Complications and functional outcomes after ileo-anal pouch excision-a systematic review of 14 retrospective observational studies.

PURPOSE: The ileo-anal pouch (IAP) has been the gold standard procedure for maintenance of bowel continuity after panproctocolectomy for ulcerative colitis, familial adenomatous polyposis or hereditary non-polyposis colorectal cancer. However, the IAP has an estimated failure rate of 13% at 10 years post-procedure (Tulchinsky et al., Ann Surg 238(2):229-34, 2003), which can result in pouch excision (P.E.). This systematic review aims to synthesise all the available studies reporting post-operative outcomes of P.E. and its impact on patient quality of life (QoL), when available, which have not previously been summarised. METHODS: PubMed, Embase, Medline and the Cochrane library databases were searched with terms 'Pouch AND excision' OR 'Pouch AND removal' OR 'Pouch AND remove' OR 'IAP AND excision'. All studies reporting post-operative morbidity, mortality or functional outcomes in patients who had P.E. were included. Studies with < 5 patients, non-English studies and conference abstracts were excluded. RESULTS: 14 studies comprising 1601 patients were included. Overall complications varied from 18 to 63% with the most common being persistent perineal sinus (9-40%) or surgical site infection (wound-2 to 30%; intra-abdominal collection-3 to 24%). The mortality rate was between 0.58 and 1.4%. QoL is generally lower in P.E. patients compared to the normal population across various QoL measures and P.E. patients often had urinary and sexual dysfunction post-operatively. CONCLUSIONS: There is a substantial incidence of complications after P.E.; however, there is no evidence describing QoL pre- and post-P.E. Further longitudinal research comparing QoL in patients undergoing P.E. and other treatment options such as indefinite diversion is required to definitively assess QoL post-procedure.

Getting under the skin of hair aging: the impact of the hair follicle environment.

Like the skin, our hair shows striking changes with age, producing hairs with altered diameter, lustre and texture. The biology of hair aging has focused predominately on various aspects of the hair cycle, follicle size and the fibre produced, but surprisingly the impact of the aging scalp dermal environment on the hair follicle and fibre has been generally overlooked. Hair loss affects both sexes with incidence increasing with age. In men, male pattern-balding (androgenetic alopecia) is driven by androgens and follows a specific pattern of frontotemporal and vertex regression. Women also experience female pattern hair loss (FPHL), presenting as more general, diffuse hair thinning. Hair thinning in women is commonly associated with the menopause, corresponding with other age-related changes in skin. The rapidly growing hair follicle undergoes continued renewal throughout the life span of an individual, where it is exposed to a substantial number of extrinsic and intrinsic stressors. As the hair follicle sits deep within the dermis with its bulb residing in the hypodermis, detrimental age-related changes in the surrounding scalp skin may likely disrupt the hair follicle machinery. The impacts of these changes are unknown, but evidence suggests that scalp skin aging and hair follicle aging go hand-in-hand. Herein, we summarize the evidence that the age-related changes observed in sun-exposed human skin also occur in scalp skin and that these changes are likely to play a contributing role in the aging hair phenotype.

Management of the airway and lung isolation for thoracic surgery during the COVID-19 pandemic: Recommendations for clinical practice endorsed by the Association for Cardiothoracic Anaesthesia and Critical Care and the Society for Cardiothoracic Surgery in Great Britain and Ireland.

Intra-operative aerosol-generating procedures are arguably unavoidable in the routine provision of thoracic anaesthesia. Airway management for such patients during the COVID-19 pandemic including tracheal intubation, lung isolation, one-lung ventilation and flexible bronchoscopy may pose a significant risk to healthcare professionals and patients. That said, there remains a need for timely thoracic surgery for patients with lung cancer or thoracic trauma. The thoracic anaesthetic community has been confronted with the need to modify existing techniques to maximise safety for patients and healthcare professionals. With appropriate modification, aerosol generation may be mitigated against in most circumstances. We developed a set of practice-based recommendations for airway management in thoracic surgical patients, which have been endorsed by the Association for Cardiothoracic Anaesthesia and Critical Care and the Society for Cardiothoracic Surgery in Great Britain and Ireland.

Neoadjuvant Endocrine Therapy Versus Neoadjuvant Chemotherapy in Node-Positive Invasive Lobular Carcinoma.

BACKGROUND: Neoadjuvant chemotherapy (NACT) is often recommended for patients with node-positive invasive lobular carcinoma (ILC) despite unclear benefit in this largely hormone receptor-positive (HR+) group. We sought to compare overall survival (OS) between patients with node-positive ILC who received neoadjuvant endocrine therapy (NET) and those who received NACT. METHODS: Women with cT1-4c, cN1-3 HR+ ILC in the National Cancer Data Base (2004-2014) who underwent surgery following neoadjuvant therapy were identified. Kaplan-Meier curves and Cox proportional hazards modeling were used to estimate unadjusted and adjusted overall survival (OS), respectively. RESULTS: Of the 5942 patients in the cohort, 855 received NET and 5087 received NACT. NET recipients were older (70 vs. 54 years) and had more comorbidities (Charlson-Deyo score ≥ 1: 21.1% vs. 11.5%), lower cT classification (cT3-4: 44.2% vs. 51.0%), lower rates of mastectomy (72.5% vs. 82.2%), lower rates of pathologic complete response (0% vs. 2.5%), and lower rates of postlumpectomy (73.2% vs. 91.0%) and postmastectomy (60.0% vs. 80.8%) radiation versus NACT recipients (all p < 0.001). NACT recipients had higher unadjusted 10-year OS versus NET recipients (57.9% vs. 36.0%), but after adjustment, there was no significant difference in OS between the two groups (p = 0.10). CONCLUSIONS: Patients with node-positive ILC who received NET presented with smaller tumors, older age, and greater burden of comorbidities versus NACT recipients but had similar adjusted OS. While there is evidence from clinical trials supporting efficacy of NET in HR+ breast cancer, our findings suggest the need for further, histology-specific investigation regarding the optimal inclusion and sequence of endocrine therapy and chemotherapy in ILC.

Does blue light restore human epidermal barrier function via activation of Opsin during cutaneous wound healing?

BACKGROUND AND OBJECTIVE: Visible light has beneficial effects on cutaneous wound healing, but the role of potential photoreceptors in human skin is unknown. In addition, inconsistency in the parameters of blue and red light-based therapies for skin conditions makes interpretation difficult. Red light can activate cytochrome c oxidase and has been proposed as a wound healing therapy. UV-blue light can activate Opsin 1-SW, Opsin 2, Opsin 3, Opsin 4, and Opsin 5 receptors, triggering biological responses, but their role in human skin physiology is unclear. MATERIALS AND METHODS: Localization of Opsins was analyzed in situ in human skin derived from face and abdomen by immunohistochemistry. An ex vivo human skin wound healing model was established and expression of Opsins confirmed by immunohistochemistry. The rate of wound closure was quantitated after irradiation with blue and red light and mRNA was extracted from the regenerating epithelial tongue by laser micro-dissection to detect changes in Opsin 3 (OPN3) expression. Retention of the expression of Opsins in primary cultures of human epidermal keratinocytes and dermal fibroblasts was confirmed by qRT-PCR and immunocytochemistry. Modulation of metabolic activity by visible light was studied. Furthermore, migration in a scratch-wound assay, DNA synthesis and differentiation of epidermal keratinocytes was established following irradiation with blue light. A role for OPN3 in keratinocytes was investigated by gene silencing. RESULTS: Opsin receptors (OPN1-SW, 3 and 5) were similarly localized in the epidermis of human facial and abdominal skin in situ. Corresponding expression was confirmed in the regenerating epithelial tongue of ex vivo wounds after 2 days in culture, and irradiation with blue light stimulated wound closure, with a corresponding increase in OPN3 expression. Expression of Opsins was retained in primary cultures of epidermal keratinocytes and dermal fibroblasts. Both blue and red light stimulated the metabolic activity of cultured keratinocytes. Low levels of blue light reduced DNA synthesis and stimulated differentiation of keratinocytes. While low levels of blue light did not alter keratinocyte migration in a scratch wound assay, higher levels inhibited migration. Gene silencing of OPN3 in keratinocytes was effective (87% reduction). The rate of DNA synthesis in OPN3 knockdown keratinocytes did not change following irradiation with blue light, however, the level of differentiation was decreased. CONCLUSIONS: Opsins are expressed in the epidermis and dermis of human skin and in the newly regenerating epidermis following wounding. An increase in OPN3 expression in the epithelial tongue may be a potential mechanism for the stimulation of wound closure by blue light. Since keratinocytes and fibroblasts retain their expression of Opsins in culture, they provide a good model to investigate the mechanism of blue light in wound healing responses. Knockdown of OPN3 led to a reduction in early differentiation of keratinocytes following irradiation with blue light, suggesting OPN3 is required for restoration of the barrier function. Understanding the function and relationship of different photoreceptors and their response to specific light parameters will lead to the development of reliable light-based therapies for cutaneous wound healing. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

Intracrine sex steroid synthesis and signaling in human epidermal keratinocytes and dermal fibroblasts.

Peripheral intracrine sex steroid synthesis from adrenal precursors dehydroepiandrosterone (DHEA) and DHEA-sulfate has evolved in humans. We sought to establish if there are differences in intracrine, paracrine, and endocrine regulation of sex steroids by primary cultures of human skin epidermal keratinocytes and dermal fibroblasts. Microarray analysis identified multifunctional genes modulated by steroids, quantitative RT-PCR (qRT-PCR) mRNA expression, enzymatic assay aromatase activity, scratch assay cell migration, immunocytochemistry α-smooth muscle actin (α-SMA), and collagen gel fibroblast contraction. All steroidogenic components were present, although only keratinocytes expressed the organic anion organic anion transporter protein (OATP) 2B1 transporter. Both expressed the G-protein-coupled estrogen receptor (GPER1). Steroids modulated multifunctional genes, up-regulating genes important in repair and aging [angiopoietin-like 4 (ANGPTL4), chemokine (C-X-C motif) ligand 1 (CXCL1), lamin B1 (LMNB1), and thioredoxin interacting protein (TXNIP)]. DHEA-sulfate (DHEA-S), DHEA, and 17ß-estradiol stimulated keratinocyte and fibroblast migration at early (4 h) and late (24-48 h) time points, suggesting involvement of genomic and nongenomic signaling. Migration was blocked by aromatase and steroid sulfatase (STS) inhibitors confirming intracrine synthesis to estrogen. Testosterone had little effect, implying it is not an intermediate. Steroids stimulated fibroblast contraction but not α-SMA expression. Mechanical wounding reduced fibroblast aromatase activity but increased keratinocyte activity, amplifying the bioavailability of intracellular estrogen. Cultured fibroblasts and keratinocytes provide a biologically relevant model system to investigate the complex pathways of sex steroid intracrinology in human skin.

Use of inertial measurement units to assess age-related changes in gait kinematics in an active population.

To study mobility in older populations it can be advantageous to use portable gait analysis systems, such as inertial measurement units (IMUs), which can be used in the community. To define a normal range, 136 active subjects were recruited with an age range of 18 to 97. Four IMUs were attached to the subjects, one on each thigh and shank. Subjects were asked to walk 10 m at their own self-selected speed. The ranges of motion of thigh, shank, and knee in both swing and stance phase were calculated, in addition to stride duration. Thigh, shank, and knee range of movement in swing and stance were significantly different only in the > 80 age group. Regressions of angle against age showed a cubic relationship. Stride duration showed a weak linear relationship with age, increasing by approximately 0.1% per year.

Transvaginal repair of recurrent pouch-vaginal fistula.

AIM: Pouch-vaginal fistula is an uncommon but unpleasant complication. The chance of successful repair with various surgical procedures is around 50% and the early promise of collagen button plugs was not followed by good long-term results. We report a series of patients who underwent transvaginal repair of pouch-vaginal fistula after failed collagen plugs accompanied by a video to show the operative technique. METHOD: Patients were identified from a prospectively maintained database. Patient demographics, operation notes, complications and ultimate outcome were recorded. RESULTS: Eleven patients, each of whom had previously undergone an attempt to close the fistula with a collagen button plug, underwent transvaginal repair. Nine (81%) were successful at a median follow-up of 14 (6-56) months. The remaining two patients reported symptomatic improvement. CONCLUSION: Pouch-vaginal fistula can be successfully closed by the transvaginal technique after a failed button plug procedure.

Mechanical load applied by Intraosseous Transcutaneous Amputation Prosthesis (ITAP) during walking on level and sloped treadmill: A case study.

This proof of concept study presents a method to collect and analyse kinetic data from one participant with a transfemoral amputation fitted with a percutaneous osseointegrated implant walking on a level and sloped treadmill. We describe the construction of and results from a bespoke wireless six axis load cell built into one participant's prosthetic assembly. The load cell does not clinically compromise the participant in any way and is an initial milestone in the development of a light-weight wireless load cell for use with percutaneous osseointegrated implants. In this case, it is the first time that kinetic data from a participant fitted with an Intraosseous Transcutaneous Amputation Prosthesis has been published. We propose that the data can be used to model the load transfer to the host bone, with several clinically significant applications. The raw dynamic data are made available and quasi-static load cases for each functional phase of gait are presented. Peak forces obtained in the medio-lateral (X), cranio-caudal (Y) and antero-posterior (Z) axes over level ground respectively were -243.8 N (0.24 BW), 1321.5 N (1.31 BW) and -421.8 N (0.42 BW); uphill were -141.0 N (0.14 BW), 1604.2 N (1.59 BW), -498.1 N (0.49 BW); downhill were -206.0 N (0.20 BW), 1103.9 N (1.09 BW), -547.2 N (0.54 BW). The kinetics broadly followed able bodied gait patterns with some gait strategies consistent in participants with other implant designs or prosthetic socket connections, for example offloading the artificial limb downhill.

Nutraceuticals known to promote hair growth do not interfere with the inhibitory action of tamoxifen in MCF7, T47D and BT483 breast cancer cell lines.

BACKGROUND: Hair loss/thinning is a common side effect of tamoxifen in estrogen receptor (ER) positive breast cancer therapy. Some nutraceuticals known to promote hair growth are avoided during breast cancer therapy for fear of phytoestrogenic activity. However, not all botanical ingredients have similarities to estrogens, and in fact, no information exists as to the true interaction of these ingredients with tamoxifen. Therefore, this study sought to ascertain the effect of nutraceuticals (+/- estrogen/tamoxifen), on proliferation of breast cancer cells and the relative expression of ERα/ß. METHODS: Kelp, Astaxanthin, Saw Palmetto, Tocotrienols, Maca, Horsetail, Resveratrol, Curcumin and Ashwagandha were assessed on proliferation of MCF7, T47D and BT483 breast cancer cell lines +/- 17ß-estradiol and tamoxifen. Each extract was analysed by high performance liquid chromatography (HPLC) prior to use. Cellular ERα and ERß expression was assessed by qRT-PCR and western blot. Changes in the cellular localisation of ERα:ERß and their ratio following incubation with the nutraceuticals was confirmed by immunocytochemistry. RESULTS: Estradiol stimulated DNA synthesis in three different breast cancer cell lines: MCF7, T47D and BT483, which was inhibited by tamoxifen; this was mirrored by a specific ERa agonist in T47D and BT483 cells. Overall, nutraceuticals did not interfere with tamoxifen inhibition of estrogen; some even induced further inhibition when combined with tamoxifen. The ERα:ERß ratio was higher at mRNA and protein level in all cell lines. However, incubation with nutraceuticals induced a shift to higher ERß expression and a localization of ERs around the nuclear periphery. CONCLUSIONS: As ERα is the key driver of estrogen-dependent breast cancer, if nutraceuticals have a higher affinity for ERß they may offer a protective effect, particularly if they synergize and augment the actions of tamoxifen. Since ERß is the predominant ER in the hair follicle, further studies confirming whether nutraceuticals can shift the ratio towards ERß in hair follicle cells would support a role for them in hair growth. Although more research is needed to assess safety and efficacy, this promising data suggests the potential of nutraceuticals as adjuvant therapy for hair loss in breast cancer patients receiving endocrine therapy.

Understanding and treating diabetic foot ulcers: Insights into the role of cutaneous microbiota and innovative therapies.

Background: Notoriously known as the silent pandemic, chronic, non-healing diabetic foot ulcers (DFUs), pose a significant rate of incidence for amputation and are a major cause of morbidity. Alarmingly, the treatment and management strategies of chronic wounds represent a significant economic and health burden as well as a momentous drain on resources with billions per annum being spent in the US and UK alone. Defective wound healing is a major pathophysiological condition which propagates an acute wound to a chronic wound, further propelled by underlying conditions such as diabetes and vascular complications which are more prevalent amongst the elderly. Chronic wounds are prone to infection, which can exacerbate the condition, occasionally resulting in amputation for the patient, despite the intervention of modern therapies. However, amputation can only yield a 5-year survival rate for 50% of patients, highlighting the need for new treatments for chronic wounds. Findings: The dynamic cutaneous microbiota is comprised of diverse microorganisms that often aid wound healing. Conversely, the chronic wound microbiome consists of a combination of common skin commensals such as Staphylococcus aureus and Staphylococcus epidermidis, as well as the opportunistic pathogen Pseudomonas aeruginosa. These bacteria have been identified as the most prevalent bacterial pathogens isolated from chronic wounds and contribute to prolific biofilm formation decreasing the efficiency of antimicrobials and further perpetuating a hyper-inflammatory state. Discussion and Conclusion: Here, we review recent advances and provide a new perspective on alternative treatments including phage and microbiome transplant therapies and how the definitive role of the cutaneous microbiota impacts the aetiology of DFUs.

Stromal Vascular Fraction Cells from Individuals Who Have Previously Undergone Radiotherapy Retain Their Pro-Wound Healing Properties.

Beneficial effects have been observed following the transplant of lipoaspirates containing adipose-derived stem cells into chronic wounds caused by oncologic radiotherapy. It is not yet certain whether adipose-derived stem cells are resistant to radiation exposure. Therefore, the aims of this study were to isolate stromal vascular fraction from human breast tissue exposed to radiotherapy and determine the presence of adipose-derived stem cells. Stromal vascular fraction from irradiated donor tissue was compared to commercially sourced pre-adipocytes. Immunocytochemistry was used to determine the presence of adipose-derived stem cell markers. Conditioned media from stromal vascular fraction isolated from irradiated donors was used as a treatment in a scratch wound assay of dermal fibroblasts also isolated from irradiated donors and compared to pre-adipocyte conditioned media and serum free control. This is the first report of human stromal vascular fraction being cultured from previously irradiated breast tissue. Stromal vascular fraction conditioned media from irradiated donors had a similar effect in increasing the migration of dermal fibroblasts from irradiated skin to pre-adipocyte conditioned media from healthy donors. Therefore, the ability of adipose-derived stem cells in the stromal vascular fraction to stimulate dermal fibroblasts in wound healing appears to be preserved following radiotherapy. This study demonstrates that stromal vascular fraction from irradiated patients is viable, functional and may have potential for regenerative medicine techniques following radiotherapy.

The Integration of Proteome-Wide PTM Data with Protein Structural and Sequence Features Identifies Phosphorylations that Mediate 14-3-3 Interactions.

14-3-3s are abundant proteins that regulate essentially all aspects of cell biology, including cell cycle, motility, metabolism, and cell death. 14-3-3s work by docking to phosphorylated Ser/Thr residues on a large network of client proteins and modulating client protein function in a variety of ways. In recent years, aided by improvements in proteomics, the discovery of 14-3-3 client proteins has far outpaced our ability to understand the biological impact of individual 14-3-3 interactions. The rate-limiting step in this process is often the identification of the individual phospho-serines/threonines that mediate 14-3-3 binding, which are difficult to distinguish from other phospho-sites by sequence alone. Furthermore, trial-and-error molecular approaches to identify these phosphorylations are costly and can take months or years to identify even a single 14-3-3 docking site phosphorylation. To help overcome this challenge, we used machine learning to analyze predictive features of 14-3-3 binding sites. We found that accounting for intrinsic protein disorder and the unbiased mass spectrometry identification rate of a given phosphorylation significantly improves the identification of 14-3-3 docking site phosphorylations across the proteome. We incorporated these features, coupled with consensus sequence prediction, into a publicly available web app, called "14-3-3 site-finder". We demonstrate the strength of this approach through its ability to identify 14-3-3 binding sites that do not conform to the loose consensus sequence of 14-3-3 docking phosphorylations, which we validate with 14-3-3 client proteins, including TNK1, CHEK1, MAPK7, and others. In addition, by using this approach, we identify a phosphorylation on A-kinase anchor protein-13 (AKAP13) at Ser2467 that dominantly controls its interaction with 14-3-3.

Evaluating the Use of CT-Derived Lung Volumes in Donor-Recipient Lung Size Matching for Lung Transplantation in Patients With Interstitial Lung Disease and/or Idiopathic Pulmonary Fibrosis.

PURPOSE: This study aims to assess the efficacy of current measurement strategies for lung sizing and the feasibility of future use of computed tomography (CT)-derived lung volumes to predict a donor-recipient lung size match during bilateral lung transplants. METHODS: We reviewed the data of 62 patients who underwent bilateral lung transplantation for interstitial lung disease and/or idiopathic pulmonary fibrosis from 2018 to 2019. Data for recipients was retrieved from the department's transplant database and medical records, and the donor's data was retrieved from the DonorNet. The data included demographic data, lung heights, measured total lung capacity (TLC) from plethysmography for recipients and estimated TLC for donors, clinical data, and CT-derived lung volumes in both pre- and post-transplant recipients. The post-transplant CT-derived lung volume in recipients was used as a surrogate for donor lung CT volumes due to inadequate or poor donor CT data. Computed tomography-derived lung volumes were calculated using thresholding, region growing, and cutting techniques on Computer-Aided Design and Mimics (Materialise NV, Leuven, Belgium) programs. Preoperative CT-derived lung volumes in recipients were compared with the plethysmography TLC, Frustum Model, and donor-predicted TLC. The ratio of the recipient's pre-and postoperative CT-derived volumes, the ratio of preoperative CT-derived lung volume, and donor-estimated TLC were studied to detect a correlation with 1-year outcomes. RESULTS: The recipient preoperative CT-derived volume correlated with the recipient preoperative plethysmography TLC (Pearson correlation coefficient [PCC] of 0.688) and with the recipient Frustum model volume (PCC of 0.593). The recipient postoperative CT-derived volume correlated with the recipient's postoperative plethysmography TLC (PCC of 0.651). There was no statistically significant correlation between recipients' CT-derived pre- or postoperative volume with donor-estimated TLC. The ratio of preoperative CT-derived volume to donor-estimated TLC correlated inversely with the length of ventilation (P value = .0031). The ratio of postoperative CT-derived volume to preoperative CT-derived volume correlated inversely with delayed sternal closure (P = .0039). No statistically significant correlations were found in evaluating outcomes related to lung oversizing in the recipient (defined as a postoperative to preoperative CT-derived lung volume ratio of >1.2). CONCLUSIONS: Generating CT-derived lung volumes is a valid and convenient method for evaluating lung volumes for transplantation in patients with ILD and/or IPF. Donor-estimated TLC should be interpreted carefully. Further studies should derive donor lung volumes from CT scans for a more accurate evaluation of lung size matching.

Pre-hospital ECPR in an Australian metropolitan setting: a single-arm feasibility assessment-The CPR, pre-hospital ECPR and early reperfusion (CHEER3) study.

INTRODUCTION: Survival from refractory out of hospital cardiac arrest (OHCA) without timely return of spontaneous circulation (ROSC) utilising conventional advanced cardiac life support (ACLS) therapies is dismal. CHEER3 was a safety and feasibility study of pre-hospital deployed extracorporeal membrane oxygenation (ECMO) during cardiopulmonary resuscitation (ECPR) for refractory OHCA in metropolitan Australia. METHODS: This was a single jurisdiction, single-arm feasibility study. Physicians, with pre-existing ECMO expertise, responded to witnessed OHCA, age < 65 yrs, within 30 min driving-time, using an ECMO equipped rapid response vehicle. If pre-hospital ECPR was undertaken, patients were transported to hospital for investigations and therapies including emergent coronary catheterisation, and standard intensive care (ICU) therapy until either cardiac and neurological recovery or palliation occurred. Analyses were descriptive. RESULTS: From February 2020 to May 2023, over 117 days, the team responded to 709 "potential cardiac arrest" emergency calls. 358 were confirmed OHCA. Time from emergency call to scene arrival was 27 min (15-37 min). 10 patients fulfilled the pre-defined inclusion criteria and all were successfully cannulated on scene. Time from emergency call to ECMO initiation was 50 min (35-62 min). Time from decision to ECMO support was 16 min (11-26 min). CPR duration was 46 min (32-62 min). All 10 patients were transferred to hospital for investigations and therapy. 4 patients (40%) survived to hospital discharge neurologically intact (CPC 1/2). CONCLUSION: Pre-hospital ECPR was feasible, using an experienced ECMO team from a single-centre. Overall survival was promising in this highly selected group. Further prospective studies are now warranted.

Eosinophil peroxidase induces the expression and function of acid-sensing ion channel-3 in allergic rhinitis: in vitro evidence in cultured epithelial cells.

BACKGROUND: Acid-sensing ion channels (ASIC) are a family of acid-activated ligand-gated cation channels. As tissue acidosis is a feature of inflammatory conditions, such as allergic rhinitis (AR), we investigated the expression and function of these channels in AR. OBJECTIVES: The aim of the study was to assess expression and function of ASIC channels in the nasal mucosa of control and AR subjects. METHODS: Immunohistochemical localization of ASIC receptors and functional responses to lactic acid application were investigated. In vitro studies on cultured epithelial cells were performed to assess underlying mechanisms of ASIC function. RESULTS: Lactic acid at pH 7.03 induced a significant rise in nasal fluid secretion that was inhibited by pre-treatment with the ASIC inhibitor amiloride in AR subjects (n = 19). Quantitative PCR on cDNA isolated from nasal biopsies from control and AR subjects demonstrated that ASIC-1 was equally expressed in both populations, but ASIC-3 was significantly more highly expressed in AR (P < 0.02). Immunohistochemistry confirmed significantly higher ASIC-3 protein expression on nasal epithelial cells in AR patients than controls (P < 0.01). Immunoreactivity for EPO+ eosinophils in both nasal epithelium and submucosa was more prominent in AR compared with controls. A mechanism of induction of ASIC-3 expression relevant to AR was suggested by the finding that eosinophil peroxidase (EPO), acting via ERK1/2, induced the expression of ASIC-3 in epithelial cells. Furthermore, using a quantitative functional measure of epithelial cell secretory function in vitro, EPO increased the air-surface liquid depth via an ASIC-dependent chloride secretory pathway. CONCLUSIONS: This data suggests a possible mechanism for the observed association of eosinophils and rhinorrhoea in AR and is manifested through enhanced ASIC-3 expression.

Draft Genome Sequence of a Multiple Antibiotic Resistant Staphylococcus aureus NCTC 6571-UB Laboratory Strain.

We report the draft genome sequence of the laboratory strain Staphylococcus aureus NCTC 6571-UB, a strain that was derived from S. aureus NCTC 6571. This strain was selected for sequencing in order to provide information on the genome dynamics and the acquired resistance genes for penicillin G, trimethoprim, and sulfamethoxazole resistance.

Odontogenic sinusitis - case series and review of literature.

BACKGROUND: Odontogenic sinusitis is a common cause of rhinosinusitis that is often undiagnosed and overlooked. No single sign or symptom is specific for odontogenic sinusitis, and failure to focus on the specific radiological features can delay diagnosis. OBJECTIVE: This paper presents four cases of chronic sinusitis that had an odontogenic origin. Each case was referred for a second opinion. Three patients had previously undergone unsuccessful surgical management. METHODS: The literature, and the associated contributory clinical, radiological and microbiological features required for correct diagnosis and management, are reviewed. RESULTS: Each case resulted in a positive patient outcome following the involvement of both otolaryngology and maxillofacial surgery departments. CONCLUSION: A high index of suspicion is advocated for odontogenic sinusitis in cases not responding to standard management plans. Collaboration with a maxillofacial specialist is important for diagnosis and management. This should be considered where standard management fails, or clinical features and radiological signs of odontogenic sinusitis are present. This paper also highlights the need for otolaryngologists to incorporate, at the very least, a basic dental history and examination as part of their assessment in recalcitrant cases.