Improving GWAS discovery and genomic prediction accuracy in biobank data.

Genetically informed, deep-phenotyped biobanks are an important research resource and it is imperative that the most powerful, versatile, and efficient analysis approaches are used. Here, we apply our recently developed Bayesian grouped mixture of regressions model (GMRM) in the UK and Estonian Biobanks and obtain the highest genomic prediction accuracy reported to date across 21 heritable traits. When compared to other approaches, GMRM accuracy was greater than annotation prediction models run in the LDAK or LDPred-funct software by 15% (SE 7%) and 14% (SE 2%), respectively, and was 18% (SE 3%) greater than a baseline BayesR model without single-nucleotide polymorphism (SNP) markers grouped into minor allele frequency-linkage disequilibrium (MAF-LD) annotation categories. For height, the prediction accuracy R2 was 47% in a UK Biobank holdout sample, which was 76% of the estimated [Formula: see text]. We then extend our GMRM prediction model to provide mixed-linear model association (MLMA) SNP marker estimates for genome-wide association (GWAS) discovery, which increased the independent loci detected to 16,162 in unrelated UK Biobank individuals, compared to 10,550 from BoltLMM and 10,095 from Regenie, a 62 and 65% increase, respectively. The average [Formula: see text] value of the leading markers increased by 15.24 (SE 0.41) for every 1% increase in prediction accuracy gained over a baseline BayesR model across the traits. Thus, we show that modeling genetic associations accounting for MAF and LD differences among SNP markers, and incorporating prior knowledge of genomic function, is important for both genomic prediction and discovery in large-scale individual-level studies.

A Case of Abnormal Right Ventricular Color-Flow Doppler Jet.

Transthoracic echocardiography is used routinely during the follow-up after heart transplant surgery to screen possible complications and adverse events such as rejection. It often results in incidental findings that bring diagnostic challenges for sonographers. This E-challenge shows a Doppler flow abnormality associated with a rare cardiovascular diagnosis. Its physiopathology and its association with echocardiography findings are reviewed.

Impact of Surgical Positioning on the Occurrence of Postoperative Ipilateral Shoulder Pain After Lung Resection by Video-Assisted Thoracoscopy: A Randomized Trial.

OBJECTIVE: The aim of this study was to evaluate the impact of the ipsilateral arm position on ipsilateral shoulder pain after lung cancer resection by video-assisted thoracic surgery. DESIGN: A prospective randomized controlled trial. SETTING: A single academic center study. PARTICIPANTS: Patients undergoing video-assisted thoracic surgery pulmonary resection for cancer at the Institut Universitaire de Cardiologie et de Pneumologie de Québec from May 2020 to May 2022 were included. INTERVENTIONS: Patients randomly were assigned with a 1:1 ratio to a supported or suspended ipsilateral arm position. MEASUREMENTS AND MAIN RESULTS: Ipsilateral shoulder pain incidence, pain score, and opioid use were recorded in the postanesthesia care unit (PACU) on postoperative days 1 and 2. One hundred thirty-three patients were randomized, 67 in the suspended-arm group and 66 in the supported-arm group. Of the patients, 31% reported ipsilateral shoulder pain in the PACU with no difference between groups (19/67 [28.4%] v 22/66 patients (33.3%), p = 0.5767). There was no significant difference between the pain score in the PACU (3 [0-6] v 4 [0-6], p = 0.9055) at postoperative day 1 (4 [2-6] v 3 [2-5], p = 0.4113) and at postoperative day 2 (2 [0-5] v 2 [1-4], p = 0.9508). Ipsilateral shoulder pain score decreased rapidly on postoperative day 2. There was no statistical difference in opioid and gabapentinoid use between the groups. CONCLUSIONS: Ipsilateral arm position seems to have no impact on ipsilateral shoulder pain.

Continuous Right Ventricular Pressure Monitoring in Cardiac Surgery.

OBJECTIVE: Right ventricular (RV) dysfunction in cardiac surgery can lead to RV failure, which is associated with increased morbidity and mortality. Abnormal RV function can be identified using RV pressure monitoring. The primary objective of the study is to determine the proportion of patients with abnormal RV early to end-diastole diastolic pressure gradient (RVDPG) and abnormal RV end-diastolic pressure (RVEDP) before initiation and after cardiopulmonary bypass (CPB) separation. The secondary objective is to evaluate if RVDPG before CPB initiation is associated with difficult and complex separation from CPB, RV dysfunction, and failure at the end of cardiac surgery. DESIGN: Prospective study. SETTING: Tertiary care cardiac institute. PARTICIPANTS: Cardiac surgical patients. INTERVENTION: Cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Automated electronic quantification of RVDPG and RVEDP were obtained. Hemodynamic measurements were correlated with cardiac and extracardiac parameters from transesophageal echocardiography and postoperative complications. Abnormal RVDPG was present in 80% of the patients (n = 105) at baseline, with a mean RVEDP of 14.2 ± 3.9 mmHg. Patients experienced an RVDPG > 4 mmHg for a median duration of 50.2% of the intraoperative period before CPB initiation and 60.6% after CPB separation. A total of 46 (43.8%) patients had difficult/complex separation from CPB, 18 (38.3%) patients had RV dysfunction, and 8 (17%) had RV failure. Abnormal RVDPG before CPB was not associated with postoperative outcome. CONCLUSION: Elevated RVDPG and RVEDP are common in cardiac surgery. RVDPG and RVEDP before CPB initiation are not associated with RV dysfunction and failure but can be used to diagnose them.

An ultra-high-affinity small organic ligand of fibroblast activation protein for tumor-targeting applications.

We describe the development of OncoFAP, an ultra-high-affinity ligand of fibroblast activation protein (FAP) for targeting applications with pan-tumoral potential. OncoFAP binds to human FAP with affinity in the subnanomolar concentration range and cross-reacts with the murine isoform of the protein. We generated various fluorescent and radiolabeled derivatives of OncoFAP in order to study biodistribution properties and tumor-targeting performance in preclinical models. Fluorescent derivatives selectively localized in FAP-positive tumors implanted in nude mice with a rapid and homogeneous penetration within the neoplastic tissue. Quantitative in vivo biodistribution studies with a lutetium-177-labeled derivative of OncoFAP revealed a preferential localization in tumors at doses of up to 1,000 nmol/kg. More than 30% of the injected dose had already accumulated in 1 g of tumor 10 min after intravenous injection and persisted for at least 3 h with excellent tumor-to-organ ratios. OncoFAP also served as a modular component for the generation of nonradioactive therapeutic products. A fluorescein conjugate mediated a potent and FAP-dependent tumor cell killing activity in combination with chimeric antigen receptor (CAR) T cells specific to fluorescein. Similarly, a conjugate of OncoFAP with the monomethyl auristatin E-based Vedotin payload was well tolerated and cured tumor-bearing mice in combination with a clinical-stage antibody-interleukin-2 fusion. Collectively, these data support the development of OncoFAP-based products for tumor-targeting applications in patients with cancer.

Pulmonary Vasodilator Response of Combined Inhaled Epoprostenol and Inhaled Milrinone in Cardiac Surgical Patients.

BACKGROUND: Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are major complications in cardiac surgery. Intraoperative management of patients at high risk of RV failure should aim to reduce RV afterload and optimize RV filling pressures, while avoiding systemic hypotension, to facilitate weaning from cardiopulmonary bypass (CPB). Inhaled epoprostenol and inhaled milrinone (iE&iM) administered in combination before CPB may represent an effective strategy to facilitate separation from CPB and reduce requirements for intravenous inotropes during cardiac surgery. Our primary objective was to report the rate of positive pulmonary vasodilator response to iE&iM and, second, how it relates to perioperative outcomes in cardiac surgery. METHODS: This is a retrospective cohort study of consecutive patients with PH or RV dysfunction undergoing on-pump cardiac surgery at the Montreal Heart Institute from July 2013 to December 2018 (n = 128). iE&iM treatment was administered using an ultrasonic mesh nebulizer before the initiation of CPB. Demographic and baseline clinical data, as well as hemodynamic, intraoperative, and echocardiographic data, were collected using electronic records. An increase of 20% in the mean arterial pressure (MAP) to mean pulmonary artery pressure (MPAP) ratio was used to indicate a positive response to iE&iM. RESULTS: In this cohort, 77.3% of patients were responders to iE&iM treatment. Baseline systolic pulmonary artery pressure (SPAP) (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.24-2.16 per 5 mm Hg; P = .0006) was found to be a predictor of pulmonary vasodilator response, while a European System for Cardiac Operative Risk Evaluation (EuroSCORE II) score >6.5% was a predictor of nonresponse to treatment (≤6.5% vs >6.5% [reference]: OR, 5.19; 95% CI, 1.84-14.66; P = .002). Severity of PH was associated with a positive response to treatment, where a higher proportion of responders had MPAP values >30 mm Hg (42.4% responders vs 24.1% nonresponders; P = .0237) and SPAP values >55 mm Hg (17.2% vs 3.4%; P = .0037). Easier separation from CPB was also associated with response to iE&iM treatment (69.7% vs 58.6%; P = .0181). A higher proportion of nonresponders had a very difficult separation from CPB and required intravenous inotropic drug support compared to responders, for whom easy separation from CPB was more frequent. Use of intravenous inotropes after CPB was lower in responders to treatment (8.1% vs 27.6%; P = .0052). CONCLUSIONS: A positive pulmonary vasodilator response to treatment with a combination of iE&iM before initiation of CPB was observed in 77% of patients. Higher baseline SPAP was an independent predictor of pulmonary vasodilator response, while EuroSCORE II >6.5% was a predictor of nonresponse to treatment.

Effect of reverse Trendelenburg position and positive pressure ventilation on safe non-hypoxic apnea period in obese, a randomized-control trial.

PURPOSE: There is an elevated incidence of hypoxemia during the airway management of the morbidly obese. We aimed to assess whether optimizing body position and ventilation during pre-oxygenation allow a longer safe non-hypoxic apnea period (SNHAP). METHODS: Fifty morbidly obese patients were recruited and randomized for this study. Patients were positioned and preoxygenated for three minutes in the ramp position associated with spontaneous breathing without additional CPAP or PEEP (RP/ZEEP group) or in the reverse Trendelenburg position associated with pressure support ventilation mode with pressure support of 8 cmH2O and an additional 10 cmH2O of PEEP while breathing spontaneously (RT/PPV group) according to randomization. RESULTS: The SNHAP was significantly longer in the RT/PPV group (258.2 (55.1) vs. 216.7 (42.3) seconds, p = 0.005). The RT/PPV group was also associated to a shorter time to obtain a fractional end-tidal oxygen concentration (FEtO2) of 0.90 (85.1(47.8) vs 145.3(40.8) seconds, p < 0.0001), a higher proportion of patients that reached the satisfactory FEtO2 of 0.90 (21/24, 88% vs. 13/24, 54%, p = 0.024), a higher FEtO2 during preoxygenation (0.91(0.05) vs. 0.89(0.01), p = 0.003) and a faster return to 97% oxygen saturation after ventilation resumption (69.8 (24.2) vs. 91.4 (39.2) seconds, p = 0.038). CONCLUSION: In the morbidly obese population, RT/PPV, compared to RP/ZEEP, lengthens the SNHAP, decreases the time to obtain optimal preoxygenation conditions, and allows a faster resuming of secure oxygen saturation. The former combination allows a more significant margin of time for endotracheal intubation and minimizes the risk of hypoxemia in this highly vulnerable population. TRIAL REGISTRATION: NCT02590406, 29/10/2015.

Preclinical Assessment of ADAM9-Responsive Mesoporous Silica Nanoparticles for the Treatment of Pancreatic Cancer.

Pancreatic adenocarcinoma (PDAC) remains largely refractory to chemotherapeutic treatment regimens and, consequently, has the worst survival rate of all cancers. The low efficacy of current treatments results largely from toxicity-dependent dose limitations and premature cessation of therapy. Recently, targeted delivery approaches that may reduce off-target toxicities have been developed. In this paper, we present a preclinical evaluation of a PDAC-specific drug delivery system based on mesoporous silica nanoparticles (MSNs) functionalized with a protease linker that is specifically cleaved by PDAC cells. Our previous work demonstrated that ADAM9 is a PDAC-enriched protease and that paclitaxel-loaded ADAM9-responsive MSNs effectively kill PDAC cells in vitro. Here, we show that paclitaxel-loaded ADAM9-MSNs result in off-target cytotoxicity in clinically relevant models, which spurred the development of optimized ADAM9-responsive MSNs (OPT-MSNs). We found that these OPT-MSNs still efficiently kill PDAC cells but, as opposed to free paclitaxel, do not induce death in neuronal or bone marrow cells. In line with these in vitro data, paclitaxel-loaded OPT-MSNs showed reduced organ damage and leukopenia in a preclinical PDAC xenograft model. However, no antitumor response was observed upon OPT-MSN administration in vivo. The poor in vivo antitumor activity of OPT-MSNs despite efficient antitumor effects in vitro highlights that although MSN-based tumor-targeting strategies may hold therapeutic potential, clinical translation does not seem as straightforward as anticipated.

Quality of life of patients treated for kidney stones 10-20mm in diameter in terms of the type of operation performed: A qualitative study.

INTRODUCTION: Urolithiasis is a common chronic disease whose effect on patients' quality of life (QOL) is considerable but depends on the treatment received, differing between types of surgery. Intrarenal stones can be treated with different techniques: extracorporeal shock wave lithotripsy (ESWL), flexible ureteroscopy (fURS), and mini percutaneous nephrolithotomy (mini-PCNL), with proportional success and complication rates. The aim of this study was to qualitatively explore the impact of the different techniques on patients' QOL and understand their experiences of treatment choices. METHODS: Patients treated for medium-sized kidney stones (10-20mm in diameter) were interviewed in a semi-structured manner. The interview data were transcribed and analyzed by theme according to consolidated criteria for reporting qualitative research (COREQ) guidelines. RESULTS: Data saturation was achieved after interviewing 15 patients. The mean interview time was 34min (standard deviation (SD), 6.8min). The mean patient age was 54 years (SD, 9.5 years). Eight patients underwent ESWL, 10 were treated with fURS, and 8 underwent mini-PCNL. Twenty-seven subthemes were coded and regrouped into eight major themes, namely: no sense of choice in the decision-making process for eleven patients; extremely negative experiences of double-J stents for fourteen patients; concern about the risk of recurrence or treatment failure for thirteen patients; complicated hygiene and dietary recommendations for nine patients; technique-dependent postoperative outcomes; relatively well-tolerated operations for thirteen patients; a poor experience of sick leave, often because of a double-J stent; different views regarding future operations. In fact, a third of patients would choose the most effective treatment, a third would choose the simplest procedure and the last third would trust their urologist. Patients' experiences of these operations are variable. CONCLUSION: Urologists must support their patients by presenting the different treatment options with clear, appropriate, and unbiased information. This should ensure patients take part in treatment decisions as part of a personalized treatment plan.

New developments in the understanding of right ventricular function in acute care.

PURPOSE OF REVIEW: Right ventricular dysfunction has an important impact on the perioperative course of cardiac surgery patients. Recent advances in the detection and monitoring of perioperative right ventricular dysfunction will be reviewed here. RECENT FINDINGS: The incidence of right ventricular dysfunction in cardiac surgery has been associated with unfavorable outcomes. New evidence supports the use of a pulmonary artery catheter in cardiogenic shock. The possibility to directly measure right ventricular pressure by transducing the pacing port has expanded its use to track changes in right ventricular function and to detect right ventricular outflow tract obstruction. The potential role of myocardial deformation imaging has been raised to detect patients at risk of postoperative complications. SUMMARY: Perioperative right ventricular function monitoring is based on echocardiographic and extra-cardiac flow evaluation. In addition to imaging modalities, hemodynamic evaluation using various types of pulmonary artery catheters can be achieved to track changes rapidly and quantitatively in right ventricular function perioperatively. These monitoring techniques can be applied during and after surgery to increase the detection rate of right ventricular dysfunction. All this to improve the treatment of patients presenting early signs of right ventricular dysfunction before systemic organ dysfunction ensue.

Perioperative Doppler ultrasound assessment of portal vein flow pulsatility in high-risk cardiac surgery patients: a multicentre prospective cohort study.

BACKGROUND: Portal vein Doppler ultrasound pulsatility measured by transoesophageal echocardiography is a marker of the haemodynamic impact of venous congestion in cardiac surgery. We investigated whether the presence of abnormal portal vein flow pulsatility is associated with a longer duration of invasive life support and postoperative complications in high-risk patients. METHODS: In this multicentre cohort study, pulsed-wave Doppler ultrasound assessments of portal vein flow were performed during anaesthesia before initiation of cardiopulmonary bypass (before CPB) and after separation of cardiopulmonary bypass (after CPB). Abnormal pulsatility was defined as portal pulsatility fraction (PPF) ≥50% (PPF50). The primary outcome was the cumulative time in perioperative organ dysfunction (TPOD) requiring invasive life support during 28 days. Secondary outcomes included major postoperative complications. RESULTS: 373 patients, 71 (22.0%) had PPF50 before CPB and 77 (24.9%) after CPB. PPF50 was associated with longer duration of TPOD (median [inter-quartile range]; before CPB: 27 h [11-72] vs 19 h [8.5-42], P=0.02; after CPB: 27 h [11-61] vs 20 h [8-42], P=0.006). After adjusting for confounders, PPF50 before CPB showed significant association with TPOD. PPF50 after CPB was associated with a higher rate of major postoperative complications (36.4% vs 20.3%, P=0.006). CONCLUSIONS: Abnormal portal vein flow pulsatility before cardiopulmonary bypass was associated with longer duration of life support therapy after cardiac surgery in high-risk patients. Abnormal portal vein flow pulsatility after cardiopulmonary bypass separation was associated with a higher risk of major postoperative complications although this association was not independent of other factors. CLINICAL TRIAL REGISTRATION: NCT03656263.

Early Detection and Correction of Cerebral Desaturation With Noninvasive Oxy-Hemoglobin, Deoxy-Hemoglobin, and Total Hemoglobin in Cardiac Surgery: A Case Series.

Regional cerebral oxygen saturation (rS o2 ) obtained from near-infrared spectroscopy (NIRS) provides valuable information during cardiac surgery. The rS o2 is calculated from the proportion of oxygenated to total hemoglobin in the cerebral vasculature. Root O3 cerebral oximetry (Masimo) allows for individual identification of changes in total (ΔcHbi), oxygenated (Δ o2 Hbi), and deoxygenated (ΔHHbi) hemoglobin spectral absorptions. Variations in these parameters from baseline help identify the underlying mechanisms of cerebral desaturation. This case series represents the first preliminary description of Δ o2 Hbi, ΔHHbi, and ΔcHbi variations in 10 cardiac surgical settings. Hemoglobin spectral absorption changes can be classified according to 3 distinct variations of cerebral desaturation. Reduced cerebral oxygen content or increased cerebral metabolism without major blood flow changes is reflected by decreased Δ o2 Hbi, unchanged ΔcHbi, and increased ΔHHbi Reduced cerebral arterial blood flow is suggested by decreased Δ o2 Hbi and ΔcHbi, with variable ΔHHbi. Finally, acute cerebral congestion may be suspected with increased ΔHHbi and ΔcHbi with unchanged Δ o2 Hbi. Cerebral desaturation can also result from mixed mechanisms reflected by variable combination of those 3 patterns. Normal cerebral saturation can occur, where reduced cerebral oxygen content such as anemia is balanced by a reduction in cerebral oxygen consumption such as during hypothermia. A summative algorithm using rS o2 , Δ o2 Hbi, ΔHHbi, and ΔcHbi is proposed. Further explorations involving more patients should be performed to establish the potential role and limitations of monitoring hemoglobin spectral absorption signals.

Pain-Related Fear in Adults Living With Chronic Pain: Development and Psychometric Validation of a Brief Form of the Tampa Scale of Kinesiophobia.

OBJECTIVE: To develop and validate a brief version of the Tampa Scale of Kinesiophobia (TSK) while preserving content validity in a mixed chronic pain population. DESIGN: Cross-sectional study. SETTING: Tertiary care interdisciplinary chronic pain clinic. PARTICIPANTS: Adults with chronic pain (N=933; mean age, 53.5±15.7 years; 63% women). INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: TSK-11 measured at intake. Self-reported data from a patient registry were extracted from November 2017 to October 2019. RESULTS: An exploratory factor analysis identified a 2-factor structure from the TSK-11 and item reduction resulted in a 7-item TSK (TSK-7) with 61.2% explained variance and Cronbach's alphas of 0.76 and 0.70 for each of the 2 factors. To maximally reduce the number of items without affecting internal consistency, a 5-item TSK (TSK-5) with 72% explained variance was also explored. Strong correlations were found between the newly developed brief TSK versions and TSK-11 (r>0.93), suggesting good concurrent validity. TSK-11, TSK-7, and TSK-5 had similar convergent validity with moderate correlations for pain catastrophizing (r=0.57, 0.58, 0.54), depression (r=0.45, 0.46, 0.42), pain interference (r=0.43, 0.44, 0.40), and pain acceptance (r=-0.57, -0.59, -0.55). CONCLUSIONS: These 2 brief versions of the TSK may help to simplify questionnaires across chronic pain centers where multiple outcome measures are used for a complete biopsychosocial assessment of patients.

Sepsis-Induced Cardiomyopathy Reviewed: The Case for Early Consideration of Mechanical Support.

Sepsis-induced cardiomyopathy (SCM) is an increasingly recognized problem encountered in critical care medicine. It generally is characterized as a decrease in left, right, or biventricular ejection fraction followed by a recovery of function over a period of days to weeks. Venoarterial extracorporeal membrane oxygenation (ECMO) has been used for the treatment of adults with various etiologies of shock, including cardiogenic and septic shock. This review summarizes current pathophysiologic mechanisms leading to SCM and provides a detection and treatment algorithm for SCM, as well as a discussion about the rationale and recent clinical data surrounding the use of ECMO and other forms of mechanical circulatory support for SCM.

Impact of Processed Electroencephalography in Cardiac Surgery: A Retrospective Analysis.

OBJECTIVE: The use of brain function monitoring with processed electroencephalography (pEEG) during cardiac surgery is gaining interest for the optimization of hypnotic agent delivery during the maintenance of anesthesia. The authors sought to determine whether the routine use of pEEG-guided anesthesia is associated with a reduction of hemodynamic instability during cardiopulmonary bypass (CPB) separation and subsequently reduces vasoactive and inotropic requirements in the intensive care unit. DESIGN: This is a retrospective cohort study based on an existing database. SETTING: A single cardiac surgical center. PARTICIPANTS: Three hundred patients undergoing cardiac surgery, under CPB, between December 2013 and March 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred and fifty patients had pEEG-guided anesthesia, and 150 patients did not have a pEEG-guided anesthesia. Multiple logistic regression demonstrated that pEEG-guided anesthesia was not associated with a successful CPB separation (p = 0.12). However, the use of pEEG-guided anesthesia reduced by 57% the odds of being in a higher category for vasoactive inotropic score compared to patients without pEEG (odds ratio = 0.43; 95% confidence interval: 0.26-0.73; p = 0.002). Duration of mechanical ventilation, fluid balance, and blood losses were also reduced in the pEEG anesthesia-guided group (p < 0.003), but there were no differences in organ dysfunction duration and mortality. CONCLUSION: During cardiac surgery, pEEG-guided anesthesia allowed a reduction in the use of inotropic or vasoactive agents at arrival in the intensive care unit. However, it did not facilitate weaning from CPB compared to a group where pEEG was unavailable. A pEEG-guided anesthetic management could promote early vasopressor weaning after cardiac surgery.

Post-pneumonectomy patients undergoing cardiac surgery: A case series.

BACKGROUND: Data regarding post-pneumonectomy patient assessment for cardiac surgery is scarce. This retrospective study was conducted to define early and late outcomes in these patients, and to identify risk factors for poor outcomes. METHODS: This study included patients with a previous history of pneumonectomy undergoing on-pump cardiac surgery with median sternotomy. The institutional database was reviewed from 1992 to 2018. RESULTS: Sixteen post-pneumonectomy patients (all lung cancer) were identified. The age range was 53-81 years. The mean FEV1/FVC was 69%. The mean EuroSCORE II was 11.6%. Four patients had heart failure symptoms in the 2 weeks before surgery. Seven patients had isolated coronary artery bypass grafting (CABG) and six patients had CABG + aortic valve replacement (AVR). The major perioperative events affecting the ease and outcomes of the surgical procedures were structural shifts (5), extensive adhesions on heart and vessels (5), and extensive calcification of heart components (5). Important postoperative complications were respiratory (7), infections (5), and acute kidney injury (5). The median hospital length of stay was 7 days. Five patients died in hospital (none with isolated CABG) with a preoperative New York Heart Association classification (NYHA) of III-IV, a cardiopulmonary bypass time of 175.2 min and an aortic cross-clamp time of 104.0 min. The long-term survival data were recorded with a mean follow-up of 7.3 ± 7.1 years (range from 0 to 19). The overall, 5-year survival, was 50% for all cardiac surgeries, 71% for isolated CABG surgeries, and 17% for CABG + AVR surgeries, respectively. CONCLUSION: Post-pneumonectomy patients have acceptable postoperative outcomes and survival. Simple and short surgeries with careful planning can yield favorable outcomes for this high-risk subgroup of patients.

Investigating Specialized Chronic Pain Care Among Emerging Adults.

BACKGROUND: AIMS: To investigate characteristics of emerging adults accessing a specialized chronic non-cancer pain clinic and describe interventions offered and utilized by this group. DESIGN: A retrospective chart review was conducted of emerging adults and middle-aged adults with chronic pain receiving care over a six-month period. SETTING: A chronic pain clinic in Southeastern Ontario. PARTICIPANTS: 82 participants comprised of 41 emerging adults (aged 18-29) and 41 middle-aged adults (aged 30-64) METHODS: Groups were matched on sex and number of pain sites. Demographic and pain characteristics, interventions, referrals, and clinic utilization were examined using bivariate and multivariate analysis. RESULTS: Emerging adults reported lower pain severity scores (t(80) = -2.15, p = .035), were more likely to receive referrals for additional consultation and/or diagnostic investigations (X2(1, n = 82) = 4.97, p = .026) and to have at least one psychology visit (X2 = 7.29, p = .007). Moreover, emerging adults with higher depression scores were more likely to see a psychologist (OR 1.23, 95% CI 1.014-1.492). CONCLUSIONS: Pain presentation and care patterns differed between emerging adults and middle-aged adults. Increased use of non-pharmacologic interventions in emerging adults may reflect differences in pain presentations as well as clinician's sensitivity to emerging adult's particular developmental needs but further research is needed. Further research is needed to contribute to nurses' understanding of the quality and efficacy of pain management approaches.

3-Dimensional Immunostaining and Automated Deep-Learning Based Analysis of Nerve Degeneration.

Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease driven by inflammation and demyelination in the brain, spinal cord, and optic nerve. Optic neuritis, characterized by inflammation and demyelination of the optic nerve, is a symptom in many patients with MS. The optic nerve is the highway for visual information transmitted from the retina to the brain. It contains axons from the retinal ganglion cells (RGCs) that reside in the retina, myelin forming oligodendrocytes and resident microglia and astrocytes. Inflammation, demyelination, and axonal degeneration are also present in the optic nerve of mice subjected to experimental autoimmune encephalomyelitis (EAE), a preclinical mouse model of MS. Monitoring the optic nerve in EAE is a useful strategy to study the presentation and progression of pathology in the visual system; however, current approaches have relied on sectioning, staining and manual quantification. Further, information regarding the spatial load of lesions and inflammation is dependent on the area of sectioning. To better characterize cellular pathology in the EAE model, we employed a tissue clearing and 3D immunolabelling and imaging protocol to observe patterns of immune cell infiltration and activation throughout the optic nerve. Increased density of TOPRO staining for nuclei captured immune cell infiltration and Iba1 immunostaining was employed to monitor microglia and macrophages. Axonal degeneration was monitored by neurofilament immunolabelling to reveal axonal swellings throughout the optic nerve. In parallel, we developed a convolutional neural network with a UNet architecture (CNN-UNet) called BlebNet for automated identification and quantification of axonal swellings in whole mount optic nerves. Together this constitutes a toolkit for 3-dimensional immunostaining to monitor general optic nerve pathology and fast automated quantification of axonal defects that could also be adapted to monitor axonal degeneration and inflammation in other neurodegenerative disease models.

A proposed algorithm for combining transcranial Doppler ultrasound monitoring with cerebral and somatic oximetry: a case report.

PURPOSE: Transcranial Doppler (TCD) ultrasound is a non-invasive monitor of cerebral blood velocity that can be used intraoperatively. The purpose of this report is to describe how different patterns seen on TCD can help identify the cause of cerebral desaturation when near-infrared spectroscopy (NIRS) oximetry is used concomitantly. CLINICAL FEATURES: A 69-yr-old male patient undergoing coronary revascularisation and aortic valve replacement developed perioperative complications that were detected using a combination of transtemporal TCD of the middle cerebral artery along with cerebral and somatic NIRS. Initial brain desaturation was secondary to hypocapnia during which TCD-derived blood velocity and somatic NIRS values remained unchanged. After the procedure, a second episode of brain desaturation occurred secondary to a technical issue with the aortic valve prosthesis requiring a return to cardiopulmonary bypass (CPB); there were no high-intensity transient signals (HITS) on TCD. Brain desaturation occurred a third time following the second attempt to separate from CPB at which time TCD detected a significant amount of HITS suggesting air emboli that were associated with acute right ventricular dysfunction; there was also a reduction in somatic NIRS. CONCLUSIONS: Combining TCD with cerebral NIRS allows for the rapid identification of three different mechanisms of brain desaturation. An algorithm is proposed to help identify the origin of NIRS cerebral desaturation. Prospective clinical trials are needed to investigate potential benefits of multimodal brain monitoring and its impact on short and/or long-term clinical outcomes.

RéSUMé: OBJECTIF: L'échographie par Doppler transcrânien (DTC) est un moniteur non invasif de la vélocité sanguine cérébrale qui peut être utilisé en période peropératoire. L'objectif de ce compte rendu est de décrire comment différents tracés observés sur le DTC peuvent aider l'anesthésiologiste à identifier la cause de la désaturation cérébrale lorsque l'oxymétrie par spectroscopie proche infrarouge (SPIR) est utilisée de manière concomitante. ÉLéMENTS CLINIQUES: Un homme de 69 ans subissant une revascularisation coronarienne et un remplacement de valve aortique a présenté des complications périopératoires détectées grâce à la combinaison d'un DTC trans-temporal de l'artère cérébrale moyenne et d'une SPIR cérébrale et somatique. La désaturation cérébrale initiale était secondaire à une hypocapnie, pendant laquelle la vélocité sanguine dérivée du DTC et les valeurs de SPIR somatique sont demeurées inchangées. Après l'intervention, un deuxième épisode de désaturation cérébrale est survenu suite à un problème technique avec la prothèse de valve aortique, nécessitant un retour sous circulation extracorporelle (CEC); il n'y avait pas de signaux transitoires de haute intensité (HITS) sur le DTC. Il y a eu un troisième épisode de désaturation cérébrale suite à la deuxième tentative de sevrage de la CEC; à ce moment-là, le DTC a détecté une quantité significative de HITS, suggérant des embolies gazeuses associées à une insuffisance ventriculaire droite aiguë; une réduction de la SPIR somatique a également été observée. CONCLUSION: La combinaison du DTC à la SPIR cérébrale a permis d'identifier trois différents mécanismes de désaturation cérébrale. Un algorithme est proposé pour aider le clinicien à déterminer l'origine de la désaturation cérébrale sur la SPIR. Des études cliniques prospectives sont nécessaires afin d'explorer les avantages potentiels d'un monitorage cérébral multimodal et son impact sur les devenirs cliniques à court et à long terme.

Double-lumen endotracheal tubes and bronchial blockers exhibit similar lung collapse physiology during lung isolation.

PURPOSE: Double-lumen endotracheal tubes (DL-ETT) and bronchial blockers (BB) are frequently used to allow one-lung ventilation (OLV) during video-assisted thoracic surgery (VATS). Recently, faster lung collapse has been documented with a BB than with a DL-ETT. The physiologic mechanisms behind this faster collapse remained unknown. We aimed to measure ambient air absorption (Vresorb) and intra-bronchial pressure (Pairway) into the non-ventilated lung during OLV using DL-ETT and BB. METHODS: Patients undergoing VATS and OLV for lung resection were randomly assigned to have measurements made of Vresorb or Pairway within the non-ventilated lung using either a DL-ETT or BB. RESULTS: Thirty-nine patients were included in the analyses. The mean (standard error of the mean [SEM]) Vresorb was similar in the DL-ETT and BB groups [504 (85) vs 630 (86) mL, respectively; mean difference, 126; 95% confidence interval [CI], -128 to 380; P = 0.31]. The mean (SEM) Pairway became progressively negative in the non-ventilated lung in both the DL-ETT and the BB groups reaching [-20 (5) and -31 (10) cmH2O, respectively; mean difference, -11; 95% CI, -34 to 12; P = 0.44] at the time of the pleural opening. CONCLUSIONS: During OLV before pleural opening, entrainment of ambient air into the non-ventilated lung occurs when the lumen of the lung isolation device is kept open. This phenomenon is prevented by occluding the lumen of the isolation device before pleural opening, resulting in a progressive build-up of negative pressure in the non-ventilated lung. Future clinical studies are needed to confirm these physiologic results and their impact on lung collapse and operative outcomes. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT02919267); registered 28 September 2016.

RéSUMé: OBJECTIF: Les tubes endotrachéaux à double lumière (TET-DL) et les bloqueurs bronchiques (BB) sont fréquemment utilisés pour l'isolation pulmonaire pendant une chirurgie thoracique assistée par vidéoscopie. Récemment, un affaissement pulmonaire plus rapide avec un BB qu'avec un TET-DL a été documenté. Les mécanismes physiologiques derrière cet affaissement plus rapide demeurent inconnus. Notre objectif était de mesurer l'absorption de l'air ambiant (Vresorb) et la pression intra-bronchique (Paérienne) dans le poumon non ventilé pendant la ventilation à un poumon en utilisant un TET-DL et un BB. MéTHODE: Les patients subissant une chirurgie thoracique assistée par vidéoscopie et recevant une ventilation unipulmonaire à l'aide d'un TET-DL ou d'un BB pour une résection pulmonaire ont été aléatoirement assignés à des mesures de Vresorb ou Paérienne dans le poumon non ventilé. RéSULTATS: Trente-neuf patients ont été inclus dans les analyses. La Vresorb moyenne (erreur-type sur la moyenne) était similaire dans les groupes TET-DL et BB [504 (85) vs 630 (86) mL, respectivement; différence moyenne, 126; intervalle de confiance [IC] 95 %, -128 à 380; P = 0,31]. La Paérienne moyenne (erreur-type sur la moyenne) est devenue progressivement négative dans le poumon non ventilé dans les groupes TET-DL et BB en atteignant [-20 (5) et -31 (10) cmH2O, respectivement; différence moyenne, -11; IC 95 %, -34 à 12; P = 0,44] au moment de l'ouverture de la plèvre. CONCLUSION: Pendant la ventilation unipulmonaire avant l'incision de la plèvre, un appel d'air ambiant dans le poumon non ventilé se produit quand la portion du dispositif d'isolation pulmonaire est maintenue ouverte. Ce phénomène peut être évité en occluant la lumière du dispositif d'isolation pulmonaire avant l'ouverture de la plèvre, ce qui entraînera une accumulation progressive de pression négative dans le poumon non ventilé. De futures études cliniques sont nécessaires pour confirmer ces résultats physiologiques et leur impact sur l'affaissement pulmonaire et les devenirs opératoires. ENREGISTREMENT DE L'éTUDE: www.clinicaltrials.gov (NCT02919267); enregistrée le 28 septembre 2016.