Institut Universitaire De Cardiologie Research Articles

Pembrolizumab Every 6 Weeks Versus Every 3 Weeks in Advanced Non-Small Cell Lung Cancer.

The survival benefits and adverse effects of pembrolizumab 2 mg/kg intravenously (IV) every 3 weeks (Q3W) in advanced non-small lung cancer (NSCLC) are well documented in the literature. Based on pharmacokinetic models, a pembrolizumab 4 mg/kg IV every 6 weeks (Q6W) dosing regimen is also approved in some countries. To date, there is no direct comparison in the literature between these 2 regimens in advanced NSCLC. This retrospective study included 80 patients with advanced NSCLC who received pembrolizumab monotherapy 4 mg/kg Q6W between March 1, 2020 and December 31, 2021 and 80 patients with advanced NSCLC who received pembrolizumab monotherapy 2 mg/kg Q3W between January 1, 2017 and January 15, 2019 at Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ). The primary outcomes of this study were to compare overall survival (OS), progression-free survival (PFS) as well as the occurrence and severity of immune-mediated adverse events (AEs) in patients with advanced NSCLC who received pembrolizumab Q6W vs Q3W. Data cutoff date was December 15, 2022. Median follow-up was 14.5 ± 8.6 months in the Q6W group and 18.3 ± 19.6 months in the Q3W group. Median PFS was 6.9 months (CI 95% 5.0-10.7) in the Q6W group vs 8.9 months (CI 95% 5.6-14.1) in the Q3W group (adjusted HR 1.27 (CI 95% 0.85-1.89), P = .25). Median OS was not reached in the Q6W group vs 20.5 months (CI 95% 13.7-29.8) in the Q3W group (adjusted HR 0.80 (CI 95% 0.50-1.29), P = .36). Immune-mediated AEs of grade ≥ 3 occurred in 18% of patients in the Q6W group and in 19% of those in the Q3W group. In this unicentric retrospective study, the pembrolizumab Q6W dosing regimen was comparable to the Q3W in terms of OS, PFS, and toxicity.

Galanin inhibition of wake-active histaminergic neurons

Histaminergic neurons are a population of wake-active neurons confined to the tuberomammillary nucleus (TMN) in the posterior hypothalamus. They form a crucial component of the ‘sleep switch’ in the brain and promote arousal when activated. The histaminergic neurons are strongly innervated by ventrolateral preoptic area (VLPO) neurons expressing galanin, a neuropeptide associated with sleep promotion. While recent studies have confirmed the importance of VLPO projections to the TMN in initiating and maintaining sleep, the ability of galanin to modulate the activity of the wake-promoting histaminergic neurons of the TMN has largely been overlooked. Therefore, we aimed to determine the mechanisms by which galanin alters the electrical excitability of genetically identified histaminergic neurons. We hypothesized that galanin inhibits histaminergic neuron activity via direct post-synaptic activation of galanin 1 receptors (GalR1). Whole-cell patch-clamp electrophysiology was performed on hypothalamic brain slices from mice expressing tdTomato fluorescence in cells expressing histidine decarboxylase (HDC), the sole enzyme required for histamine synthesis (HDCCre::tdTomato mice). RNAscope ® in situ hybridization was used to explore Gal1R mRNA expression in HDC expressing neurons. Whole-cell current-clamp recordings in male mice revealed that galanin (100nM) inhibits the majority of HDC neurons. The galanin-induced inhibition was associated with a hyperpolarization of the membrane potential and a decrease in firing frequency. Consistent with our hypothesis, a selective galanin 2 receptor (Gal2R) agonist (M1145 - 200nM) had no effect on male HDC neuron activity. RNAscope ® studies in male mice revealed co-expression of Gal1R mRNA in a large proportion of HDC-expressing neurons. Interestingly, the galanin-induced inhibition of HDC neuron electrical excitability was less pronounced in female mice. Overall, our data point to an important role of post-synaptic Gal1Rs expressed on histaminergic neurons in mediating galanin’s inhibitory effects in the TMN. Our data also suggest that sex differences exist in histaminergic neuron responsiveness to galanin. These findings are consistent with the idea that some of the sleep promoting effects of VLPO neuron activation occur through galanin’s ability to inhibit the wake-active histaminergic neurons. Sleep Research Society (SRS), Canada First Research Excellence Fund (Sentinel North Partnered Research Chair in Sleep Pharmacometabolism), Fondation Institut Universitaire de Cardiologie et de Pneumologie de Quebec (FIUCPQ), Fonds de recherche de Quebec - Sante (FRQS). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Development and Evaluation of a Height-Based Tobramycin Initial Dosing Nomogram for the Treatment of Adult Cystic Fibrosis Pulmonary Exacerbations.

Tobramycin is widely used to treat pulmonary exacerbations of cystic fibrosis. Height has been previously found to be significantly more predictive of tobramycin pharmacokinetics than body weight. This study aimed to develop a height-based initial dosing nomogram and evaluate its performance in peak concentration (Cmax) precision relative to standard and fixed dosing. Monte Carlo simulations were performed to develop a nomogram representing the doses required to reach Cmax targets at different heights. Cmax data observed at 2 clinical centers [McGill University Health Centre (MUHC) and Institut universitaire de cardiologie et pneumologie de Québec (IUCPQ-UL)] were compared with population-predicted Cmax using the doses derived from the nomogram alongside a fixed dose. Height-based dosing resulted in significantly less variable-predicted Cmax values [coefficient of variation (CV) MUHC = 15.7% and IUCPQ-UL = 10.8%] than the Cmax values observed in clinical practice (CV MUHC = 30.0% and CV IUCPQ-UL = 26.9%) and predicted Cmax values obtained from a fixed dose (CV MUHC = 21.2% and CV IUCPQ-UL = 16.3%). An initial dosing nomogram was developed to help reduce pharmacokinetic variability in the observed Cmax. More precise dosing would allow for better clinical outcomes in adult patients with cystic fibrosis.

Transthoracic needle biopsy versus surgical diagnosis for solid pulmonary nodules.

BackgroundWhen investigating solitary pulmonary nodules (SPN), non-surgical [such as transthoracic needle biopsy (TTNB)] or surgical biopsies can be performed. There is a paucity of data comparing these two approaches.MethodsThis descriptive study is a retrospective analysis of a cohort of 149 patients who underwent TTNB and/or surgery for a SPN >8 mm but ≤3 cm between January and December 2016, at Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ). Our primary objective was to evaluate the proportion of patients investigated with TTNB vs. surgical diagnosis in our center. Secondary objectives were to examine the distribution of diagnoses (malignancy vs. benign lesion), to evaluate the proportion of TTNB that would yield a benign diagnosis and permit to avoid surgery, to evaluate if delays to surgery were longer when preoperative TTNB was performed, and if operative times were longer with upfront surgery.ResultsIn our cohort, 87 patients (58%) underwent TTNB, while 62 (42%) had an upfront surgical procedure. One hundred and twenty-eight patients (86%) had a malignant diagnosis. Thirteen patients out of the 87 biopsied (15%) avoided surgery owing to a benign biopsy result, or a non-specific diagnosis and a physician reassured enough to decide for radiological surveillance, while 5/62 patients (8%) who underwent upfront surgery had a benign diagnosis. There was no significant difference in delays from imaging to surgery or in operative time between patients with or without prior TTNB.ConclusionsIn this unicentric retrospective cohort of patients investigated for SPN, the malignancy rate was high (86%), which seemed to limit the applicability of prediction models. Adherence to guidelines for the investigation of SPN by physicians seemed suboptimal. More real-world prospective studies are needed to compare non-surgical and surgical biopsies. There is also a need for simpler nodule evaluation algorithms.

Palliative Systemic Therapy Given near the End of Life for Metastatic Non-Small Cell Lung Cancer.

Background: The use of chemotherapy near end of life (EOL) for various cancers is increasing and has been shown to be associated with delayed access to palliative care (PC) and increased aggressiveness in EOL care, without any benefit on survival. Methods: This retrospective study included 90 patients with metastatic non-small cell lung cancer (NSCLC) who received at least one line of palliative systemic anticancer therapy (SACT) and died between 1 November 2014, and 31 October 2016, at Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ). Our primary objective was to evaluate the proportion of patients with NSCLC receiving SACT within 30 days of death. Secondary outcomes were to determine the mean and median delays between the administration of the last treatment and death, and to evaluate if there were differences in characteristics and outcomes (including overall survival (OS)) between patients treated or not within 30 days of death. Results: In our cohort, 22% of patients received SACT within 30 days of death. For the entire cohort, the mean delay between the last treatment and death was 94 days, and the median was 57 days. There were no statistically significant differences between the two groups in terms of baseline characteristics. Use of SACT near EOL was associated with decreased access to PC, higher rates of in hospital death, decreased use of medical aid in dying (MAiD), and a shorter median OS (4.0 vs. 9.0 months). Conclusions: In this retrospective cohort of patients with metastatic NSCLC, 22% of patients received SACT within 30 days of death, with a negative impact on access to PC, higher rates of in hospital death, decreased use of MAiD and palliative sedation, and a shorter median OS.

Impact of COVID-19 on the Prescribing Pattern of Oral Anticoagulants for Atrial Fibrillation After Cardiac Surgery.

Because of logistic challenges associated with the COVID-19 pandemic, direct oral anticoagulants (DOAC) were favored over warfarin in patients presenting postoperative atrial fibrillation (AF) after cardiac surgery in our institution. Considering the limited evidence supporting the use of DOAC in this context, we sought to evaluate the safety and efficacy of this practice change. A retrospective study was performed with patients from the Quebec City metropolitan area who were hospitalized at the Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval following cardiac surgery and who required oral anticoagulant (OAC) for postoperative AF. The primary objective was to compare the pre- and peri-COVID-19 period for OAC prescribing patterns and the incidence of thrombotic and bleeding events at 3 months post-surgery. The secondary objective was to compare DOAC to warfarin in terms of thrombotic events and bleeding events. A total of 233 patients were included, 142 from the pre-COVID-19 and 91 from the peri-COVID-19 period, respectively. Both groups had equivalent proportions of preoperative AF (48%) and new-onset postoperative AF (52%). The proportion of patients treated with a DOAC increased from 13% pre-COVID-19 to 82% peri-COVID-19. This change in practice was not associated with a significant difference in the incidence of thrombotic or bleeding events 3 months postoperatively. However, compared to DOAC, warfarin was associated with a higher incidence of major bleeding. Only 1 thrombotic event was reported with warfarin, and none were reported with DOAC. This study suggests that DOAC are an effective and safe alternative to warfarin to treat postoperative AF after cardiac surgery and that this practice can be safely maintained.

Consideration of height-based tobramycin dosing regimens for the treatment of adult cystic fibrosis pulmonary exacerbations.

Some population pharmacokinetic models have been developed using height to explain some of the interindividual variability in tobramycin pharmacokinetics in cystic fibrosis patients. However, their predictive performance when extrapolated to other clinical centres is unclear. Therefore, the aim of this study was to externally evaluate the predictability of tobramycin population pharmacokinetic models with an independent dataset and perform simulations using previously recommended height-based dosing regimens. A literature search was conducted through the PubMed database to identify relevant population pharmacokinetic models. Tobramycin plasma concentration data from April 2014 to November 2019 were retrospectively collected from the Institut universitaire de cardiologie et de pneumologie de Québec, Canada. External evaluations were performed using NONMEM® v7.5 and RStudio® v1.3.1073. Monte Carlo simulations were performed to evaluate the probability of target attainment of Cmax /MIC ratios for several dosing regimens. The validation dataset included 27 patients and 143 concentration samples. Three models were evaluated. Only the ones by Crass et al. and Alghanem et al. performed satisfactorily in terms of prediction-based diagnostics with MDPE values of -3.4% and 29.3% and MDAPE values of 19.0 and 29.5%, respectively. In simulation-based evaluations, both pcVPC and NPDE showed no evidence of model misspecification. Our simulations suggest that patients treated with a once-daily dose of 3.4mg/cm should produce peak and trough levels consistent with current guidelines. Our results show that the models by Crass et al. and Alghanem et al. are appropriate for simulation-based applications to aid individualized dosing in our population and that height-based dosing regimens could be considered in cystic fibrosis patients.

Impact of a 12-week supervised exercise program on weight loss trajectory, daily physical activity levels and sedentary behaviors after bariatric surgery

Abstract Background The evidence suggests that physical activity (PA) following bariatric surgery can enhance weight loss and other metabolic outcomes. However, most individuals with severe obesity are insufficiently active, and without support, fail to make substantial increases in their daily PA levels postoperatively. Purpose The aim of this study was to investigate the effectiveness of a 12-week supervised exercise program on daily PA levels, sedentary time, and on maintenance of the weight loss trajectory following bariatric surgery. Methods Fifty-nine individuals with severe obesity (body mass index [BMI] ≥40 or ≥35 kg/m2 with comorbidities) eligible for bariatric surgery were randomly assigned (1:2) to either standard of care (CG, n=19) or a 12-week supervised exercise program (ExG, n=40). Daily PA levels and sedentary time were assessed using an armband accelerometer worn over a 3-day period (2 week-day and 1 weekend day). Body weight, body fat and fat-free mass were assessed using bioelectrical impedance balance. The exercise training program (60 min, 3 times per week for 12 weeks) started 3 months after the bariatric surgery and was supervised by a certified clinical exercise physiologist. Daily PA levels, sedentary time and anthropometric measurements were obtained preoperatively, and at 3, 6 and 12 months after bariatric surgery. Results Age of participants was 42±12 years, BMI was 46±6 kg/m2, and 76% were women. Before the exercise training program, PA parameters (daily PA levels, sedentary time and moderate to vigorous intensity PA [MVPA] were comparable between groups. Following the exercise training program, the ExG showed a significant reduction in sedentary time (753±113 to 721±88 min/day), an increase in daily PA levels (4544±1863 to 5853±3101 steps/day) and in MVPA levels (18.8±25.1 to 30.5±38.1 min/day). Further increase in daily MVPA levels were observed at the 12 months follow-up visit (p=0.05). In the standard of care group, changes in PA parameters were also comparable to those in the ExG. All anthropometric measurements indicate statistically significant changes postoperatively, after the intervention and up to 12 months follow-up (p<0.001) without showing any difference between groups. Anthropometric changes up to 12 months follow-up show, respectively for CG and ExG, a total weight loss of 37.8±9.3% and 38.4±10.3%, a body fat reduction of 60.4±13.7% and 61.9±15.2% and fat-free mass loss of 16.6±5.4% and 15.1±7.9%. Conclusion This study shows that bariatric surgery candidates have low PA levels and rarely engage in MVPA. We found no additional effect to the standard of care treatment of a postoperative 12-week supervised exercise training program on weight loss trajectory, daily PA levels and sedentary behaviors. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Canadian Institutes of Health Research (CIHR)Institut Universitaire de Cardiologie et de Pneumologie de Québec - Université Laval (IUCPQ - UL)

Routine Neuroimaging in Patients with Stage IV Non-Small Cell Lung Cancer: A Single Center Experience.

Background: There is a lack of consensus in current practice guidelines regarding routine neuroimaging in patients with stage IV non-small cell lung cancer (NSCLC) without neurologic symptoms, and there is a paucity of data on the impact of such imaging on overall survival (OS). Methods: This retrospective study included 257 patients with stage IV NSCLC without neurologic symptoms diagnosed between January 1, 2013 and December 31, 2016 at Institut universitaire de cardiologie et de pneumologie de Québec (IUCPQ). The primary objective of this study was to compare the evolution of patients with stage IV NSCLC who had baseline brain imaging versus with who did not. Secondary objectives were to determine the proportion of patients who underwent brain imaging in their initial investigation and the proportion of patients who developed metachronous central nervous system (CNS) metastasis. Results: CNS imaging, mainly with computed tomography (CT), was performed at diagnosis in 56% of patients, and the prevalence of synchronous CNS metastasis among these patients was 32%. There was no difference in median OS between patients who underwent initial CNS imaging and those who did not, but we did show a tendency for a higher cumulative incidence of metachronous CNS metastasis in patients without baseline imaging. These metachronous metastases were symptomatic and were more often not treated when compared to synchronous metastases. Conclusions: In this small, unicentric retrospective study, there was no benefit with routine neuroimaging in terms of median OS in stage IV NSCLC patients without neurologic symptoms.

Effects of High-Flow Nasal Cannula on the Work of Breathing in Patients Recovering From Acute Respiratory Failure.

High-flow nasal cannula is increasingly used in the management of respiratory failure. However, little is known about its impact on respiratory effort, which could explain part of the benefits in terms of comfort and efficiency. This study was designed to assess the effects of high-flow nasal cannula on indexes of respiratory effort (i.e., esophageal pressure variations, esophageal pressure-time product/min, and work of breathing/min) in adults. A randomized controlled crossover study was conducted in 12 patients with moderate respiratory distress (i.e., after partial recovery from an acute episode, allowing physiologic measurements). Institut Universitaire de Cardiologie et de Pneumologie de Québec, QC, Canada. Twelve adult patients with respiratory distress symptoms were enrolled in this study. Four experimental conditions were evaluated: baseline with conventional oxygen therapy and high-flow nasal cannula at 20, 40, and 60 L/min. The primary outcomes were the indexes of respiratory effort (i.e., esophageal pressure variations, esophageal pressure-time product/min, and work of breathing/min). Secondary outcomes included tidal volume, respiratory rate, minute volume, dynamic lung compliance, inspiratory resistance, and blood gases. Esophageal pressure variations decreased from 9.8 (5.8-14.6) cm H2O at baseline to 4.9 (2.1-9.1) cm H2O at 60 L/min (p = 0.035). Esophageal pressure-time product/min decreased from 165 (126-179) to 72 (54-137) cm H2O • s/min, respectively (p = 0.033). Work of breathing/min decreased from 4.3 (3.5-6.3) to 2.1 (1.5-5.0) J/min, respectively (p = 0.031). Respiratory pattern variables and capillary blood gases were not significantly modified between experimental conditions. Dynamic lung compliance increased from 38 (24-64) mL/cm H2O at baseline to 59 (43-175) mL/cm H2O at 60 L/min (p = 0.007), and inspiratory resistance decreased from 9.6 (5.5-13.4) to 5.0 (1.0-9.1) cm H2O/L/s, respectively (p = 0.07). High-flow nasal cannula, when set at 60 L/min, significantly reduces the indexes of respiratory effort in adult patients recovering from acute respiratory failure. This effect is associated with an improvement in respiratory mechanics.

Wait times for diagnosis and treatment of lung cancer: a single-centre experience.

Multiple clinical practice guidelines recommend rapid evaluation of patients with suspected lung cancer. It is uncertain whether delays in diagnosis and management have a negative effect on outcomes. This retrospective study included 551 patients diagnosed with lung cancer through the diagnostic assessment program at the Institut universitaire de cardiologie et de pneumologie de Québec between September 2013 and March 2015. Median wait times between initial referral, diagnosis, and first treatment were calculated and compared with recommended targets. Analyses were performed to evaluate for specific factors associated with longer wait times and for the effect of delays on the outcomes of progression-free survival (pfs), relapse-free survival (rfs) after primary surgical resection, and overall survival (os). Most patients were investigated and treated within recommended targets. Of the entire cohort, 379 patients were treated at our institution. Of those 379 patients, 311 (82%) were treated within recommended targets. In comparing patients within and outside target times, the only statistically significant difference was found in the distribution of treatment modalities: patients meeting targets were more likely to be treated with surgery or chemotherapy rather than with radiation. The pfs on first treatment modality was influenced by clinical stage, but not by time to therapy [hazard ratio (hr): 1.10; p = 0.65]. The os for the entire cohort was also influenced by stage, but not by delays (hr: 1.04; p = 0.87). For the 209 patients treated by surgery with curative intent, a significant reduction in rfs was associated with male sex and TNM stage, but not with delays (hr: 1.11; p = 0.83). The os after primary surgical resection was also associated with TNM stage, but not with delays (hr: 1.82; p = 0.43). Recommended targets for wait times in the investigation and treatment of lung cancer can be achieved within a diagnostic assessment program. Compared with radiation treatment, treatment with surgery or chemotherapy is more likely to be completed within targets. Delays in investigation and treatment do not appear to negatively affect the clinical outcomes of os, rfs, and pfs. Prospective studies are needed to evaluate whether efficient work-up and treatment influence other important variables, such as quality of life, cost of care, and access to therapies while performance status is adequate.

Outcomes of a Canadian Cohort of Subjects Treated With Lung Volume Reduction Coils: Analysis From the Renew Study

SESSION TITLE: Late-Breaking Abstracts 1 SESSION TYPE: Late-Breaking Abstract Slide PRESENTED ON: Tuesday, October 31, 2017 at 02:45 PM - 04:15 PM PURPOSE: Bronchoscopic lung volume reduction using nitinol coils (LVRC) is a novel technique to treat severe emphysema. The RENEW study, a multicenter randomized controlled trial comparing LVRC to usual care in 315 subjects with severe emphysema, showed modest improvement in exercise tolerance with LVRC. Our local experience included two subjects treated in an implementation phase, 11 during the randomized phase, and 2 in a crossover phase. We evaluated data from our cohort to compare outcomes to the RENEW study outcomes and described factors possibly accounting for observed differences, if any. METHODS: The Institut universitaire de cardiologie et pneumologie de Québec, a tertiary hospital specializing in chest diseases, was the only Canadian center participating in the RENEW trial. We reviewed baseline, treatment, and follow-up data from coil-treated participants in RENEW as well as post-hoc quantitative CT analyses from baseline and 12-month inspiratory and expiratory HRCT provided by PneumRx. Fifteen subjects (mean age 60 years, 53% male) underwent bilateral LVRC in two separate sessions. One subject opted out of the study after unilateral treatement due to complications. When compared to the cohort of LVRC completed case subjects in the RENEW study (n=128), subjects in our cohort were younger, had higher baseline exercise tolerance, and lower BODE scores. They also had more air trapping per quantitative CT analysis. RESULTS: At 12 months, median improvement in the primary endpoint of 6-minute walking distance (6MWD) was 54 meters (IQR -1, 128m) vs. 9 meters (IQR -33.2, 40m) in the RENEW completed case cohort (p=0.05). A higher proportion of our subjects met the 25m clinically significant response for 6MWD (71% vs 35%, p= 0,01). Other outcomes (FEV1, and St-George’s Respiratory Questionnaire) were similar between the cohorts. Post-hoc quantitative CT analyses revealed significantly greater expiratory lobar volume reduction in our patients compared to RENEW (-440mL vs. -205mL). CONCLUSIONS: Subjects treated with LVRC in Canada demonstrated strong clinical response one year post-treatment. Our patients were largely recruited from the community and were younger, had more hyperinflation and a better baseline exercise tolerance. We observed a significant 6MWT response in our RENEW patients, associated with greater degrees of volume reduction. CLINICAL IMPLICATIONS: Patient selection could play an important role in predicting subsequent response to LVRC therapy in severe emphysema. Lung volume reduction coils for severe emphysema (not yet approved in the US or Canada for this indication)

Effectiveness of adjuvant carboplatin-based chemotherapy compared to cisplatin in non-small cell lung cancer.

Cisplatin and vinorelbine given intravenously is a well-established adjuvant chemotherapy regimen after surgery for early non-small cell lung cancer. However, few validated alternatives exist when cisplatin is not indicated or tolerated. Carboplatin is frequently used in this setting. We evaluated the 5-year overall survival, progression-free survival and toxicity in patients treated for stage IB to IIIB resected non-small cell lung cancer receiving adjuvant carboplatin-based chemotherapy compared to cisplatin in association with vinorelbine. Single-center retrospective study of patients having received adjuvant chemotherapy between January 2004 and December 2013 at the oncology clinic at Institut Universitaire de Cardiologie et de Pneumologie de Québec (Canada). Three sub-groups, cisplatin/vinorelbine, carboplatin/vinorelbine and the substitution of cisplatin/vinorelbine for carboplatin/vinorelbine (cisplatin/vinorelbine/carboplatin/vinorelbine), were studied during treatment. One hundred twenty-seven patients were included in this study. The median PFS was not significantly different, with 50.4 months for cisplatin/vinorelbine, 57.3 months for cisplatin/vinorelbine/carboplatin/vinorelbine and not yet achieved for the carboplatin/vinorelbine group ( p = 0.80). Overall survival also did not differ significantly between the three groups. The 5-year overall survival rates were 66% in cisplatin/vinorelbine group, 55% in carboplatin/vinorelbine group and 70% in cisplatin/vinorelbine/carboplatin/vinorelbine group ( p = 0, 95). No differences were noted between groups concerning high-grade hematologic toxicity. Although the effectiveness and hematologic toxicity are comparable between cisplat in and carboplatin in the adjuvant treatment of resected non-small cell lung cancer, the results obtained corroborate the practice used at our oncology clinic. Nevertheless, more prospective studies would be needed to confirm these results.

Cardiovascular medicine at the Québec Heart and Lung Institute.

Celebrating 60 years of excellence in specialized clinical care and research ![Graphic][1] Founded in 1918, what would eventually become the Quebec Heart and Lung Institute [in French, the Institut Universitaire de Cardiologie et de Pneumologie de Quebec—Universite Laval (IUCPQ-UL)] was initially built as a sanatorium to offer the most contemporary treatments at the time to patients with tuberculosis. In 1955, clinicians of the centre felt that there was a need to build a pavilion that would be entirely devoted to research. Two years later, a Department of Cardiology was created and the mission of the hospital evolved, allowing scientists to initiate an additional research program on the aetiology and treatment of cardiovascular disease. In 1979, a pavilion devoted to prevention was built, showing the importance given to this field by our institution. In the 80’s, themes of excellence in research began to emerge beyond the contribution of individual pioneers of the time. During that period, one of our prominent academic cardiologists, Dr. Gilles Dagenais, launched the Quebec Cardiovascular Study, a prospective observational study of middle-aged men which would then make, in the 90’s, several seminal contributions to cardiovascular epidemiology by reporting original findings in high-impact journals. As of today, these articles remain the most cited original articles ever published in cardiovascular medicine from our Institute. At the same time, the late Dr. Paul Cartier, one of our leading heart surgeons, had … [1]: /embed/inline-graphic-1.gif

Pericardiocentesis versus pericardiotomy for malignant pericardial effusion: a retrospective comparison.

Treatment of malignant pericardial effusion remains controversial, because no randomized controlled trials have been conducted to determine the best approach, and results of retrospective studies have been inconsistent. The objective of the present study was to compare pericardiocentesis and pericardiotomy with respect to efficacy for preventing recurrence, and to determine, for those two procedures, diagnostic yields, complication rates, and effects on survival. We also aimed to identify clinical and procedural factors that could predict effusion recurrence. We retrospectively assessed 61 patients who underwent a procedure for treatment of a malignant pericardial effusion at the Institut universitaire de cardiologie et de pneumologie de Québec between February 2004 and September 2013. Pericardiocentesis was performed in 42 patients, and pericardiotomy, in 19 patients. The effusion recurrence rate was significantly higher in patients treated with pericardiocentesis than with pericardiotomy (31.0% vs. 5.3%, p = 0.046). The diagnostic yield of the procedures was not significantly different (92.9% vs. 86.7%, p = 0.6). The overall rate of complications was similar in the two groups, as was the median overall survival (2.4 months vs. 2.6 months, p = 0.5). In univariate analyses, the procedure type was the only predictor of recurrence that approached statistical significance. Age, sex, type of cancer, presence of effusion at the time of cancer diagnosis, prior chest irradiation, tamponade upon presentation, and total volume of fluid removed did not influence the recurrence rate. Compared with pericardiocentesis, pericardiotomy had higher success rate in preventing recurrence of malignant pericardial effusion, with similar diagnostic yields, complication rates, and overall survival.

Stoelting’s Handbook of Pharmacology & Physiology in Anesthetic Practice - 3rd Edition

This 808-page handbook is a condensed version of the fifth edition of the textbook, Stoelting’s Pharmacology & Physiology in Anesthetic Practice, and follows an identical structure with the same chapter titles and headings as in the main textbook. The handbook is intended to ‘‘serve as a companion’’ and to provide, as stated in Dr. Stoelting’s preface, ‘‘a rapid and accurate source of information’’ relevant to the pharmacology and physiology that clinicians will face in their anesthesiology practice. The physical size of the handbook is ideal to put in the pocket of a typical white lab coat. While the book has a softcover, both the bookbinding and the pages are of excellent quality. In addition, the page corners are rounded, which helps to protect the handbook. The font size and the quality of the color figures are excellent, and each of these attributes contributes to the comfortable handling and reading of this book. The handbook consists of 47 chapters grouped into nine parts, with each part comprising as few as two chapters to as many as eleven. Part I is a very brief (two chapters) section on the basic principles of physiology and pharmacology. Parts II to VII are divided into physiologic systems (neurologic, circulatory, pulmonary, blood and hemostasis, gastrointestinal and metabolism, endocrine), with nephrology included with the circulatory system. The last two parts of the handbook, Parts VIII and IX, are dedicated to miscellaneous topics (e.g., antimicrobial agents, chemotherapeutic drugs, drugs for psychopharmacologic therapy) and special populations (e.g., newborns, maternal and fetal physiology and pharmacology, the elderly, and resuscitation). Parts II to VII, dedicated to physiologic systems, represent 80% of the book and follow a similar structure. The first chapter typically describes the physiology of the system and the following chapters are organized by drug classification. The two most sizeable parts are Parts II and III on the neurologic and circulatory systems, respectively. The ‘‘Neurologic System’’ consists of eleven chapters. Its first chapter, ‘‘Neurophysiology’’, covers the full range of neurologic aspects, including nerve and neurotransmitters physiology; brain, brainstem, and spinal cord anatomy; the sympathetic and parasympathetic nervous system; the chemoreceptor trigger zone; electroencephalogram and evoked potentials; and thermoregulation. The related chapters that follow include inhaled anesthetics, intravenous sedatives and hypnotics, pain physiology, opioids, nonopioid analgesics, local anesthetics, neuromuscular physiology and blocking agents, and antiepileptic drugs. The systemic approach is ideal for the anesthesia trainee as there is a logical progression from the physiology of a system to the pharmacology of the drugs being used on that system. While not perfect, this handbook is relatively comprehensive for such a compact manual. Nevertheless, by condensing the text for brevity, some explanations of concepts and figures have been omitted, occasionally at the expense of clarity. In some cases, I found it necessary to read the main textbook to understand some of the figures or concepts presented in the handbook. In other cases, entire sections of the textbook were completely omitted. While most of these omissions are justified, one or two sentences to describe some of these topics could have been included J. Somma, MD (&) Institut universitaire de cardiologie et de pneumologie de Quebec (IUCPQ), Universite Laval, Quebec, QC, Canada e-mail: sommaduke@yahoo.com

Prescribing exercise training in pulmonary rehabilitation: A clinical experience

Built around exercise training, pulmonary rehabilitation (PR) is a multidisciplinary, evidence‐based, comprehensive approach to working with the patient as a whole and not just the pulmonary component of the disease. Integrated into the individualized treatment, this intervention aims to reduce symptoms, optimize functional status, increase participation in daily life, and reduce health care costs through stabilizing or reversing systemic manifestations of the disease. Although there are many other components that should be considered to manage the impairment and symptom burden, supervised exercise training is considered the cornerstone of effective pulmonary rehabilitation. This paper addresses our clinical experience at Institut universitaire de cardiologie et de pneumologie de Québec to assess and manage exercise training in line with the current recommendations and guidelines surrounding PR.

Prescribing exercise training in pulmonary rehabilitation: A clinical experience

Built around exercise training, pulmonary rehabilitation (PR) is a multidisciplinary, evidence‐based, comprehensive approach to working with the patient as a whole and not just the pulmonary component of the disease. Integrated into the individualized treatment, this intervention aims to reduce symptoms, optimize functional status, increase participation in daily life, and reduce health care costs through stabilizing or reversing systemic manifestations of the disease. Although there are many other components that should be considered to manage the impairment and symptom burden, supervised exercise training is considered the cornerstone of effective pulmonary rehabilitation. This paper addresses our clinical experience at Institut universitaire de cardiologie et de pneumologie de Québec to assess and manage exercise training in line with the current recommendations and guidelines surrounding PR.

Hypersensitivity pneumonitis (extrinsic allergic alveolitis): a Canadian historical perspective.

Hypersensitivity pneumonitis (extrinsic allergic alveolitis): a Canadian historical perspective.

Surgical site infections following transcatheter apical aortic valve implantation: incidence and management

ObjectiveThe present study was undertaken to examine the incidence and management of surgical site infection (SSI) in patients submitted to transapical transcatheter aortic valve implantation (TA-TAVI).MethodsFrom April 2007 to December 2011, 154 patients underwent TA-TAVI with an Edwards Sapien bioprosthesis (ES) at the Institut Universitaire de Cardiologie et Pneumologie de Québec (IUCPQ) as part of a multidisciplinary program to prospectively evaluate percutaneous aortic valve implantation. Patient demographics, perioperative variables, and postoperative complications were recorded in a prospective registry.ResultsFive (3.2%) patients in the cohort presented with an SSI during the study period. The infections were all hospital-acquired (HAI) and were considered as organ/space SSI’s based on Center for Disease Control criteria (CDC). Within the first few weeks of the initial procedure, these patients presented with an abscess or chronic draining sinus in the left thoracotomy incision and were re-operated. The infection spread to the apex of the left ventricle in all cases where pledgeted mattress sutures could be seen during debridement. Patients received multiple antibiotic regimens without success until the wound was surgically debrided and covered with viable tissue. The greater omentum was used in three patients and the pectoralis major muscle in the other two. None of the patients died or had a recurrent infection. Three of the patients were infected with Staphylococcus epidermidis, one with Staphylococcus aureus, and one with Enterobacter cloacae. Patients with surgical site infections were significantly more obese with higher BMI (31.4±3.1 vs 26.2±4.4 p=0.0099) than the other patients in the cohort.ConclusionsWhile TA-TAVI is a minimally invasive technique, SSIs, which are associated with obesity, remain a concern. Debridement and rib resection followed by wound coverage with the greater omentum and/or the pectoralis major muscle were used successfully in these patients.