Objectives To assess the effect of rituximab (RTX) on the lung function parameters in SSc interstitial lung disease (SSc-ILD) patients. Methods PubMed and Embase were searched to identify studies on SSc-ILD treated with RTX, confined to a predefined inclusion and exclusion criteria. A systematic review and meta-analysis were performed on the included studies on changes in forced vital capacity (FVC) and diffusion capacity of carbon monoxide (DLCO) from baseline to 6 and 12 months of follow-up. Results A total of 20 studies (2 randomized controlled trials, 6 prospective studies, 5 retrospective studies and 7 conference abstracts) were included (n = 575). RTX improved FVC from baseline by 4.49% (95% CI 0.25, 8.73) at 6 months and by 7.03% (95% CI 4.37, 9.7) at 12 months. Similarly, RTX improved DLCO by 3.47% (95% CI 0.99, 5.96) at 6 months and 4.08% (95% CI 1.51, 6.65) at 12 months. In the two studies comparing RTX with other immunosuppressants, improvement of FVC by 6 months in the RTX group was 1.03% (95% CI 0.11, 1.94) greater than controls. At the 12 month follow-up, RTX treatment was similar to controls in terms of both FVC and DLCO. Patients treated with RTX had a lower chance of developing infections compared with controls [odds ratio 0.256 (95% CI 0.104, 0.626), I2 = 0%, P = 0.47). Conclusions Treatment with RTX in SSc-ILD was associated with a significant improvement of both FVC and DLCO during the first year of treatment. RTX use was associated with lower infectious adverse events.
Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COrona VIrus Disease 2019 (COVID-19). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-19 patients for other indications. IHC for CD61 and CD163 was performed for the assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. In a total of 55, 44 COVID-19 post-mortem lung samples were tested for ACE2, 36 for CD163, and 26 for CD61, compared to 15 non-covid 19 control lung sections. Quantification of immunostaining, random sampling, and correlation analysis were used to substantiate the morphologic findings. Our results show that ACE2 protein expression was significantly higher in COVID-19 post-mortem lung tissues than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels were positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.
Infrared thermal screening, via the use of handheld non-contact infrared thermometers (NCITs) and thermal scanners, has been widely implemented all over the world. We performed a systematic review and meta-analysis to investigate its diagnostic accuracy for the detection of fever. We searched PubMed, Embase, the Cochrane Library, medRxiv, bioRxiv, ClinicalTrials.gov, COVID-19 Open Research Dataset, COVID-19 research database, Epistemonikos, EPPI-Centre, World Health Organization International Clinical Trials Registry Platform, Scopus and Web of Science databases for studies where a non-contact infrared device was used to detect fever against a reference standard of conventional thermometers. Forest plots and Hierarchical Summary Receiver Operating Characteristics curves were used to describe the pooled summary estimates of sensitivity, specificity and diagnostic odds ratio. From a total of 1063 results, 30 studies were included in the qualitative synthesis, of which 19 were included in the meta-analysis. The pooled sensitivity and specificity were 0.808 (95%CI 0.656-0.903) and 0.920 (95%CI 0.769-0.975), respectively, for the NCITs (using forehead as the site of measurement), and 0.818 (95%CI 0.758-0.866) and 0.923 (95%CI 0.823-0.969), respectively, for thermal scanners. The sensitivity of NCITs increased on use of rectal temperature as the reference. The sensitivity of thermal scanners decreased in a disease outbreak/pandemic setting. Changes approaching statistical significance were also observed on the exclusion of neonates from the analysis. Thermal screening had a low positive predictive value, especially at the initial stage of an outbreak, while the negative predictive value (NPV) continued to be high even at later stages. Thermal screening has reasonable diagnostic accuracy in the detection of fever, although it may vary with changes in subject characteristics, setting, index test, and the reference standard used. Thermal screening has a good NPV even during a pandemic. The policymakers must take into consideration the factors surrounding the screening strategy while forming ad-hoc guidelines.
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