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Background Adding a slow vital capacity (SVC) to multiple breath washout (MBW) allows quantification of otherwise overlooked signal from under/un-ventilated lung units (UVLU) and may provide a more comprehensive assessment of airway disease than conventional lung clearance index (LCI2.5). Methods We conducted a pilot study on people undergoing MBW tests: 10 healthy controls (HC) and 43 cystic fibrosis (CF) subjects performed an SVC after the standard end of test. We term the new outcome LCI with Short extension (LCIShX). We assessed (i) CF/ HC differences, (ii) variability (iii) effect of pulmonary exacerbation (PEx)/treatment and (iv) relationship with CF computed tomography (CFCT) scores. Results HC/ CF group differences were larger with LCIShX than LCI2.5 (P Conclusions UVLU captured within the LCIShX varies between individuals; the lack of relationship with LCI2.5 demonstrates that new, additional information is being captured. LCIShX repeatability during clinical stability combined with its larger signal around episodes of PEx may lend it superior sensitivity as an outcome measure. Further studies will build on this pilot data to fully establish its utility in monitoring disease status.

Background Pseudomonas aeruginosa (Pa) and Aspergillus species (Asp) are the most common bacterial and fungal organisms respectively in CF airways. Our aim was to examine impacts of Asp infection and Pa/Asp co-infection. Methods Patients on the UK CF Registry in 2016 were grouped into: absent (Pa-), intermittent (Pai) or chronic Pa (Pac), each with Asp positive (Asp+) or negative (Asp-). Primary outcome was best percentage predicted FEV1 (ppFEV1) that year. Secondary outcomes were intravenous (IV) antibiotic courses, growth (height, weight, BMI) and additional disease complications. Associations between outcomes and infection-status were assessed using regression models adjusting for significant confounders (age, sex, Phe508del homozygosity and CF-related diabetes (CFRD)). Results 9,270 patients were included (median age 19 [IQR 9-30] years, 54% male, 50% Phe508del/F508del). 4,142 patients (45%) isolated Pa, 1,460 (16%) Asp. Pa-/Asp+ subjects had an adjusted ppFEV1 that was 5.9% lower than Pa-/Asp- (p Conclusions Co-infection with Pa and Asp was not associated with reduced lung function compared with Pa alone, but was associated with additional use of IV antibiotics. Asp infection itself is associated with several important indicators of disease severity. Longitudinal analyses should explore the impact of co-infection on disease progression.

Cystic fibrosis is the most common inherited condition in the Caucasian population and is associated with significantly reduced life expectancy. Recent advances in treatment have focussed on addressing the underlying cause of the condition, the defective production, expression and function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Several drugs with different modes of action have produced promising results in clinical trials, and some have been incorporated into routine clinical care for specific patients in many countries worldwide. Further trials continue to explore the safety and efficacy of these drugs in the youngest age groups and to search for more effective therapies to treat the most common disease-causing gene mutations in an ever-expanding drug pipeline. As evidence mounts for the early onset of disease in young patients, the prospect of introducing disease-modifying therapy in early life becomes more pertinent, although the cost implications of these expensive drugs are significant. In this review, we summarise these new therapy advances and review those currently being explored in clinical trials.

Variceal haemorrhage can be a life-threatening complication of chronic liver disease in children. There is limited evidence about the optimal prophylactic management and selection criteria of children who will benefit from upper gastrointestinal endoscopy.Children presenting in our centre with suspected portal hypertension or gastrointestinal bleeding and undergoing their first oesophagogastroduodenoscopy between 2005 and 2012 were included. Clinical, biochemical, and radiological data were collected. A separate validation cohort from May 2013 to October 2014 was obtained.Data on 124 treatment-naïve patients were collected; 50% had biliary atresia. Thirty-five (28%) children presented with gastrointestinal bleeding and overall 79 (64%) had clinically significant (grade II-III) varices. Clinical prediction rule, aspartate aminotransferase-platelet ratio index, and varices prediction rule had at optimal cut-off sensitivity and specificity of 76% and 59%, 60% and 55%, and 80% and 59%, respectively. Logistic regression yielded a new prediction rule of (3 × albumin ([g/dL]) - (2 - equivalent adult spleen size [cm]). This King's variceal prediction score had a favourable areas under the curve of 0.772 (0.677-0.867) compared to clinical prediction rule 0.732 (0.632-0.832). At the optimal cut-off of 76 this yielded a sensitivity and specificity of 72% and 73% and a positive and negative predictive value of 82% and 60%, respectively. In the validation cohort areas under the curve was 0.818 (0.654-0.995) with sensitivity and specificity of 78% and 73%, respectively.Our new prediction score may be a useful tool in the selection of children with clinically significant varices eligible for a screening endoscopy.

Purpose: To report a salvage maneuver for accidental coverage of both renal arteries during endovascular aneurysm repair (EVAR) of an infrarenal aortic aneurysm (AAA) and survey our surgical colleagues in the UK for their use of this bypass procedure.Methods:A 74-year-old woman who had an EVAR complicated by renal failure secondary to malposition of the stent-graft underwent successful delayed renal revascularization with hepatorenal and splenorenal bypasses. This case prompted a literature review and preparation of an online 6-part questionnaire regarding the incidence and management of renal impairment following EVAR. The survey invitation was sent to all listed members of the Vascular Society of Great Britain and Ireland.Results: Responses from 68 (10.5%) of the 650 vascular surgeons invited to participate in the survey were analyzed. The combined experience of those who completed the survey was >1500 EVAR procedures per annum. Forty percent (27/68) of the respondents had experienced a case of bilateral renal artery occlusion during EVAR. Two thirds (67%, 18/27) of these surgeons stated a preference for revascularizing the kidneys endovascularly, 7 surgeons would convert to open repair, 1 surgeon favored iliorenal bypass, and another suggested splenorenal bypass. Following intervention, 15 (56%) of 27 surgeons achieved revascularization that resulted in a return to baseline serum creatinine, 7 (26%) achieved partial recovery of the patient's serum creatinine, 3 (11%) had a patient on permanent dialysis, and 2 (7%) had patients who died (after open repair and endovascular procedure, respectively).Conclusion: Bilateral renal artery occlusion caused by malposition of a stent-graft is probably underreported. If revascularization of the kidneys by endovascular techniques fails, there is no consensus as to the optimal approach. Delayed revascularization should be considered if the kidneys show concentration of imaging contrast. Hepato-spleno-renal bypass, which has not heretofore been indicated for renal salvage post EVAR, can provide a good functional result in this situation. J Endovasc Ther. 2010;17:326-331

Auditory neuropathy is characterized by mild-to-moderate pure-tone hearing loss, poor speech discrimination out of proportion with this loss, absent or abnormal auditory brainstem responses and normal outer hair cell function as measured by otoacoustic emissions and cochlear microphonics. We followed three patients in our clinic whom we classified as auditory neuropathy patients. These patients also complained of balance disorders and we report our auditory and vestibular system analyses of these patients. The data presented herein include results of audiometric tests (serial pure-tone audiometry and speech discrimination tests), otoacoustic emissions, auditory-evoked brainstem responses and vestibular function tests (clinical tests of balance, electronystagmography, damped rotation tests and vestibular-evoked myogenic potentials). In all patients, pure-tone audiometry revealed mild-to-moderate sensorineural hearing loss, markedly poor speech discrimination scores and absent auditory-evoked brainstem responses, all in the presence of normal otoacoustic emissions. Balance tests (caloric tests and damped rotation test) were abnormal. Saccades, smooth pursuit eye movements and optokinetic nystagmus were normal in all patients. Neurological and motor system evaluations were normal in all patients. These three auditory neuropathy patients manifest a disorder of cochlear nerve function in the presence of normal outer hair cell activity. They additionally manifest a disorder of the vestibular nerve and its end organs. We conclude that, in patients with isolated auditory neuropathy, the vestibular branch of the VIIIth cranial nerve and its innervated structures may also be affected. We suggest the use of the term "cochlear neuropathy" to characterize those patients with involvement of only the auditory branch of the VIIIth cranial nerve and its innervation.

The depressive effects of lidocaine hydrochloride on cochlear function were observed in 18 cats. Round window cochlear microphonics and action potentials were recorded before and after lidocaine application onto the round window membrane. Lidocaine hydrochloride depressed both CM and AP and these effects were always reversible with a maximum recovery time of six hours. The times of maximum depression and recovery of cochlear function were directly related to lidocaine concentration. It seems possible that fairly reproducible, reversible cochlear lesions can be made by expanding on this study.

The effects of the monaural and binaural stimulation to the auditory-evoked brain stem response (BSR) were studied in 16 normal hearing adults. The BSRs were recorded from the scalp using computer averaging technique. A click was used for a stimulating sound. The latencies of waves I through VII, the overall BSR amplitude and probability of detection of the various waves were compared as a function of monaural stimulation (with ipsilateral and contralateral recording) and binaural stimulation (with unilateral recording). Overall amplitude of the BSR waveform following binaural stimulation was larger than the amplitude following monaural stimulation. Also, the waveform and the amplitude of the BSR following binaural stimulation were quite similar to the simple summation of the monaural ipsilateral and contralateral recordings. This finding may be comparable to psychoacoustic data wherein simultaneous binaural auditory stimulation results in a threshold which is about 3dB lower than monaural stimulation.

The effect of click repetition rate and intensity on wave V latency, amplitude and probability of wave detection (I-VII) was observed in 10 normal listeners. Click repetition rates of 10, 30, 50 and 70c/s were presented at each of 70, 50 and 30dBHL intensities.Results as follows.1. Increasing the click rate results in an increase in the latency of wave V (a click rate increase from 10 to 70c/s cause a 0.5msec shift). Also an increase in the click rate results in a decrease in the amplitude and a lowering of the probability of wave detection.2. Increasing the click intensity results in a shortening of wave V latency (An intensity increase from 30 to 70dBHL results in a 1.4msec shift). Also an increse in the click intensity results in an increase in the amplitude and an increase in the probability of detection of all waves.3. A convienient click repetition rate in the clinical routine examination is 10 to 30c/s.

A significant number of schizophrenic patients show patterns of smooth pursuit eye-tracking patterns that differ strikingly from the generally smooth eye-tracking seen in normals and in nonschizophrenic patients. These deviations are probably referable not only to motivational or attentional factors, but also to oculomotor involvement that may have a critical relevance for perceptual dysfunction in schizophrenia.