Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report

BackgroundCoronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death. MethodsThe Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality. Results2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 454 (21.6%) patients allocated dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P<0.001). The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p<0.001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65 [95% CI 0.51 to 0.82]; p<0.001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002), but did not reduce mortality in patients not receiving respiratory support at randomization (17.0% vs. 13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14). ConclusionsIn patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support. Trial registrationsThe RECOVERY trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936). FundingMedical Research Council and National Institute for Health Research (Grant ref: MC_PC_19056).

Lung herniation after supraclavicular thoracic outlet decompression.

Lung herniation after first rib resection for thoracic outlet syndrome (TOS) has not been reported to our knowledge. We present a unique case of cervical lung herniation causing displacement of the brachial plexus and chronic pain in a patient who had previously undergone supraclavicular thoracic outlet decompression with first rib resection. This was successfully treated with thoracoscopic reduction and resection of the herniated lung and pleural flap closure of the defect.

Impact of video-assisted thoracoscopic surgery on benign resections for solitary pulmonary nodules.

BACKGROUND: Differentiating benign from malignant pulmonary lesions is an important part of surgical decision making. We reviewed our experience of resecting suspicious pulmonary nodules to test the hypothesis that the increased use of video-assisted thoracic surgery (VATS) has increased the resection rate of benign lesions. METHODS: A retrospective analysis was carried out on 3,217 patients who underwent resection for focal pulmonary lesions between 1995 and 2009. Resection method, computed tomography (CT) results, positron emission tomography (PET) results, and operative and pathology reports were reviewed. RESULTS: Pulmonary resection was by thoracotomy/median sternotomy in 2,632 of 3,217 (82%) patients and by VATS in 585 of 3,217 (18%). Resections performed by VATS increased from 129 of 2,150 (6%) between 1995 and 2005 to 453 of 1,067 (42.4%) between 2006 and 2009. From 2006 to 2009, 31.4% of lobectomies and 63.9% of wedge resections were performed by VATS. Benign lesions were found in 350 of 3,217 (10.8%) patients. Between 1995 and 2005 our resection rate of benign lesions was 192 of 2,150 (8.9%). From 2006 to 2009, it increased to 158 of 1,067 (14.8%), of which 85 of 456 (20.8%) were VATS and 63 of 611(10.3%) were open procedures. The benign lesion resection rate was 91 of 237 (38.3%) for VATS wedges, 49 of 134 (36.6%) for open wedges, 4 of 219 (1.8%) for VATS lobectomies, and 14 of 477 (2.9%) for open lobectomies. 257 of 456 (52.0%) of the VATS resections were wedges compared with 134 of 611 (21.9%) of the open procedures. CONCLUSIONS: There has been an increase in pulmonary resections performed by VATS. This is associated with an increase in benign lesion resections. The benign lesion resection rate for VATS was twice that of the open procedure rate. However the benign lesion resection rates for wedge resections and lobectomies were not significantly different in regard to approach. VATS has led to an increase in our overall benign lesion resection rate, which can be explained by the increased number of VATS wedge resections that are being performed.

Endoscopic ultrasound for early stage esophageal adenocarcinoma: implications for staging and survival.

BACKGROUND: Patients often receive induction therapy based on endoscopic ultrasound (EUS)-identified nodal spread (N1) or deep tumor invasion (T3), although controversy exists regarding the role of induction therapy for early stage disease. We aim to evaluate the reliability of EUS in identifying early stage disease and the subsequent impact on treatment and outcomes. METHODS: We retrospectively studied 149 patients who underwent EUS and esophagectomy for adenocarcinoma between January 2000 and December 2008. Computed tomography (CT) was performed in all patients, whereas positron emission tomography (PET) was performed in 91%. Clinical stage (c), pathologic stage (p), operative mortality, and survival were recorded. RESULTS: Unanticipated pathologic nodal disease was similar in patients with cT1N0 and cT2N0 tumors (6/25 [24%] versus 7/18 [38.8%]; p=0.6). Among the 18 cases of cT2N0 disease, 9 (50%) were pathologically staged as T1N0, 8 (44%) were upstaged to pT3N0-1, and 1 (6%) was pT2N0. One case of cT1N0 tumor (4%) was upstaged to pT3N0. Among patients with cT1-2N0 tumors, 5-year disease-free survival for the group that was appropriately staged was 89.8% versus 39.9% for the group that had a higher pathologic stage than their clinical stage (ie, >T2N0) (p<0.001). Operative mortality for patients with cT1-2N0 tumors was 0/43 (0%), which was no different from that in the higher clinical stage groups with (1/37, 2.7%) or without (2/68, 2.9%) induction therapy (p=0.5). Multivariate analysis identified marked/intense uptake on staging PET (odds ratio, 5.76, 95%; confidence interval, 1.25 to 26.52; p=0.021) to be a factor predictive of upstaging of cT1-2N0 tumors. CONCLUSIONS: Current staging techniques are inadequate for predicting T1-2N0 disease in esophageal adenocarcinoma. Survival is excellent with operation alone in patients with tumors appropriately staged as T1-2N0, although patients with tumors upstaged to greater than T2N0 have significantly worse survival. Other preoperative factors such as PET uptake may help select patients with cT1-2N0 tumors that will be upstaged at resection.

Lymph node evaluation in video-assisted thoracoscopic lobectomy versus lobectomy by thoracotomy.

BACKGROUND: With the emergence of video-assisted thoracic surgery (VATS) lobectomy, concern remains regarding the adequacy of nodal assessment versus thoracotomy. METHODS: All clinical stage I non-small cell lung cancer patients treated with VATS or open lobectomy were retrospectively evaluated. Total nodes, N2 nodes, and nodes at each station were evaluated for associations with surgery type and location of involved lobe. RESULTS: There were 79 VATS and 464 open lobectomy or segmental resections for stage I tumors. Overall, fewer lymph nodes were sampled with VATS compared with thoracotomy (7.4 +/- 0.6 vs 8.9 +/- 0.2, respectively; p = 0.029), and fewer N2 nodes were sampled with VATS versus thoracotomy as well (2.5 +/- 3.0 vs 3.7 +/- 3.3, p = 0.004). There were no differences in N1 node sampling between the two groups (5.2 +/- 3.6 vs 4.9 +/- 4.2, p = 0.592). Furthermore, there were more station 7 nodes with thoracotomy versus VATS (1.2 +/- 0.1 vs 0.6 +/- 0.1, p = 0.002). Among right-sided lesions, there was no difference in 4R nodes between groups (1.4 +/- 0.4 vs 1.6 +/- 0.2, p = 0.7) although there was a trend toward more level 7 nodes with thoracotomy (1.0 +/- 0.2 vs 1.4 +/- 0.2, p < 0.08). Among left-sided resections there were more station 7 nodes with thoracotomy versus VATS (1.0 +/- 0.1 vs 0.4 +/- 0.1, p < 0.001) and more station 5/6 nodes (1.1 +/- 0.1 vs 0.5 +/- 0.1, p < 0.04). For upper lobe resections, the total nodes (8.9 +/- 0.3 vs 7.4 +/- 0.7, p = 0.05) and station 7 nodes (1.0 +/- 0.1 vs 0.6 +/- 0.1, p < 0.01) were higher with thoracotomy than VATS. There was no difference in 2-year survival between groups (81% vs 83%, p = 0.4). CONCLUSIONS: Our early experience with VATS has been associated with fewer lymph nodes sampled compared with open lobectomy although there was no survival difference. Analysis of these differences has directed us toward a more focused lymph node sampling with VATS lobectomy.

Recurrent subcutaneous air of the face and neck.

Subcutaneous air of the face and neck can be seen after trauma to the lungs, airway, and esophagus. We present a case of a 29-year-old with recurrent subcutaneous air of the face and neck with minimal pneumomediastinum. In this report, we discuss the workup of this patient and review the literature regarding self-inflicted causes.

Risk factors for occult nodal metastasis in clinical T1N0 lung cancer: a negative impact on survival.

BACKGROUND: The application of CT imaging has increased the identification of patients with clinical T1N0 (cT1N0) lung cancer. The optimal management strategy for these early stage lung cancers remains unclear. We analyzed the impact of occult nodal metastasis on cT1N0 lung cancer patients. METHODS: We studied patients with cT1N0 lung cancer enrolled in our database from January 1995 to December 2002. Preoperative staging was confirmed by review of CT and PET scan studies. Pathology specimens were reviewed. Multivariate analysis was performed to determine the risk of occult nodal involvement. Kaplan-Meier method was applied to analyze survival. RESULTS: Two hundred and ninety-seven patients with cT1N0 disease were identified. Fifty-eight percent of patients were pathological T1N0. Overall, 15% of patients had occult nodal metastasis. Logistic regression analysis demonstrated a three-fold increase in the risk of having pathologic stage II or stage III disease with every 1.0 cm increase in tumor size (odds ratio 3.2; 95% CI: 2.3-4.6). Multivariate analysis demonstrated tumor size to be a significant predictor of nodal metastasis (adjusted odds ratio 3.5; 95% CI: 2.4-5.1). Median survival was different between pathological stage I (96.3 months), stage II (41.4 months), and stage III (36.1 months) disease (p=0.002). CONCLUSION: Clinical T1N0 tumors are often understaged. The risk of occult nodal disease increases with tumor size, and this occult disease negatively impacts survival. Because of the limitations of clinical staging, we believe that lobectomy and lymph node analysis should be offered to cT1N0 lung cancer patients to provide accurate staging and to optimize multimodality adjuvant treatment of lung cancer.

Cost-effectiveness of routine mediastinoscopy in computed tomography- and positron emission tomography-screened patients with stage I lung cancer.

OBJECTIVE: Accurate preoperative staging is essential for the optimal management of patients with lung cancer. An important goal of preoperative staging is to identify mediastinal lymph node metastasis. Computed tomography and positron emission tomography may identify mediastinal lymph node metastasis with sufficient sensitivity to allow omission of mediastinoscopy. This study utilizes our experience with patients with clinical stage I lung cancer to perform a decision analysis addressing whether mediastinoscopy should be performed in clinical stage I lung cancer patients staged by computed tomography and positron emission tomography. METHODS: We retrospectively reviewed our thoracic surgery database for cases between May 1999 and May 2004. Patients deemed clinical stage I by computed tomography and positron emission tomography were chosen for further study. Individual computed tomography, positron emission tomography, and operative and pathology reports were reviewed. The postresection pathologic staging and long-term survival were recorded. A decision model was created using TreeAgePro software and our observed data for the prevalence of mediastinal lymph node metastases and for the rate of benign nodules. Data reported in the literature were also utilized to complete the decision analysis model. A sensitivity analysis of key variables was performed. RESULTS: A total of 248 patients with clinical stage I lung tumors were identified. One hundred seventy-eight patients (72%) underwent mediastinoscopy before resection, and 5/178 (3%) showed N2 disease. An additional 9 patients were found to have N2 metastasis in the final resected specimen, resulting in a total of 14/248 patients (5.6%) with occult mediastinal lymph node metastases. Benign nodules were found in 19/248 (8%) of patients. Decision analysis determined that mediastinoscopy added 0.008 years of life expectancy at a cost of 250,989 dollars per life-year gained. The outcome was sensitive to the prevalence of N2 disease in the population and the benefit of induction versus adjuvant therapy for N2 lung cancer. If the prevalence of N2 disease exceeds 10%, the sensitivity analysis predicts that mediastinoscopy would lengthen life at a cost of less than 100,000 dollars per life-year gained. CONCLUSION: Patients with clinical stage I lung cancer staged by computed tomography and positron emission tomography benefit little from mediastinoscopy. The survival advantage it confers is very small and is dependent on the prevalence of N2 metastasis and the unproven superiority of induction therapy over adjuvant therapy.

Prevalence of benign disease in patients undergoing resection for suspected lung cancer.

BACKGROUND: In this era of expanded lung cancer screening, accurate differentiation of benign from malignant lesions remains an important problem. We sought to characterize our experience with focal pulmonary lesions suggestive of lung cancer and subsequently proven benign on surgical resection. METHODS: A retrospective analysis was performed on 1,560 patients who underwent resection for focal pulmonary lesions at our institution from January 1995 to December 2002. Computed tomography and pathology reports were reviewed for all patients. Fluorine-18-fluorodeoxyglucose positron emission tomography studies were performed on 43 patients. RESULTS: Benign processes were found on pathologic examination in 140 patients (9%). Resection was accomplished by thoracotomy in 103 patients (74%), video-assisted thoracoscopy in 36 patients (26%), and sternotomy in 1 patient (0.7%). Seventy patients (50%) underwent mediastinoscopy before resection. There was 1 (0.7%) perioperative death. Pathologic diagnoses from the pulmonary resections revealed granulomatous inflammation in 91 patients (65%), hamartoma in 17 patients (12%), pneumonia or pneumonitis in 14 patients (10%), fibrosis in 5 patients (4%), and other in 13 patients (9%). Fluorine-18-fluorodeoxyglucose positron emission tomography imaging suggested malignancy in 22 of 43 patients and benign lesion in 20 of 43 patients (1 study was not interpretable). Thirty-eight patients underwent needle biopsy before surgery. Of these, 29 samples were nondiagnostic, 5 samples were negative, and 4 samples were considered positive for malignancy. CONCLUSIONS: Despite thorough clinical assessment, advanced imaging technology, and needle biopsy, many patients continue to undergo surgery for benign disease. Aggressive attempts to diagnose and treat early stage lung cancer must be tempered with this understanding.

Bronchial airway anastomotic complications after pediatric lung transplantation: incidence, cause, management, and outcome.

OBJECTIVE: Airway complications are a recognized surgical complication and an important source of morbidity after adult lung transplantation. Little is known about these complications after pediatric lung transplantation. METHODS: Data of pediatric lung transplants performed between January 1990 and December 2002 in a single pediatric institution were reviewed retrospectively. RESULTS: A total of 214 patients, with a mean age of 9.8 +/- 6.1 years (range 0.01-19.7 years), underwent 239 lung transplants: 231 bilateral and 8 single. Mean follow-up was 3.4 years. Forty-two airway complications requiring interventions (stenosis = 36; dehiscence = 4; malacia = 2) developed in 30 recipients (complication rate: 9% of 470 bronchial anastomoses at risk). There were airway complications in 29 bilateral lung transplants (13%) and 1 single lung transplant (13%). Mean time to diagnosis was 51 +/- 27 days (median: 53, range 1-96 days), and diagnoses were made in 90% of patients within the first 3 months after transplantation. Preoperative Pseudomonas cepacia, postoperative fungal lung infection, and days on mechanical ventilator were found to be significant risk factors on multivariate analysis (P = .002, P = .013 and P = .003, respectively). Treatment included rigid bronchoscopic dilatation in 17 patients, balloon dilatation in 13 patients, and stent placement in 12 patients. Other treatments consisted of debridement, fibrin glue application, chest tube placement, and pneumonectomy followed by retransplantation. No patients died as a direct result of airway complications. There was no significant difference in the incidence of bronchiolitis obliterans or overall survival in comparison with patients who did not have airway complications. CONCLUSIONS: Airway complications are a significant cause of morbidity after pediatric lung transplantation. The majority are successfully treated, and patient outcomes are not adversely affected.