;134(13):e294-5
Authors: Koh KK
PMID: 27672200 [PubMed - in process]
Long-Term Follow-Up of the Randomized (BIOMArCS-2) Glucose Trial: Intensive Glucose Regulation in Hyperglycemic Acute Coronary Syndrome.
Circulation. 2016 Sep 27;134(13):984-6
Authors: van den Berg VJ, Umans VA, Stam F, de Mulder M, Akkerhuis KM, Cornel JH, Kardys I, Boersma E
PMID: 27672199 [PubMed - in process]
Highlights from the Circulation Family of Journals.
Circulation. 2016 Sep 27;134(13):978-83
PMID: 27672198 [PubMed - in process]
Superficial Femoral Artery Is Not Left Anterior Descending Artery.
Circulation. 2016 Sep 27;134(13):901-3
Authors: Banerjee S
PMID: 27672197 [PubMed - in process]
Telestroke: Is it safe and effective?
Neurology. 2016 Sep 27;87(13):e145-8
Authors: Madhavan M, Karceski S
PMID: 27672174 [PubMed - in process]
Teaching NeuroImages: Acquired hepatocerebral degeneration: An underrecognized complication of advanced liver disease.
Neurology. 2016 Sep 27;87(13):e144
Authors: Bateman JR, Roque DA
PMID: 27672173 [PubMed - in process]
Clinical Reasoning: A 52-year-old man with diplopia and ataxia.
Neurology. 2016 Sep 27;87(13):e140-3
Authors: Bradshaw MJ, Pawate S, Bloch KC, Moots P, Reddy NM
PMID: 27672172 [PubMed - in process]
Clinical Reasoning: An 87-year-old man with chronic obstructive pulmonary disease and acute encephalopathy.
Neurology. 2016 Sep 27;87(13):e135-9
Authors: Spera K, Rubin D, Gupta T, Fantaneanu T, Henderson GV
PMID: 27672171 [PubMed - in process]
Mystery Case: Terson syndrome on CT head.
Neurology. 2016 Sep 27;87(13):e133-4
Authors: George JS, Elston JS
PMID: 27672170 [PubMed - in process]
Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis.
Neurology. 2016 Sep 27;87(13):1424
Authors: Kantor D, Sotirchos ES, Calabresi PA
PMID: 27672169 [PubMed - in process]
Pearls & Oy-sters: Tacrolimus neurotoxicity presenting as an isolated brainstem lesion.
Neurology. 2016 Sep 27;87(13):1423
Authors: Chang GY, Saadi A, Schmahmann JD
PMID: 27672168 [PubMed - in process]
A case of sudden deterioration in Parkinson disease.
Neurology. 2016 Sep 27;87(13):1422
Authors: Umemoto G, Fujioka S, Yanamoto S, Fukae J, Tsuboi Y
PMID: 27672167 [PubMed - in process]
A rare case of extensive primary meningeal osteosarcoma in childhood.
Neurology. 2016 Sep 27;87(13):1420-1
Authors: Zhang S, Ju Y, You C
PMID: 27672166 [PubMed - in process]
The terrorist inside my husband's brain.
Neurology. 2016 Sep 27;87(13):1308-11
Authors: Williams SS
PMID: 27672165 [PubMed - in process]
An update on gastric cancer.
Curr Probl Surg. 2016 Oct;53(10):449-90
Authors: Ahmad SA, Xia BT, Bailey CE, Abbott DE, Helmink BA, Daly MC, Thota R, Schlegal C, Winer LK, Ahmad SA, Al Humaidi AH, Parikh AA
PMID: 27671911 [PubMed - in process]
Curr Probl Surg. 2016 Oct;53(10):444-6
Authors: Ahmad SA, Xia BT, Bailey CE, Abbott DE, Helmink BA, Daly MC, Thota R, Schlegal C, Winer LK, Ahmad SA, Al Humaidi AH, Parikh AA
PMID: 27671910 [PubMed - in process]
Curr Probl Surg. 2016 Oct;53(10):443
Authors: Ashley SW
PMID: 27671909 [PubMed - in process]
Am J Med. 2016 Oct;129(10):e267
Authors: Grant PJ, Greene MT, Flanders SA
PMID: 27671859 [PubMed - in process]
Caprini Score in Hospitalized Medical Patients.
Am J Med. 2016 Oct;129(10):e265
Authors: Tafur AJ, Arcelus JI
PMID: 27671858 [PubMed - in process]
Don't Overlook the Role of Intraabdominal Pressure.
Am J Med. 2016 Oct;129(10):e261
Authors: Taleb-Bendiab T, Jacobs FM
PMID: 27671857 [PubMed - in process]
Am J Med. 2016 Oct;129(10):e259
Authors: Dalen JE
PMID: 27671856 [PubMed - in process]
Organic Chemistry: A Vital Part of Basic Understanding of Disease.
Am J Med. 2016 Oct;129(10):e257-8
Authors: Hashemzadeh M, Peyton LR
PMID: 27671855 [PubMed - in process]
Am J Med. 2016 Oct;129(10):e255
Authors: Horton WB, Subauste JS
PMID: 27671854 [PubMed - in process]
One More Fact to Know About Inpatient Glycemic Control.
Am J Med. 2016 Oct;129(10):e253
Authors: Thoelke M
PMID: 27671853 [PubMed - in process]
Am J Med. 2016 Oct;129(10):e251
Authors: Wakeman SE
PMID: 27671852 [PubMed - in process]
Science Alone Is Not Enough.
Am J Med. 2016 Oct;129(10):e249
Authors: Ruan X, Chiravuri S, Kaye AD
PMID: 27671851 [PubMed - in process]
Shedding Light on Shingles: The Power of Prevention.
Am J Med. 2016 Oct;129(10):1137
Authors: Herman L, Levin MJ, Rehm S
Shingles, or herpes zoster (HZ), is a common secondary infection caused by a reactivated varicella zoster virus (VZV). More than 95% of immunocompetent individuals aged at least 50 years are seropositive for VZV and are therefore at risk for developing HZ. Age-related increased incidence of HZ and its complications are thought to be related to the decline in cell-mediated immunity. Complications of HZ, which create a significant patient and economic burden, may be neurological, ophthalmological, dermatological, or visceral. HZ vaccination is essential for the prevention of HZ and its consequences. This CME activity reviews the clinical presentations and complications of HZ as well as discusses strategies for prevention (Online access: http://courses.elseviercme.com/shingles/626).
PMID: 27671850 [PubMed - in process]
Spinal Cord Injury Model Systems: Review of Program and National Database From 1970 to 2015.
Arch Phys Med Rehabil. 2016 Oct;97(10):1797-804
Authors: Chen Y, DeVivo MJ, Richards JS, SanAgustin TB
The Spinal Cord Injury Model Systems (SCIMS) centers have provided continuous, comprehensive multidisciplinary care for persons with spinal cord injury (SCI) in the United States since their inception in 1970. In addition, the research conducted and the analysis of data collected at these centers facilitate advances in the care and the overall quality of life for people with SCI. Over the past 45 years, the SCIMS program and National Spinal Cord Injury Database (NSCID) have undergone major revisions, which must be recognized in the planning, conduct, and interpretation of SCIMS research to prevent misinterpretation of findings. Therefore, we provide herein a brief review of the SCIMS program and the associated NSCID throughout its history, emphasizing changes and accomplishments within the past 15 years, to facilitate a better understanding and interpretation of the data presented in SCIMS research publications, including the articles published in this special issue of the Archives.
PMID: 27671806 [PubMed - in process]
Current Research Outcomes From the Spinal Cord Injury Model Systems.
Arch Phys Med Rehabil. 2016 Oct;97(10):1607-9
Authors: Chen Y, Heinemann AW
PMID: 27671805 [PubMed - in process]
What Are the New Nutrition Standards for the Child and Adult Care Food Program?
J Acad Nutr Diet. 2016 Oct;116(10):1728
Authors: Marcason W
PMID: 27671763 [PubMed - in process]
Translating the Dietary Guidelines to Promote Behavior Change: Perspectives from the Food and Nutrition Science Solutions Joint Task Force.
J Acad Nutr Diet. 2016 Oct;116(10):1697-702
Authors: Ivens BJ, Smith Edge M, Food and Nutrition Science Solutions Joint Task Force
PMID: 27671762 [PubMed - in process]
Distinctions in Entry-Level Registered Dietitian Nutritionist and Nutrition and Dietetics Technicians, Registered, Practice: Further Results from the 2015 Commission on Dietetic Registration Entry-Level Dietetics Practice Audit.
J Acad Nutr Diet. 2016 Oct;116(10):1685-96
Authors: Rogers D, Griswold K, Kellogg Leibovitz P, Sauer KL, Doughten S
PMID: 27671761 [PubMed - in process]
Entry-Level Dietetics Practice Today: Results from the 2015 Commission on Dietetic Registration Entry-Level Dietetics Practice Audit.
J Acad Nutr Diet. 2016 Oct;116(10):1632-84
Authors: Griswold K, Rogers D, Sauer KL, Kellogg Leibovitz P, Finn JR
PMID: 27671760 [PubMed - in process]
Practice Paper of the Academy of Nutrition and Dietetics: Role of the Registered Dietitian Nutritionist in the Diagnosis and Management of Food Allergies.
J Acad Nutr Diet. 2016 Oct;116(10):1621-31
Authors: Collins SC
Incidence of food allergy has increased significantly over the past decade and represents an important health issue for millions of Americans. Diagnosis of immunoglobulin E-mediated food allergies is sometimes difficult because blood and skin tests have high rates of false positives, and oral food challenges are uncommon due to the expense and potential for serious reactions. Accurate diagnosis is crucial to avoid unnecessary dietary restriction, especially in children. Because registered dietitian nutritionists often work independently, receiving referrals for dietary education and guidance for a patient who is followed by one or several other practitioners, navigating the data available and making the appropriate follow-up contact optimizes treatment. The purpose of this paper is to provide guidance to the registered dietitian nutritionists and nutrition and dietetics technician, registered on appropriate and evidence-based nutrition counseling for diagnosis and management of food allergies.
PMID: 27671759 [PubMed - in process]
MyPlate at FNCE & Beyond: Join the Fun!
J Acad Nutr Diet. 2016 Oct;116(10):1538-9
Authors: Leone A, Psota TL, Holland C
PMID: 27671758 [PubMed - in process]
It Takes Vision to Prepare for Our Future.
J Acad Nutr Diet. 2016 Oct;116(10):1529
Authors: Beseler L
PMID: 27671757 [PubMed - in process]
Most American Association of Oral and Maxillofacial Surgeons Members Have Not Adopted the American Society of Anesthesiologists-Recommended Nil Per Os Guidelines.
J Oral Maxillofac Surg. 2016 Oct;74(10):1926-31
Authors: Johnson RE, Eckert PP, Gilmore W, Viswanath A, Finkelman M, Rosenberg MB
PURPOSE: The purpose of this study was to determine if American Association of Oral and Maxillofacial Surgeons members have integrated the current American Society of Anesthesiologists (ASA) nil per os (NPO) guidelines into their preoperative instructions.
MATERIALS AND METHODS: We designed and implemented a cross-sectional study and enrolled a random sample of private-practice American Association of Oral and Maxillofacial Surgeons members who practice in the United States. The predictor variables were year of graduation from residency, dual degree (MD and DDS or DMD) or single degree, and region. The primary outcome variable was adoption of the ASA NPO guidelines, defined as recommending fasting times of 2 hours for clear liquids and 6 hours for solid foods. To collect data, a systematic online search was implemented. Appropriate univariate and bivariate statistics were computed, and the level of significance was set at .05; in addition, 95% confidence intervals were calculated.
RESULTS: The study sample was composed of 431 oral and maxillofacial surgeons (OMSs). Almost all of the study sample (99.1%) did not adopt the ASA guidelines. The fasting recommendations were different from 2 hours for clear liquids and 6 hours for solid foods. However, recommendations of 2 hours or greater for clear liquids were made by 99.8% of OMSs, and recommendations of 6 hours or greater for solid foods were made by 99.3%. Only 4.4% of OMSs made different recommendations for clear liquids and solid foods. No substantial association was found between whether OMSs adopted the most current ASA guidelines and the year they graduated from residency or the obtainment of dual degrees.
CONCLUSIONS: OMSs in private practice are overwhelmingly recommending longer fasting times for clear liquids and solid foods on their Web sites when compared with the current ASA guidelines before ambulatory anesthesia. The ASA guidelines are based on meta-analysis; therefore, deviations in practice, although not incorrect, may call for discussion.
PMID: 27670066 [PubMed - in process]
The Perfect Match.
J Oral Maxillofac Surg. 2016 Oct;74(10):1905-7
Authors: Miloro M
PMID: 27670065 [PubMed - in process]
Prophylaxis With a Middle East Respiratory Syndrome Coronavirus (MERS-CoV)-Specific Human Monoclonal Antibody Protects Rabbits From MERS-CoV Infection.
J Infect Dis. 2016 May 15;213(10):1557-61
Authors: Houser KV, Gretebeck L, Ying T, Wang Y, Vogel L, Lamirande EW, Bock KW, Moore IN, Dimitrov DS, Subbarao K
With >1600 documented human infections with Middle East respiratory syndrome coronavirus (MERS-CoV) and a case fatality rate of approximately 36%, medical countermeasures are needed to prevent and limit the disease. We examined the in vivo efficacy of the human monoclonal antibody m336, which has high neutralizing activity against MERS-CoV in vitro. m336 was administered to rabbits intravenously or intranasally before infection with MERS-CoV. Prophylaxis with m336 resulted in a reduction of pulmonary viral RNA titers by 40-9000-fold, compared with an irrelevant control antibody with little to no inflammation or viral antigen detected. This protection in rabbits supports further clinical development of m336.
PMID: 26941283 [PubMed - indexed for MEDLINE]
Immunological Characterization and Neutralizing Ability of Monoclonal Antibodies Directed Against Botulinum Neurotoxin Type H.
J Infect Dis. 2016 May 15;213(10):1606-14
Authors: Fan Y, Barash JR, Lou J, Conrad F, Marks JD, Arnon SS
BACKGROUND: Only Clostridium botulinum strain IBCA10-7060 produces the recently described novel botulinum neurotoxin type H (BoNT/H). BoNT/H (N-terminal two-thirds most homologous to BoNT/F and C-terminal one-third most homologous to BoNT/A) requires antitoxin to toxin ratios ≥1190:1 for neutralization by existing antitoxins. Hence, more potent and safer antitoxins against BoNT/H are needed.
METHODS: We therefore evaluated our existing monoclonal antibodies (mAbs) to BoNT/A and BoNT/F for BoNT/H binding, created yeast-displayed mutants to select for higher-affinity-binding mAbs by using flow cytometry, and evaluated the mAbs' ability to neutralize BoNT/H in the standard mouse bioassay.
RESULTS: Anti-BoNT/A HCC-binding mAbs RAZ1 and CR2 bound BoNT/H with high affinity. However, only 1 of 6 BoNT/F mAbs (4E17.2A) bound BoNT/H but with an affinity >800-fold lower (equilibrium dissociation binding constant [KD] = 7.56 × 10(-8)M) than its BoNT/F affinity (KD= 9.1 × 10(-11)M), indicating that the N-terminal two-thirds of BoNT/H is immunologically unique. The affinity of 4E17.2A for BoNT/H was increased >500-fold to KD= 1.48 × 10(-10)M (mAb 4E17.2D). A combination of mAbs RAZ1, CR2, and 4E17.2D completely protected mice challenged with 280 mouse median lethal doses of BoNT/H at a mAb dose as low as 5 µg of total antibody.
CONCLUSIONS: This 3-mAb combination potently neutralized BoNT/H and represents a potential human antitoxin that could be developed for the prevention and treatment of type H botulism.
PMID: 26936913 [PubMed - indexed for MEDLINE]
Vaccine-Induced Immunogenicity and Protection Against Pneumocystis Pneumonia in a Nonhuman Primate Model of HIV and Pneumocystis Coinfection.
J Infect Dis. 2016 May 15;213(10):1586-95
Authors: Kling HM, Norris KA
BACKGROUND: The ubiquitous opportunistic pathogen Pneumocystis jirovecii causes pneumonia in immunocompromised individuals, including human immunodeficiency virus (HIV)-infected individuals, and pulmonary colonization with P. jirovecii is believed to be a cofactor in the development of chronic obstructive pulmonary disease. There is no vaccine for P. jirovecii; however, most adults are seropositive, indicating natural immune priming to this pathogen. We have shown that humoral response to a recombinant subunit of the P. jirovecii protease kexin (KEX1) correlates with protection from P. jirovecii colonization and pneumonia.
METHODS: Here we evaluated the immunogenicity and protective capacity of the recombinant KEX1 peptide vaccine in a preclinical, nonhuman primate model of HIV-induced immunosuppression and Pneumocystis coinfection.
RESULTS: Immunization with KEX1 induced a robust humoral response remained at protective levels despite chronic simian immunodeficiency virus/HIV-induced immunosuppression. KEX1-immunized macaques were protected from Pneumocystis pneumonia, compared with mock-immunized animals (P= .047), following immunosuppression and subsequent natural, airborne exposure to Pneumocystis
CONCLUSIONS: These data support the concept that stimulation of preexisting immunological memory to Pneumocystis with a recombinant KEX1 vaccine prior to immunosuppression induces durable memory responses and protection in the context of chronic, complex immunosuppression.
PMID: 26823337 [PubMed - indexed for MEDLINE]
Phagocytosis and Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils.
J Infect Dis. 2016 May 15;213(10):1615-22
Authors: Kobayashi SD, Porter AR, Dorward DW, Brinkworth AJ, Chen L, Kreiswirth BN, DeLeo FR
Carbapenem-resistant Klebsiella pneumoniae strains classified as multilocus sequence type 258 (ST258) are among the most widespread multidrug-resistant hospital-acquired pathogens. Treatment of infections caused by these organisms is difficult, and mortality is high. The basis for the success of ST258, outside of antibiotic resistance, remains incompletely determined. Here we tested the hypothesis that ST258K. pneumoniae has enhanced capacity to circumvent killing by human neutrophils, the primary cellular defense against bacterial infections. There was limited binding and uptake of ST258 by human neutrophils, and correspondingly, there was limited killing of bacteria. On the other hand, transmission electron microscopy revealed that any ingested organisms were degraded readily within neutrophil phagosomes, thus indicating that survival in the neutrophil assays is due to limited phagocytosis, rather than to microbicide resistance after uptake. Our findings suggest that enhancing neutrophil phagocytosis is a potential therapeutic approach for treatment of infection caused by carbapenem-resistant ST258K. pneumoniae.
PMID: 26768252 [PubMed - indexed for MEDLINE]
Combination Emtricitabine and Tenofovir Disoproxil Fumarate Prevents Vaginal Simian/Human Immunodeficiency Virus Infection in Macaques Harboring Chlamydia trachomatis and Trichomonas vaginalis.
J Infect Dis. 2016 May 15;213(10):1541-5
Authors: Radzio J, Henning T, Jenkins L, Ellis S, Farshy C, Phillips C, Holder A, Kuklenyik S, Dinh C, Hanson D, McNicholl J, Heneine W, Papp J, Kersh EN, García-Lerma JG
Genital inflammation associated with sexually transmitted infections increases susceptibility to human immunodeficiency virus (HIV), but it is unclear whether the increased risk can reduce the efficacy of pre-exposure prophylaxis (PrEP). We investigated whether coinfection of macaques with Chlamydia trachomatis and Trichomonas vaginalis decreases the prophylactic efficacy of oral emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). Macaques were exposed to simian/human immunodeficiency virus (SHIV) vaginally each week for up to 16 weeks and received placebo or FTC/TDF pericoitally. All animals in the placebo group were infected with SHIV, while 4 of 6 PrEP recipients remained uninfected (P= .03). Oral FTC/TDF maintains efficacy in a macaque model of sexually transmitted coinfection, although the infection of 2 macaques signals a modest loss of PrEP activity.
PMID: 26743846 [PubMed - indexed for MEDLINE]
Influenza Vaccine Effectiveness Against 2009 Pandemic Influenza A(H1N1) Virus Differed by Vaccine Type During 2013-2014 in the United States.
J Infect Dis. 2016 May 15;213(10):1546-56
Authors: Gaglani M, Pruszynski J, Murthy K, Clipper L, Robertson A, Reis M, Chung JR, Piedra PA, Avadhanula V, Nowalk MP, Zimmerman RK, Jackson ML, Jackson LA, Petrie JG, Ohmit SE, Monto AS, McLean HQ, Belongia EA, Fry AM, Flannery B
BACKGROUND: The predominant strain during the 2013-2014 influenza season was 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09). This vaccine-component has remained unchanged from 2009.
METHODS: The US Flu Vaccine Effectiveness Network enrolled subjects aged ≥6 months with medically attended acute respiratory illness (MAARI), including cough, with illness onset ≤7 days before enrollment. Influenza was confirmed by reverse-transcription polymerase chain reaction (RT-PCR). We determined the effectiveness of trivalent or quadrivalent inactivated influenza vaccine (IIV) among subjects ages ≥6 months and the effectiveness of quadrivalent live attenuated influenza vaccine (LAIV4) among children aged 2-17 years, using a test-negative design. The effect of prior receipt of any A(H1N1)pdm09-containing vaccine since 2009 on the effectiveness of current-season vaccine was assessed.
RESULTS: We enrolled 5999 subjects; 5637 (94%) were analyzed; 18% had RT-PCR-confirmed A(H1N1)pdm09-related MAARI. Overall, the effectiveness of vaccine against A(H1N1)pdm09-related MAARI was 54% (95% confidence interval [CI], 46%-61%). Among fully vaccinated children aged 2-17 years, the effectiveness of LAIV4 was 17% (95% CI, -39% to 51%) and the effectiveness of IIV was 60% (95% CI, 36%-74%). Subjects aged ≥9 years showed significant residual protection of any prior A(H1N1)pdm09-containing vaccine dose(s) received since 2009, as did children <9 years old considered fully vaccinated by prior season.
CONCLUSIONS: During 2013-2014, IIV was significantly effective against A(H1N1)pdm09. Lack of LAIV4 effectiveness in children highlights the importance of continued annual monitoring of effectiveness of influenza vaccines in the United States.
PMID: 26743842 [PubMed - indexed for MEDLINE]
Flow-Tolerant Adhesion of a Bacterial Pathogen to Human Endothelial Cells Through Interaction With Biglycan.
J Infect Dis. 2016 May 15;213(10):1623-31
Authors: Salo J, Pietikäinen A, Söderström M, Auvinen K, Salmi M, Ebady R, Moriarty TJ, Viljanen MK, Hytönen J
BACKGROUND: Bacterial pathogens causing systemic infections disseminate from the initial infection focus to the target organs usually through the blood vasculature. To be able to colonize various organs, bacteria need to adhere to the endothelial cells of the vascular wall, and the adhesion must be strong enough to resist the shear force of the blood flow.Borrelia burgdorferi sensu lato spirochetes, the causative agents of the tick-borne disease Lyme borreliosis, disseminate hematogenously from the tick bite site to the joints, the heart, and the central nervous system of the patient.
METHODS: We used both wild-type and genetically modified B. burgdorferi s. l. bacteria, recombinant borrelia adhesins, and an array of adhesion assays carried out both under stationary and flow conditions to investigate the molecular mechanisms of borrelial adhesion to human endothelial cells.
RESULTS: Borrelia garinii, a member of the B. burgdorferi s. l. complex, adhered to biglycan expressed by human endothelial cells in a flow-tolerant manner. The adhesion was mediated by the decorin-binding protein A (DbpA) and DbpB surface molecules of B. garinii.
CONCLUSIONS: The proteoglycan biglycan is a receptor molecule for flow-resistant adhesion of the bacterial pathogen B. garinii on human endothelial cells.
PMID: 26740275 [PubMed - indexed for MEDLINE]
Low Prolactin and High 20-α-Hydroxysteroid Dehydrogenase Levels Contribute to Lower Progesterone Levels in HIV-Infected Pregnant Women Exposed to Protease Inhibitor-Based Combination Antiretroviral Therapy.
J Infect Dis. 2016 May 15;213(10):1532-40
Authors: Papp E, Balogun K, Banko N, Mohammadi H, Loutfy M, Yudin MH, Shah R, MacGillivray J, Murphy KE, Walmsley SL, Silverman M, Serghides L
BACKGROUND: It has been reported that pregnant women receiving protease inhibitor (PI)-based combination antiretroviral therapy (cART) have lower levels of progesterone, which put them at risk of adverse birth outcomes, such as low birth weight. We sought to understand the mechanisms involved in this decline in progesterone level.
METHODS: We assessed plasma levels of progesterone, prolactin, and lipids and placental expression of genes involved in progesterone metabolism in 42 human immunodeficiency virus (HIV)-infected and 31 HIV-uninfected pregnant women. In vitro studies and a mouse pregnancy model were used to delineate the effect of HIV from that of PI-based cART on progesterone metabolism.
RESULTS: HIV-infected pregnant women receiving PI-based cART showed a reduction in plasma progesterone levels (P= .026) and an elevation in placental expression of the progesterone inactivating enzyme 20-α-hydroxysteroid dehydrogenase (20α-HSD; median, 2.5 arbitrary units [AU]; interquartile range [IQR], 1.00-4.10 AU), compared with controls (median, 0.89 AU; IQR, 0.66-1.26 AU;P= .002). Prolactin, a key regulator of 20α-HSD, was lower (P= .012) in HIV-infected pregnant women. We observed similar data in pregnant mice exposed to PI-based cART. In vitro inhibition of 20α-HSD activity in trophoblast cells reversed PI-based cART-induced decreases in progesterone levels.
CONCLUSIONS: Our data suggest that the decrease in progesterone levels observed in HIV-infected pregnant women exposed to PI-based cART is caused, at least in part, by an increase in placental expression of 20α-HSD, which may be due to lower prolactin levels observed in these women.
PMID: 26740274 [PubMed - indexed for MEDLINE]
Limited Effector Memory B-Cell Response to Envelope Glycoprotein B During Primary Human Cytomegalovirus Infection.
J Infect Dis. 2016 May 15;213(10):1642-50
Authors: Dauby N, Sartori D, Kummert C, Lecomte S, Haelterman E, Delforge ML, Donner C, Mach M, Marchant A
BACKGROUND: Following primary human cytomegalovirus (HCMV) infection, the production of antibodies against envelope glycoprotein B (gB) is delayed, compared with production of antibodies against tegument proteins, and this likely reduces the control of HCMV dissemination.
METHODS: The frequency and the phenotype of gB-specific and tegument protein-specific B cells were studied in a cohort of pregnant women with primary HCMV infection. Healthy adults who had chronic HCMV infection or were recently immunized with tetanus toxoid (TT) were included as controls.
RESULTS: Primary HCMV infection was associated with high and similar frequencies of gB-specific and tegument protein-specific B cells following primary HCMV infection. During primary infection, tegument protein-specific B cells expressed an activated (CD21(low)) memory B-cell (MBC) phenotype. Activated MBCs were also induced by TT booster immunization, indicating that the expansion of this subset is part of the physiological B-cell response to protein antigens. In contrast, gB-specific B cells had a predominant classical (CD21(+)) MBC phenotype during both primary and chronic infections.
CONCLUSIONS: The delayed production of gB-specific immunoglobulin G (IgG) during primary HCMV infection is associated with a limited induction of MBCs with effector potential. This novel mechanism by which HCMV may interfere with the production of neutralizing antibodies could represent a target for therapeutic immunization.
PMID: 26715677 [PubMed - indexed for MEDLINE]
Role of the Gut Microbiota of Children in Diarrhea Due to the Protozoan Parasite Entamoeba histolytica.
J Infect Dis. 2016 May 15;213(10):1579-85
Authors: Gilchrist CA, Petri SE, Schneider BN, Reichman DJ, Jiang N, Begum S, Watanabe K, Jansen CS, Elliott KP, Burgess SL, Ma JZ, Alam M, Kabir M, Haque R, Petri WA
BACKGROUND: An estimated 1 million children die each year before their fifth birthday from diarrhea. Previous population-based surveys of pediatric diarrheal diseases have identified the protozoan parasite Entamoeba histolytica, the etiological agent of amebiasis, as one of the causes of moderate-to-severe diarrhea in sub-Saharan Africa and South Asia.
METHODS: We prospectively studied the natural history of E. histolytica colonization and diarrhea among infants in an urban slum of Dhaka, Bangladesh.
RESULTS: Approximately 80% of children were infected with E. histolytica by the age of 2 years. Fecal anti-galactose/N-acetylgalactosamine lectin immunoglobulin A was associated with protection from reinfection, while a high parasite burden and expansion of the Prevotella copri level was associated with diarrhea.
CONCLUSIONS: E. histolytica infection was prevalent in this population, with most infections asymptomatic and diarrhea associated with both the amount of parasite and the composition of the microbiota.
PMID: 26712950 [PubMed - indexed for MEDLINE]
The Interleukin-1 Balance During Encephalitis Is Associated With Clinical Severity, Blood-Brain Barrier Permeability, Neuroimaging Changes, and Disease Outcome.
J Infect Dis. 2016 May 15;213(10):1651-60
Authors: Michael BD, Griffiths MJ, Granerod J, Brown D, Keir G, Wnęk G, Cox DJ, Vidyasagar R, Borrow R, Parkes LM, Solomon T
BACKGROUND: Encephalitis is parenchymal brain inflammation, commonly due to herpes simplex virus (HSV). Key host inflammatory mediators and their relationship to blood-brain barrier (BBB) permeability, neuroimaging changes, and disease outcome are poorly understood.
METHODS: We measured levels of 38 mediators in serum (n = 78) and cerebrospinal fluid (n = 37) specimens from patients with encephalitis, including 17 with disease due to HSV infection. Outcome measures were Glasgow coma and outcome scores; CSF to serum albumin ratio, reflecting BBB permeability; and, in patients with HSV infection, magnetic resonance imaging-based temporal lobe volume.
RESULTS: Serum interleukin 1 receptor antagonist (IL-1RA) levels were elevated in patients with a good outcome (P= .004). Among patients infected with HSV, the ratio of CSF IL-1β to IL-1RA was associated with a worse outcome (P= .009); a ratio of ≥0.55 pg/mL had high specificity and sensitivity for a poor outcome (100% and 83%;P= .015). Temporal lobe volume had a negative correlation with serum IL-1RA level (P= .012) and a positive correlation with serum IL-1α level (P= .0003) and CSF IL-1β level (P= .007). A normal coma score was associated with an elevated interleukin 10 (IL-10) level in serum specimens from HSV-infected patients (P= .007) and CSF specimens from all patients (P= .016); the IL-10 level correlated inversely with BBB permeability (P= .005).
CONCLUSIONS: A proinflammatory cytokine response is associated with greater clinical severity, BBB permeability, and neuroimaging damage during encephalitis. IL-1 antagonists should be investigated as adjunctive treatment in encephalitis.
PMID: 26712949 [PubMed - indexed for MEDLINE]
Epidemiological Markers for Interactions Among Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in Upper Respiratory Tract Carriage.
J Infect Dis. 2016 May 15;213(10):1596-605
Authors: Lewnard JA, Givon-Lavi N, Huppert A, Pettigrew MM, Regev-Yochay G, Dagan R, Weinberger DM
BACKGROUND: Cocolonization by Streptococcus pneumoniae and Haemophilus influenzae among children has been noted in numerous studies, as has an inverse relationship involving colonization with these species and Staphylococcus aureus. Interactions among these pathogens could mediate unanticipated outcomes of clinical interventions, including changes in H. influenzae and S. aureus disease incidence following pneumococcal vaccine introduction. However, it remains unclear whether cocolonization patterns represent true interspecies interactions or whether they result from confounding factors.
METHODS: We investigated polymicrobial carriage using longitudinal data from 369 Bedouin children and 400 Jewish children in Israel who were enrolled in a 7-valent pneumococcal conjugate vaccine (PCV7) trial. Children were swabbed 10 times between 2 and 30 months of age.
RESULTS: The pathogens followed distinct age and seasonal distributions, but polymicrobial carriage associations persisted after controlling for these and other confounding factors. Receipt of PCV7 resulted in pneumococcal serotype replacement but did not influence total carriage of S. pneumoniae, H. influenzae, or S. aureus.
CONCLUSIONS: The fact that S. pneumoniae, H. influenzae, and S. aureus polymicrobial carriage patterns do not result from confounding by age and season supports the idea of active interspecies interactions. However, pneumococcal serotype replacement may prevent changes in H. influenzae and S. aureus carriage among PCV7 recipients.
PMID: 26704617 [PubMed - indexed for MEDLINE]
Inhibition of MicroRNA 195 Prevents Apoptosis and Multiple-Organ Injury in Mouse Models of Sepsis.
J Infect Dis. 2016 May 15;213(10):1661-70
Authors: Zheng D, Yu Y, Li M, Wang G, Chen R, Fan GC, Martin C, Xiong S, Peng T
BACKGROUND: MicroRNAs (miRs) are a class of short RNA molecules, which negatively regulate gene expression. The levels of circulating miR-15 family members are elevated in septic patients and may be associated with septic death. This study investigated whether inhibition of miR-195, a member of the miR-15 family, provided beneficial effects in sepsis.
METHODS AND RESULTS: Sepsis was induced by injection of feces into the peritoneum in mice. miR-195 was upregulated in the lung and liver of septic mice. Silencing of miR-195 increased the protein levels of BCL-2, Sirt1, and Pim-1; prevented apoptosis; reduced liver and lung injury; and improved the survival in septic mice. Silencing of miR-195 provided similar protection in lipopolysaccharide-induced endotoxemic mice. In endothelial cells, upregulation of miR-195 induced apoptosis, and inhibition of miR-195 prevented lipopolysaccharide-induced apoptosis. miR-195 repressed expression of its protein targets, BCL-2, Sirt1, and Pim-1. Furthermore, overexpression of Pim-1 prevented apoptosis induced by lipopolysaccharide and miR-195 mimic. Inhibition of Pim-1 attenuated the protective effects of miR-195 silencing in septic mice.
CONCLUSIONS: Silencing of miR-195 reduced multiple-organ injury and improved the survival in sepsis, and the protective effects of miR-195 inhibition were associated with upregulation of Bcl-2, Sirt1, and Pim-1. Thus, inhibition of miR-195 may represent a new therapeutic approach for sepsis.
PMID: 26704614 [PubMed - indexed for MEDLINE]
Interferons Induce STAT1-Dependent Expression of Tissue Plasminogen Activator, a Pathogenicity Factor in Puumala Hantavirus Disease.
J Infect Dis. 2016 May 15;213(10):1632-41
Authors: Strandin T, Hepojoki J, Laine O, Mäkelä S, Klingström J, Lundkvist Å, Julkunen I, Mustonen J, Vaheri A
Hantaviruses are zoonotic viruses that show various degrees of vasculopathy in humans. In this study, we analyzed the regulation of 2 fibrinolytic parameters, tissue plasminogen activator (tPA) and its physiological inhibitor, plasminogen activator inhibitor 1 (PAI-1), in Puumala hantavirus (PUUV)-infected patients and in human microvascular endothelial cells. We detected strong upregulation of tPA in the acute phase of illness and in PUUV-infected macaques and found the tPA level to positively correlate with disease severity. The median levels of PAI-1 during the acute stage did not differ from those during the recovery phase. In concordance, hantaviruses induced tPA but not PAI-1 in microvascular endothelial cells, and the induction was demonstrated to be dependent on type I interferon. Importantly, type I and II interferons directly upregulated tPA through signal transducer and activator of transcription 1 (STAT1), which regulated tPA gene expression via a STAT1-responsive enhancer element. These results suggest that tPA may be a general factor in the immunological response to viruses.
PMID: 26704613 [PubMed - indexed for MEDLINE]
Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Healthy Children and Adults in Dengue-Endemic Regions: A Randomized, Placebo-Controlled Phase 2 Study.
J Infect Dis. 2016 May 15;213(10):1562-72
Authors: Sirivichayakul C, Barranco-Santana EA, Esquilin-Rivera I, Oh HM, Raanan M, Sariol CA, Shek LP, Simasathien S, Smith MK, Velez ID, Wallace D, Gordon GS, Stinchcomb DT
BACKGROUND: A safe, effective tetravalent dengue vaccine is a global health priority. The safety and immunogenicity of a live attenuated, recombinant tetravalent dengue vaccine candidate (TDV) were evaluated in healthy volunteers from dengue-endemic countries.
METHODS: This multicenter, double-blind, phase 2 study was conducted in Puerto Rico, Colombia, Singapore, and Thailand. During stage I, 148 volunteers aged 1.5-45 years were sequentially enrolled into 4 age-descending groups and randomized at a ratio of 2:1 to receive TDV or placebo. In stage II (group 5), 212 children aged 1.5-11 years were randomized at a ratio of 3:1 to receive TDV or placebo. Participants received a subcutaneous injection of TDV or placebo on days 0 and 90 and were followed for analysis of safety, seropositivity, and neutralizing antibodies to DENV-1-4.
RESULTS: Injection site pain, itching, and erythema (mostly mild) were the only solicited adverse events more frequently reported with TDV than with placebo in all age groups. After 2 TDV doses, seropositivity was >95% in all 5 groups for DENV-1-3 and 72.7%-100% for DENV-4; geometric mean titers ranged from 582 to 1187 for DENV-1, from 582 to 1187 for DENV-2, from 196 to 630 for DENV-3, and from 41 to 210 for DENV-4 among the 5 groups.
CONCLUSIONS: TDV was well tolerated and immunogenic in volunteers aged 1.5-45 years, irrespective of prevaccination dengue exposure.
PMID: 26704612 [PubMed - indexed for MEDLINE]
Transient Increase in Herpes Simplex Virus Type 2 (HSV-2)-Associated Genital Ulcers Following Initiation of Antiretroviral Therapy in HIV/HSV-2-Coinfected Individuals.
J Infect Dis. 2016 May 15;213(10):1573-8
Authors: Fife KH, Mugwanya K, Thomas KK, Baeten JM, Celum C, Bukusi E, de Bruyn G, Mujugira A, Vwalika B, Wald A, Lingappa JR, Partners in Prevention HSV/HIV Transmission Study Team
BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected persons beginning antiretroviral therapy (ART) has been incompletely characterized for herpes simplex virus type 2 (HSV-2).
METHODS: We evaluated genital ulcer disease (GUD) and HSV-2-associated GUD at quarterly visits or when spontaneously reported at monthly visits in 3381 HIV/HSV-2-coinfected individuals in a placebo-controlled trial of suppressive acyclovir therapy to prevent HIV transmission, 349 of whom initiated ART during the study. Incidence was calculated for months before and after ART initiation, and incidence rate ratios (IRRs) were calculated.
RESULTS: GUD incidence increased from 15.0 episodes per 100 person-years before ART to 26.9 episodes per 100 person-years in the first full quarter after ART initiation (IRR, 1.83;P= .03), and the incidence of HSV-2-associated GUD increased from 8.1 to 19.0 episodes per 100 person-years (IRR, 2.20;P= .02). Subsequently, the incidence of GUD was similar to that before ART, although the numbers were small. Persons receiving suppressive acyclovir had fewer GUD episodes, but the IRR after beginning ART was similar in the acyclovir and placebo groups.
CONCLUSIONS: Initiation of ART in HIV/HSV-2-coinfected persons is associated with a transient increase in GUD and HSV-2 GUD. Acyclovir reduces the incidence of GUD but does not prevent an increase in GUD incidence during the first quarter following initiation of ART.
PMID: 26704611 [PubMed - indexed for MEDLINE]
Potential Clinical and Economic Value of Long-Acting Preexposure Prophylaxis for South African Women at High-Risk for HIV Infection.
J Infect Dis. 2016 May 15;213(10):1523-31
Authors: Walensky RP, Jacobsen MM, Bekker LG, Parker RA, Wood R, Resch SC, Horstman NK, Freedberg KA, Paltiel AD
BACKGROUND: For young South African women at risk for human immunodeficiency virus (HIV) infection, preexposure prophylaxis (PrEP) is one of the few effective prevention options available. Long-acting injectable PrEP, which is in development, may be associated with greater adherence, compared with that for existing standard oral PrEP formulations, but its likely clinical benefits and additional costs are unknown.
METHODS: Using a computer simulation, we compared the following 3 PrEP strategies: no PrEP, standard PrEP (effectiveness, 62%; cost per patient, $150/year), and long-acting PrEP (effectiveness, 75%; cost per patient, $220/year) in South African women at high risk for HIV infection (incidence of HIV infection, 5%/year). We examined the sensitivity of the strategies to changes in key input parameters among several outcome measures, including deaths averted and program cost over a 5-year period; lifetime HIV infection risk, survival rate, and program cost and cost-effectiveness; and budget impact.
RESULTS: Compared with no PrEP, standard PrEP and long-acting PrEP cost $580 and $870 more per woman, respectively, and averted 15 and 16 deaths per 1000 women at high risk for infection, respectively, over 5 years. Measured on a lifetime basis, both standard PrEP and long-acting PrEP were cost saving, compared with no PrEP. Compared with standard PrEP, long-acting PrEP was very cost-effective ($150/life-year saved) except under the most pessimistic assumptions. Over 5 years, long-acting PrEP cost $1.6 billion when provided to 50% of eligible women.
CONCLUSIONS: Currently available standard PrEP is a cost-saving intervention whose delivery should be expanded and optimized. Long-acting PrEP will likely be a very cost-effective improvement over standard PrEP but may require novel financing mechanisms that bring short-term fiscal planning efforts into closer alignment with longer-term societal objectives.
PMID: 26681778 [PubMed - indexed for MEDLINE]