Arterial distensibility in children and teenagers: Normal evolution and the effect of childhood vasculitis

Background: Polyarteritis nodosa is a necrotising vasculitis of the medium sized and small muscular arteries. The inflammatory and subsequent reparative processes may alter the arterial mechanical properties. The effect of vasculitic damage on arterial distensibility has never been explored however. Aim: To determine the normal values and the effect of childhood vasculitis on arterial distensibility in children and teenagers. Methods: Distensibility of the brachioradial arterial segment was studied using pulse wave velocity (PWV ∝1/√distensibility), in 13 children with polyarteritis nodosa at a median age of 11.8 (range 4.9-16) years. As a control group, 155 healthy schoolchildren (6-18 years, 81 boys) were studied. PWV was assessed using a photoplethysmographic technique; blood pressure was measured by an automatic sphygmomanometer (Dinamap). Data from patients were expressed as z scores adjusted for age and compared to a population mean of 0 by a single sample t test. Determinants of PWV in normal children were assessed by univariate and multivariate linear regression analyses. Results: Age, height, weight, and systolic blood pressure correlated individually with the brachioradial PWV. Multivariate analysis identified age as the only independent determinant. Ten of the patients were in clinical remission, while three had evidence of disease activity at the time of study. The PWV in the patient group as a whole was significantly greater than those in healthy children (mean z score +0.99). Raised C reactive protein concentration (>2 mg/dl) in the three patients with active disease was associated with a higher PWV when compared to those in remission (z score +2.78 v +0.45). The diastolic blood pressure of the patients was higher than those of the controls (z score + 1.04) while the systolic pressure was similar (z score -0.36). Conclusions: PWV in the brachioradial arterial segment increases gradually during childhood independent of body weight, height, mass, and blood pressure. Increased PWV, and hence decreased distensibility, in this peripheral arterial segment occurs in polyarteritis nodosa and is amplified during acute inflammatory exacerbation.published_or_final_versio

Characteristics of Mid-Frequency Sensorineural Hearing Loss Progression.

OBJECTIVES:To characterize the progression of mid-frequency sensorineural hearing loss (MFSNHL) over time. METHODS:A retrospective chart review spanning 2012 to 2017 was performed at a tertiary care audiology and neurotology center. Our cohort included 37 patients met the criteria for MFSNHL also known as "cookie bite hearing loss." It was defined as having a 1, 2, and 4 kHz average pure tone audiometry greater than 10 dB in intensity compared with the average threshold at 500 Hz and 8 kHz. RESULTS:Average age at initial presentation was 11.8 years (range, 8 mo to 70 yr). Across all individuals, the average mid-frequency threshold was 47 dB, compared with 27 dB at 500 Hz and 8 kHz. Twenty-three patients (62%) had multiple audiograms with 4-year median follow up time. Average values across all frequencies (0.5, 1, 2, 4, 8 kHz) in the initial audiogram was 37 dB, compared with an average of 39 dB demonstrated on final audiogram. Of those with serial audiograms, only five patients demonstrated threshold changes of 10 dB or more. Of these five patients, only one was found to have clinical worsening of MFSNHL. CONCLUSIONS:MFSNHL is an uncommon audiometric finding with unspecified long-term outcomes. We demonstrated that most patients (96%) with MFSNHL do not experience clinical worsening of their hearing threshold over almost 4 years of follow up. Future prospective studies aimed at collecting longer-term data are warranted to further elucidate the long-term trajectory of MFSNHL patients

Medical Malpractice of Vestibular Schwannoma: A 40-Year Review of the United States Legal Databases.

OBJECTIVES:To analyze medical malpractice lawsuit trends pertaining to cases of vestibular schwannomas (VS). METHODS:Two major computerized legal databases (LexisNexis and WestLaw) were queried and reviewed for evaluation of all the US state and federal court records from civil trials alleging malpractice between 1976 and 2016. RESULTS:A total of 32 VS cases were identified. Allegations were divided into four categories: misdiagnosis/delayed diagnosis (47%), postoperative complications (44%), failure of informed consent or information sharing (16%), and other (3%). Postoperative complications included facial nerve paralysis, myocardial infarction, meningitis, and intracranial hemorrhage. Judgment amounts ranged from $300,000 to$2,000,000. The specialist type was specified for 24 of the 32 cases (75%): neurosurgeons (n = 9; 37%), neurotologists (n = 6; 25%), general otolaryngologists (n = 5; 21%), primary care physicians (n = 4; 17%), neurologists (n = 3; 12%), radiologists (n = 3; 12%), anesthesiologists (n = 2; 8%), radiation oncologists (n = 1; 4%), and general surgeon (n = 1; 4%). Of these 24 cases, (n = 9; 37%) two or more physicians were named as defendants in the lawsuit. CONCLUSIONS:Enhanced physician-patient communication, ensuring proper and adequate patient consent procedures, and proper documentation are good practices that may decrease the likelihood of lawsuits

Driving chronicity in rheumatoid arthritis: perpetuating role of myeloid cells

Acute inflammation is a complex and tightly regulated homeostatic process that includes leukocyte migration from the vasculature into tissues to eliminate the pathogen/injury, followed by a pro-resolving response promoting tissue repair. However, if inflammation is uncontrolled as in chronic diseases such as Rheumatoid Arthritis (RA) it leads to tissue damage and disability. Synovial tissue inflammation in RA patients is maintained by sustained activation of multiple inflammatory positive-feedback regulatory pathways in a variety of cells including myeloid cells. In this review, we will highlight recent evidence uncovering biological mechanisms contributing to the aberrant activation of myeloid cells that contributes to perpetuation of inflammation in RA, and discuss emerging data on anti-inflammatory mediators contributing to sustained remission that may inform a novel category of therapeutic targets

Structural Coupling between RNA Polymerase Composition and DNA Supercoiling in Coordinating Transcription: a Global Role for the Omega Subunit?

In growing bacterial cells, the global reorganization of transcription is associated with alterations of RNA polymerase composition and the superhelical density of the DNA. However, the existence of any regulatory device coordinating these changes remains elusive. Here we show that in an exponentially growing Escherichia coli rpoZ mutant lacking the polymerase ω subunit, the impact of the Eσ38 holoenzyme on transcription is enhanced in parallel with overall DNA relaxation. Conversely, overproduction of σ70 in an rpoZ mutant increases both overall DNA supercoiling and the transcription of genes utilizing high negative superhelicity. We further show that transcription driven by the Eσ38 and Eσ70 holoenzymes from cognate promoters induces distinct superhelical densities of plasmid DNA in vivo. We thus demonstrate a tight coupling between polymerase holoenzyme composition and the supercoiling regimen of genomic transcription. Accordingly, we identify functional clusters of genes with distinct σ factor and supercoiling preferences arranging alternative transcription programs sustaining bacterial exponential growth. We propose that structural coupling between DNA topology and holoenzyme composition provides a basic regulatory device for coordinating genome-wide transcription during bacterial growth and adaptation

Medium-size-vessel vasculitis

Medium-size-artery vasculitides do occur in childhood and manifest, in the main, as polyarteritis nodosa (PAN), cutaneous PAN and Kawasaki disease. Of these, PAN is the most serious, with high morbidity and not inconsequential mortality rates. New classification criteria for PAN have been validated that will have value in epidemiological studies and clinical trials. Renal involvement is common and recent therapeutic advances may result in improved treatment options. Cutaneous PAN is a milder disease characterised by periodic exacerbations and often associated with streptococcal infection. There is controversy as to whether this is a separate entity or part of the systemic PAN spectrum. Kawasaki disease is an acute self-limiting systemic vasculitis, the second commonest vasculitis in childhood and the commonest cause of childhood-acquired heart disease. Renal manifestations occur and include tubulointerstitial nephritis and renal failure. An infectious trigger and a genetic predisposition seem likely. Intravenous immunoglobulin (IV-Ig) and aspirin are effective therapeutically, but in resistant cases, either steroid or infliximab have a role. Greater understanding of the pathogenetic mechanisms involved in these three types of vasculitis and better long-term follow-up data will lead to improved therapy and prediction of prognosis

Recent advances in understanding hypertension development in sub-Saharan Africa

Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the Human Immunodeficiency Virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions, as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies, and (c) policymakers and health advocates to collectively contribute in creating health-promoting environments in Africa