Extracorporeal life support in trauma: Indications and techniques.

BACKGROUND: Clarity about indications and techniques in extracorporeal life support (ECLS) in trauma is essential for timely and effective deployment, and to ensure good stewardship of an important resource. Extracorporeal life support deployments in a tertiary trauma center were reviewed to understand the indications, strategies, and tactics of ECLS in trauma. METHODS: The provincial trauma registry was used to identify patients who received ECLS at a Level I trauma center and ECLS organization-accredited site between January 2014 and February 2021. Charts were reviewed for indications, technical factors, and outcomes following ECLS deployment. Based on this data, consensus around indications and techniques for ECLS in trauma was reached and refined by a multidisciplinary team discussion. RESULTS: A total of 25 patients underwent ECLS as part of a comprehensive trauma resuscitation strategy. Eighteen patients underwent venovenous ECLS and seven received venoarterial ECLS. Nineteen patients survived the ECLS run, of which 15 survived to discharge. Four patients developed vascular injuries secondary to cannula insertion while four patients developed circuit clots. On multidisciplinary consensus, three broad indications for ECLS and their respective techniques were described: gas exchange for lung injury, extended damage control for severe injuries associated with the lethal triad, and circulatory support for cardiogenic shock or hypothermia. CONCLUSION: The three broad indications for ECLS in trauma (gas exchange, extended damage control and circulatory support) require specific advanced planning and standardization of corresponding techniques (cannulation, circuit configuration, anticoagulation, and duration). When appropriately and effectively integrated into the trauma response, ECLS can extend the damage control paradigm to enable the management of complex multisystem injuries. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

18 F-sodium fluoride positron emission tomography quantitation of bone metastases in African American and non-African American men with metastatic prostate cancer.

BACKGROUND: Bone is the most common site of metastases in men with prostate cancer. The objective of this study was to explore potential racial differences in the distribution of tumor metastases in the axial and appendicular skeleton. METHODS: We conducted a retrospective review of patients with metastatic prostate cancer to the bone as detected by 18 F-sodium fluoride positron emission tomography/computed tomography (18 F-NaF PET/CT) scans. In addition to describing patients' demographics and clinical characteristics, the metastatic bone lesions, and healthy bone regions were detected and quantified volumetrically using a quantitative imaging platform (TRAQinform IQ, AIQ Solutions). RESULTS: Forty men met the inclusion criteria with 17 (42%) identifying as African Americans and 23 (58%) identifying as non-African Americans. Most of the patients had axial (skull, ribcage, and spine) disease. The location and the number of lesions in the skeleton of metastatic prostate cancer patients with low disease burden were not different by race. CONCLUSIONS: In low-disease burden patients with metastatic prostate cancer, there were no overall differences by race in the location and number of lesions in axial or appendicular skeleton. Therefore, given equal access to molecular imaging, African Americans might derive similar benefits. Whether this holds true for patients with a higher disease burden or for other molecular imaging techniques is a topic for further study.

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.

CONTEXT: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy. OBJECTIVE: To evaluate safety and efficacy of intranasal carbetocin in PWS. DESIGN: Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up. SETTING: Twenty-four ambulatory clinics at academic medical centers. PARTICIPANTS: A total of 130 participants with PWS aged 7 to 18 years. INTERVENTIONS: Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose. MAIN OUTCOME MEASURES: Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C). RESULTS: Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing. CONCLUSIONS: Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS. CLINICAL TRIALS REGISTRATION NUMBER: NCT03649477.

Quality of life and functional status of patients treated with venovenous extracorporeal membrane oxygenation at 6 months.

PURPOSE: Quality of life (QoL) outcomes of patients treated with extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome (ARDS) have been conflicting. This study reports on QoL outcomes for a broad group of ARDS patients managed with up-to-date treatment modalities. METHODS: We prospectively recruited patients at a quaternary hospital in the United Kingdom from 2013 to 2015 who were treated with ECMO for ARDS. We evaluated their pulmonary function and QoL at 6-months after admission using three QoL instruments: EuroQoL 5D (EQ-5), HADS, and PTSS-14. RESULTS: Forty-three patients included in the analysis had near-normal pulmonary function at 6 months. HADS showed moderate-to-severe anxiety and depression in 32% and 11% of patients, respectively. PTSS-14 showed 29% had signs of post-traumatic stress disorder. EQ-5D showed that 67% of patients had difficulty returning to usual activities, 74% suffered some pain, none reported severe problems and 77% were able to return to work. No clinical or demographic variables were associated with poor 6-month QoL. CONCLUSIONS: Patients with ARDS treated with ECMO generally had good QoL outcomes, similar to outcomes reported for patients managed without ECMO. With respect to QoL, VV-EMCO represents a valid treatment modality for patients with refractory ARDS.

Cryoablation Without Excision for Low-Risk Early-Stage Breast Cancer: 3-Year Interim Analysis of Ipsilateral Breast Tumor Recurrence in the ICE3 Trial.

BACKGROUND: The ICE3 trial is designed to evaluate the safety and efficacy of breast cryoablation, enabling women older than 60 years with low-risk early-stage breast cancers to benefit from a nonsurgical treatment and to avoid the associated surgical risks. METHODS: The ICE3 trial is a prospective, multi-center, single-arm, non-randomized trial including women age 60 years or older with unifocal, ultrasound-visible invasive ductal carcinoma size 1.5 cm or smaller and classified as low to intermediate grade, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative. Ipsilateral breast tumor recurrence (IBTR) at 5 years was the primary outcome. A 3-year interim analysis of IBTR was performed, and the IBTR probability was estimated using the Kaplan-Meier method. RESULTS: Full eligibility for the study was met by 194 patients, who received successful cryoablation per protocol. The mean age was 75 years (range, 55-94 years). The mean tumor length was 8.1 mm (range, 8-14.9 mm), and the mean tumor width was 7.4 mm (range, 2.8-14 mm). During a mean follow-up period of 34.83 months, the IBTR rate was 2.06% (4/194 patients). Device-related adverse events were reported as mild in 18.4% and moderate in 2.4% of the patients. No severe device-related adverse events were reported. More than 95% of the patients and 98% of the physicians reported satisfaction with the cosmetic results at the clinical follow-up evaluation. CONCLUSIONS: Breast cryoablation presents a promising alternative to surgery while offering the benefits of a minimally invasive procedure with minimal risks. Further study within a clinical trial or registry is needed to confirm cryoablation as a viable alternative to surgical excision for appropriately selected low-risk patients.

The ECLIPSE Study: Efficacy of Cryoablation on Metastatic Lung Tumors With a 5-Year Follow-Up.

INTRODUCTION: The ECLIPSE study aimed to evaluate the feasibility and efficacy of cryoablation (CA) for local tumor control in patients with pulmonary metastatic disease in 5 years of follow-up. METHODS: ECLIPSE was a prospective, multicenter, single-arm study that included patients treated with CA if they had one to five metastatic lung tumors, each with a diameter of less than or equal to 3.5 cm. Patients were followed up in the course of 5 years. The primary end point was local tumor control, both per tumor and per patient; secondary end points included cancer-specific survival, overall survival, and quality of life (QoL). QoL was evaluated using the Karnofsky Performance Score, the Eastern Cooperative Oncology Group performance score, and the Short Form-12 health survey. RESULTS: The study included 40 patients across four sites (three in United States and one in Europe). A total of 60 metastatic pulmonary tumors were treated with 48 CA procedures. Overall local tumor control rates were 87.9% (29 of 33) and 79.2% (19 of 24) per tumor, 83.3% (20 of 24) and 75.0% (15 of 20) per patient, at 3 and 5 years, respectively. A total of five treated patients had local progression throughout the duration of the study. Disease-specific survival rate was 74.8% at 3 years and 55.3% at 5 years, whereas overall survival at 3 and 5 years was 63.2% and 46.7%, respectively. Patient QoL scores did not reach statistical significance. CONCLUSIONS: CA is an effective means of long-term local tumor control in patients with metastatic pulmonary tumors.

Current Use, Capacity, and Perceived Barriers to the Use of Extracorporeal Cardiopulmonary Resuscitation for Out-of-Hospital Cardiac Arrest in Canada.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is a therapeutic option for refractory cardiac arrest. We sought to perform an environmental scan to describe ECPR utilization in Canada and perceived barriers for application to out-of-hospital cardiac arrest (OHCA). METHODS: This was a national cross-sectional study. We identified all cardiovascular surgery- and extracorporeal membrane oxygenation (ECMO)-capable hospitals in Canada and emergency medical services (EMS) agencies delivering patients to those centres. We requested the medical lead from each hospital's ECMO service and each EMS agency to submit data regarding ECMO and ECPR utilization, as well as perceived barriers to ECPR provision for OHCA. RESULTS: We identified and received survey data from 39 of 39 Canadian hospital institutions and 21 of 22 EMS agencies. Of hospitals, 38 (97%) perform ECMO and 27 (69%) perform ECPR (74% of which perform ≤5 cases per year). Of the 18 (46%) sites offering ECPR for OHCA, 8 apply a formal protocol for eligibility and initiation procedures. EMS agencies demonstrate heterogeneity with intra-arrest transport practices. The primary rationale for nontransport of refractory OHCA is that hospital-based care offers no additional therapies. Perceived barriers to the use of ECPR for OHCA were primarily related to limited evidence supporting its use, rather than resources required. CONCLUSION: Many Canadian cardiovascular surgery- or ECMO-equipped hospitals use ECPR; roughly half employ ECPR for OHCAs. Low case volumes and few formal protocols indicate that this is not a standardized therapy option in most centres. Increased application may be dependent on a stronger evidence base including data from randomized clinical trials currently underway.

CONTEXTE: La réanimation cardiorespiratoire (RCR) extracorporelle est une option thérapeutique en cas d'arrêt cardiaque réfractaire. Nous avons voulu faire une analyse contextuelle de l'utilisation de la RCR extracorporelle au Canada et des obstacles perçus quant à son emploi dans les cas d'arrêt cardiaque en dehors de l'hôpital. MÉTHODOLOGIE: Il s'agissait d'une étude nationale transversale. Nous avons repéré tous les hôpitaux en mesure d'effectuer des chirurgies cardiovasculaires et d'offrir l'oxygénation extracorporelle au Canada et les fournisseurs de services médicaux d'urgence (SMU) transportant les patients vers ces centres. Nous avons demandé au chef médical du service d'oxygénation extracorporelle de chacun des hôpitaux et de chacun des fournisseurs de SMU de présenter leurs données concernant l'utilisation de l'oxygénation extracorporelle et de la RCR extracorporelle, ainsi que les obstacles perçus quant à l'emploi de la RCR extracorporelle dans les cas d'arrêt cardiaque en dehors de l'hôpital. RÉSULTATS: Nous avons obtenu les données de 39 des 39 établissements hospitaliers canadiens ciblés, et de 21 des 22 fournisseurs de SMU. Parmi les hôpitaux, 38 (97%) utilisent l'oxygénation extracorporelle et 27 (69 %), la RCR extracorporelle (74 % ayant eu recours à celle-ci dans ≤ 5 cas par année). Parmi les 18 (46 %) centres offrant la RCR extracorporelle en cas d'arrêt cardiaque en dehors de l'hôpital, 8 appliquaient un protocole officiel pour l'admissibilité et les procédures de mise en place. Les fournisseurs de SMU ont montré des pratiques hétérogènes concernant la réanimation en déplacement. La principale raison justifiant de ne pas transporter les patients présentant un arrêt cardiaque réfractaire en dehors de l'hôpital est que les soins en milieu hospitalier n'offrent pas de traitements additionnels. Les obstacles perçus quant à l'emploi de la RCR extracorporelle dans les cas d'arrêt cardiaque en dehors de l'hôpital étaient principalement liés au peu de données appuyant son utilisation, plutôt qu'aux ressources nécessaires. CONCLUSION: De nombreux hôpitaux canadiens équipés pour la chirurgie cardiovasculaire et l'oxygénation extracorporelle utilisent la RCR extracorporelle; environ la moitié d'entre eux utilisent la RCR extracorporelle en cas d'arrêt cardiaque en dehors de l'hôpital. Le faible nombre de cas et le peu de protocoles officiels indiquent qu'il ne s'agit pas d'une option de traitement standardisée dans la plupart des centres. Une utilisation plus fréquente pourrait nécessiter davantage de données probantes, y compris les résultats des études cliniques à répartition aléatoire qui sont en cours.

Percutaneous cryoablation of adrenal metastases: technical feasibility and safety.

PURPOSE: To assess the technical feasibility and outcomes of adrenal metastases cryoablation. MATERIALS AND METHODS: This is an IRB approved retrospective review of adrenal metastases cryoablation between April 2003 and October 2018. Forty percutaneous cryoablation procedures were performed on 40 adrenal metastases in 34 patients. Histology, tumor size, ablation zone size, major vessel proximity, local recurrences, complications, and anesthesia-managed hypertension monitoring was collected. Complications were graded according to the Common Terminology of Complications and Adverse Events (CTCAE). RESULTS: Mean tumor and ablation size was 3.2 cm and 5.2 cm, respectively. Local recurrence rate was 10.0% (N = 4/40) for a mean follow-up time of 1.8 years. Recurrences for tumors > 3 cm (21.0%, N = 4/19) was greater than for tumors ≤ 3 cm (0.0%, N = 0/21) (p = 0.027). Proximity of major vasculature (i.e., IVC & aorta) did not statistically effect recurrence rates (p = 0.52), however, those that recurred near vasculature were > 4 cm. Major complication (≥ grade 3) rate was 5.0% (N = 2/40), with one major complication attributable to the procedure. Immediate escalation of blood pressure during the passive stick phase (between freeze cycles) or post procedure thaw phase was greater in patients with residual adrenal tissue (N = 21/38) versus masses replacing the entire adrenal gland (N = 17/38), (p = 0.0020). Lower blood pressure elevation was noted in patients with residual adrenal tissue who were pre-treated with alpha blockade (p = 0.015). CONCLUSIONS: CT-guided percutaneous cryoablation is a safe, effective and low morbidity alternative for patients with adrenal metastases. Transient hypertension is related only to residual viable adrenal tissue but can be safely managed and prophylactically treated.

Adrenal Metastases as Sanctuary Sites in Advanced Renal Cancer.

Involvement of the adrenal gland in kidney cancer represents a unique site of metastasis with a distinct clinical course. The cases are typically resistant to immune therapy and need local therapy management. A case series of patients with adrenal metastases was reviewed to highlight the nuances of clinical course and therapy. We reviewed renal cancer carcinoma (RCC) cases with adrenal metastases at Karmanos Cancer Center, Detroit MI. Medical records were reviewed to collect relevant case information. Next-generation sequencing, tumor mutation burden testing, and programmed death ligand biomarkers were evaluated in five cases. Twelve cases were reviewed; all were males with a median age of 49.5 years. Three patients presented with adrenal metastases only and were treated with local therapy. Three received interleukin-2 (IL-2). One patient relapsed with bilateral adrenal lesions after 11 years of remission, post-IL-2 therapy. Five cases received immune checkpoint inhibitor (ICI) and one received antivascular therapy. ICI therapy was followed by ablation of residual adrenal metastases in three patients. Genomic profiling was available in five cases. All were BAP1 and PD-L1 negative.Pathogenic mutations in PBRM1, SETD2, and VHL were noted. All patients with residual adrenal metastases responded to antivascular therapies or to local ablation. One patient died 17 years after diagnosis and 11 patients are alive at a median follow-up of 9.5 years. Adrenal metastases in RCC have a distinct clinical course. They can represent a sanctuary site of relapse/residual disease following treatment with immune therapy. Management with local therapy can induce durable remissions. Systemic management with antivascular therapies also demonstrated favorable responses. Further investigation should focus on the unique clinical course and optimal management of adrenal metastases in kidney cancer.

Caractéristiques de départ et issues chez des patients atteints de COVID-19 hospitalisés dans des unités de soins intensifs à Vancouver (Canada) : série de cas.

CONTEXTE: La pandémie de maladie à coronavirus du syndrome respiratoire aigu sévère 2 (SRAS-CoV-2) est associée à une mortalité élevée dans les unités de soins intensifs (USI). Nous avons voulu décrire les caractéristiques cliniques et les issues des patients gravement atteints de la maladie à coronavirus 2019 (COVID-19) en contexte canadien. MÉTHODES: Nous avons procédé à l'étude rétrospective d'une série de cas graves d'infection au SRAS-CoV-2 confirmée en laboratoire hospitalisés dans l'une des 6 USI du Vancouver métropolitain, en Colombie-Britannique (Canada), entre le 21 février et le 14 avril 2020. Les données démographiques, les renseignements sur la prise en charge et les résultats ont été recueillis à partir des dossiers médicaux, électroniques ou non, des patients. RÉSULTATS: Entre le 21 février et le 14 avril 2020, 117 patients ont été admis dans une USI avec un diagnostic confirmé de COVID-19. L'âge médian était de 69 ans (écart interquartile [EI] 60­75 ans); et 38 (32,5 %) étaient des femmes. Au moins une comorbidité était présente chez 86 patients (73,5 %). La ventilation mécanique a été nécessaire chez 74 patients (63,2 %). La durée de la ventilation mécanique a été de 13,5 jours (EI 8­22 jours) dans l'ensemble et de 11 jours (II 6­16) chez les patients qui ont reçu leur congé de l'USI. Du tocilizumab a été administré à 4 patients et de l'hydroxychloroquine à 1 patient. En date du 5 mai 2020, 18 patients (15,4 %) étaient décédés, 12 (10,3 %) étaient toujours à l'USI, 16 (13,7 %) avaient obtenu leur congé de l'USI, mais restaient hospitalisés, et 71 (60,7 %) avaient pu retourner à la maison. INTERPRÉTATION: Dans cette étude, la mortalité chez les patients gravement malades de la COVID-19 hospitalisés dans une USI a été moins élevée que chez les patients d'études précédentes. Ces résultats donnent à penser que le pronostic des cas graves de COVID-19 pourrait ne pas être aussi sombre que ce qui avait d'abord été rapporté.

The Association of Inflammatory Cytokines in the Pulmonary Pathophysiology of Respiratory Failure in Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: The majority of coronavirus disease 2019 mortality and morbidity is attributable to respiratory failure from severe acute respiratory syndrome coronavirus 2 infection. The pathogenesis underpinning coronavirus disease 2019-induced respiratory failure may be attributable to a dysregulated host immune response. Our objective was to investigate the pathophysiological relationship between proinflammatory cytokines and respiratory failure in severe coronavirus disease 2019. DESIGN: Multicenter prospective observational study. SETTING: ICU. PATIENTS: Critically ill patients with coronavirus disease 2019 and noncoronavirus disease 2019 critically ill patients with respiratory failure (ICU control group). INTERVENTIONS: Daily measurement of serum inflammatory cytokines. MEASUREMENTS AND MAIN RESULTS: Demographics, comorbidities, clinical, physiologic, and laboratory data were collected daily. Daily serum samples were drawn for measurements of interleukin-1ß, interleukin-6, interleukin-10, and tumor necrosis factor-α. Pulmonary outcomes were the ratio of Pao2/Fio2 and static lung compliance. Twenty-six patients with coronavirus disease 2019 and 22 ICU controls were enrolled. Of the patients with coronavirus disease 2019, 58% developed acute respiratory distress syndrome, 62% required mechanical ventilation, 12% underwent extracorporeal membrane oxygenation, and 23% died. A negative correlation between interleukin-6 and Pao2/Fio2 (rho, -0.531; p = 0.0052) and static lung compliance (rho, -0.579; p = 0.033) was found selectively in the coronavirus disease 2019 group. Diagnosis of acute respiratory distress syndrome was associated with significantly elevated serum interleukin-6 and interleukin-1ß on the day of diagnosis. CONCLUSIONS: The inverse relationship between serum interleukin-6 and Pao2/Fio2 and static lung compliance is specific to severe acute respiratory syndrome coronavirus 2 infection in critically ill patients with respiratory failure. Similar observations were not found with interleukin-ß or tumor necrosis factor-α.

Methylene Blue/Collagen Mixture for CT-Guided Presurgical Lung Nodule Marking: High Efficacy and Safety.

PURPOSE: To assess outcomes of computed tomography (CT)-guided methylene blue/collagen marking of preoperative lung nodules before video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracic surgery (RATS). MATERIALS AND METHODS: A retrospective cohort study assessing 25 methylene blue/collagen solution CT-guided lung nodule localization procedures on 26 nodules in 25 patients was performed. The procedures were performed by a fellowship-trained radiologist 1-2 hours before scheduled surgery under local anesthesia. Approximately 4-6 ml of methylene blue/collagen solution was injected in a perinodular location under CT guidance with a 19-gauge trocar needle and along the track to the visceral pleural surface. Post-procedural CT images confirmed appropriate lung nodule location marking. RESULTS: Perinodular CT-guided trocar needle placement was achieved in all marking procedures (n = 26/26). Increased consolidation near the target nodule was also demonstrated in all patients on the post-procedural localized CT scans. One patient with moderate emphysema developed a small to moderate-sized pneumothorax (∼20%-30%), and an 8-Fr thoracentesis catheter was placed under CT guidance before surgery. There was no bleeding or hemoptysis in any patient. Methylene blue/collagen solution was readily visible by the thoracic surgeon in association with all target nodules. One patient required conversion to open procedure due to the proximal portion of the right lower lobe pulmonary artery segmental branch. Of the 26 identified nodules, pathology specimens confirmed the adequacy of nodule resection in all cases. CONCLUSIONS: Preoperative CT-guided methylene blue/collagen solution injection offers a safe and highly effective technique for marking subpleural lung nodules undergoing VATS or RATS.

Clinical and immune responses to anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (EGFR BATs) in pancreatic cancer patients.

Purpose This was a phase I/II adoptive T cell trial in 7 locally advanced and metastatic pancreatic cancer patients using 3-8 infusions of anti-CD3 x anti-EGFR bispecific antibody armed activated T cells (BATs) to determine safety, the maximum tolerated dose (MTD), immune responses, time to progression (TTP), and overall survival (OS). Study Design: T cells obtained by apheresis were expanded and armed with EGFRBi, cryopreserved for infusions. In a phase I dose escalation, five patients received three weekly infusions of 10-40 × 109 BATs/infusion followed by a booster infusion 3 months later, and 2 patients received 8 infusions twice weekly for 4 weeks in a phase II. The trials were registered at http://www.clinicaltrials.gov, NCT01420874 and NCT02620865. Results: There were no dose-limiting toxicities (DLTs), and the targeted dose of 80 × 109 BATs was met. The median TTP is 7 months, and the median OS is 31 months. Two patients had stable disease for 6.5 and 25+ months, and two patients developed complete responses (CRs) after restarting chemotherapy. Infusions of BATs induced anti-pancreatic cancer cytotoxicity, innate immune responses, cytokine responses (IL-12, IP-10), and shifts in CD4 and CD8 Vß repertoire with enhanced cytoplasmic IFN-γ staining in the Vß repertoire of the CD8 subset that suggest specific clonal TCR responses. Conclusions: Infusions of BATs are safe, induce endogenous adaptive anti-tumor responses, and may have a potential to improve overall survival.

Transfusion Thresholds for Adult Respiratory Extracorporeal Life Support: An Expert Consensus Document.

Severe acute respiratory distress syndrome (ARDS) can complicate novel pandemic coronavirus disease (COVID-19). Extracorporeal life support (ECLS) represents the final possible rescue strategy. Variations in practice, combined with a paucity of rigourous guidelines, may complicate blood-product resource availability and allocation during a pandemic. We conducted a literature review around venovenous extracorporeal membrane oxygenation (VV-ECMO) transfusion practices for platelets, packed red blood cells, fresh frozen plasma, prothrombin complex concentrate, and antithrombin. Pertinent society guidelines were examined, and the practice of Canadian ECLS experts was sampled through an environmental scan. This paper represents a synthesis of these explorations, combined with input from the Canadian Cardiovascular Critical Care (CANCARE) Society, Canadian Society of Cardiac Surgeons, and the Canadian Critical Care Society. We offer a pragmatic guidance document for restrictive transfusion thresholds in nonbleeding patients on VV-ECMO, which may attenuate transfusion-related complications and simultaneously shield national blood product inventory from strain during pandemic-induced activation of the National Plan for the Management of Shortages of Labile Blood Components.

The relationship between no-flow interval and survival with favourable neurological outcome in out-of-hospital cardiac arrest: Implications for outcomes and ECPR eligibility.

BACKGROUND: The "no flow" interval is the time from out-of-hospital cardiac arrest (OHCA) to cardiopulmonary resuscitation (CPR). Its prognostic value is important to define for prehospital resuscitation decisions, post-resuscitation care and prognostication, and extracorporeal cardiopulmonary resuscitation (ECPR) candidacy assessment. METHODS: We examined bystander-witnessed OHCAs without bystander CPR from two Resuscitation Outcomes Consortium datasets. We used modified Poisson regression to model the relationship between the no-flow interval (9-1-1 call to professional resuscitation) and favourable neurological outcome (Modified Rankin Score ≤ 3) at hospital discharge. Furthermore, we identified the no-flow interval beyond which no patients had a favourable outcome. We analysed a subgroup to simulate ECPR-treated patients (witnessed arrest, age < 65, non-asystole initial rhythm, and >30 min until return of circulation). RESULTS: Of 43,593 cases, we included 7299; 616 (8.4%) had favourable neurological outcomes. Increasing no-flow interval was inversely associated with favourable neurological outcomes (adjusted relative risk 0.87, 95% CI 0.85-0.90); the adjusted probability of a favourable neurological outcome decreased by 13% (95% CI 10-15%) per minute. No patients (0/7299, 0%; 1-sided 97.5% CI 0-0.051%) had both a no-flow interval >20 min and a favourable neurological outcome. In the hypothetical ECPR group, 0/152 (0%; 1-sided 97.5% CI 0-2.4%) had both a no-flow interval >10 min and a favourable neurological outcome. CONCLUSIONS: The probability of a favourable neurological outcome in OHCA decreases by 13% for every additional minute of no-flow time until high-quality CPR, with the possibility of favourable outcomes up to 20 min.

Baseline characteristics and outcomes of patients with COVID-19 admitted to intensive care units in Vancouver, Canada: a case series.

BACKGROUND: Pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with high intensive care unit (ICU) mortality. We aimed to describe the clinical characteristics and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19) in a Canadian setting. METHODS: We conducted a retrospective case series of critically ill patients with laboratory-confirmed SARS-CoV-2 infection consecutively admitted to 1 of 6 ICUs in Metro Vancouver, British Columbia, Canada, between Feb. 21 and Apr. 14, 2020. Demographic, management and outcome data were collected by review of patient charts and electronic medical records. RESULTS: Between Feb. 21 and Apr. 14, 2020, 117 patients were admitted to the ICU with a confirmed diagnosis of COVID-19. The median age was 69 (interquartile range [IQR] 60-75) years, and 38 (32.5%) were female. At least 1 comorbidity was present in 86 (73.5%) patients. Invasive mechanical ventilation was required in 74 (63.2%) patients. The duration of mechanical ventilation was 13.5 (IQR 8-22) days overall and 11 (IQR 6-16) days for patients successfully discharged from the ICU. Tocilizumab was administered to 4 patients and hydroxychloroquine to 1 patient. As of May 5, 2020, a total of 18 (15.4%) patients had died, 12 (10.3%) remained in the ICU, 16 (13.7%) were discharged from the ICU but remained in hospital, and 71 (60.7%) were discharged home. INTERPRETATION: In our setting, mortality in critically ill patients with COVID-19 admitted to the ICU was lower than in previously published studies. These data suggest that the prognosis associated with critical illness due to COVID-19 may not be as poor as previously reported.

A Blended Prehospital Ultrasound Curriculum for Critical Care Paramedics.

OBJECTIVE: Point-of-care ultrasound is a nascent and growing area of prehospital care. Most previously described ultrasound curricula for paramedics examine a single type of ultrasound scan. Here, we describe the implementation and evaluation of a prehospital ultrasound curriculum using a blended model of traditional didactics and hands-on experience with online prereading. METHODS: We recruited a prospective convenience sample of critical care paramedics without prior ultrasound experience to take part in a 2-day ultrasound course. All participants completed prereading modules built from online resources followed by a didactic review of the material and hands-on practice. Ultrasound examinations included extended focused abdominal sonography in trauma, cardiac ultrasound, thoracic ultrasound, and vascular ultrasound. A written examination evaluated ultrasound theory and image interpretation, and a practical examination evaluated image acquisition. RESULTS: Seventeen critical care paramedics completed the course with a mean grade on the written examination of 76%, with 76% of paramedics achieving the predetermined passing mark of 70% or greater. All paramedics passed the practical examination. CONCLUSION: The implementation of a prehospital critical care ultrasound program is feasible in our provincial emergency medical services system. Further assessment is necessary to determine future knowledge and skill retention as well as clinical application and utility in real-world settings.

Interferon-γ enhances the antifibrotic effects of pirfenidone by attenuating IPF lung fibroblast activation and differentiation.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) pathogenesis involves multiple pathways, and combined antifibrotic therapy is needed for future IPF therapy. Inhaled interferon-γ (IFN-γ) was recently shown to be safe and without systemic effects in patients with IPF. AIM: To examine the in vitro effects of individual and combined treatment with IFN-γ and pirfenidone (PFD) on normal and IPF fibroblast activation and extracellular matrix remodeling after TGF-ß1 and PDGF-BB stimulation. METHODS: IPF and normal human lung fibroblasts (NHLF) were treated with IFN-γ, PFD or a combination of both drugs in the presence of either TGF-ß1 or PDGF-BB. The effects of TGF-ß1 and PDGF-BB treatment on cell viability, proliferation, differentiation and migration were examined. The expression of collagen 1, matrix metalloproteinases (MMPs) and tissue inhibitors of MMP (TIMPs) was analyzed using qPCR, Western blotting and gelatin zymography. Total collagen content in conditioned media was also measured using a Sircol assay. RESULTS: Compared to that of PFD, the effect of IFN-γ in downregulating normal and IPF lung fibroblast differentiation to myofibroblasts in response to TGF-ß1 was more potent. Importantly, the combination of IFN-γ and PFD had a possibly synergistic/additive effect in inhibiting the TGF-ß1- and PDGF-BB-induced proliferation, migration and differentiation of normal and IPF lung fibroblasts. Furthermore, both drugs reversed TGF-ß1-induced effects on MMP-1, - 2, - 3, - 7, and - 9, while only PFD promoted TIMP-1 and-2 expression and release. CONCLUSIONS: Our findings demonstrate that the antifibrotic effects of IFN-γ and PFD on normal and IPF lung fibroblasts are different and complementary. Combination therapy with inhaled IFN-γ and PFD in IPF is promising and should be further explored in IPF clinical trials.