Rickettsia species causing human illness are present globally and can cause significant disease. Diagnosis and identification of this intracellular bacteria are challenging with many available ...diagnostic modalities suffering from several shortcomings. Detection of antibodies directed against Rickettsia spp. via serological methods remains widely used with a broad range of sensitivity and specificity values reported depending on the assay. Molecular methods, including polymerase chain reaction (PCR) testing, enables species-specific identification with a fast turnaround time; however, due to resource requirements, use in some endemic settings is limited. Reports on the use of next-generation sequencing (NGS) and metagenomics to diagnose Rickettsia spp. infection have been increasing. Despite offering several potential advantages in the diagnosis and surveillance of disease, genomic approaches are currently only limited to reference and research laboratories. Continued development of Rickettsia spp. diagnostics is required to improve disease detection and epidemiological surveillance, and to better understand transmission dynamics.
Context:
Patients with treated adrenal insufficiency (AI) have increased morbidity and mortality rate. Our goal was to improve outcome by developing a once-daily (OD) oral hydrocortisone dual-release ...tablet with a more physiological exposure-time cortisol profile.
Objective:
The aim was to compare pharmacokinetics and metabolic outcome between OD and the same daily dose of thrice-daily (TID) dose of conventional hydrocortisone tablets.
Design and Setting:
We conducted an open, randomized, two-period, 12-wk crossover multicenter trial with a 24-wk extension at five university hospital centers.
Patients:
The trial enrolled 64 adults with primary AI; 11 had concomitant diabetes mellitus (DM).
Intervention:
The same daily dose of hydrocortisone was administered as OD dual-release or TID.
Main Outcome Measure:
We evaluated cortisol pharmacokinetics.
Results:
Compared with conventional TID, OD provided a sustained serum cortisol profile 0–4 h after the morning intake and reduced the late afternoon and the 24-h cortisol exposure. The mean weight (difference = −0.7 kg, P = 0.005), systolic blood pressure (difference = −5.5 mm Hg, P = 0.0001) and diastolic blood pressure (difference: −2.3 mm Hg; P = 0.03), and glycated hemoglobin (absolute difference = −0.1%, P = 0.0006) were all reduced after OD compared with TID at 12 wk. Compared with TID, a reduction in glycated hemoglobin by 0.6% was observed in patients with concomitant DM during OD (P = 0.004).
Conclusion:
The OD dual-release tablet provided a more circadian-based serum cortisol profile. Reduced body weight, reduced blood pressure, and improved glucose metabolism were observed during OD treatment. In particular, glucose metabolism improved in patients with concomitant DM.
The Task Force zealously avoids actual, potential, or perceived conflicts of interest that might arise through relationships with industry or other entities (RWI).\n Jaff Content Reviewer ...Newton-Wellesley Hospital; Harvard Medical School--Professor of Medicine AOPA Cardinal Health Covidiendagger Micell Vascular Therapies None MC10dagger Janacaredagger Northwind PQ Bypass Primacea SanoV Valiant Medical Abbottdagger Boston Scientificdagger Cordisdagger IC Sciences Medtronicdagger Novello CBSET Intersocietal Accreditation Commission SCAIdagger VIVA Physicians Grouplow * None José A. Joglar Content Reviewer--ACC/AHA Task Force on Clinical Practice Guidelines UT Southwestern Medical Center--Professor of Internal Medicine; Clinical Cardiac Electrophysiology--Fellowship Program Director None None None None None None Glenn N. Levine Content Reviewer--ACC/AHA Task Force on Clinical Practice Guidelines Baylor College of Medicine--Professor of Medicine; Director, Cardiac Care Unit None None None None None None Khusrow Niazi Content Reviewer--ACC Peripheral Vascular Disease Member Section Emory University Department of Medicine--Associate Professor of Medicine None Medtroniclow * None Bard Impeto Terumo None Plaintiff, MI resulting in death, 2015low * Paul D. Varosy Content Reviewer--Task Force on Performance Measures VA Eastern Colorado Health Care System--Associate Professor None None None VA Health Services Research and Development (PI)low * AHA (Guest Editor)dagger None Christopher J. White Content Reviewer Ochsner Clinical School, University of Queensland--Chairman, Department of Cardiology Neovasc None None AstraZeneca Pharmaceuticals NIH Neovasc Surmodics ACE (Board of Directors)dagger None black square This table represents all relationships of reviewers with industry and other entities that were reported by authors, including those not deemed to be relevant to this document, at the time this document was under development. Please refer to http://www.acc.org/guidelines/about-guidelines-and-clinical-documents/relationships-with-industry-policy for definitions of disclosure categories or additional information about the ACC/AHA Disclosure Policy for Writing Committees.AACVPR indicates American Association of Cardiovascular and Pulmonary Rehabilitation; ACC, American College of Cardiology; ACE, Accreditation for Cardiovascular Excellence; AHA, American Heart Association; AMA, American Medical Association; DSMB, data and safety monitoring board; EUCLID, Effects of Ticagrelor and Clopidogrel in Patients with Peripheral Artery Disease; FDA, U.S. Food and Drug Administration; HRS, Heart Rhythm Society; MI, myocardial infarction; NCDR, National Cardiovascular Data Registry; NIH, National Institutes of Health; NHLBI, National Heart, Lung, and Blood Institute; PCORI, Patient-Centered Outcomes Research Institute; PI, primary investigator; PLX-PAD, placental-derived adherent stromal cell; SCAI, Society for Cardiovascular Angiography and Interventions; SCVS, Society for Clinical Vascular Surgery; SIR, Society of Interventional Radiology; SVM, Society for Vascular Medicine; SVN, Society for Vascular Nursing; SVS, Society for Vascular Surgery; TASC, Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease; VA, Veterans Affairs; VESS, Vascular and Endovascular Surgery Society; and VIVA, Vascular Intervention Advances.
Extramedullary hematopoiesis (EMH) expands hematopoietic capacity outside of the bone marrow in response to inflammatory conditions, including infections and cancer. Because of its inducible nature, ...EMH offers a unique opportunity to study the interaction between hematopoietic stem and progenitor cells (HSPCs) and their niche. In cancer patients, the spleen frequently serves as an EMH organ and provides myeloid cells that may worsen pathology. Here, we examined the relationship between HSPCs and their splenic niche in EMH in a mouse breast cancer model. We identify tumor produced IL-1α and leukemia inhibitory factor (LIF) acting on splenic HSPCs and splenic niche cells, respectively. IL-1α induced TNFα expression in splenic HSPCs, which then activated splenic niche activity, while LIF induced proliferation of splenic niche cells. IL-1α and LIF display cooperative effects in activating EMH and are both up-regulated in some human cancers. Together, these data expand avenues for developing niche-directed therapies and further exploring EMH accompanying inflammatory pathologies like cancer.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
The objective of this study was to describe the first US‐based study to use the European Position Paper on Rhinosinusitis (EPOS) criteria to study the prevalence of chronic rhinosinusitis ...(CRS) in a general‐population sample.
Methods
A CRS symptom questionnaire was mailed to 23 700 primary care patients from Geisinger Clinic, a health system serving 45 counties in Pennsylvania. CRS cases were categorized into four unique subgroups based on EPOS symptoms: obstruction and discharge with no smell loss or pain/pressure; smell loss without pain/pressure; facial pain and/or pressure without smell loss; and both smell loss and pain/pressure. All cases were required to have nasal obstruction or discharge. Logistic regression was used to evaluate potential factors associated with CRS subgroups.
Results
We found that 11.9% of patients met criteria for CRS. Prevalence peaked at 15.9% between ages 50 and 59 years and then dropped to 6.8% after age 69. The odds of CRS was higher among patients who were white, younger, smokers, had a history of Medical Assistance, and had other diseases. When CRS subgroups were modeled separately, these associations were no longer significant for some CRS subgroups. Comorbid diseases were most strongly associated with CRS cases who reported smell loss and facial pain and/or pressure and had the weakest associations with CRS cases who did not report these symptoms.
Conclusions
CRS is a highly prevalent and heterogeneous condition. Differences in risk factors and health outcomes across symptom subgroups may be indicative of differences in etiology that have implications for disease management.
Rickettsial infections are a common cause of hospitalization in tropical settings, although early diagnosis is challenging in the rural locations where these infections are usually seen.
This ...retrospective, clinical audit of microbiologically-confirmed cases of scrub typhus or spotted fever group (SFG) rickettsial infection between 1997 and 2016 was performed a tertiary referral hospital in tropical Australia. Clinical, laboratory and radiological findings at presentation were correlated with the patients' subsequent clinical course.
There were 135 locally-acquired cases (95 scrub typhus, 37 SFG, 3 undifferentiated). There were nine hospitalizations during the first 5 years of the study period and 81 in the last 5 years (p for trend = 0.003). Eighteen (13%) of the 135 cases required ICU admission, all of whom were adults. A greater proportion of patients with SFG infection required ICU support (8/37 (22%) compared with 10/95 (11%) scrub typhus cases), although this difference did not reach statistical significance (p = 0.10). Three (8%) of the 37 patients with SFG infection had severe disease (1 died, 2 developed permanent disability) versus 0/95 scrub typhus patients (p = 0.02). Adults with a high admission qSOFA score (≥2) had an odds ratio (OR) of 19 (95% CI:4.8-74.5) for subsequent ICU admission (p<0.001); adults with a high NEWS2 score (≥7) had an OR of 14.3 (95% CI:4.5-45.32) for ICU admission (p<0.001). A patient's respiratory rate at presentation had strong prognostic utility: if an adult had an admission respiratory rate <22 breaths/minute, the negative predictive value for subsequent ICU admission was 95% (95% CI 88-99).
In the well-resourced Australian health system outcomes are excellent, but the local burden of rickettsial disease appears to be increasing and the clinical phenotype of SFG infections may be more severe than previously believed. Simple, clinical assessment on admission has prognostic utility and may be used to guide management.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Multiple myeloma is a plasma cell disorder that is characterised by clonal proliferation of malignant plasma cells in the bone marrow, monoclonal paraprotein in the blood or urine and associated ...organ dysfunction. It accounts for approximately 1% of cancers and 13% of haematological cancers. Myeloma arises from an asymptomatic proliferation of monoclonal plasma cells termed monoclonal gammopathy of undetermined significance (MGUS).
MicroRNA expression profiling of serum samples was performed on three patient groups as well as normal controls. Validation of the nine microRNAs detected as promising biomarkers was carried out using TaqMan quantitative reverse transcription PCR. MicroRNA levels in serum were normalised using standard curves to determine the numbers of microRNAs per μl of serum.
Three serum microRNAs, miR-720, miR-1308 and miR-1246, were found to have potential as diagnostic biomarkers in myeloma. Use of miR-720 and miR-1308 together provides a powerful diagnostic tool for distinguishing normal healthy controls, as well as patients with unrelated illnesses, from pre-cancerous myeloma and myeloma patients. In addition, the combination of miR-1246 and miR-1308 can distinguish MGUS from myeloma patients.
We have developed a biomarker signature using microRNAs extracted from serum, which has potential as a diagnostic and prognostic tool for multiple myeloma.
The continued focus of attention on the diversity of mechanisms underpinning inflammation has improved our understanding of the potential to target specific pathways in the inflammatory network to ...achieve meaningful therapeutic gains. In this themed issue of the British Journal of Pharmacology our scope was deliberately broad, ranging across both acute and chronic disease in various organs. Pro‐ and anti‐inflammatory mechanisms receive attention as does the phenotype of macrophages. Whilst the manifestations of neuro‐inflammation are less obvious than those in peripheral tissues, central innate and adaptive immunity in brain and the M1/M2 phenotypes of microglia are topics of special interest. The contributions to the inflammatory milieu of cytokines, chemokines and associated signalling cascades are considered. Overall, the coverage herein advances the basic science underpinning our understanding of inflammation and emphasizes its importance in different pathologies.
Linked Articles
This article is part of a themed section on Inflammation: maladies, models, mechanisms and molecules. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2016.173.issue-4
CONTEXT A low ankle brachial index (ABI) indicates atherosclerosis and an increased risk of cardiovascular and cerebrovascular events. Screening for a low ABI can identify an asymptomatic higher risk ...group potentially amenable to preventive treatments. OBJECTIVE To determine the effectiveness of aspirin in preventing events in people with a low ABI identified on screening the general population. DESIGN, SETTING, AND PARTICIPANTS The Aspirin for Asymptomatic Atherosclerosis trial was an intention-to-treat double-blind randomized controlled trial conducted from April 1998 to October 2008, involving 28 980 men and women aged 50 to 75 years living in central Scotland, free of clinical cardiovascular disease, recruited from a community health registry, and had an ABI screening test. Of those, 3350 with a low ABI (≤0.95) were entered into the trial, which was powered to detect a 25% proportional risk reduction in events. INTERVENTIONS Once daily 100 mg aspirin (enteric coated) or placebo. MAIN OUTCOME MEASURES The primary end point was a composite of initial fatal or nonfatal coronary event or stroke or revascularization. Two secondary end points were (1) all initial vascular events defined as a composite of a primary end point event or angina, intermittent claudication, or transient ischemic attack; and (2) all-cause mortality. RESULTS After a mean (SD) follow-up of 8.2 (1.6) years, 357 participants had a primary end point event (13.5 per 1000 person-years, 95% confidence interval CI, 12.2-15.0). No statistically significant difference was found between groups (13.7 events per 1000 person-years in the aspirin group vs 13.3 in the placebo group; hazard ratio HR, 1.03; 95% CI, 0.84-1.27). A vascular event comprising the secondary end point occurred in 578 participants (22.8 per 1000 person-years; 95% CI, 21.0-24.8) and no statistically significant difference between groups (22.8 events per 1000 person-years in the aspirin group vs 22.9 in the placebo group; HR, 1.00; 95% CI, 0.85-1.17). There was no significant difference in all-cause mortality between groups (176 vs 186 deaths, respectively; HR, 0.95; 95% CI, 0.77-1.16). An initial event of major hemorrhage requiring admission to hospital occurred in 34 participants (2.5 per 1000 person-years) in the aspirin group and 20 (1.5 per 1000 person-years) in the placebo group (HR, 1.71; 95% CI, 0.99-2.97). CONCLUSION Among participants without clinical cardiovascular disease, identified with a low ABI based on screening a general population, the administration of aspirin compared with placebo did not result in a significant reduction in vascular events. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN66587262
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