Variation in outcome of invasive mechanical ventilation between different countries for patients with severe COVID-19: A systematic review and meta-analysis.

BACKGROUND: COVID 19 is the most recent cause of Adult respiratory distress syndrome ARDS. Invasive mechanical ventilation IMV can support gas exchange in patients failing non-invasive ventilation, but its reported outcome is highly variable between countries. We conducted a systematic review and meta-analysis on IMV for COVID-associated ARDS to study its outcome among different countries. METHODS: CENTRAL, MEDLINE/PubMed, Cochrane Library, and Scopus were systematically searched up to August 8, 2020. Studies reporting five or more patients with end point outcome for severe COVID 19 infection treated with IMV were included. The main outcome assessed was mortality. Baseline, procedural, outcome, and validity data were systematically appraised and pooled with random-effect methods. Subgroup analysis for different countries was performed. Meta-regression for the effect of study timing and patient age and were tested. Publication bias was examined. This trial was registered with PROSPERO under registration number CRD42020190365. FINDINGS: Our electronic search retrieved 4770 citations, 103 of which were selected for full-text review. Twenty-one studies with a combined population of 37359 patients with COVID-19 fulfilled the inclusion criteria. From this population, 5800 patients were treated by invasive mechanical ventilation. Out of those, 3301 patients reached an endpoint of ICU discharge or death after invasive mechanical ventilation while the rest were still in the ICU. Mortality from IMV was highly variable among the included studies ranging between 21% and 100%. Random-effect pooled estimates suggested an overall in-hospital mortality risk ratio of 0.70 (95% confidence interval 0.608 to 0.797; I2 = 98%). Subgroup analysis according to country of origin showed homogeneity in the 8 Chinese studies with high pooled mortality risk ratio of 0.97 (I2 = 24%, p = 0.23) (95% CI = 0.94-1.00), similar to Italy with a low pooled mortality risk ratio of 0.26 (95% CI 0.08-0.43) with homogeneity (p = 0.86) while the later larger studies coming from the USA showed pooled estimate mortality risk ratio of 0.60 (95% CI 0.43-0.76) with persistent heterogeneity (I2 = 98%, p<0.001). Meta-regression showed that outcome from IMV improved with time (p<0.001). Age had no statistically significant effect on mortality (p = 0.102). Publication bias was excluded by visualizing the funnel plot of standard error, Egger's test with p = 0.714 and Begg&Mazumdar test with p = 0.334. INTERPRETATION: The study included the largest number of patients with outcome findings of IMV in this current pandemic. Our findings showed that the use of IMV for selected COVID 19 patients with severe ARDS carries a high mortality, but outcome has improved over the last few months and in more recent studies. The results should encourage physicians to use this facility when indicated for severely ill COVID-19 patients.

Recurrence of mesothelioma after a macroscopic complete resection procedure: is a second radical surgery justified?

A best evidence topic was written according to a structured protocol. The question addressed was: In patients with mesothelioma who develop a local recurrence after macroscopic complete resection (MCR) surgery, does performing a second radical surgery lead to improvement in survival? A total of 2076 papers were identified using the reported search, of which 3 represented the best evidence to answer the clinical question. The authors, date, journal, country, study type, population, outcomes and key results are tabulated. The 2 largest studies included 16 patients each who underwent a second surgery for radical resection of recurrence after MCR for mesothelioma. One study (with 16 chest wall resections) had no in-hospital mortality, whereas the other study showed 2/16 (12.5%) patients dying in the hospital, both of whom had a contralateral pleurectomy. One study correlated the median survival after the second surgery with the time to recurrence and epithelioid pathology. The other study showed better post-recurrence survival after a second surgery, with patients having a significantly longer median post-recurrence survival (16 months) compared with those who received other types of second-line therapy (9 months) and those who received no therapy at all (2 months) (P < 0.0005), although selection bias is a possibility. The last study included 8 patients who underwent a second surgery for radical intent after MCR for mesothelioma. The median time to recurrence was 29 months and the survival after second surgery was 14.5 months with no correlation to disease-free interval (expected due to the small number of patients). In patients presenting with recurrence of mesothelioma after an MCR procedure, radical surgery to resect the recurrent tumour could have a role in improvement of survival in selected patients. Positive prognostic factors include epithelioid pathology and a longer disease-free interval after the first procedure.

Extracorporeal membrane oxygenation (ECMO) in patients with severe COVID-19 adult respiratory distress syndrome: a systematic review and meta-analysis.

Background: COVID 19 is the most recent cause of adult respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients failing conventional mechanical ventilation, but its role is still controversial. We conducted a systematic review and meta-analysis on ECMO for COVID-associated ARDS to study its outcome. Main body: CENTRAL, MEDLINE/PubMed, Cochrane Library, and Scopus were systematically searched from inception to May 28, 2020. Studies reporting five or more patients with COVID-19 infection treated venovenous with ECMO were included. The main outcome assessed was mortality and ICU/hospital discharge. Baseline, procedural, outcome, and validity data were systematically appraised and pooled with random-effect methods. The validity of all the included observational studies was appraised with the Newcastle Ottawa scale. Meta-regression and publication bias were tested. This trial was registered with PROSPERO under registration number CRD42020183861.From 1647 initial citations, 34 full-text articles were analyzed and 12 studies were selected, including 194 patients with confirmed COVID-19 infection requiring ICU admission and venovenous ECMO treatment. Median Newcastle-Ottawa scale was 6 indicating acceptable study validity. One hundred thirty-six patients reached an endpoint of weaning from ECMO with ICU/hospital discharge or death while the rest were still on ECMO or in the ICU. The median Berlin score for ARDS prior to starting ECMO was III. Patients received mechanical ventilation before ECMO implementation for a median of 4 days and ECMO was maintained for a median of 13 days. In hospital and short-term mortality were highly variable among the included studies ranging between 0 and 100%. Random-effect pooled estimates suggested an overall in-hospital mortality risk ratio of 0.49 (95% confidence interval 0.259 to 0.721; I2 = 94%). Subgroup analysis according to country of origin showed persistent heterogeneity only in the 7 Chinese studies with pooled estimate mortality risk ratio of 0.66 (I2 = 87%) (95% CI = 0.39-0.93), while the later larger studies coming from the USA showed pooled estimate mortality risk ratio of 0.41 (95% CI 0.28-0.53) with homogeneity (p=0.67) similar to France with a pooled mortality risk ratio of 0.26 (95% CI 0.08-0.43) with homogeneity (p=0.86). Meta-regression showed only younger age as a predictor of mortality (p=0.02). Publication bias was excluded by visualizing the funnel plot of standard error, Egger's test with p=0.566, and Begg and Mazumdar test with p=0.373. Conclusion: The study included the largest number of patients with outcome findings of ECMO in this current pandemic. Our findings showed that the use of venovenous ECMO at high-volume ECMO centers may be beneficial for selected COVID 19 patients with severe ARDS. However, none of the included studies involve prospective randomized analyses; and therefore, all the included studies were of low or moderate quality according to the Newcastle-Ottawa scale. In the current era and environment of the pandemic, it will likely be very challenging to conduct a prospective randomized trial of ECMO versus no-ECMO for COVID-19. Therefore, the information contained in this systematic review of the literature is valuable and provides important guidance. Trial registration: The study protocol link is at www.crd.yorl.ac.uk/PROSPERO under registration number CRD42020183861.