Nodular Sarcoidosis Masquerading as Cancer.

Nodular lung disease is a rare pulmonary manifestation of sarcoidosis and resembles metastatic neoplasm disease. Nodular sarcoidosis is rare, varying from 1.6% to 4% of patients with sarcoidosis. Radiographic nodules measure from 1 to 5 cm in diameter that typically consist of coalescent granulomas. There is limited data on this form of sarcoidosis and its presentation can mimic primary or metastatic pulmonary neoplasms. Nodular sarcoidosis has a favorable prognosis, and resolution can be seen with oral corticosteroids. Herein, we present such a case of nodular pulmonary sarcoidosis with a lung nodule measured up to 6 cm

Nodular Sarcoidosis Masquerading as Cancer

Nodular lung disease is a rare pulmonary manifestation of sarcoidosis and resembles metastatic neoplasm disease. Nodular sarcoidosis is rare, varying from 1.6% to 4% of patients with sarcoidosis. Radiographic nodules measure from 1 to 5 cm in diameter that typically consist of coalescent granulomas. There is limited data on this form of sarcoidosis and its presentation can mimic primary or metastatic pulmonary neoplasms. Nodular sarcoidosis has a favorable prognosis, and resolution can be seen with oral corticosteroids. Herein, we present such a case of nodular pulmonary sarcoidosis with a lung nodule measured up to 6 cm

Neurofibromatosis type 1: a case highlighting pulmonary and other rare clinical manifestations.

Neurofibromatosis type 1 (NF1)-related lung disease is a rare but increasingly recognised, high morbidity associated feature of the condition. We present a 48-year-old male patient with NF1, who was initially admitted for a subarachnoid haemorrhage requiring aneurysmal coil embolisation. During his recovery, he developed a left-sided pneumothorax requiring chest tube placement followed by concerns for re-expansion pulmonary oedema requiring intubation. Subsequently, the patient also developed a right-sided pneumothorax requiring additional chest tube placement but did not develop right-sided pulmonary oedema. During his hospitalisation, the patient also exemplified other important NF1-related pathophysiology including pheochromocytoma, cerebrovascular abnormalities and cardiovascular manifestations. Due to his multiple comorbidities and poor prognosis, we held a goals of care discussion with the patient's mother, and with her agreement, the patient underwent compassionate withdrawal of artificial life support

Protected code blue: using in situ simulation to develop a protected code blue and modify staff training protocol—experience in a large community teaching hospital during the COVID-19 pandemic

The surge in clinical demand, shortage in personal protective equipment and high-exposure risk for healthcare workers during the COVID-19 pandemic has challenged hospital common practices and forced a reassessment of care delivery models. Code blue teams are highly specialised units that partake in life-saving situations that can jeopardise the safety of team members. There is a paucity of guidance in regards to proper infection control measures to protect the responders.This study describes a methodical approach to assessing vulnerabilities to transmission of SARS-CoV-2 within existing code blue practices, modalities to limit the number of code blue team responders and modifications to the protocol at a large community teaching hospital. The effort undertaken faced challenges due to the nature of the pandemic and the increased demand on healthcare workers. Quality improvement methods facilitated our protocol design and implementation. To this date, there has been no identified COVID-19 disease in any protected code blue (PCB) team members. We recommend that similar practices be considered and adopted widely and practised periodically

Auxora vs. placebo for the treatment of patients with severe COVID-19 pneumonia: A randomized-controlled clinical trial

Background: Calcium release-activated calcium (CRAC) channel inhibitors block proinflammatory cytokine release, preserve endothelial integrity and may effectively treat patients with severe COVID-19 pneumonia. Methods: CARDEA was a phase 2, randomized, double-blind, placebo-controlled trial evaluating the addition of Auxora, a CRAC channel inhibitor, to corticosteroids and standard of care in adults with severe COVID-19 pneumonia. Eligible patients were adults with ≥ 1 symptom consistent with COVID-19 infection, a diagnosis of COVID-19 confirmed by laboratory testing using polymerase chain reaction or other assay, and pneumonia documented by chest imaging. Patients were also required to be receiving oxygen therapy using either a high flow or low flow nasal cannula at the time of enrolment and have at the time of enrollment a baseline imputed PaO2/FiO2 ratio \u3e 75 and ≤ 300. The PaO2/FiO2 was imputed from a SpO2/FiO2 determine by pulse oximetry using a non-linear equation. Patients could not be receiving either non-invasive or invasive mechanical ventilation at the time of enrolment. The primary endpoint was time to recovery through Day 60, with secondary endpoints of all-cause mortality at Day 60 and Day 30. Due to declining rates of COVID-19 hospitalizations and utilization of standard of care medications prohibited by regulatory guidance, the trial was stopped early. Results: The pre-specified efficacy set consisted of the 261 patients with a baseline imputed PaO2/FiO2≤ 200 with 130 and 131 in the Auxora and placebo groups, respectively. Time to recovery was 7 vs. 10 days (P = 0.0979) for patients who received Auxora vs. placebo, respectively. The all-cause mortality rate at Day 60 was 13.8% with Auxora vs. 20.6% with placebo (P = 0.1449); Day 30 all-cause mortality was 7.7% and 17.6%, respectively (P = 0.0165). Similar trends were noted in all randomized patients, patients on high flow nasal cannula at baseline or those with a baseline imputed PaO2/FiO2 ≤ 100. Serious adverse events (SAEs) were less frequent in patients treated with Auxora vs. placebo and occurred in 34 patients (24.1%) receiving Auxora and 49 (35.0%) receiving placebo (P = 0.0616). The most common SAEs were respiratory failure, acute respiratory distress syndrome, and pneumonia. Conclusions: Auxora was safe and well tolerated with strong signals in both time to recovery and all-cause mortality through Day 60 in patients with severe COVID-19 pneumonia. Further studies of Auxora in patients with severe COVID-19 pneumonia are warranted. Trial registration NCT04345614

Integrated multiomics analysis to infer COVID-19 biological insights

Abstract Three years after the pandemic, we still have an imprecise comprehension of the pathogen landscape and we are left with an urgent need for early detection methods and effective therapy for severe COVID-19 patients. The implications of infection go beyond pulmonary damage since the virus hijacks the host's cellular machinery and consumes its resources. Here, we profiled the plasma proteome and metabolome of a cohort of 57 control and severe COVID-19 cases using high-resolution mass spectrometry. We analyzed their proteome and metabolome profiles with multiple depths and methodologies as conventional single omics analysis and other multi-omics integrative methods to obtain the most comprehensive method that portrays an in-depth molecular landscape of the disease. Our findings revealed that integrating the knowledge-based and statistical-based techniques (knowledge-statistical network) outperformed other methods not only on the pathway detection level but even on the number of features detected within pathways. The versatile usage of this approach could provide us with a better understanding of the molecular mechanisms behind any biological system and provide multi-dimensional therapeutic solutions by simultaneously targeting more than one pathogenic factor

Variation in diurnal sedation in mechanically ventilated patients who are managed with a sedation protocol alone or a sedation protocol and daily interruption

Background: Mechanically ventilated patients may receive more sedation during the night than during the day, potentially delaying extubation. We compared nighttime and daytime benzodiazepine and opioid administration in adult patients enrolled in a multicenter sedation trial comparing protocolized sedation alone or protocolized sedation combined with daily sedation interruption; and we evaluated whether nighttime and daytime doses were associated with liberation from mechanical ventilation. Methods: This is a secondary analysis of a randomized trial which was conducted in 16 North American medical-surgical ICUs. In all 423 patients, nurses applied a validated sedation scale hourly to titrate benzodiazepine and opioid infusions to achieve a light level of sedation. Using fentanyl equivalents and midazolam equivalents, we compared dosages administered during night (19:00 to 07:00) and day (07:00 to 19:00) shifts. Using multivariable logistic regression we evaluated the association between nighttime and daytime opioid and sedative doses, and spontaneous breathing trial (SBT) conduct, SBT success, and extubation. Results: Nighttime benzodiazepine and opioid doses were significantly higher than daytime doses (mean difference midazolam equivalents 23.3 mg, 95 % CI 12.9, 33.8, p < 0.0001; mean difference fentanyl equivalents 356 mcg, 95 % CI 130, 582, p = 0.0021). Mean Sedation Agitation Scale score was similar between night and day, and was at target (3.2 vs 3.3, 95 % CI −0.05, 0.02, p = 0.35). Self-reported nurse workload was similar during the night and day. Patients were more often restrained during day shifts (76.3 % vs 73.7 %, p < 0.0001), and there were more unintentional device removals during the day compared with night (15.9 % vs 9.1 %, p < 0.0001). Increases in nighttime drug doses were independently associated with failure to meet SBT screening criteria, SBT failure, and the decision not to extubate the patient despite successful SBT. Conclusion: Patients received higher doses of opioids and benzodiazepines at night. Higher nighttime doses were associated with SBT failure and delayed extubation. Trial registration: ClinicalTrials.gov NCT00675363 . Registered 7 May 2008.Medicine, Faculty ofOther UBCNon UBCCritical Care Medicine, Division ofMedicine, Department ofReviewedFacult

Variation in diurnal sedation in mechanically ventilated patients who are managed with a sedation protocol alone or a sedation protocol and daily interruption

Abstract Background Mechanically ventilated patients may receive more sedation during the night than during the day, potentially delaying extubation. We compared nighttime and daytime benzodiazepine and opioid administration in adult patients enrolled in a multicenter sedation trial comparing protocolized sedation alone or protocolized sedation combined with daily sedation interruption; and we evaluated whether nighttime and daytime doses were associated with liberation from mechanical ventilation. Methods This is a secondary analysis of a randomized trial which was conducted in 16 North American medical-surgical ICUs. In all 423 patients, nurses applied a validated sedation scale hourly to titrate benzodiazepine and opioid infusions to achieve a light level of sedation. Using fentanyl equivalents and midazolam equivalents, we compared dosages administered during night (19:00 to 07:00) and day (07:00 to 19:00) shifts. Using multivariable logistic regression we evaluated the association between nighttime and daytime opioid and sedative doses, and spontaneous breathing trial (SBT) conduct, SBT success, and extubation. Results Nighttime benzodiazepine and opioid doses were significantly higher than daytime doses (mean difference midazolam equivalents 23.3 mg, 95 % CI 12.9, 33.8, p < 0.0001; mean difference fentanyl equivalents 356 mcg, 95 % CI 130, 582, p = 0.0021). Mean Sedation Agitation Scale score was similar between night and day, and was at target (3.2 vs 3.3, 95 % CI −0.05, 0.02, p = 0.35). Self-reported nurse workload was similar during the night and day. Patients were more often restrained during day shifts (76.3 % vs 73.7 %, p < 0.0001), and there were more unintentional device removals during the day compared with night (15.9 % vs 9.1 %, p < 0.0001). Increases in nighttime drug doses were independently associated with failure to meet SBT screening criteria, SBT failure, and the decision not to extubate the patient despite successful SBT. Conclusion Patients received higher doses of opioids and benzodiazepines at night. Higher nighttime doses were associated with SBT failure and delayed extubation. Trial registration ClinicalTrials.gov NCT00675363 . Registered 7 May 2008

Frequency of Screening and SBT Technique Trial - North American Weaning Collaboration (FAST-NAWC): a protocol for a multicenter, factorial randomized trial

Rationale: In critically ill patients receiving invasive mechanical ventilation (MV), research supports the use of daily screening to identify patients who are ready to undergo a spontaneous breathing trial (SBT) followed by conduct of an SBT. However, once daily (OD) screening is poorly aligned with the continuous care provided in most intensive care units (ICUs) and the best SBT technique for clinicians to use remains controversial. Objectives: To identify the optimal screening frequency and SBT technique to wean critically ill adults in the ICU. Methods: We aim to conduct a multicenter, factorial design randomized controlled trial with concealed allocation, comparing the effect of both screening frequency (once versus at least twice daily [ALTD]) and SBT technique (Pressure Support [PS] + Positive End-Expiratory Pressure [PEEP] vs T-piece) on the time to successful extubation (primary outcome) in 760 critically ill adults who are invasively ventilated for at least 24 h in 20 North American ICUs. In the OD arm, respiratory therapists (RTs) will screen study patients between 06:00 and 08:00 h. In the ALTD arm, patients will be screened at least twice daily between 06:00 and 08:00 h and between 13:00 and 15:00 h with additional screens permitted at the clinician’s discretion. When the SBT screen is passed, an SBT will be conducted using the assigned technique (PS + PEEP or T-piece). We will follow patients until successful extubation, death, ICU discharge, or until day 60 after randomization. We will contact patients or their surrogates six months after randomization to assess health-related quality of life and functional status. Relevance: The around-the-clock availability of RTs in North American ICUs presents an important opportunity to identify the optimal SBT screening frequency and SBT technique to minimize patients’ exposure to invasive ventilation and ventilator-related complications. Trial registration: Clinical Trials.gov, NCT02399267 . Registered on Nov 21, 2016 first registered.Other UBCNon UBCReviewedFacult