Diagnostic value and safety of medical thoracoscopy in undiagnosed pleural effusions-a prospective observational cohort study.

Background: With the need for "actionable histology" in the current era of targeted cancer treatment, and the increasing practice of upfront thoracoscopy (without a prior diagnostic thoracentesis) or a "biopsy first" approach in suspected malignant pleural effusions (MPEs), we sought to prospectively evaluate the diagnostic accuracy, including full molecular profiling of cancer, and safety of medical thoracoscopy (MT) at a tertiary referral hospital. Methods: Patients with MT performed for an undiagnosed pleural effusion between January 2020 and December 2022 were included in this observational cohort study. All procedures were performed with a semirigid thoracoscope under conscious sedation. Clinical outcomes and adverse events were recorded prospectively. Results: We evaluated 141 patients, with a mean age of 67±12 years. Talc poudrage was performed in 67 (47.5%) patients with a median of 2 [interquartile range (IQR), 1-4] hospitalisation days after MT. Upfront thoracoscopy was performed in approximately half (55.3%) of patients. The overall diagnostic accuracy of MT was 95.7% in our cohort. A final diagnosis of cancer was made in 116 (82.3%) patients, with lung (67.2%) and breast cancer (8.6%) the most common. The diagnostic sensitivity of MT for malignancy was 94.8%, and molecular profiling of relevant cancer types for oncogenic mutations was achieved in all patients with malignancy seen on histopathology. The most common non-malignant diagnosis was tuberculous pleuritis in 14 patients (9.9%). Major complications occurred in 3 (2.1%) patients. Two patients had re-expansion pulmonary edema that resolved with low flow oxygen supplementation in the general ward, and one patient required intensive care unit admission for cardiac tamponade from a malignant pericardial effusion. There were no cases of mortality, bleeding complications or persistent air leaks. Conclusions: MT is a well-tolerated and effective option for the evaluation of undiagnosed pleural effusions. With expanding utility and expertise with MT and other pleural interventions, the challenge for respiratory physicians is integrating these into expeditious diagnostic and effective therapeutic pathways, individualised to patients' needs.

A Retrospective Cohort Study Evaluating the Safety and Efficacy of Sequential versus Concurrent Intrapleural Instillation of Tissue Plasminogen Activator and DNase for Pleural Infection.

Methods: We conducted a retrospective review of patients with pleural infection requiring intrapleural therapy at two tertiary referral centres. Results: We included 84 (62.2%) and 51 (37.8%) patients who received sequential and concurrent intrapleural therapy, respectively. Patient demographics and clinical characteristics, including age, RAPID score, and percentage of pleural opacity on radiographs before intrapleural therapy, were similar in both groups. Treatment failure rates (defined by either in-hospital mortality, surgical intervention, or 30-day readmission for pleural infection) were 9.5% and 5.9% with sequential and concurrent intrapleural therapy, respectively (p = 0.534). This translates to a treatment success rate of 90.5% and 94.1% for sequential and concurrent intrapleural therapy, respectively. There was no significant difference in the decrease in percentage of pleural effusion size on chest radiographs (15.1% [IQR 6-35.7] versus 26.6% [IQR 9.9-38.7], p = 0.143) between sequential and concurrent therapy, respectively. There were also no significant differences in the rate of pleural bleeding (4.8% versus 9.8%, p = 0.298) and chest pain (13.1% versus 9.8%, p = 0.566) between sequential and concurrent therapy, respectively. Conclusion: Our study adds to the growing literature on the safety and efficacy of concurrent intrapleural therapy in pleural infection.

Performance of the ROX index in predicting high flow nasal cannula failure in COVID-19 patients: a systematic review and meta-analysis.

COVID-19 patients with acute hypoxemic respiratory failure (AHRF) benefit from high flow nasal cannula (HFNC) oxygen therapy. However, delays in initiating invasive ventilation after HFNC failure are associated with poorer outcomes. The respiratory oxygenation (ROX) index, combining SpO2/FiO2 and respiratory rate, can predict HFNC failure. This meta-analysis evaluated the optimal ROX index cut-offs in predicting HFNC failure among COVID-19 patients at different measurement timings and clinical settings. Three databases were searched for eligible papers. From each study, we reconstructed the confusion matrices at different cut-offs, fitted linear mixed models to estimate the ROX index distribution function, and derived the area under the summary receiver operator characteristic curve (sAUC) and optimal cut-offs to predict HFNC failure. 24 studies containing 4790 patients were included. Overall sAUC was 0.771 (95% CI: 0.666-0.847) (optimal cut-off: 5.23, sensitivity: 0.732, specificity: 0.690). The cut-off values to achieve 80%, 90% sensitivity, 80%, 90% specificity were 5.70, 6.69, 4.45, 3.37, respectively. We stratified the analysis by ROX measurement time and estimated optimal cut-offs and cut-offs to achieve 80% sensitivity and specificity. For 2-6 h and 6-12 h post-HFNC initiation, we propose the use of 80% specific cut-offs to rule in HFNC failure of < 5.33 and < 3.69, respectively. For 12-24 h post-HFNC initiation, we propose the use of the 80% sensitive cut-off of > 6.07 to rule out HFNC failure. Our analysis confirms the overall utility of the ROX index in risk stratification of COVID-19 patients with AHRF receiving HFNC and provides potentially useful cut-offs for different times from HFNC initiation.

Airway interventions for tracheobronchial involvement in esophageal carcinoma: a retrospective cohort outcome study and algorithmic approach.

Background: In advanced esophageal carcinoma (EC), there is limited data on risk factors predicting tracheobronchoesophageal fistula (TEF) formation and survival among patients who required airway interventions. Methods: A retrospective analysis of consecutive patients with EC, who had airway involvement requiring intervention, was conducted from 1998 to 2018. Demographics, clinical progress, disease stage, treatment and survival outcomes were recorded. Patients were followed up till death or until completion of the study. Survival was estimated with the Kaplan-Meier method and curves compared by log-rank test. Multivariate analyses of risk factors were performed using Cox proportional hazard regression. Results: A total of 122 patients were included. The median (IQR) survival from time of airway intervention was 3.30 (1.57-6.88) months, while the median (IQR) survival from time of histological diagnosis was 8.90 (4.91-14.45) months. Tumour location within 20 mm of the carina, prior radiotherapy and/or esophageal stenting were significantly associated with formation of TEF. Mid EC [adjusted hazard ratio (HR) 1.9; 95% confidence interval (CI): 1.1-3.2] or presence of TEF (adjusted HR 1.8; 95% CI: 1.0-3.2) were associated with lower survival. Patients receiving chemotherapy (adjusted HR 0.46; 95% CI: 0.25-0.84), or esophageal stenting whether before or after airway intervention (adjusted HR 0.32; 95% CI: 0.15-0.68 and adjusted HR 0.51; 95% CI: 0.29-0.90) were associated with increased survival. Conclusions: Factors associated with TEF formation include airway location, radiotherapy and prior esophageal stenting, and the development of TEF was associated with poorer survival. An algorithmic approach towards tracheobronchial involvement in EC is proposed based on these findings and a review of the literature.

Mortality Trends of Oncology and Hematopoietic Stem Cell Transplant Patients Supported on Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

BACKGROUND: There is an increasing frequency of oncology and hematopoietic stem cell transplant (HSCT) patients seen in the intensive care unit and requiring extracorporeal membrane oxygenation (ECMO), however, prognosis of this population over time is unclear. METHODS: MEDLINE, EMBASE, Cochrane and Web of Science were searched from earliest publication until April 10, 2020 for studies to determine the mortality trend over time in oncology and HSCT patients requiring ECMO. Primary outcome was hospital mortality. Random-effects meta-analysis model was used to obtain pooled estimates of mortality and 95% confidence intervals. A priori subgroup metanalysis compared adult versus pediatric, oncology versus HSCT, hematological malignancy versus solid tumor, allogeneic versus autologous HSCT, and veno-arterial versus veno-venous ECMO populations. Multivariable meta-regression was also performed for hospital mortality to account for year of study and HSCT population. RESULTS: 17 eligible observational studies (n = 1109 patients) were included. Overall pooled hospital mortality was 72% (95% CI: 65, 78). In the subgroup analysis, only HSCT was associated with a higher hospital mortality compared to oncology subgroup [84% (95% CI: 70, 93) vs. 66% (95% CI: 56, 74); P = 0.021]. Meta-regression showed that HSCT was associated with increased mortality [adjusted odds ratio (aOR) 3.84 (95% CI 1.77, 8.31)], however, mortality improved with time [aOR 0.92 (95% CI: 0.85, 0.99) with each advancing year]. CONCLUSION: This study reports a high overall hospital mortality in oncology and HSCT patients on ECMO which improved over time. The presence of HSCT portends almost a 4-fold increased risk of mortality and this finding may need to be taken into consideration during patient selection for ECMO.

Outcomes of second-tier rapid response activations in a tertiary referral hospital: A prospective observational study.

INTRODUCTION: A second-tier rapid response team (RRT) is activated for patients who do not respond to first-tier measures. The premise of a tiered response is that first-tier responses by a ward team may identify and correct early states of deterioration or establish goals of care, thereby reducing unnecessary escalation of care to the RRT. Currently, utilisation and outcomes of tiered RRTs remain poorly described. METHODS: A prospective observational study of adult patients (age ≥18 years) who required RRT activations was conducted from February 2018 to December 2019. RESULTS: There were 951 consecutive RRT activations from 869 patients and 76.0% patients had a National Early Warning Score (NEWS) ≥5 at the time of RRT activation. The majority (79.8%) of patients required RRT interventions that included endotracheal intubation (12.7%), point-of-care ultrasound (17.0%), discussing goals of care (14.7%) and intensive care unit (ICU) admission (24.2%). Approximately 1 in 3 (36.6%) patients died during hospitalisation or within 30 days of RRT activation. In multivariate analysis, age ≥65 years, NEWS ≥7, ICU admission, longer hospitalisation days at RRT activation, Eastern Cooperative Oncology Group performance scores ≥3 (OR [odds ratio] 2.24, 95% CI [confidence interval] 1.45-3.46), metastatic cancer (OR 2.64, 95% CI 1.71-4.08) and haematological cancer (OR 2.78, 95% CI 1.84-4.19) were independently associated with mortality. CONCLUSION: Critical care interventions and escalation of care are common with second-tier RRTs. This supports the need for dedicated teams with specialised critical care services. Poor functional status, metastatic and haematological cancer are significantly associated with mortality, independent of age, NEWS and ICU admission. These factors should be considered during triage and goals of care discussion.

Characteristics and Outcomes of Airway Involvement in Esophageal Cancer.

BACKGROUND: Airway involvement, such as airway invasion, compression, and tracheobronchoesophageal fistula (TEF), in esophageal cancer is associated with significant morbidity. However, the risk factors and outcomes of airway complications remain unclear, with limited evidence to guide management. METHODS: This retrospective analysis included 804 patients with a diagnosis of esophageal cancer from 1998 to 2018 at a tertiary care medical center (Singapore General Hospital, Singapore). Patients' demographics, treatment details, and airway involvement, as determined by bronchoscopic evaluation or computed tomographic imaging, were recorded and analyzed to determine risk factors and outcomes of airway involvement. RESULTS: The incidence of airway involvement and TEF was 36.6% and 13.1%, respectively. Airway involvement was associated with reduced survival from the time of diagnosis (hazard ratio, 1.52; 95% confidence interval [CI], 1.30 to 1.79) and increased hospitalizations per year (4.53 ± 4.80 vs 2.75 ± 3.68; P < .001). On multivariate analysis, midesophageal tumors (odds ratio [OR], 11.0; 95% CI, 6.3 to 19.0) and upper esophageal tumors (OR, 8.5; 95% CI, 4.7 to 15.6), previous treatment with esophageal stenting (OR, 17.8; 95% CI, 4.1 to 77.6), and chemotherapy or radiotherapy were associated with development of airway involvement. In patients with TEF, treatment with chemotherapy (OR, 0.34; 95% CI, 0.20 to 0.60) and combined airway and esophageal stenting (OR, 0.48; 95% CI, 0.25 to 0.91) were independently associated with improved survival. CONCLUSIONS: Airway involvement and TEF are common and are associated with increased morbidity and poorer survival. Clinicians should remain vigilant for airway complications after treatment with esophageal stenting, chemotherapy, or radiotherapy, especially in patients with midesophageal and upper esophageal cancers. In patients with TEFs, survival is improved when they are treated with airway stenting, esophageal stenting, or chemotherapy.

Impact of an Extracorporeal Membrane Oxygenation Intensivist-Led Multidisciplinary Team on Venovenous Extracorporeal Membrane Oxygenation Outcomes.

OBJECTIVES: Venovenous extracorporeal membrane oxygenation is increasingly being established as a treatment option for severe acute respiratory failure. We sought to evaluate the impact of a dedicated specialist team-based approach on patient outcomes. DESIGN: Retrospective cohort study. SETTING: Single-center medical ICU in an academic tertiary hospital. PATIENTS: Adult patients initiated on venovenous extracorporeal membrane oxygenation for severe acute respiratory failure. INTERVENTIONS: Initiation of an extracorporeal membrane oxygenation intensivist-led multidisciplinary team; critical decisions on extracorporeal membrane oxygenation management were jointly made by a dedicated team of extracorporeal membrane oxygenation intensivists, together with the multidisciplinary team. MEASUREMENTS AND MAIN RESULTS: Eighty-one patients (75%) and 27 patients (35%) were initiated on venovenous extracorporeal membrane oxygenation in the preextracorporeal membrane oxygenation intensivist-led multidisciplinary team (before January 2018) and postextracorporeal membrane oxygenation intensivist-led multidisciplinary team period (after January 2018), respectively. Inhospital (14.8% vs 44.4%, p = 0.006) and ICU mortality (11.1% vs 40.7%, p = 0.005) were significantly lower in the postextracorporeal membrane oxygenation intensivist-led multidisciplinary team period. On multivariate analysis correcting for possible confounding factors (ICU severity and extracorporeal membrane oxygenation-specific mortality prediction scores, body mass index, preextracorporeal membrane oxygenation vasopressor support, preextracorporeal membrane oxygenation cardiac arrest, and days on mechanical ventilation before extracorporeal membrane oxygenation initiation), management by an extracorporeal membrane oxygenation intensivist-led multidisciplinary team remained associated with improved hospital survival (odds ratio, 5.06; 95% CI, 1.20-21.28). Patients in the postextracorporeal membrane oxygenation intensivist-led multidisciplinary team period had less nosocomial infections (18.5% vs 46.9%, p = 0.009), a shorter ICU stay (12 days [interquartile range, 6-16 d] vs 15 days [interquartile range, 10-24 d]; p = 0.049), and none suffered an intracranial hemorrhage or nonhemorrhagic stroke. CONCLUSIONS: An extracorporeal membrane oxygenation intensivist-led multidisciplinary team approach is associated with improved outcomes in patients initiated on venovenous extracorporeal membrane oxygenation for severe acute respiratory failure.

Early prediction of high flow nasal cannula therapy outcomes using a modified ROX index incorporating heart rate.

BACKGROUND: The ROX index (ratio of pulse oximetry/FIO2 to respiratory rate) has been validated to predict high flow nasal cannula therapy (HFNC) outcomes in patients with pneumonia. We evaluated a modified ROX index incorporating heart rate (HR) in patients initiated on HFNC for acute hypoxemic respiratory failure and as a preventative treatment following planned extubation. METHODS: We performed a prospective observational cohort study of 145 patients treated with HFNC. ROX-HR index was defined as the ratio of ROX index over HR (beats/min), multiplied by a factor of 100. Evaluation was performed using area under the receiving operating characteristic curve (AUROC) and cutoffs assessed for prediction of HFNC failure: defined as the need for mechanical ventilation. RESULTS: Ninety-nine (68.3%) and 46 (31.7%) patients were initiated on HFNC for acute hypoxemic respiratory failure and following a planned extubation, respectively. The majority (86.9%) of patients had pneumonia as a primary diagnosis, and 85 (56.6%) patients were immunocompromised. Sixty-one (42.1%) patients required intubation (HFNC failure). Amongst patients on HFNC for acute respiratory failure, HFNC failure was associated with a lower ROX and ROX-HR index recorded at time points between 1 and 48 h. Within the first 12 h, both indices performed with the highest AUROC at 10 h as follows: 0.723 (95% CI 0.605-0.840) and 0.739 (95% CI 0.626-0.853) for the ROX and ROX-HR index respectively. A ROX-HR index of > 6.80 was significantly associated with a lower risk of HFNC failure (hazard ratio 0.301 (95% CI 0.143-0.663)) at 10 h. This association was also observed at 2, 6, 18, and 24h, even with correction for potential confounding factors. For HFNC initiated post-extubation, only the ROX-HR index remained significantly associated with HFNC failure at all recorded time points between 1 and 24 h. A ROX-HR > 8.00 at 10 h was significantly associated with a lower risk of HFNC failure (hazard ratio 0.176 (95% CI 0.051-0.604)). CONCLUSION: While validation studies are required, the ROX-HR index appears to be a promising tool for early identification of treatment failure in patients initiated on HFNC for acute hypoxemic respiratory failure or as a preventative treatment after a planned extubation.

Preparing your intensive care unit for the COVID-19 pandemic: practical considerations and strategies.

The coronavirus disease 2019 (COVID-19) has rapidly evolved into a worldwide pandemic. Preparing intensive care units (ICU) is an integral part of any pandemic response. In this review, we discuss the key principles and strategies for ICU preparedness. We also describe our initial outbreak measures and share some of the challenges faced. To achieve sustainable ICU services, we propose the need to 1) prepare and implement rapid identification and isolation protocols, and a surge in ICU bed capacity; (2) provide a sustainable workforce with a focus on infection control; (3) ensure adequate supplies to equip ICUs and protect healthcare workers; and (4) maintain quality clinical management, as well as effective communication.

A 53-Year-Old Man Presenting With Diplopia and Cavitary Lung Nodules.

CASE PRESENTATION: A 53-year-old Chinese man presented with 1 week of worsening diplopia and left-sided facial droop. His symptoms developed during a readmission for elective drainage and curettage of a perianal abscess that recurred despite drainage 2 weeks before. He denied having other neurologic symptoms, and did not report any cough, sputum production, night sweats, or fever. He was a lifelong nonsmoker with a history of polymyositis treated with mycophenolate mofetil for the last 4 years. He had undergone surgical resection for jejunal adenocarcinoma 12 years prior to this presentation. No evidence of recurrence was detected on surveillance gastrointestinal endoscopies and CT scans.

Choosing the right mask for your Asian patient with sleep apnoea: A randomized, crossover trial of CPAP interfaces.

BACKGROUND AND OBJECTIVE: A major challenge with the treatment of obstructive sleep apnoea (OSA) is adherence to continuous positive airway pressure (CPAP) therapy. Mask tolerability is an important determinant of adherence, however evidence to guide selection of mask interfaces is lacking. METHODS: We conducted a randomized crossover trial of mask interfaces in CPAP therapy for moderate-to-severe OSA to assess adherence and efficacy of CPAP therapy with nasal mask, nasal pillow and oronasal masks. Demographic data, Nasal Obstruction Symptom Evaluation (NOSE) scores and craniofacial measurements were also analysed for associations with adherence with oronasal masks. RESULTS: Eighty-five patients were included in the study (mean ± SD age: 46 ± 12 years; body mass index: 29.9 ± 5.6 kg/m2 ; apnoea-hypopnoea index (AHI): 53.6 ± 24.0 events/h). Patients had better adherence with nasal masks (average night use: 3.96 ± 2.26 h/night) compared to oronasal masks (3.26 ± 2.18 h/night, P < 0.001) and nasal pillows (3.48 ± 2.20 h/night, P = 0.007). Residual AHI was higher with oronasal masks (7.2 ± 5.2) compared to nasal masks (4.0 ± 4.2, P < 0.001) and nasal pillows (4.1 ± 3.3, P < 0.001). Twenty-two (25.9%) patients had the best adherence with oronasal masks (4.22 ± 2.14 vs 2.93 ± 2.12 h/night, P = 0.016). These patients had lower NOSE scores (15 (0-35) vs 40 (10-55), P = 0.024) and larger menton-labrale inferioris/biocular width ratios (31 ± 3% vs 28 ± 4%, P = 0.019). CONCLUSION: Nasal masks are the preferred interface during CPAP initiation. Patients with less nasal obstruction and a proportionally increased chin-lower lip distance to mid-face width may have better CPAP adherence with an oronasal mask interface.

Sensitization to Aspergillus species is associated with frequent exacerbations in severe asthma.

BACKGROUND: Severe asthma is a largely heterogeneous disease with varying phenotypic profiles. The relationship between specific allergen sensitization and asthma severity, particularly in Asia, remains unclear. We aim to study the prevalence of specific allergen sensitization patterns and investigate their association with outcomes in a severe asthma cohort in an Asian setting. METHODS: We conducted a cross-sectional study of patients receiving step 4 or 5 Global Initiative for Asthma treatment. Univariate and multivariate analyses were performed to assess the association between sensitization to a specific identifiable allergen by skin prick test (SPT) and uncontrolled asthma (defined in our study as the use of ≥2 steroid bursts or hospitalization in the past year, a history of near-fatal asthma or evidence of airflow obstruction on spirometry). RESULTS: Two hundred and six severe asthma patients (mean age 45±17 years, 99 [48.1%] male) were evaluated. Of them, 78.2% had a positive SPT to one or more allergens. The most common allergen to which patients were sensitized was house dust mites (Blomia tropicalis, Dermatophagoides pteronyssinus and Dermatophagoides farinae). Also, 11.7% were sensitized to Aspergillus species. On multivariate analysis, Aspergillus sensitization was associated with uncontrolled asthma (odds ratio 6.07, 95% confidence interval 1.80-20.51). In particular, Aspergillus sensitization was independently associated with the use of ≥2 steroid bursts in the past year (odds ratio 3.05, 95% confidence interval 1.04-8.95). No similar associations of uncontrolled asthma with sensitization to any other allergens were found. CONCLUSION: High allergen, specifically Aspergillus sensitization was observed in the Asian population with severe asthma by SPT. Aspergillus sensitization was specifically associated with frequent exacerbations and a greater corticosteroid requirement. An improved understanding of the severe asthma with Aspergillus sensitization phenotype is warranted, which is likely a subgroup of severe asthma with fungal sensitization.

Functional reconstruction of corneal endothelium using nanotopography for tissue-engineering applications.

Dysfunction in the corneal endothelium, which controls the hydration and transparency of the cornea, is one of the common reasons for transplantation. A tissue-engineered corneal endothelium is of interest for corneal regeneration and for in vitro testing of ocular drugs. In the native environment, corneal endothelial cells interact with the nanotopography of the underlying Descemet's membrane. This study showed that nanotopography enhanced bovine corneal endothelial cell (BCEC) responses, creating a monolayer which resembled the healthy corneal endothelium. Topographies of different geometries were first tested to identify those that would elicit the most significant responses. A BCEC monolayer was then generated on both micro- and nanoscale pillars and wells. The BCEC monolayer cultured on topographies exhibited polygonal geometries with well-developed tight junction proteins. Scanning electron microscopy revealed that cells on pillars showed a higher density of microvilli, which was similar to native corneal endothelium. BCECs on nanopillars displayed a lower coefficient of variation of area (0.31) that was within the range of healthy corneal endothelium. More importantly, a BCEC monolayer cultured on nanopillars also had an enhanced Na(+)/K(+)-ATPase immunofluorescence expression, mRNA upregulation and a higher Na(+)/K(+)-ATPase activity. These results suggest that nanopillar substrate topography may provide relevant topographical cues, which could significantly enhance the formation and function of corneal endothelium.