Real time monitoring of carbon dioxide levels in surgical helmet systems worn during hip and knee arthroplasty.

Background: Orthopaedic surgical helmet systems (SHS) rely on an intrinsic fan to force clean external air over the wearer. Carbon dioxide (CO2) is produced through aerobic metabolism and can potentially accumulate inside the SHS. Levels above 2500 ppm have previously been shown to affect cognitive and practical function. Maximum Health and Safety Executive (HSE) 8-h exposure limit is 5000 ppm. There is a paucity of data on real-world CO2 levels experienced during arthroplasty surgery whilst wearing a SHS. Objectives: To determine intra-operative levels of CO2 experienced within SHS. Methods: CO2 levels were continuously recorded during 30 elective arthroplasties, both primary and revision. Data was recorded at 0.5Hz throughout the procedure utilising a Bluetooth CO2 detector, worn inside a surgical helmet worn with a toga gown. Five surgeons contributed real time data to the study. Results: The average CO2 level across all procedures was 3006 ppm, with 23 of the cases measured within the surgeons' helmets having a mean above 2500 ppm, but none having a mean above 5000 ppm. For each procedure, the time spent above 2500 and 5000 ppm was calculated, with the means being 72.6 % and 5.4 % respectively. Minimum fan speed was associated with only a marginally higher mean CO2 value than maximum fan speed. Discussion: The use of surgical helmet systems for elective orthopaedic surgery, can result in CO2 levels regularly rising to a point which may affect cognitive function. Conclusion: Further research is needed to corroborate these findings however, we recommend that future designs of SHS include active management of exhaust gases, possibly returning to Charnley's original design principles of the body exhaust system.

Examining the Quasi-Static Uniaxial Compressive Behaviour of Commercial High-Performance Epoxy Matrices.

Four commercial high-performance aerospace aromatic epoxy matrices, CYCOM®890, CYCOM®977-2, PR520, and PRISM EP2400, were cured to a standardised 2 h, 180 °C cure cycle and evaluated in quasi-static uniaxial compression, as well as by dynamic scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The thermoplastic toughened CYCOM®977-2 formulation displayed an overall increase in true axial stress values across the entire stress-strain curve relative to the baseline CYCOM®890 sample. The particle-toughened PR520 sample exhibited an overall decrease in true axial stress values past the yield point of the material. The PRISM EP2400 resin, with combined toughening agents, led to true axial stress values across the entire plastic region of the stress-strain curve, which were in line with the stress values observed with the CYCOM®890 material. Interestingly, for all formulations, the dilation angles (associated with the volume change during plastic deformation), recorded at 0.3 plastic strain, were close to 0°, with the variations reflecting the polymer structure. Compression data collected for this series of commercial epoxy resins are in broad agreement with a selection of model epoxy resins based on di- and tetra-functional monomers, cured with polyamines or dicarboxylic anhydrides. However, the fully formulated resins demonstrate a significantly higher compressive modulus than the model resins, albeit at the expense of yield stress.

A Multicentre Retrospective Study of Fulvestrant Use and Efficacy in Advanced/Metastatic Breast Cancer.

AIMS: Fulvestrant is a selective oestrogen receptor (ER) degrader used in postmenopausal women with hormone receptor-positive advanced breast cancer. The study aim was to analyse demographics and outcomes of UK patients treated with fulvestrant monotherapy at nine representative centres. MATERIALS AND METHODS: Medical records of 459 patients with locally advanced or metastatic ER-positive, HER2-negative breast cancer treated with fulvestrant between August 2011 and November 2018 at nine UK centres were reviewed. Data were collated on demographics, progression-free survival, overall survival and disease response at first radiological assessment following fulvestrant initiation. Patients still alive by December 2018 were censored. RESULTS: Data from 429 of the 459 patients identified were eligible for inclusion in the analysis. The median age was 69 (range 21-95) and 64% (n = 275) had Eastern Cooperative Oncology Group performance status 0-1. Bone was the most commonly involved metastatic site (72%, n = 306). However, 295 (69%) patients had visceral involvement. Patients had received a median 2 (range 0-5) prior lines of endocrine therapy and median 0 (range 0-6) prior chemotherapies. Fulvestrant was first-line therapy in 43 patients (10%). The median duration of treatment was 5 months (range 1-88). The median progression-free survival was 5.5 months. In 51% of 350 patients radiologically assessed, there was evidence of disease response to fulvestrant. Fifteen per cent of these had a complete/partial response. Fulvestrant was discontinued predominantly due to disease progression, with 3% discontinued solely due to adverse events. The median overall survival for the whole cohort was 22.5 months (range 0-88). CONCLUSIONS: This is one of the largest studied cohorts of breast cancer patients treated with fulvestrant. This heavily endocrine-pretreated population reflects real-life use in the UK. Within this context, our retrospective data show that patients can experience maintained disease response when treated with fulvestrant, supporting the importance of equitable availability for all UK patients.

Current role of sentinel lymph node biopsy in the management of cutaneous melanoma: A UK consensus statement.

Sentinel node biopsy (SNB) has been at the forefront of the surgical staging of melanoma patients for the past 15 years. The high accuracy of this prognostic staging procedure is now recognised in all international guidelines for melanoma. However during this period there have been a number of important changes in the management of melanoma, many occurring within the past five years. The outcomes of five recent randomised Phase 3 trials have established the role of adjuvant targeted therapy and immunotherapy in resected Stage 3 and Stage 4 disease and have potentially changed the role of SNB. Two landmark international prospective studies have examined the benefit of performing a completion lymph node dissection (CLND) following the detection of microscopicallyinvolved sentinel nodes. Finally, the marked increase in the incidence of melanoma and the role of SNB in potentially guiding therapy has resulted in a significant increase in the pathological workload of the dermatopathology services. To address these issues a multi-disciplinary consensus meeting involving many melanoma experts from the UK was convened in May 2018. Three main areas were considered: oncology, surgery and pathology. This report is a summary of the conclusions reached, which were agreed by the clinicians attending the meeting and then externally peer reviewed. The recommendations summarised in this Consensus Statement.

Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18-88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P = 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P = 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64.

Metastatic melanoma: prognostic factors and survival in patients with brain metastases.

Brain metastases from malignant melanoma carry a poor prognosis. Novel systemic agents have improved overall survival (OS), but the value of whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) remains uncertain. The melanoma-specific graded prognostic assessment (msGPA) provides useful prognostic information, but the relevance to the modern-day population has not been validated. Since 2011, 53 patients received treatment for brain metastases from malignant melanoma at the Rosemere Cancer Centre medical oncology clinic. Data were collated on demographic factors and survival. Survival analyses were performed using Kaplan-Meier methods. Cox regression was used to identify prognostic factors on univariate and multivariate analysis. OS from the date of diagnosis of brain metastases was 4.83 months (range 0.27-30.4 months). On univariate analysis, BRAF, performance status and msGPA were significant prognostic indicators for OS (p = 0.0056, p = 0.0039 and p = 0.0001 respectively). msGPA remained significant on multivariate analysis (p = 0.0006). OS for BRAF-positive patients receiving targeted treatment (n = 22) was significantly better than for BRAF-negative patients (n = 26), with median survival times of 8.2 and 3.7 months respectively (p = 0.0039, HR 2.36). SRS combined with systemic agents (n = 16) produced an OS of 13.5 months. Patients receiving WBRT alone (n = 21) had a poor prognosis (2.2 months). The msGPA remains a valid prognostic indicator in the era of novel systemic treatments for melanoma. BRAF-positive patients receiving targeted agents during their treatment had favorable survival outcomes. WBRT alone should be use with caution in the active management of melanoma brain metastases.

A pilot study to explore circulating tumour cells in pancreatic cancer as a novel biomarker.

BACKGROUND: Obtaining tissue for pancreatic carcinoma diagnosis and biomarker assessment to aid drug development is challenging. Circulating tumour cells (CTCs) may represent a potential biomarker to address these unmet needs. We compared prospectively the utility of two platforms for CTC enumeration and characterisation in pancreatic cancer patients in a pilot exploratory study. PATIENTS AND METHODS: Blood samples were obtained prospectively from 54 consenting patients and analysed by CellSearch and isolation by size of epithelial tumour cells (ISET). CellSearch exploits immunomagnetic capture of CTCs-expressing epithelial markers, whereas ISET is a marker independent, blood filtration device. Circulating tumour cell expression of epithelial and mesenchymal markers was assessed to explore any discrepancy in CTC number between the two platforms. RESULTS: ISET detected CTCs in more patients than CellSearch (93% vs 40%) and in higher numbers (median CTCs/7.5 ml, 9 (range 0-240) vs 0 (range 0-144)). Heterogeneity observed for epithelial cell adhesion molecule, pan-cytokeratin (CK), E-Cadherin, Vimentin and CK 7 expression in CTCs may account for discrepancy in CTC number between platforms. CONCLUSION: ISET detects more CTCs than CellSearch and offers flexible CTC characterisation with potential to investigate CTC biology and develop biomarkers for pancreatic cancer patient management.

Current status and future potential of somatic mutation testing from circulating free DNA in patients with solid tumours.

Genetic alterations can determine the natural history of cancer and its treatment response. With further advances in DNA sequencing technology, multiple novel genetic alterations will be discovered which could be exploited as prognostic, predictive and pharmacodynamic biomarkers in the development and use of cancer therapeutics. As such, the importance in clinical practice of efficient and robust somatic mutation testing in solid tumours cannot be overemphasized in the current era of personalized medicine. However, significant challenges remain regarding the testing of genetic biomarkers in clinical practice. Reliance on archived formalin fixed, paraffin embedded tumour, obtained from diagnostic biopsies, for testing somatic genetic alterations could restrict the scientific community in asking relevant questions about a patient's cancer biology. Problems inherent with using formalin fixed, archival tissue are well recognized and difficult to resolve. It could be argued that to achieve rapid and efficient incorporation of genetic biomarkers into clinical practice, somatic mutation testing in cancer patients should be simpler, less invasive using a readily available clinical sample, whilst maintaining robustness and reproducibility. In this regard, use of circulating free DNA (cfDNA) from plasma or serum as an alternative and/or additional source of DNA to test cancer specific genetic alterations is an attractive proposition. In light of encouraging results from recent studies, this mini review will discuss the current role and future potential of somatic mutation testing from circulating or cell free DNA derived from the blood of patients with solid tumours.

Detection of BRAF mutations in the tumour and serum of patients enrolled in the AZD6244 (ARRY-142886) advanced melanoma phase II study.

BACKGROUND: This study investigated the potential clinical utility of circulating free DNA (cfDNA) as a source of BRAF mutation detection in patients enrolled into a phase II study of AZD6244, a specific MEK1/2 inhibitor, in patients with advanced melanoma. METHODS: BRAF mutations were detected using Amplification Refractory Mutation System allele-specific PCR. BRAF mutation status was assessed in serum-derived cfDNA from 126 patients enrolled into the study and from 94 matched tumour samples. RESULTS: Of 94 tumour samples, 45 (47.9%) were found to be BRAF mutation positive (BRAF+). Serum-derived cfDNA was BRAF+ in 33 of 126 (26.2%) samples, including in five samples for which tumour data were unavailable. Of BRAF+ tumours, 25 of 45 (55.6%) were BRAF+ in cfDNA. In three cases in which the tumour was negative, cfDNA was BRAF+. Progression-free survival (PFS) of patients with BRAF+ tumour and cfDNA was not significantly different compared with tumour BRAF+ but cfDNA BRAF-negative patients, indicating that cfDNA BRAF detection is not associated with poorer prognosis on PFS in stage III/IV advanced melanoma. CONCLUSIONS: These data demonstrate the feasibility of BRAF mutation detection in cfDNA of patients with advanced melanoma. Future studies should aim to incorporate BRAF mutation testing in cfDNA to further validate this biomarker for patient selection.

Subretinal hemorrhage after lens-sparing vitrectomy in infants born at or under 24 weeks gestation.

PURPOSE: To describe short term outcomes in a case series of infants with rapidly progressive retinopathy of prematurity (ROP) requiring laser and lens-sparing vitrectomies (LSV) at early postmenstrual ages (PMAs). METHODS: Retrospective chart review of infants born at or under 24 0/7 weeks consecutively referred for management of severe ROP between August 2006 and January 2007. RESULTS: Five female infants (mean gestational age 23 4/7 weeks, mean birthweight 514.4 g) required laser treatment bilaterally for zone 1 or posterior zone II ROP at 35-37 weeks PMA. LSV was performed for progressive stage 4 ROP in eight eyes at 37-39 weeks PMA (mean 38.2 weeks). Subretinal hemorrhage occurred after LSV in five eyes, with three developing subretinal fibrosis preventing complete retinal reattachment. CONCLUSION: Premature infants in this series had rapidly progressive ROP requiring laser and LSV at early PMAs. Subretinal hemorrhage occurred and may be related to the amount of laser necessary to treat large zones of avascular retina, and the early timing of vitrectomy when postoperative contracting preretinal vitreous no longer has the natural tamponading force of formed gel against it. Improved therapies for premature infants of very young gestational ages and large avascular zones are needed.

The prophylaxis and treatment of heterotopic ossification following lower limb arthroplasty.

Heterotopic ossification following joint replacement in the lower limb occurs in 3% to 90% of cases. Higher grades of heterotopic ossification can result in significant limitation of function and can negate the benefits of joint replacement. The understanding of the pathophysiology of this condition has improved in recent years. It would appear to be related to a combination of systemic and local factors, including over-expression of bone morphogenetic protein-4. There is currently little evidence to support the routine use of prophylaxis for heterotopic ossification in arthroplasty patients, but prophylaxis is recommended by some for high-risk patients. Radiotherapy given as one dose of 7 Gy to 8 Gy, either pre-operatively (< four hours before) or post-operatively (within 72 hours of surgery), appears to be more effective than indometacin therapy (75 mg daily for six weeks). In cases of prophylaxis against recurrent heterotopic ossification following excision, recent work has suggested that a combination of radiotherapy and indometacin is effective. Advances in our understanding of this condition may permit the development of newer, safer treatment modalities.

Stage- and CA125-related survival in patients with epithelial ovarian cancer treated at a cancer center.

Current accepted prognostic indicators in ovarian cancer include performance status, surgical (FIGO) staging, and residual disease after operation. Here we present data from a prospective analysis of patients with ovarian cancer treated at the Christie Hospital. We confirm the independent prognostic effects of FIGO staging, performance status, and residual disease in our group of patients and furthermore show that CA125 levels at presentation to the oncology service are of independent prognostic significance (P= 0.02). We present survival data and show that the 3-year, cancer-specific survival for stage I disease is 90%. We postulate that this good survival may in part be due to the use of computed tomography scanning at presentation to allow accurate staging. Further clinical trials are needed to test whether combinations of surgical, histologic, biochemical, and radiologic parameters can be used to identify a population with such a good prognosis that adjuvant therapy is not required.

Chitosan potentiates the antimicrobial action of sodium benzoate on spoilage yeasts.

AIMS: The objective of this study was to determine whether low concentrations of chitosan and benzoate in combination could be used to enhance the antimicrobial action of either compound alone against three spoilage yeasts in saline solutions. METHODS AND RESULTS: Saccharomyces exiguus, Saccharomycodes ludwigii and Torulaspora delbrueckii were suspended in 0.05 and 0.005% chitosan glutamate and 0.025% sodium benzoate, alone or in combination, in 0.9% saline solutions at pH 6.2 and 4.5. Survivor curves were constructed from viable counts determined periodically for up to 120 min. Chitosan at 0.005% almost doubled the extent of death caused by 0.025% benzoate alone, from about 1-2 log to about 2-4 log cfu ml(-1), depending on pH and target organism. CONCLUSIONS: Chitosan (0.005%) and 0.025% sodium benzoate acted synergistically against spoilage yeasts in saline solutions. SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that the natural compound chitosan may be useful as an adjunct in the potentiation of the biocidal efficacy of antimicrobial compounds such as benzoates.

Novel combinations of chitosan, carnocin and sulphite for the preservation of chilled pork sausages.

The aim of this study was to develop novel preservation systems for fresh pork sausages based on combinations of chitosan (polymeric ß-1,4-N-acetylglucosamine) carnocin (a bacteriocin produced by Carnobacterium piscicola) and low concentrations of sulphite. Two pilot-scale trials showed that 0.6% chitosan combined with low sulphite (170 ppm) retarded the growth of spoilage organisms more effectively (3-4 log cfu/g) than high levels (340 ppm) of sulphite alone at 4 °C for up to 24 days. Microbial counts for frozen sausages showed that the preservative efficacy of the chitosan/sulphite combination was maintained following frozen storage. Carnocin did not protect sausages from spoilage but in a challenge trial, it reduced the numbers of Listeria innocua by up to 2.0 log cfu/g in the first 5 days of chill-storage. Sulphite was degraded rapidly within the first 3 days of storage in all the sausages that contained only this preservative but levels decreased less rapidly and persisted for longer in the presence of chitosan. Results of Quantitative Descriptive Analysis using 31 trained panellists reflected the gradual deterioration of all the sausages during storage. The batch containing chitosan and sulphite deteriorated less rapidly and was judged to be more acceptable for a longer period than all the other batches.

State of the science on parental stress and family functioning in pediatric intensive care units.

BACKGROUND: Critical illness of a child is stressful for parents and may affect family functioning. Most research on hospitalization in pediatric intensive care units has focused on the immediate responses of parents to the experience. OBJECTIVE: To critically review literature about pediatric intensive care units and to link those studies to a theoretical framework: McCubbin and McCubbin's resiliency model of family stress, adjustment, and adaptation. An updated synthesis of the literature is essential to prevent unnecessary duplication of research. METHODS: Guidelines presented by Ryan-Wenger were used to critique the scientific credibility and integrity of 38 research reports found by searching MEDLINE, the Cumulative Index to Nursing and Allied Health, and reference lists. The critique was organized according to the components of the research process, and then study results were reviewed according to the variables of the resiliency model. RESULTS: Most publications focused on variables in the adjustment phase, including stressors, resources, perceptions of stressors, and outcomes for patients' families. Obvious gaps in knowledge were related to families' vulnerability, type, and problem-solving and coping strategies. Many of the studies were biased toward white persons and toward mothers. CONCLUSIONS: Further research is warranted on (1) families of various ethnic backgrounds; (2) fathers and their low participation rates; (3) mother and father comparisons; (4) replication of interventional research with larger and more diverse samples; (5) exploratory and prospective, longitudinal research; and (6) research with children in pediatric intensive care units.

Attributes of microbial associations of meat growing as xenic batch cultures in a meat juice at 4 degrees C.

Strains of Gram-positive (Carnobacterium piscicola, Leuconostoc mesenteroides subsp. mesenteroides, Brochothrix thermosphacta) and Gram-negative (Pseudomonas fragi and Hafnia alvei) bacteria isolated from minced lamb packaged under a modified atmosphere were cultivated in a meat (lamb) juice at 4 degrees C. Carbohydrates were catabolised in the order glucose > glucose 6-phosphate during the development of the population. Under an atmosphere enriched with carbon dioxide the Gram-negative portion of the population was suppressed during the exponential phase but H. alvei became the dominant organism towards the end of a protracted stationary phase of growth. With the aerobic atmosphere P. fragi catabolised creatine and became the dominant species in the stationary phase. The inability of C. piscicola to catabolise glucose 6-phosphate was reflected in its population being smaller than those of the other Gram-positive organisms (C. piscicola < L. mesenteroides subsp. mesenteroides < B. thermosphacta). During the stationary phase of growth, indigenous L-lactic acid and the D-isomer produced by leuconostocs were oxidised to acetic acid by the Gram-positive flora under an atmosphere enriched with carbon dioxide. These oxidations, which occurred after depletion of glucose, were supported by the oxygen in the system. D-Lactic and acetic acid appeared to be possible parameters for the estimation of the microbiological quality of packaged meat.

The influence of sodium chloride and pH on the growth of Salmonella enteritidis PT4.

Sodium or potassium chlorides at concentrations of ca 2.0% (w/v) stimulated the growth of Salmonella enteritidis PT4 and PT6 but not PT8 in nutrient broth acidified to < or = 5.5 with acetic but not with citric, propionic or hydrochloric acids. Stimulation was noted also with an acidified defined medium. The most pronounced stimulation occurred with incubation at 37 degrees C. Supplementation of acidified nutrient broth with sucrose or glycerol had no effect on the growth of salmonellas.