Mesenchymal stromal cell therapy for COVID-19-induced ARDS patients: a successful phase 1, control-placebo group, clinical trial.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is the devastating complication of the new COVID-19 pandemic, directly correlated with releasing large amounts of inflammatory cytokines. Due to their immunoregulatory features, mesenchymal stromal cells (MSCs) provide a promising approach against this disease. In this regard, this study was designed as a single-center, open-label, phase 1 clinical trial with a control group to examine the safety and explore the possible potency of three injections of umbilical cord-derived MSCs (UC-MSCs) in mild-moderate COVID-19-induced ARDS patients. METHODS: Twenty confirmed COVID-19 patients with mild-to-moderate ARDS degree entered the study and were divided into two groups: control group (standard care) and intervention group (standard care + UC-MSCs). The patients received three intravenous infusions of UC-MSCs (1 × [Formula: see text] cells/kg BW per injection) every other day. Respiratory markers, CRP levels and specific serum cytokines were assessed four times (days of 0, 5, 10 and 17) during the 17-day follow-up period. RESULTS: During the study, there were no serious adverse effects after cell transplantations. Besides, significant improvement in SPO2/FIO2 ratio and serum CRP levels was observed. On the other hand, a significant decrease (P < 0.05) in serum cytokine levels of IL-6, IFN-g, TNF-α, IL-17 A and a significant increase in serum cytokine levels of TGF-B, IL-1B and IL-10 were observed. Also, no significant changes were observed in CT scan images of patients during the study period. CONCLUSION: Our obtained results demonstrated that multiple intravenous transplantations of allogenic UC-MSCs in non-severe COVID-19-induced ARDS patients are a safe procedure. In addition, this intervention is a hopeful approach to decline cytokine storm and recover respiratory functions. Indeed, more clinical trials with larger sample sizes are required to confirm these results. Trial registration This clinical trial was registered with the Iranian Registry of Clinical Trials (ID: IRCT20160809029275N1 at 2020.05.30).

Specific Clinical and Immunological Changes Following Mesenchymal Stem Cell Transplantation in COVID-19-induced Acute Respiratory Distress Syndrome Patients: A Phase-I Clinical Trial.

Acute respiratory distress syndrome (ARDS) is a systemic inflammation resulting from immune system overactivity. ARDS is also a fatal complication of COVID-19. Mesenchymal stem cells (MSCs) have immune modulatory properties. This study evaluated the safety and efficacy of three times transplantation of umbilical cord-derived MSCs (UC-MSCs) in terms of specific immunological and clinical changes in mild-to-moderate COVID-19-induced ARDS patients. In this single-center, open-label, phase 1 clinical trial, 20 patients diagnosed with COVID-19 and mild-to-moderate ARDS were included and were divided into two groups: a control group receiving standard care and an intervention group receiving UC-MSC in addition to standard care. Three consecutive intravenous transplants of UC-MSC (1×  cells/kg body weight per each transplant) were performed in the intervention group on days 1, 3, and 5. The biological assay was investigated four times (days 0, 5, 10, and 17). UC-MSCs improved the patients' clinical and paraclinical parameters, including leukocytosis, lymphopenia, thrombocytopenia, and liver enzyme abnormalities compared to the control group. They also decreased pro-inflammatory lymphocytes (TH1 and TH17) and increased anti-inflammatory T lymphocytes. Cell therapy also reduced the mean fluorescence intensity (MFI) in overactivated CD8+ T cells.  These findings show that three UC-MSC injections could regulate a hyperactivated immune system in COVID-19-induced ARDS patients by decreasing the inflammatory T lymphocyte subset and can improve the patient's hematological condition and liver function. However, more studies are needed in this area.

The Experiences of Women who Live with Pelvic Floor Disorders: A Qualitative Study.

BACKGROUND: Pelvic floor disorders (PFDs) are common and complicated problems that occur in women with different ages and cultural backgrounds and affect various dimensions of their life. Because of the dearth of information about how the Iranian women manage these disorders, this study was conducted to explore the experiences of women who live with PFDs. METHODS: This qualitative study was conducted between 2018 -2019 on women who referred to the clinics of Mashhad educational hospitals . 25 deep and semi-structured interview with 22 patients with PFDs was done. They were recruited through a purposive sampling method among women with diagnosis of PFDs. Data were analyzed using conventional content analysis adopted by Graneheim and Lundman and organized using the MAXQDA software (Ver.10). RESULTS: The analysis of the data led to the emergence of a theme of "Acceptance and Tolerance", including four categories: "Trying to adopt sexual conflicts", " Concealing the disease", "Trying to modify the lifestyle", and "Controlling negative emotions", and 15 sub-categories. CONCLUSION: This study provides an insight into self-management strategies for different aspects of challenges faced by women with PFDs.They try to resolve, conceal, modify, and control some issues to accept and tolerate their disease. By identifying self-management strategies, care providers can design and implement counseling, educating and supporting interventions, and also a program through which the patients help and guide each other.

The effect of a natural vaginal product based on honey on the success of intrauterine insemination (IUI) in infertility treatment.

OBJECTIVE: Due to high prevalence of infertility and increasing tendency towards complementary medicine, this study was conducted to investigate the effect of a vaginal natural product based on honey and 1% extract of Myristica fragrans on the extent of success of intrauterine insemination (IUI). MATERIALS AND METHODS: This non-randomized clinical trial study with a historic control group, was performed on infertile women. In this trial, 159 patients were assigned to the intervention group, and 288 patients were recruited to the control group. All the participants received clomiphene or letrozole from the third up to seventh day of menstruation, and on days 6, 7, and 8, they received human menopausal gonadotrophin (HMG) injections. IUI was performed 36 hours after human chorionic gonadotrophin (HCG) injection. In the intervention group, a natural vaginal product was used besides the above treatments, from menstruation day 7 until the day before performing IUI. Sixteen days after IUI, serum beta HCG was measured to investigate chemical pregnancy, and six weeks following IUI, vaginal sonography was performed to investigate clinical pregnancy. RESULTS: Analysis showed that the pregnancy rate was higher in the group that receiving the natural product compared to the control group. Chemical pregnancy rate was 18.1% vs. 15.4%, and clinical pregnancy rate was 15.2% vs. 13.8% for intervention and control groups, respectively; but, this difference was not significant. CONCLUSION: It seems that the use of this vaginal product for a longer period of time and across several menses cycles before IUI, may produce more positive results. Further studies, however, are needed to be done.