Adipose Mesenchymal Stem Cell Metabolites Oral Gel Enhance Pro-Angiogenic Factors Expression, Angiogenesis, and Clinical Outcome of Oral Ulcer Rat Model.

OBJECTIVE: Enhancing wound healing capacity is one of the main principles in oral ulcer management. Efficient oral ulcer management will accelerate clinical symptom amelioration and prevent complications. Adipose mesenchymal stem cell metabolites (AdMSCM), a novel biological product, contains a plethora of bioactive mediators that can induce a series of processes in wound healing. This study will analyze the clinical outcome, angiogenesis, and expression of FGF-2 and VEGFA in the oral ulcer rat model after AdMSCM oral gel application. MATERIALS AND METHODS: Twenty healthy male Wistar rats (Rattus novergicus) were used to create oral ulcer animal models. AdMSCM oral gel treatment was performed three times daily for 3 and 7 days. Clinical outcome was assessed by measuring the major diameter of the ulcer; the angiogenesis was evaluated through histological assessment; the expression of VEGFA and FGF-2 was assessed using the immunohistochemistry method. STATISTICAL ANALYSIS: This study uses parametric comparative analysis using one-way analysis of variance (ANOVA) and post-hoc Tukey's HSD test RESULTS: The application of AdMSCM oral gel in an oral ulcer rat model significantly enhanced the clinical outcome (p < 0.05). In addition, similar results were shown in the histologic assessment of angiogenesis and supported by the significant increase of VEGFA and FGF-2 expression. CONCLUSIONS: AdMSCM oral gel accelerates oral ulcer healing processes, proven by the enhancement of angiogenesis, pro-angiogenic factors expression, and clinical outcomes.

Comparison of the Administration Route of Stem Cell Therapy for Ischemic Stroke: A Systematic Review and Meta-Analysis of the Clinical Outcomes and Safety.

Stem cell treatment is emerging as an appealing alternative for stroke patients, but there still needs to be an agreement on the protocols in place, including the route of administration. This systematic review aimed to assess the efficacy and safety of the administration routes of stem cell treatment for ischemic stroke. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A comprehensive literature search was undertaken using the PubMed, Scopus, and Cochrane databases. A total of 21 publications on stem cell therapy for ischemic stroke were included. Efficacy outcomes were measured using the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel index (BI). Intracerebral administration showed a better outcome than other routes, but a greater number of adverse events followed due to its invasiveness. Adverse events were shown to be related to the natural history of stroke not to the treatment. However, further investigation is required, since studies have yet to compare the different administration methods directly.

Clinical outcome and safety of stem cell therapy for ischemic stroke: A systematic review and meta-analysis.

Background: Several reports on stem cell administration have emerged proving it to be an ideal therapeutic approach for improving neurological functions in ischemic stroke patients. However, some studies also show disappointing results, with some reporting no statistically significant improvements among several different parameters. Several challenges also arise relating to safety and nonscientific aspects, such as ethics. Methods: We performed a systematic review and meta-analysis to evaluate the effect of stem cell therapy on the clinical outcomes of ischemic stroke patients. A systematic review and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A thorough literature search was conducted on PubMed, Scopus, and Cochrane databases. Articles were selected systematically based on the PRISMA protocol and reviewed completely. A total of 19 publications pertaining to stem cell therapy on the ischemic route were included and reviewed. Efficacy outcomes were measured with the National Institutes of Health Stroke Scale, modified Rankin Scale, or Barthel Index. Results: The results of the meta-analysis indicate that the efficacy outcomes suggest favorable results after stem cell therapy, although not all study results are statistically significant. Stem cell therapy in stroke cases showed a better outcome than standard conservative therapy alone, although our analysis shows that many factors can influence this outcome, and significant effects can only be seen after several months. Conclusion: The results of this study show promising and satisfying efficacy and a relatively low rate of serious adverse events.

Antiviral Treatment in COVID-19 Outpatients: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Most COVID-19 patients have mild or moderate illnesses that can progress to severe illness, leading to hospitalization and/or mortality. The use of antivirals to prevent the progression of COVID-19 in non-hospitalized patients shows conflicting result and efficacy remain unclear. This study evaluates the efficacy and safety of antivirals therapy in COVID-19 outpatients. METHODS: Search were conducted in Pubmed, ScienceDirect, Cochrane Library, Springer, medRxiv, Journal Storage [JSTOR], and Directory of Open Access Journals [DOAJ] for articles investigating antivirals in COVID-19 outpatients. In addition, clinical and virological outcomes, COVID-19 hospitalization, all caused mortality, and adverse events were assessed. RESULTS: Thirteen studies were included in this review. The consecutive data from these studies suggested that favipiravir is more optimally used in early disease, but improvement in symptoms shows inconsistent results. Meanwhile, molnupiravir shows consistent results, which can reduce hospitalization and mortality risk. In addition, remdesivir and nirmatrelvir-ritonavir have the potential to prevent the progression of COVID-19 in outpatients, but the data provided in this study are very limited. Finally, there is no significant difference in serious and non-serious adverse events, highlighting that antivirals have a good safety profile. CONCLUSION: This study provides an overview of the role of various antivirals therapy in COVID-19 outpatients. Molnupiravir, remdesivir, and nirmatrelvir-ritonavir have shown potential to prevent the progression of COVID-19 in early disease. However, this review was based on very limited data. Therefore, further clinical trials are needed to confirm this finding.

Correlation between serum surfactant protein-D level with respiratory compliance and acute respiratory distress syndrome in critically ill COVID-19 Patients: A retrospective observational study.

Background: Acute respiratory distress syndrome (ARDS) is one of the manifestations of severe coronavirus disease 2019 (COVID-19) with low respiratory compliance and poor oxygenation as main characteristics and mortality rate of 50%-94%. Surfactants, including surfactant protein D (SP-D), have a role in maintaining respiratory compliance. This study aimed to analyze the relationship between serum SP-D levels with respiratory compliance and ARDS in patients with critically ill COVID-19 pneumonia. Methods: This study was a cross-sectional study. Subjects were adult reverse transcription-polymerase chain reaction-confirmed COVID-19 patients who had ARDS treated with invasive mechanical ventilation. All data were obtained from medical records. Statistical analysis was done using Spearman test, Mann-Whitney test, and receiver operating characteristic curve. Results: Serum level of SP-D was significantly correlated with static respiratory compliance (P = 0.009; correlation coefficient [rs] = 0.467). Serum SP-D levels correlated with ARDS severity (P < 0.001). SP-D levels had a very strong diagnostic value for ARDS severity, with an optimal cutoff value of 44.24 ng/mL (sensitivity 92.3%; specificity 94.1%). ARDS severity also correlated significantly with respiratory compliance (P = 0.005; correlation coefficient 0.496). Conclusion: Higher serum SP-D levels were associated with lower respiratory compliance, ARDS severity, and may be utilized diagnostically to identify patients with severe ARDS.

Maternal Perinatal Outcomes Related to Advanced Maternal Age in Preeclampsia Pregnant Women.

Objective: This study aims to analyze the effect of advanced maternal age (>35 years old) in maternal and perinatal outcomes of preeclampsia women. Materials and methods: This is a retrospective cross-sectional study involved all women who were diagnosed with preeclampsia at Universitas Airlangga Hospital (Surabaya, Indonesia) between January 2016 until May 2017. The participant was divided into two groups based on maternal ages: the first group was women older than 35 years old (advanced maternal age - AMA), and the other group was 20-34 years old (reproductive age - RA). The primary outcomes of this study were the maternal and perinatal outcome. Results: There were a total of 43 AMA preeclampsia women and 105 RA preeclampsia women. The AMA preeclampsia group had a higher proportion of poor maternal outcome (the occurence of any complication: pulmonary edema, HELLP syndrome, visual impairment, post partum hemorrhage, and eclampsia) compared to RA preeclampsia group (60,5% vs 33,3%, p = 0,002; OR 3,059, CI 1,469-6,371). There was no significant difference in the other maternal complications such as HELLP syndrome, pulmonary oedema, and eclampsia. The only difference was the occurrence of postpartum haemorrhage which was higher in the AMA group (16,3% vs 4,8%, p = 0,02; OR 3,889, CI 1,161-13,031). The prevalence of cesarean delivery was more common in AMA group (53,3% vs 28,6%, p = 0,004; OR 2.825, CI 1.380-5.988). The AMA preeclampsia women also had poorer perinatal outcomes compared to the RA group (81,4% vs 59%, p = 0,009; OR 3.034 CI 1.283-7.177). AMA women had a higher risk of perinatal complication such as prematurity (OR 3.266 CI 1.269-8.406), IUGR (OR 4.474 CI 1.019-19.634), asphyxia (OR 4.263 CI 2.004-9.069), and infection (OR 2.138 CI 1.040-4.393). Conclusion: Advanced maternal age increases the risk of poorer maternal and neonatal outcomes in preeclampsia patients. The addition of advanced maternal ages in preeclampsia should raise the awareness of the health provider, tighter monitoring, complete screening and early intervention if needed to minimize the risk of complications.

Effect of BCG vaccination and non-tuberculous Mycobacterium infection on interferon gamma specific assay and a tuberculin skin test among children with a tuberculosis contact in Surabaya, Indonesia.

The tuberculin skin test (TST) as a diagnostic tool for tuberculosis (TB) infection is used in many countries, including Indonesia, but lacks specificity. Interferon-gamma is a highly specific assay because it is not influenced by previous BCG vaccination or non-tuberculous mycobacteria (NTM) infections. We aimed to study the effect of BCG vaccination and NTM infection on the results of the interferon-gamma specific assay and TST among children with a TB contact. We carried out a cross-sectional study of children at an outpatient clinic in Surabaya, Indonesia. We studied 37 children aged 1-15 years having a household contact with an acid-fast bacilli positive adult index case. BCG vaccination was determined by the presence of a BCG scar. A PPD RT23 2 tuberculin test was used for the TST. ESAT-6, CFP-10, and TB 7.7(p4) antigens were used for the interferon-gamma assay by ELISA. Gastric aspirates were cultured in Lowenstein-Jensen media. A comparison of the two diagnostic tools among children aged 1-5 years without a BCG scar, revealed high agreement, while children with a BCG scar it revealed disagreement. Among children aged > 5 years with or without a BCG scar the comparisons revealed disagreement. Among children aged > 5-10 years, a comparison of the two diagnostic tools among NTM positive and negative children, there was a disagreement in results. Among children aged 1-5 years, the TST was influenced by a BCG scar. Infection with NTM had no influence on the results of the TST among children aged > 5-10 years, while in children aged 1-5 years and > 10 years the results could not be determined in this study.