ABSTRACT
Background: Despite patients with severe coronavirus disease (COVID-19) receiving standard triple therapy, including steroids, antiviral agents, and anticytokine therapy, health condition of certain patients continue to deteriorate. In Taiwan, the COVID-19 mortality has been high since the emergence of previous variants of this disease (such as alpha, beta, or delta). We aimed to evaluate whether adjunctive infusion of human umbilical cord mesenchymal stem cells (MSCs) (hUC-MSCs) on top of dexamethasone, remdesivir, and tocilizumab improves pulmonary oxygenation and suppresses inflammatory cytokines in patients with severe COVID-19. Methods: Hospitalized patients with severe or critical COVID-19 pneumonia under standard triple therapy were separated into adjuvant hUC-MSC and non-hUC-MSC groups to compare the changes in the arterial partial pressure of oxygen (PaO2)/fraction of inspired oxygen (FiO2) ratio and biological variables. Results: Four out of eight patients with severe or critical COVID-19 received either one (n = 2) or two (n = 2) doses of intravenous infusions of hUC-MSCs using a uniform cell dose of 1.0 × 108. Both high-sensitivity C-reactive protein (hs-CRP) level and monocyte distribution width (MDW) were significantly reduced, with a reduction in the levels of interleukin (IL)-6, IL-13, IL-12p70 and vascular endothelial growth factor following hUC-MSC transplantation. The PaO2/FiO2 ratio increased from 83.68 (64.34-126.75) to 227.50 (185.25-237.50) and then 349.56 (293.03-367.92) within 7 days after hUC-MSC infusion (P < 0.001), while the change of PaO2/FiO2 ratio was insignificant in non-hUC-MSC patients (admission day: 165.00 [102.50-237.61]; day 3: 100.00 [72.00-232.68]; day 7: 250.00 [71.00-251.43], P = 0.923). Conclusion: Transplantation of hUC-MSCs as adjunctive therapy improves pulmonary oxygenation in patients with severe or critical COVID-19. The beneficial effects of hUC-MSCs were presumably mediated by the mitigation of inflammatory cytokines, characterized by the reduction in both hs-CRP and MDW.
ABSTRACT
BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). It has brought tremendous challenges to public health and medical systems around the world. The current strategy for drug repurposing has accumulated some evidence on the use of N -acetylcysteine (NAC) in treating patients with COVID-19. However, the evidence remains debated. METHODS: We performed the systematic review and meta-analysis that complies with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five databases and reference lists were searched from inception to May 14, 2022. Studies evaluating the efficacy of NAC in treating patients with COVID-19 were regarded as eligible. The review was registered prospectively on PROSPERO (CRD42022332791). RESULTS: Of 778 records identified from the preliminary search, four studies were enrolled in the final qualitative review and quantitative meta-analysis. A total of 355 patients were allocated into the NAC group and the control group. The evaluated outcomes included intubation rate, improvement, duration of intensive unit stay and hospital stay and mortality. The pooled results showed nonsignificant differences in intubation rate (OR, 0.55; 95% CI, 0.16-1.89; p = 0.34; I2 = 75%), improvement of oxygenation ([MD], 80.84; 95% CI, -38.16 to 199.84; p = 0.18; I2 = 98%), ICU stay (MD, -0.74; 95% CI, -3.19 to 1.71; p = 0.55; I2 = 95%), hospital stay (MD, -1.05; 95% CI, -3.02 to 0.92; p = 0.30; I2 = 90%), and mortality (OR, 0.58; 95% CI, 0.23-1.45; p = 0.24; I2 = 54%). Subsequent trial sequential analysis (TSA) showed conclusive nonsignificant results for mortality, while the TSA for the other outcomes suggested that a larger sample size is essential. CONCLUSIONS: The current evidence reveals NAC is not beneficial for treating patients with COVID- 19 with regard to respiratory outcome, mortality, duration of ICU stay and hospital stay.
Subject(s)
COVID-19 , Humans , Acetylcysteine/therapeutic use , SARS-CoV-2 , Length of StayABSTRACT
Traditional otoscopy has some limitations, including poor visualization and inadequate time for evaluation in suboptimal environments. Smartphone-enabled otoscopy may improve examination quality and serve as a potential diagnostic tool for middle ear diseases using a telemedicine approach. The main objectives are to compare the correctness of smartphone-enabled otoscopy and traditional otoscopy and to evaluate the diagnostic confidence of the examiner via meta-analysis. From inception through 20 January 2022, the Cochrane Library, PubMed, EMBASE, Web of Science, and Scopus databases were searched. Studies comparing smartphone-enabled otoscopy with traditional otoscopy regarding the outcome of interest were eligible. The relative risk (RR) for the rate of correctness in diagnosing ear conditions and the standardized mean difference (SMD) in diagnostic confidence were extracted. Sensitivity analysis and trial sequential analyses (TSAs) were conducted to further examine the pooled results. Study quality was evaluated by using the revised Cochrane risk of bias tool 2. Consequently, a total of 1840 examinees were divided into the smartphone-enabled otoscopy group and the traditional otoscopy group. Overall, the pooled result showed that smartphone-enabled otoscopy was associated with higher correctness than traditional otoscopy (RR, 1.26; 95% CI, 1.06 to 1.51; p = 0.01; I2 = 70.0%). Consistently significant associations were also observed in the analysis after excluding the simulation study (RR, 1.10; 95% CI, 1.00 to 1.21; p = 0.04; I2 = 0%) and normal ear conditions (RR, 1.18; 95% CI, 1.01 to 1.40; p = 0.04; I2 = 65.0%). For the confidence of examiners using both otoscopy methods, the pooled result was nonsignificant between the smartphone-enabled otoscopy and traditional otoscopy groups (SMD, 0.08; 95% CI, -0.24 to 0.40; p = 0.61; I2 = 16.3%). In conclusion, smartphone-enabled otoscopy was associated with a higher rate of correctness in the detection of middle ear diseases, and in patients with otologic complaints, the use of smartphone-enabled otoscopy may be considered. More large-scale studies should be performed to consolidate the results.