The Tritube: Facilitating Upper Airway Surgery With an Ultrathin Cuffed Airway Device.

The Tritube is a narrow-bore cuffed tracheal tube (outer diameter 4.4 mm and inner diameter ~2.4 mm) that permits effective alveolar gas exchange using flow-controlled ventilation. Constant gas flow delivers physiological minute volumes, within preset pressure limits, and applies suction to the airway during expiration. The technique has attracted interest for laryngotracheal microsurgery as it provides superior surgical exposure and avoids many of the complications associated with high-frequency jet ventilation. Cuff inflation protects the lower airway and produces a motionless operating field. We describe the structure of the device, discuss its benefits, and suggest how it should be used clinically.

A quarter of a century fundamental and translational research in perioperative hypersensitivity and anaphylaxis at the Antwerp university hospital, a Belgian Centre of Excellence of the World Allergy Organization.

Perioperative hypersensitivity constitutes an important health issue, with potential dramatic consequences of diagnostic mistakes. However, safe and correct diagnosis is not always straightforward, mainly because of the application of incorrect nomenclature, absence of easy accessible in-vitro/ex-vivo tests and uncertainties associated with the non-irritating skin test concentrations. In this editorial we summarize the time line, seminal findings, and major realizations of 25 years of research on the mechanisms, diagnosis, and management of perioperative hypersensitivity.

Safety of extended interval dosing immune checkpoint inhibitors: a multicenter cohort study.

BACKGROUND: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown. METHODS: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED). irAEs spectrum in patients treated upfront with ED and association between irAEs and overall survival were also described. RESULTS: A total of 550 (68%) patients started ICIs with CD and switched to ED. During CD, 225 (41%) patients developed any grade and 17 (3%) G3 or G4 irAEs; after switching to ED, any grade and G3 or G4 irAEs were experienced by 155 (36%) and 20 (5%) patients. Switching to ED was associated with a lower probability of any grade irAEs (adjusted odds ratio [aOR] = 0.83, 95% confidence interval [CI] = 0.64 to 0.99; P = .047), whereas no difference for G3 or G4 events was noted (aOR = 1.55, 95% CI = 0.81 to 2.94; P = .18). Among patients who started upfront with ED (n = 232, 32%), 107 (41%) developed any grade and 14 (5%) G3 or G4 irAEs during ED. Patients with irAEs during ED had improved overall survival (adjusted hazard ratio [aHR] = 0.53, 95% CI = 0.34 to 0.82; P = .004 after switching; aHR = 0.57, 95% CI = 0.35 to 0.93; P = .025 upfront). CONCLUSIONS: Switching ICI treatment from CD and ED did not increase the incidence of irAEs and represents a safe option also outside clinical trials.

High-intensity statins are associated with improved clinical activity of PD-1 inhibitors in malignant pleural mesothelioma and advanced non-small cell lung cancer patients.

BACKGROUND: In preclinical models, statins showed vaccine adjuvant activities and synergized with PD-1 inhibitors. We analyzed the impact of statin treatment on clinical outcome in thoracic cancer patients treated with PD-1 inhibitors. METHODS: A total of 82 malignant pleural mesothelioma (MPM) and 179 advanced non-small cell lung cancer (aNSCLC) patients treated with PD-1 inhibitors as second or further line treatment were examined. Seventy-seven MPM patients treated with standard chemotherapy were analyzed as control cohort. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were calculated. RESULTS: Among 253 patients with available data, statin use was associated with increased ORR (32% versus 18%, P = .02), PFS (median 6.7 versus 2.9 months, hazard ratio [HR] 0.57, 95% CI 0.39-0.83, P < .01), and OS (median 13.1 versus 8.7 months, HR 0.67, 95% CI 0.45-1.00, P = .05). In the control MPM cohort treated with chemotherapy (n = 77), no association was found. MPM patients who used statins showed improved ORR (22% versus 6%, P = .05), PFS (median 6.7 versus 2.4 months, P < .01), and OS (median not reached versus 6.0 months, P = .01). In aNSCLC patients, statin use was associated with improved ORR (40% versus 22%, P = .04) and PFS (median 7.8 versus 3.6 months, P = .03), but no significant difference in OS was found (median 13.1 versus 10.1 months, P = .30). Multivariable analysis confirmed the correlation between statin use and better PFS and OS in MPM and better PFS in aNSCLC. In the whole cohort, high but not low/moderate-intensity statins were associated with better OS compared to no user (P = .02 and P = .59, respectively). CONCLUSIONS: Our study showed that statins are associated with better clinical outcome in MPM and aNSCLC patients treated with PD-1 inhibitors in an intensity-dependent manner.

The Gustave Roussy Immune (GRIm)-Score Variation Is an Early-on-Treatment Biomarker of Outcome in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with First-Line Pembrolizumab.

BACKGROUND: The Gustave Roussy Immune (GRIm)-Score takes into account neutrophil-to-lymphocyte ratio (NLR), serum albumin concentration and lactate dehydrogenase (LDH) and its prognostic value has been investigated in patients treated with immune check-point inhibitors (ICIs). To further assess the prognostic and predictive value of baseline GRIm-Score (GRImT0) in advanced non-small cell lung cancer (aNSCLC) patients, we separately investigated two cohorts of patients treated with first-line pembrolizumab or chemotherapy. We also investigated whether GRIm-Score at 45 days since treatment initiation (GRImT1) and GRIm-Score difference between the two timepoints may better predict clinical outcomes (GRImΔ = GRImT0 - GRImT1). METHODS: We retrospectively evaluated 222 aNSCLC patients: 135 treated with pembrolizumab and 87 treated with chemotherapy as the first-line regimen. NLR, serum albumin and LDH concentrations were assessed at T0 and at T1. According to the GRIm-Score, patients were assigned 1 point if they had NLR > 6, LDH > upper limit normal or albumin < 3.5 g/dL. Patients with a GRIm-Score < 2 were considered as having a low Score. RESULTS: In both cohorts, no difference in terms of overall survival (OS) between patients with low and high GRImT0 was found. Otherwise, median OS and progression free survival (PFS) of the low GRImT1 group were significantly longer than those of the high GRImT1 group in pembrolizumab-treated patients, but not in the CHT cohort (pembrolizumab cohort: low vs. high; median OS not reached vs. 9.2 months, p = 0.004; median PFS 10.8 vs. 2.3 months, p = 0.002). Patients receiving pembrolizumab with stable/positive GRImΔ had better OS (median OS not reached vs. 12.0 months, p < 0.001), PFS (median PFS 20.6 vs. 2.6 months, p < 0.001) and objective response rate (58.2% vs. 7.6%, p = 0.003) compared to patients with negative GRImΔ. CONCLUSION: Our data shown that GRImT1 and GRImΔ are more reliable peripheral blood biomarkers of outcome compared to GRImT0 in aNSCLC patients treated with pembrolizumab and might represent useful biomarkers to drive clinical decisions in this setting.

The Ventrain Device: A Future Role in Difficult Airway Algorithms?

The Ventrain is a small, manually operated, single-use, inspiratory flow-adjustable ventilation device that generates positive pressure during inspiration and, through a Bernoulli effect within the device, active suction during expiration. It was designed to provide emergency ventilation during airway obstruction via narrow-bore cannulae. The device has been used successfully in elective procedures lasting >1 hour. It remains to be seen if its theoretical advantages in "can't intubate, can't oxygenate" (CICO) scenarios translate to reliable clinical benefit and allow inclusion in future airway algorithms. We advocate for regular simulation training and the detailed reporting of clinical experience with this encouraging new tool.

Failed Awake Intubation for Critical Airway Obstruction Rescued With the Ventrain Device and an Arndt Exchange Catheter: A Case Report.

A 71-year-old man with advanced vocal cord carcinoma presented with severe airway obstruction. Therapeutic anticoagulation with enoxaparin complicated management. Failure of an oral awake bronchoscopic intubation was rescued by passing a guidewire through the working channel and threading an Arndt exchange catheter into the trachea under videoscopic vision. Ventilation with the Ventrain device lasting 40 minutes (15 L/min, inspiration/expiration 1:1, 15 breaths/min), during IV anesthesia with muscle paralysis, resulted in excellent blood gas values until placement of the tracheal cannula. This case report highlights the effectiveness of a novel ventilation technique that should be considered as back-up when bronchoscopic intubation fails.

Donor B-type natriuretic peptide predicts early cardiac performance after heart transplantation.

BACKGROUND: Decision processes in heart donation remain difficult and are often based on subjective evaluation. We measured B-type natriuretic peptide (BNP) in heart donors and analyzed its value as a discriminator for early post-transplant cardiac performance. METHODS: Blood samples were prospectively obtained in 94 brain-dead patients, among whom 56 were scheduled for heart donation. BNP values were not available prior to donor selection. BNP of heart donors was related to invasively measured cardiac output and hemodynamic parameters, early after transplantation. RESULTS: BNP, expressed as median (interquartile range), was 65 (32 to 149) pg/ml in brain-dead donors scheduled for heart donation. BNP was higher (287 pg/ml, range 65 to 457; p = 0.0001) in donors considered ineligible for heart donation. In 45 heart recipients, cardiac output (CO) of 5.6 (4.8 to 6.2) liters/min was measured at Day 12 (10-15). In the univariate analysis, recipient CO correlated significantly with donor BNP (r = -0.34, p = 0.025). Stepwise multiple regression, including donor variables such as body mass index, age, BNP, norepinephrine dose, gender and total ischemic time, identified donor BNP and age as the best independent predictors of CO in recipients (p = 0.02 and p = 0.005, respectively, R(2) of the model = 0.27). Donor BNP of >160 pg/ml had 89% accuracy to predict poor cardiac performance in the recipient (cardiac index <2.2 liters/min/m(2)). High donor BNP was independently correlated with a longer hospital stay. CONCLUSIONS: Donor BNP was found to be related to cardiac performance, early after cardiac transplantation. BNP measurement in heart donors could become a useful tool in the evaluation of donor hearts.