Investigating balance, gait, and physical function in people who have undergone thoracic surgery for a diagnosis of lung cancer: A mixed-methods study.

OBJECTIVES: Symptoms associated with lung cancer and thoracic surgery might increase fall risk. We aimed to investigate: 1) balance, gait and functional status in people post-thoracic surgery compared to healthy controls; 2) perceptions of balance, gait and functional status. METHODS: Recruitment targeted older adults (≥50 years) who had undergone thoracic surgery for a diagnosis of lung cancer in the previous 3 months, and healthy age-matched controls. Dynamic and static balance, gait velocity, knee-extension strength and physical activity levels were assessed using the BESTest, Kistler force plate, GAITRite system, Biodex System 3 and CHAMPS questionnaire, respectively. Two-part semi-structured interviews were conducted post-surgery. RESULTS: Individuals post-surgery (n = 15) had worse dynamic balance and gait, and lower levels of moderate/vigorous physical activity (MVPA) (all p<0.05) versus healthy controls (n = 15). Strength did not differ between groups (p > 0.05). No associations between BESTest and strength or physical activity existed post-surgery (p > 0.05). Three themes were identified: 1) Symptoms affect daily activities; 2) Functional assessments alter perceptions of balance ability and 3) Open to supervised rehabilitation. CONCLUSION: Balance, gait and MVPA are impaired post-thoracic surgery, yet balance was not viewed to be important in enabling activities of daily living. However, supervised rehabilitation was considered acceptable.

SABRTooth: a randomised controlled feasibility study of stereotactic ablative radiotherapy (SABR) with surgery in patients with peripheral stage I nonsmall cell lung cancer considered to be at higher risk of complications from surgical resection.

OBJECTIVES: Stereotactic ablative radiotherapy (SABR) is a well-established treatment for medically inoperable peripheral stage I nonsmall cell lung cancer (NSCLC). Previous nonrandomised evidence supports SABR as an alternative to surgery, but high-quality randomised controlled trial (RCT) evidence is lacking. The SABRTooth study aimed to establish whether a UK phase III RCT was feasible. DESIGN AND METHODS: SABRTooth was a UK multicentre randomised controlled feasibility study targeting patients with peripheral stage I NSCLC considered to be at higher risk of surgical complications. 54 patients were planned to be randomised 1:1 to SABR or surgery. The primary outcome was monthly average recruitment rates. RESULTS: Between July 2015 and January 2017, 318 patients were considered for the study and 205 (64.5%) were deemed ineligible. Out of 106 (33.3%) assessed as eligible, 24 (22.6%) patients were randomised to SABR (n=14) or surgery (n=10). A key theme for nonparticipation was treatment preference, with 43 (41%) preferring nonsurgical treatment and 19 (18%) preferring surgery. The average monthly recruitment rate was 1.7 patients against a target of three. 15 patients underwent their allocated treatment: SABR n=12, surgery n=3. CONCLUSIONS: We conclude that a phase III RCT randomising higher risk patients between SABR and surgery is not feasible in the National Health Service. Patients have pre-existing treatment preferences, which was a barrier to recruitment. A significant proportion of patients randomised to the surgical group declined and chose SABR. SABR remains an alternative to surgery and novel study approaches are needed to define which patients benefit from a nonsurgical approach.

Determination of psilocybin and psilocin content in multiple Psilocybe cubensis mushroom strains using liquid chromatography - tandem mass spectrometry.

A method for clinical potency determination of psilocybin and psilocin in hallucinogenic mushroom species Psilocybe cubensis was developed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Five strains of dried, intact mushrooms were obtained and analyzed: Blue Meanie, Creeper, B-Plus, Texas Yellow, and Thai Cubensis. An extraction protocol was developed; this included an evaluation of sample milling technique, extraction solvents, and recovery/stability. Reversed phase chromatography on fused-core particle phases was developed for the determination of the two analytes using internal standard calibration with deuterated isotopologues of each analyte. The separation takes less than 5 min. Matrix effects were investigated by comparing signal response of calibration samples in neat solution and several mushroom matrices; no significant matrix effects were observed. The limit of detection for psilocybin was 1.5 ng/mL (1.5 pg on-column; 300 ng/g mushroom) and for psilocin was 0.15 ng/mL (0.15 pg on-column; 30 ng/g mushroom) using a Shimadzu LCMS-8050 triple quadrupole mass spectrometer. Assessment of the accuracy and precision of the method indicated percent error and RSD were <6 % at all concentration levels. Three whole, intact mushrooms from each strain were analyzed individually to obtain average content differences both between strains and between mushrooms of the same strain. From most to least potent, the study found that the average total psilocybin and psilocin concentrations for the Creeper, Blue Meanie, B+, Texas Yellow, and Thai Cubensis strains were 1.36, 1.221, 1.134, 1.103, and 0.879 % (w/w), respectively. A subset of these mushrooms was also tested in a separate non-affiliated laboratory, and the results were comparable between the two laboratories. Results from the secondary laboratory showed improved precision when multiple mushrooms were homogenized together, prior to extraction.

The Importance of Culture Change Associated With Novel Surgical Approaches and Innovation: Does Perioperative Care Transcend Technical Considerations for Pulmonary Lobectomy?

Robotic thoracic surgery for pulmonary lobectomy was introduced at our unit in 2015, along with enhanced perioperative patient care pathways. We evaluated the effect of this practice change on short-term outcomes. Data on all adult patients who underwent a lobectomy in our unit between 2015 and 2019 were obtained retrospectively from our surgical database. Patients fell into three groups: conventional open surgery via thoracotomy, video-assisted thoracoscopic surgery (VATS), and robot-assisted thoracoscopic surgery (RATS). Survival was defined as survival to discharge. Our cohort included 722 patients. Three hundred and ninety-two patients (54.3%) underwent an open operation, 259 patients (35.9%) underwent VATS surgery, and 71 patients (9.8%) underwent a robotic procedure. Comparing these surgical approaches, there was no statistically significant difference in the overall incidence of post-operative complications (p = 0.15) as well as the incidence of wound infections, arrhythmias, prolonged air leaks, respiratory failure, or ICU readmissions. Additionally, there was no statistically significant difference in survival to discharge (p = 0.66). However, patients who had a VATS procedure were less likely to develop a post-operative chest infection (p = 0.01). Evaluating our practice over time, we found a decrease in the overall incidence of post-operative complications (p = 0.01) with an improvement in survival to discharge (p = 0.02). In our experience, VATS lobectomy was associated with a lower incidence of post-operative chest infections. However, the limitations of our study must be considered; factors such as patient selection that may have had a substantial impact. The culture change associated with adoption of a VATS and robotic surgical programme appears to have corresponded with an improved survival to discharge for all lobectomy patients, irrespective of surgical approach. Perioperative care may therefore have a more significant impact on outcomes than technical considerations.

Cardiac surgery in nonagenarians: single-centre series and review.

BACKGROUND: Cardiac surgery is widely believed to be an excessively high-risk intervention for very elderly patients with coronary artery or valvular disease. However, as life expectancy and the prospect of sustained quality of life into older age increase, this assumption should be challenged so that surgery is not denied to patients who may derive significant symptomatic benefit with acceptable levels of operative risk. OBJECTIVE: To evaluate outcomes from cardiac surgery in nonagenarian patients. DESIGN: Analysis of prospectively collected single-centre data and review of outcomes reported in the literature. RESULTS: Twenty-three patients (13 males) aged 90 years or more underwent open cardiac surgery between 1998 and 2007. Four patients died within 30 days of surgery (surgical mortality 17.4%) and all-cause in-hospital morbidity was 74%. Actuarial survival at 1 and 5 years was estimated at 72 and 54%, respectively. Comparison of patients' survival against age-matched life tables for the English population found a standardised mortality ratio of 0.57 (95% CI: 0.24-0.99; one-sample log-rank test chi(2) = 3.93; p < 0.05) representing a significant survival benefit associated with surgery. The majority of patients reported symptomatic improvement reflected by significant decreases in angina and dyspnoea scores. Six single-centre series of nonagenarians and 3 reviews from national databases in the US and UK were identified in the literature. Pooled surgical mortality was 12.7% (95% CI: 8.7-17.3%) with no significant heterogeneity (chi(2) = 4.12; p = 0.77; I(2) = 0). CONCLUSION: Cardiac surgery in the elderly carries higher operative risk than in younger patients. However, in selected nonagenarians, surgery can be performed with acceptable morbidity and early mortality, and patients gain significant symptomatic relief and survival benefit.

The Milwaukee Youth Belongingness Scale (MYBS): Development and validation of the scale utilizing item response theory.

The examination of belonging in schools, connecting school belonging to a plethora of academic and psychosocial outcomes, has been well established in the literature. Researchers have measured school belonging most frequently with the Psychological Sense of School Membership, but its psychometric properties have been called into question by several researchers. Further, the scale measures 1 subset of belonging (i.e., school), leaving out powerful belonging connections in other areas of a student's life, namely peers and family. The current study examines the development and validation of the Milwaukee Youth Belongingness Scale. This process was examined by utilizing item response theory and a secondary analysis confirming the factor structure and the validation of the scale by comparing it to other constructs. The results confirm a 9-item scale that involves a total scale score and 3 factors (School, Peers, Family). Implications for mental health professionals and future research are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Versatile online-offline engine for automated acquisition of high-resolution tandem mass spectra.

For automated production of tandem mass spectrometric data for proteins and peptides >3 kDa at >50 000 resolution, a dual online-offline approach is presented here that improves upon standard liquid chromatography-tandem mass spectrometry (LC-MS/MS) strategies. An integrated hardware and software infrastructure analyzes online LC-MS data and intelligently determines which targets to interrogate offline using a posteriori knowledge such as prior observation, identification, and degree of characterization. This platform represents a way to implement accurate mass inclusion and exclusion lists in the context of a proteome project, automating collection of high-resolution MS/MS data that cannot currently be acquired on a chromatographic time scale at equivalent spectral quality. For intact proteins from an acid extract of human nuclei fractionated by reversed-phase liquid chromatography (RPLC), the automated offline system generated 57 successful identifications of protein forms arising from 30 distinct genes, a substantial improvement over online LC-MS/MS using the same 12 T LTQ FT Ultra instrument. Analysis of human nuclei subjected to a shotgun Lys-C digest using the same RPLC/automated offline sampling identified 147 unique peptides containing 29 co- and post-translational modifications. Expectation values ranged from 10 (-5) to 10 (-99), allowing routine multiplexed identifications.

"Proteotyping": population proteomics of human leukocytes using top down mass spectrometry.

Characterizing combinations of coding polymorphisms (cSNPs), alternative splicing and post-translational modifications (PTMs) on a single protein by standard peptide-based proteomics is challenging owing to <100% sequence coverage and the uncoupling effect of proteolysis on such variations >10-20 residues apart. Because top down MS measures the whole protein, combinations of all the variations affecting primary sequence can be detected as they occur in combination. The protein form generated by all types of variation is here termed the "proteotype", akin to a haplotype at the DNA level. Analysis of proteins from human primary leukocytes harvested from leukoreduction filters using a dual on-line/off-line top down MS strategy produced >600 unique intact masses, 133 of which were identified from 67 unique genes. Utilizing a two-dimensional platform, termed multidimensional protein characterization by automated top down (MudCAT), 108 of the above protein forms were subsequently identified in the absence of MS/MS in 4 days. Additionally, MudCAT enables the quantitation of allele ratios for heterozygotes and PTM occupancies for phosphorylated species. The diversity of the human proteome is embodied in the fact that 32 of the identified proteins harbored cSNPs, PTMs, or were detected as proteolysis products. Among the information were three partially phosphorylated proteins and three proteins heterozygous at known cSNP loci, with evidence for non-1:1 expression ratios obtained for different alleles.

Characterization of proteomic and metabolomic responses to dietary factors and supplements.

Over the past decade there has been a renewed interest in research and development of both dietary and nutritional supplements. Significant advancements have been made in the scientific assessment of the quality, safety, and efficacy of these products because of the strong interest in and financial support of these projects. As research in both fields continues to advance, opportunities to use new and innovative research technologies and methodologies, such as proteomics and metabolomics, are critical for the future progress of the science. The purpose of the symposium was to begin the process of communicating new innovative proteomic and metabolomic methodologies that may be applied by researchers in both the nutrition and the natural product communities. This symposium highlighted 2 proteomic approaches, protein fingerprinting in complex mixtures with peptoid microarrays and top-down mass spectrometry for annotation of gene products. Likewise, an overview of the methodologies used in metabolomic profiling of natural products was presented, and an illustration of an integrated metabolomics approach in nutrition research was highlighted.

Developing a VATS lobectomy programme--can VATS lobectomy be taught?

OBJECTIVE: Although VATS lobectomy has been demonstrated to be safe and effective, the technique is not widely practiced. This may, in part, reflect difficulty in acquiring appropriate skills. We have evaluated the effect of experience and training on surgical outcomes during the development and establishment of a VATS lobectomy programme. METHODS: Data were collected prospectively on 276 consecutive VATS lobectomies under the care of a single consultant as either the primary surgeon or supervising four trainees. The series was divided into cohorts of 46 patients. These comprised one trainee cohort and five sequential consultant cohorts. Statistical analysis utilised standard tests of significance. RESULTS: Increasing experience with the VATS lobectomy programme was associated with a significant reduction in operating time but intraoperative blood loss and postoperative stay were not influenced by increasing consultant surgical experience. Training was associated with a mean increase of 22 min operative time (p=0.0005) but no increase in intraoperative blood loss, morbidity, mortality or postoperative stay. The 46 trainee operative times were similar to the first 46 consultant cases. CONCLUSIONS: VATS lobectomy can be safely taught to trainee thoracic surgeons. However, in view of the limited number of centres undertaking VATS lobectomy, training should be coordinated at a national level to concentrate experience and improve uptake of this technique.

Selective oxidation of CO in the presence of H2, H2O and CO2 via gold for use in fuel cells.

An Au/Fe2O3 catalyst prepared using a two-stage calcination procedure achieves target conversion and selectivity for the competitive oxidation of dilute CO in the presence of moist excess H2 and CO2.

Manubrium-limited sternotomy decreases blood loss after aortic valve replacement surgery.

OBJECTIVES: Minimally invasive surgical approaches for aortic valve replacement (AVR) are growing in popularity in an attempt to decrease morbidity from conventional surgery. We have adopted a technique that divides only the manubrium and spares the body of the sternum. We sought to determine whether patients benefit from this less-invasive approach. METHODS: We retrospectively analysed our prospectively maintained database to review all isolated aortic valve replacements performed in an 18-month period from November 2011 to April 2013. RESULTS: One hundred and ninety-one patients were identified, 98 underwent manubrium-limited sternotomy (Mini-AVR) and 93 had a conventional median sternotomy (AVR). The two groups were well matched for preoperative variables and risk (mean logistic EuroSCORE mini-AVR 7.15 vs AVR 6.55, P = 0.47). Mean cardiopulmonary bypass and aortic cross-clamp times were 10 and 6 min longer, respectively, in the mini-AVR group (mean values 88 vs 78 min, P = 0.00040, and 66 vs 60 min, P = 0.0078, respectively). Mini-AVR patients had significantly less postoperative blood loss, 332 vs 513 ml, P = 0.00021, and were less likely to require blood products (fresh-frozen plasma and platelets), 24 vs 36%, P = 0.042. Postoperative complications and length of stay were similar (discharge on or before Day 4; mini-AVR 15 vs AVR 8%, P = 0.17). Valve outcome (paravalvular leak mini-AVR 2 vs AVR 1%, P = 1.00) and survival (mini-AVR 99 vs AVR 97%, P = 0.36) were equal. CONCLUSIONS: A manubrium-limited approach maintains outcomes achieved for aortic valve replacement by conventional sternotomy while significantly reducing postoperative blood loss and transfusion of blood products.

Stake through the chest.

We present a fascinating case of major penetrating trauma to the chest which resulted in a successful outcome. Often such trauma is associated with a poor outcome due to injury to the heart, lungs or major blood vessels with subsequent massive blood loss, pnuemothorax or haemo-pneumothorax. Late complications include infection rarely mediastinitis, empyema and occasionally chylothorax from damage to the thoracic duct.

Top-down proteomics reveals novel protein forms expressed in Methanosarcina acetivorans.

Using both automated nanospray and online liquid chromatography mass spectrometry LC-MS strategies, 99 proteins have been newly identified by top-down tandem mass spectrometry (MS/MS) in Methanosarcina acetivorans, the methanogen with the largest known genome [5.7 mega base pairs (Mb)] for an Archaeon. Because top-down MS/MS was used, 15 proteins were detected with mispredicted start sites along with an additional five from small open reading frames (SORFs). Beyond characterization of these more common discrepancies in genome annotation, one SORF resulted from a rare start codon (AUA) as the initiation site for translation of this protein. Also, a methylation on a 30S ribosomal protein (MA1259) was localized to Pro59-Val69, contrasting sharply from its homologue in Escherichia coli (rp S12) known to harbor an unusual beta-thiomethylated aspartic acid residue.

Global amine and acid functional group modification of proteins.

A sequential reaction methodology is employed for the complete derivatization of protein thiols, amines, and acids in high purity under denaturing conditions. Following standard thiol alkylation, protein amines are modified via reductive methylation with formaldehyde and pyridine-borane. Protein acids are subsequently amidated under buffered conditions in DMSO using the coupling reagent (7-azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate. The generality of the approach is demonstrated with four proteins and with several amines yielding near-quantitative transformations as characterized by high-resolution Fourier transform mass spectrometry. The developed approach has numerous implications for protein characterization and general protein chemistry. Applications in mass spectrometry (MS) based proteomics of intact proteins (top-down MS) are explored, including the addition of stable isotopes for relative quantitation and protein identification through functional group counting. The methodology can be used for altering the physical and chemical properties of proteins, as demonstrated with amidation to modify protein isoelectric point and through derivatization with quaternary amines. Additionally, the chemistry has applications in the semisynthesis of monodisperse polymers based on protein scaffolds. We prepare proteins modified with azides and alkynes to enable further functionalization via copper(I)-catalyzed 1,3-dipolar Huisgen cycloaddition ("click") chemistry.

Does body mass index (BMI) affect cost in cardiac surgery? 'A pound (pound) for pound (lb) analysis'.

The effect of BMI on cost of intensive care unit (ICU) stay and ward stay in cardiac surgery is currently unknown. To assess these data on BMI, ICU stay and EuroSCORE were prospectively collected for 6100 patients undergoing cardiac surgery between 2000 and 2004. Patients were categorised according to BMI and comparisons were conducted, using non-parametric tests (Kruskal-Wallis and Mann-Whitney U-tests). One day in ICU was costed at pound1,300 and one ward-day pound300/day by this hospital's finance department. Despite similar median (due to a distribution skewed to a short ICU stay), a significant difference is observed between all 6 groups (Kruskal-Wallis; P<0.001) for ICU stay and ward stay. Underweight and morbidly obese patients had longer ICU stays compared with the ideal weight patients (P=0.010 and P=0.004, respectively); while overweight and obese patients had shorter ICU stays (P<0.001 and P=0.007, respectively). Underweight patients had a longer ward stay than ideal weight patients (P=0.005) but there was no difference between ideal and morbidly obese patients (P=0.789). These results demonstrate that BMI has a significant impact on ICU and ward stay with 'ideal weight' not always being ideal for patients undergoing cardiac surgery. This cost appears to be independent of EuroSCORE.

Top down mass spectrometry of < 60-kDa proteins from Methanosarcina acetivorans using quadrupole FRMS with automated octopole collisionally activated dissociation.

A fragmentation geometry based upon axial acceleration of m/z-selected protein ions into a linear octopole ion trap allowed simultaneous production and external accumulation of fragment ions prior to m/z measurement in a FT mass spectrometer. Improved dynamic range resulting from this octopole collisionally activated dissociation resulted in a 2.5x increase in experimental throughput and a 2x increase in fragment ion matches to gene products identified and characterized in the top down fashion. The acceleration voltage for optimal fragmentation has a m/z and mass dependence, knowledge of which facilitated an automated platform for top down MS/MS on a quadrupole FT hybrid mass spectrometer. Controlled by improved software for data acquisition (e.g. using dynamic exclusion of previously identified species), automated octopole collisionally activated dissociation of samples fractionated using chromatofocusing and reversed-phase liquid chromatography achieved a significant increase in protein identification rate versus previous benchmarks. Also a batch analysis version of ProSight PTM facilitated probability-based identification of intact proteins obtained in a higher throughput fashion. In total, 101 unique proteins (5-59 kDa) were identified from whole cell lysates of Methanosarcina acetivorans grown anaerobically, including the characterization of several mispredicted start sites and biologically relevant mass discrepancies.

VATS lung biopsy in suspected, diffuse interstitial lung disease provides diagnosis, and alters management strategies.

OBJECTIVES: In patients with suspected diffuse interstitial lung disease, open lung biopsy is associated with high mortality (16%). This risk is only acceptable if diagnosis is made and management enhanced. We reviewed the role of VATS techniques in this group to determine the morbidity, mortality and outcomes in terms of diagnosis and enhanced management. METHODS: Over the period of 5 years, 78 patients with suspected diagnosis of diffuse interstitial lung disease on clinical and radiological grounds were referred to a single surgical team. The patients' case notes and histology reports were reviewed retrospectively. Correlation was made with histopathological diagnosis. RESULTS: All 78 patients had sufficient provision of material for histological analysis. Eight patients had a histological diagnosis not consistent with diffuse interstitial lung disease; in all eight patients, this significantly altered the subsequent management. Of the 70 patients with diffuse lung disease, 26 patients (37.1%) had a histological diagnosis of usual interstitial pneumonia. Thirteen patients (18.6%) had a histological diagnosis of unclassifiable diffuse lung disease despite an adequate biopsy. The remaining 31 patients (44.3%) had other positive histological diagnosis made. A difference between pre-operative clinico-radiological and final histological diagnosis sufficient to change prognosis and definitive management was made in 19 patients (27.1%). The mean and median post-operative stay was 2.8 days and 2 days, respectively. The in-hospital mortality was one patient (1.5%) due to adult respiratory distress syndrome. CONCLUSIONS: VATS lung biopsy can be performed in this group of patient with low mortality of 1.5%. It provides sufficient material for histological diagnosis in 100% of patients and alters the management and prognosis in a significant number of patients. We propose that the role of VATS and clinico-radiological techniques should be compared in a prospective controlled clinical trial.