Can serum IgE or blood eosinophil count predict postoperative oral corticosteroid response in chronic rhinosinusitis with nasal polyps?

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterised by inflammatory mucosa and polyp formation in the paranasal sinuses. The study's primary objective was to evaluate the outcomes of postoperative oral corticosteroid (OCS) in treating patients with bilateral CRSwNP. The secondary objective was to determine whether preoperative serum IgE levels (sIgE)and/or blood eosinophil count (BEC) correlate with postoperative outcomes following OCS use. METHODS: Patients with bilateral CRSwNP (n=236) who underwent endoscopic sinus surgery (ESS) were randomly assigned to receive 15 mg OCS twice daily or a placebo for 2 weeks. We investigated the treatment effects based on the subjective visual analogue scale (VAS), Sino-Nasal Outcome Test 22 (SNOT-22), and objective Lund-Kennedy Endoscopy Score (LKES) over 6 months; subgroups were stratified preoperatively as follows: sIgE <150 IU/mL, sIgE>=150 IU/mL, BEC <0.39x10(9) cells/L, and BEC>=0.39x10(9) cells/L. RESULTS: A total of 193 participants completed the study up to the 6-month follow-up; no apparent linear relationship was noted between sIgE and BEC. No significant differences in scores were noted upon assessment of the VAS, SNOT-22, and LKES among the follow-up timepoints in the primary analysis. However, in the primary or subgroup analyses with sIgE or BEC, significant differences in the longitudinal scores of sleep dysfunction were observed at the 1-month follow-up. CONCLUSION: Postoperative OCS did not significantly affect bilateral CRSwNP outcomes. sIgE levels and BEC may not be surrogate predictive biomarkers to assess the role of postoperative OCS use. OCS may increase the risk of transient sleep disturbance.

ABO-Nonidentical Liver Transplantation in the United States.

Under the United Network for Organ Sharing (UNOS) policy, deceased donor livers may be offered to ABO-nonidentical candidates at each given Model for End-Stage Liver Disease (MELD) score and to blood type B candidates at MELD ≥30. To evaluate ABO-nonidentical liver transplantation (LT) in the United States, we examined all adult LT non-status 1 candidates, recipients and deceased liver donors from 2013 to 2015. There were 34 920 LT candidates (47% type O, 38% type A, 12% type B, 3% type AB) and 10 479 deceased liver donors (47% type O, 38% type A, 12% type B, 3% type AB). ABO-nonidentical LT occurred in 2%, 3%, 20% and 36% of types O, A, B and AB recipients, respectively, which led to a net liver loss of 6% for type O and 2% for type A recipients but a net liver gain of 14% for type B and 55% for type AB recipients. The LT MELD scores of ABO-identical versus -nonidentical recipients were 29 versus 34 for type O, 29 versus 19 for type A, 25 versus 38 for type B, and 22 versus 28 for type AB (p < 0.01). ABO-nonidentical LT increased liver supply for candidates with blood types B and AB but decreased supply for type O and A candidates. We urge refinement of UNOS policy surrounding ABO-nonidentical LT.

Frailty predicts waitlist mortality in liver transplant candidates.

We aimed to determine whether frailty, a validated geriatric construct of increased vulnerability to physiologic stressors, predicts mortality in liver transplant candidates. Consecutive adult outpatients listed for liver transplant with laboratory Model for End-Stage Liver Disease (MELD) ≥ 12 at a single center (97% recruitment rate) underwent four frailty assessments: Fried Frailty, Short Physical Performance Battery (SPPB), Activities of Daily Living (ADL) and Instrumental ADL (IADL) scales. Competing risks models associated frailty with waitlist mortality (death/delisting for being too sick for liver transplant). Two hundred ninety-four listed liver transplant patients with MELD ≥ 12, median age 60 years and MELD 15 were followed for 12 months. By Fried Frailty score ≥3, 17% were frail; 11/51 (22%) of the frail versus 25/243 (10%) of the not frail died/were delisted (p = 0.03). Each 1-unit increase in the Fried Frailty score was associated with a 45% (95% confidence interval, 4-202) increased risk of waitlist mortality adjusted for MELD. Similarly, the adjusted risk of waitlist mortality associated with each 1-unit decrease (i.e. increasing frailty) in the Short Physical Performance Battery (hazard ratio 1.19, 95% confidence interval 1.07-1.32). Frailty is prevalent in liver transplant candidates. It strongly predicts waitlist mortality, even after adjustment for liver disease severity demonstrating the applicability and importance of the frailty construct in this population.

Reducing infection transmission in solid organ transplantation through donor nucleic acid testing: a cost-effectiveness analysis.

For solid organ transplant (SOT) donors, nucleic acid-amplification testing (NAT) may reduce human immunodeficiency virus (HIV) and hepatitis C virus (HCV) transmission over antibody (Ab) testing given its shorter detection window period. We compared SOT donor NAT + Ab versus Ab alone using decision models to estimate incremental cost-effectiveness ratios (ICERs; cost per quality-adjusted life year [QALY] gained) from the societal perspective across a range of HIV/HCV prevalence values and NAT costs. The cost per QALY gained was calculated for two scenarios: (1) favorable: low cost ($150/donor)/high prevalence (HIV: 1.5%; HCV: 18.2%) and (2) unfavorable: high cost ($500/donor)/low prevalence (HIV: 0.1%; HCV: 1.5%). In the favorable scenario, adding NAT screening cost $161 013 per QALY gained for HIV was less costly) for HCV, and cost $86 653 per QALY gained for HIV/HCV combined. For the unfavorable scenario, the costs were $15 568 484, $221 006 and $10 077 599 per QALY gained, respectively. Universal HCV NAT + Ab for donors appears cost-effective to reduce infection transmission from SOT donors, while HIV NAT + Ab is not, except where HIV NAT is ≤$150/donor and prevalence is ≥1.5%. Our analyses provide important data to facilitate the decision to implement HIV and HCV NAT for deceased SOT donors and shape national policy regarding how to reduce infection transmission in SOT.

Patient, center and geographic characteristics of nationally placed livers.

Once a liver offer has been refused locally and regionally, it is offered nationally. We characterized nationally (n = 1567) versus locally (n = 19 893) placed grafts from adult, nonfulminant, deceased donor liver transplants (LT) from 2/1/05 to 1/31/10. Donors of nationally versus locally placed livers differed by age (50 vs. 42 years), positive HCV antibody (11 vs. 2%) and death from stroke (51 vs. 42%) (p < 0.001 for all). Recipients of nationally versus locally placed livers differed by LT-MELD (20 vs. 24), rates of ascites (35 vs. 37%), encephalopathy (12 vs. 15%), hepatocellular (17 vs. 24%) and nonhepatocellular exceptions (6 vs. 11%) (p ≤ 0.03 for all). Six (5%) centers utilized 64% of the nationally placed grafts while 43 (38%) centers accepted zero during the 5-year period; all high volume centers used ≥1. Compared to local distribution, transplantation with a nationally placed liver was associated with a similar adjusted risk of graft (HR, 0.99; 95% CI, 0.86-1.14) and patient (HR, 0.98; 95% CI, 0.84-1.14; p = 0.77) survival. In conclusion, utilization of nationally placed livers is highly concentrated in very few centers, with no increased adjusted risk of graft loss. These findings provide the foundation for a more informed discussion about changing our current liver allocation and distribution policies.

Gender differences in liver donor quality are predictive of graft loss.

Some studies have found that donor-recipient gender mismatch predicts posttransplant outcomes but whether this is independent of donor quality is unknown. To evaluate the association between gender mismatch and graft loss, 11 508 females (F) and 16 714 males (M) who underwent liver transplant from March 1, 2002 to December 31, 2007 were studied. Of 11 donor characteristics, clinically relevant differences between F and M donors were median age (47 vs. 39 years), height (165 vs. 178 cm) and proportion dying of stroke (59 vs. 35%) (p < 0.001 for all). The donor risk index was significantly lower for F than M donors (1.3 vs. 1.6, p < 0.001). Recipients of gender-mismatched grafts had an 11% higher risk of graft loss (p < 0.001). Compared to M→M donor-recipient-matched transplants in univariable analysis, F→M mismatch was associated with a 17% increased risk of graft loss (95% CI = 1.11-1.24, p < 0.001), whereas M→F mismatch was not (HR = 1.02; 95% CI = 0.96-1.09; p = 0.46). However, adjustment for significant recipient and donor factors eliminated the association between F→M mismatch and graft loss (HR = 0.95; 95% CI = 0.89-1.02; p = 0.18). In conclusion, donor quality differs significantly between female and male donors-female donors are older, shorter and die more frequently of stroke-and gender differences in donor quality, rather than gender mismatch are predictive of graft loss.

Height contributes to the gender difference in wait-list mortality under the MELD-based liver allocation system.

This study examined factors associated with the gender disparity in wait-list mortality in the MELD era. Adult patients listed for liver transplantation from 2002 to 2008 were included. Females [12 585(36%)] and males [22 126(64%)] differed clinically by age (54 vs. 52 years), height (1.6 vs. 1.8 m), listing estimated glomerular filtration rate [(eGFR); 70 vs. 83 mL/min] and cirrhosis etiology. Holding MELD constant, females were at 19% (95% CI, 1.13-1.25, p < 0.001) higher risk of wait-list mortality than males under the current allocation system. The relative hazard increased with worsening renal function, whether measured by serum creatinine or eGFR. Adjustment for MELD, age, African-American race, cirrhosis etiology, region and ABO group attenuated this relative hazard (HR 1.16; 95% CI, 1.10-1.22; p < 0.001) but additional adjustment for height completely explained this gender disparity in wait-list mortality (HR 1.05; 95% CI, 0.98-1.12; p = 0.2). Transplantation rates, however, remained lower among females, even after adjustment for height (HR 0.88; 95% CI, 0.82-0.92; p < 0.001). In conclusion, under the current liver allocation system, women have a 19% increased risk of wait-list mortality compared to men with the same MELD scores. Height contributes to this gender disparity, possibly reflecting differences in transplantation rates for shorter individuals.

Schwannoma of the auricle.

OBJECTIVES: We report an extremely rare case of schwannoma of the auricle. METHODOLOGY: A case report and review of the world literature concerning schwannoma of the auricle are presented. RESULTS: Schwannoma is a benign, encapsulated, slow-growing neoplasm. Approximately 25-45% of all schwannomas occur in the head and neck, whereas schwannomas of the external ear are extremely uncommon, with only nine cases reported in the English literature since the first report in 1977. In this report, we describe the case of a 47-year-old male patient who presented with a 2-year history of a slow-growing mass in the left auricle, which was managed by wide surgical excision. We believe this case to be the second case of schwannoma of the auricle reported. CONCLUSIONS: To our knowledge, this is the second report in the world literature of auricle schwannoma. Schwannoma should be considered in the evaluation of any tumour of the auricle.

A pre-paid newborn hearing screening programme: a community-based study.

OBJECTIVES: To help obstetric hospitals and clinics to implement newborn hearing screening and to test the feasibility of a pre-paid model for screening. PATIENTS AND METHODS: From July 2005 to August 2008, we organised a coordinated newborn hearing screening team with portable automated auditory brainstem response (AABR) to provide in-patient screening after delivery and out-patient re-screening at one month of age in birthing facilities throughout Changhua County, Taiwan. This was a community-based study organised by otolaryngologists at a tertiary referral centre. RESULTS: Ten medical facilities participated in our screening programme. 7,139 out of 12,901 neonates delivered in these facilities during the period were screened for hearing loss. 105 (1.47%) babies who did not pass the in-patient screening were re-screened at one month old. Forty (0.56%) babies referred from the re-screening were sent for diagnostic work-up and six of them failed to show up. The overall follow-up rate was 94.3% (99/105). Eleven babies with bilateral hearing loss and eight babies with unilateral hearing loss were diagnosed. The incidence of bilateral hearing loss in our programme was 1.5/1000. The screening rate descended from medical centre to clinic (p < 0.0001). There was no significant difference between the referral rates for different levels of birthing facilities (p = 0.5611). CONCLUSIONS: Our study demonstrates that a pre-paid model using AABR is feasible at all three levels of medical facilities. Pre-paid community-based screening might be an option for developing countries in the implementation of universal newborn hearing screening.

Resource utilization of living donor versus deceased donor liver transplantation is similar at an experienced transplant center.

Although living donor liver transplantation (LDLT) has been shown to decrease waiting-list mortality, little is known of its financial impact relative to deceased donor liver transplantation (DDLT). We performed a retrospective cohort study of the comprehensive resource utilization, using financial charges as a surrogate measure-from the pretransplant through the posttransplant periods-of 489 adult liver transplants (LDLT n = 86; DDLT n = 403) between January 1, 2000, through December 31, 2006, at a single center with substantial experience in LDLT. Baseline characteristics differed between LDLT versus DDLT with regards to age at transplantation (p = 0.02), male gender (p < 0.01), percentage Caucasians (p < 0.01) and transplant model for end-stage liver disease (MELD) score (p < 0.01). In univariate analysis, there was a trend toward decreased total transplant charges with LDLT (p = 0.06), despite increased surgical charges associated with LDLT (p < 0.01). After adjustment for the covariates that were associated with financial charges, there was no significant difference in total transplant charges (p = 0.82). MELD score at transplant was the strongest driver of resource utilization. We conclude that at an experienced transplant center, LDLT imposes a similar overall financial burden than DDLT, despite the increased complexity of living donor surgery and the addition of the costs of the living donor. We speculate that LDLT optimizes transplantation by transplanting healthier and younger recipients.

Effect of vibratory soldier alarm signals on the foraging behavior of subterranean termites (Isoptera: Rhinotermitidae).

Termite soldiers produce a vibratory alarm signal to warn conspecific workers. This study recorded and characterized the alarm signals of Coptotermes acinaciformis (Froggatt) (Isoptera: Rhinotermitidae) and then investigated the effect of playing these recorded alarm signals on C. acinaciformis feeding activity. Foraging groups of termites were offered paired wooden blocks: either one block, continuously stimulated with a vibratory alarm signal, paired with a nonstimulated block (the alarm treatment), continuously stimulated with a pink noise signal, paired with a nonstimulated block (control for nonspecific vibrations) or two nonstimulated blocks (control for environmental effects), for 4 wk. The amount of wood eaten in the blocks stimulated by the alarm signals was significantly less than the paired nonstimulated blocks, while there seemed to be no preference in the case of the pink noise playback or control for direction. Importantly, the termites seemed not to have adapted to the recorded alarm signal over the 4-wk duration of the experiment, unlike previous studies using nonbiologically derived signals.

Characterisation of plasmids encoding CTX-M-3 extended-spectrum beta-lactamase from Enterobacteriaceae isolated at a university hospital in Taiwan.

CTX-M-3 is the most common extended-spectrum beta-lactamase produced by Enterobacteriaceae in Taiwan. The present study was conducted to characterise the genetic environment surrounding bla(CTX-M-3). A total of 11 ceftriaxone-resistant isolates were studied: Escherichia coli (n=4), Klebsiella pneumoniae (n=5) and Salmonella enterica serotypes Anatum (SA831R) and Potsdam (SC72). Molecular methods used included polymerase chain reaction, sequencing, DNA-DNA hybridisation, conjugation, physical mapping and restriction fragment length polymorphism (RFLP) analysis. All isolates examined carried bla(CTX-M-3) on large plasmids (>70kb). The resistance plasmids of the two Salmonella and two K. pneumoniae strains (KP104 and KP116) were confirmed to be conjugative in vitro. RFLP analysis indicated that the plasmids were different. Physical mapping also revealed the difference between the two Salmonella plasmids, pSA831R (82kb) and pSC72 (74kb). An insertion sequence, ISEcp1, was found upstream of each bla(CTX-M-3) gene. However, sequencing of downstream regions of the bla genes showed two different patterns: the presence of orf477 in pSA831R and of orf1-mucA in pSC72, pKP104 and pKP116. IncI1-type oriT and nikA sequences were present in the plasmids of all the clinical isolates tested, except S. Anatum. Different bla(CTX-M-3)-carrying plasmids were identified among the enterobacteria studied. The presence of ISEcp1 in all isolates may be associated with the widespread resistance among Enterobacteriaceae. Although the plasmids were not identical, they appeared to belong to the same incompatibility group (IncI1-like plasmids), suggesting that they are genetically related but may have evolved divergently over time.

Cationic surfactants and other factors that affect enzymatic activities and transport.

Surfactants influence functions of proteins in cell signalling. Because molecular mechanisms of surfactants are poorly understood, the cationic surfactant effect on three metabolically important enzymes--L-glutamate dehydrogenase, L-lactate dehydrogenase, and L-malate dehydrogenase--were investigated at a physiologically relevant pH range (6.5-7.4). How a cationic, a non-ionic, and an anionic surfactant could differentially influence these enzymes, and how these surfactants could influence the interfacial mass transport of these enzymes across a polycarbonate membrane in a separation cell were also investigated. Provided the charge density was the same, cationic surfactants affected enzymatic activities similarly, regardless of their molecular masses. Hence, a cationic surfactant behaved similarly to a hydrophilic anionic surfactant; however, the cationic surfactant also enhanced enzymatic activity at pH 6.5 and a moderately high concentration (150 ppm). The hydrophilic surfactant enhanced enzymatic activity and the hydrophobic surfactant depressed enzymatic activity. Addition of 0.1 ppm of the hydrophilic anionic surfactant decreased the amount of enzyme permeation through the membrane, but 0.1 ppm of the non-ionic surfactant had no effect, whereas 0.1 ppm of the hydrophobic surfactant increased enzyme permeation. These results have physiological and signalling implications in nanobiotechnology.

Prosthetic devices: challenges and implications of robotic implants and biological interfaces.

Although among designs of prosthetics there have been some successes in the design of functional robotic implants, there remain many issues and challenges concerned with the failure to meet the 'ideal' requirements of a satisfactory prosthetic. These 'ideals' require the device to be easy to control, comfortable to wear, and cosmetically pleasing. Because the literature on prosthetics and robotic implants are voluminous, this review focuses on four topics to determine key challenges and opportunities underlying these interdisciplinary research areas: firstly, an artificial hand as a biomimetic; secondly, prosthetic implants (electromyography signals and control); thirdly, prosthetic implants and tissue reactions to the material(s) of implants; fourthly, how inflammatory responses of cells and tissues surrounding implanted sensors interfere with the signal transmission of such sensors. This review also notes the importance of the biological interfaces that robotic implants and other prosthetic devices are in contact with and how an improved knowledge of pathophysiological changes at such biological interfaces will lead to improved and more biocompatible designs of prosthetics. This review concludes with the vision that, to develop a design that satisfies the above 'ideals', an interdisciplinary team of biomedical and tissue engineers, and biomaterial and biomedical scientists is needed to work together holistically and synergistically.

The calcium-sensitive large-conductance potassium channel (BK/MAXI K) is present in the inner mitochondrial membrane of rat brain.

Large-conductance voltage- and calcium-sensitive channels are known to be expressed in the plasmalemma of central neurons; however, recent data suggest that large-conductance voltage- and calcium-sensitive channels may also be present in mitochondrial membranes. To determine the subcellular localization and distribution of large-conductance voltage- and calcium-sensitive channels, rat brain fractions obtained by Ficoll-sucrose density gradient centrifugation were examined by Western blotting, immunocytochemistry and immuno-gold electron microscopy. Immunoblotting studies demonstrated the presence of a consistent signal for the alpha subunit of the large-conductance voltage- and calcium-sensitive channel in the mitochondrial fraction. Double-labeling immunofluorescence also demonstrated that large-conductance voltage- and calcium-sensitive channels are present in mitochondria and co-localize with mitochondrial-specific proteins such as the translocase of the inner membrane 23, adenine nucleotide translocator, cytochrome c oxidase or complex IV-subunit 1 and the inner mitochondrial membrane protein but do not co-localize with calnexin, an endoplasmic reticulum marker. Western blotting of discrete subcellular fractions demonstrated that cytochrome c oxidase or complex IV-subunit 1 was only expressed in the mitochondrial fraction whereas actin, acetylcholinesterase, cadherins, calnexin, 58 kDa Golgi protein, lactate dehydrogenase and microtubule-associated protein 1 were not, demonstrating the purity of the mitochondrial fraction. Electron microscopic examination of the mitochondrial pellet demonstrated gold particle labeling within mitochondria, indicative of the presence of large-conductance voltage- and calcium-sensitive channels in the inner mitochondrial membrane. These studies provide concrete morphological evidence for the existence of large-conductance voltage- and calcium-sensitive channels in mitochondria: our findings corroborate the recent electrophysiological evidence of mitochondrial large-conductance voltage- and calcium-sensitive channels in glioma and cardiac cells.

Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy.

BACKGROUND: High extracellular glutamate concentrations have been identified as a likely trigger of epileptic seizures in mesial temporal lobe epilepsy (MTLE), but the underlying mechanism remains unclear. We investigated whether a deficiency in glutamine synthetase, a key enzyme in catabolism of extracellular glutamate in the brain, could explain the perturbed glutamate homoeostasis in MTLE. METHODS: The anteromedial temporal lobe is the focus of the seizures in MTLE, and surgical resection of this structure, including the hippocampus, leads to resolution of seizures in many cases. By means of immunohistochemistry, western blotting, and functional enzyme assays, we assessed the distribution, quantity, and activity of glutamine synthetase in the MTLE hippocampus. FINDINGS: In western blots, the expression of glutamine synthetase in the hippocampus was 40% lower in MTLE than in non-MTLE samples (median 44 [IQR 30-58] vs 69 [56-87]% of maximum concentration in standard curve; p=0.043; n=8 and n=6, respectively). The enzyme activity was lower by 38% in MTLE vs non-MTLE (mean 0.0060 [SD 0.0031] vs 0.0097 [0.0042] U/mg protein; p=0.045; n=6 and n=9, respectively). Loss of glutamine synthetase was particularly pronounced in areas of the MTLE hippocampus with astroglial proliferation, even though astrocytes normally have high content of the enzyme. Quantitative immunoblotting showed no significant change in the amount of EAAT2, the predominant glial glutamate transporter in the hippocampus. INTERPRETATION: A deficiency in glutamine synthetase in astrocytes is a possible molecular basis for extracellular glutamate accumulation and seizure generation in MTLE. Further studies are needed to define the cause, but the loss of glutamine synthetase may provide a new focus for therapeutic interventions in MTLE.