Human placenta-derived mesenchymal stem cells transplantation in patients with acute respiratory distress syndrome (ARDS) caused by COVID-19 (phase I clinical trial): safety profile assessment.

BACKGROUND: High morbidity and mortality rates of the COVID-19 pandemic have made it a global health priority. Acute respiratory distress syndrome (ARDS) is one of the most important causes of death in COVID-19 patients. Mesenchymal stem cells have been the subject of many clinical trials for the treatment of ARDS because of their immunomodulatory, anti-inflammatory, and regenerative potentials. The aim of this phase I clinical trial was the safety assessment of allogeneic placenta-derived mesenchymal stem cells (PL-MSCs) intravenous injection in patients with ARDS induced by COVID-19. METHODS: We enrolled 20 patients suffering from ARDS caused by COVID-19 who had been admitted to the intensive care unit. PL-MSCs were isolated and propagated using a xeno-free/GMP compliant protocol. Each patient in the treatment group (N = 10) received standard treatment and a single dose of 1 × 106 cells/kg PL-MSCs intravenously. The control groups (N = 10) only received the standard treatment. Clinical signs and laboratory tests were evaluated in all participants at the baseline and during 28 days follow-ups. RESULTS: No adverse events were observed in the PL-MSC group. Mean length of hospitalization, serum oxygen saturation, and other clinical and laboratory parameters were not significantly different in the two groups (p > 0.05). CONCLUSION: Our results demonstrated that intravenous administration of PL-MSCs in patients with COVID-19 related ARDS is safe and feasible. Further studies whit higher cell doses and repeated injections are needed to evaluate the efficacy of this treatment modality. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); IRCT20200621047859N4. Registered 1 March 2021, https://en.irct.ir/trial/52947 .

Comparing the short-term therapeutic effects and safety profiles of rituximab therapy in pemphigus vulgaris patients either early treated or later than six months.

Introduction: Rituximab is a recent treatment in recalcitrant pemphigus vulgaris (PV) patients. This study aims to establish the optimal time for rituximab therapy in PV patients. Methods: In this retrospective study, patients who received rituximab within six months of diagnosis were classified as the early treatment group, and patients who have received it later than six months were classified as the delayed treatment group. Results: Ninety-five PV patients were reviewed. Fourteen (14.8%) and 81 (85.2%) patients received rituximab within the first six-months from diagnosis and after that, respectively. In the former group, seven patients have received rituximab as the first-line therapy. The rate of complete remission off therapy (CR off therapy) was significantly higher in this early treatment group (92.9%) compared with the delayed treatment group (66.6%) (p = .47). The patients in early treated group significantly sooner achieved remission (p < .001) and it lasts for a longer time (p = .006). The relapse rate was also significantly lower in the early treatment group (five patients, 38.5%) compared with the delayed treatment group (54 patients, 71.1%) (p = .02). Conclusions: Early treatment with rituximab can lead to a higher rate of complete remission, a lower rate of disease relapse, and longer duration of complete remission in PV patients.

Characteristic features of cutaneous melanoma in a dermatology referral centre in Tehran, Iran.

BACKGROUND/OBJECTIVES: The characteristics of cutaneous melanoma in the Middle-Eastern countries is poorly described. Therefore we conducted this study to determine the characteristics of melanoma in Iran. METHODS: A retrospective, cross sectional study of melanoma patients seen at a tertiary referral centre, Iran, from May 2004 to October 2014. Clinical data included age and gender of the patients at the time of diagnosis, tumour location and tumour size. Histological characteristics included Breslow thickness, Clark level and subtype of tumour. RESULTS: A total of 450 cases of melanoma with a male/female ratio of 1.1:1 were reviewed. The mean age of patients was 57.5 years. The most frequent histological subtypes were acral lentiginous melanoma (30%) and lentigo maligna melanoma (29%). In 215 cases (49%) the tumour was located on the extremities. The second most common site was the face. Tumour invasion was mainly at Clark level III and IV. The mean Breslow thickness was 2.8 mm; 143 (38%) melanomas had a Breslow thickness less than 1 mm (T1) and 86 (23%) were more than 4 mm (T4). CONCLUSION: This study indicates that clinical and histological features of melanoma in Iranians (who are mainly of skin phototypes 3-4) are different from those observed in Western countries. Further cohort studies are required to evaluate the role of ethnic and environmental risk factors for melanoma in different populations.

Oral Doxycycline Reduces the Total Number of Intraocular Bevacizumab Injections Needed to Control Neovascular Age-related Macular Degeneration.

Tetracyclines, especially doxycycline, play a role in the regulation of inflammation, immunomodulation, cell proliferation, and angiogenesis. Treatment of corneal angiogenesis or choroidal neovascularization with tetracyclines has been shown to be effective in animal models. The aim of this study was to evaluate the efficacy of oral doxycycline in reducing the total number of intraocular injections needed for controlling neovascular age-related macular degeneration in human patients. In this interventional case series, 28 random consecutive patients with neovascular age-related macular degeneration from Farabi Eye Hospital, Tehran, Iran were treated for 4 months with 200 mg doxycycline once a day after the first intravitreal bevacizumab injection in addition to standard therapy in agreement with as-needed regimen. After 12 months of follow-up, total number of injections, foveal thickness and visual acuity were compared to those at baseline and of similar studies. Similar to standard treatment, co-treatment with doxycycline was able to control active disease (intraretinal or subretinal fluid or leakage, new-onset of macular hemorrhage, and reduction of visual acuity more than 5 letters based on Early Treatment Diabetic Retinopathy Study [ETDRS] charts) yet with fewer injections (for current study and standard treatment, respectively 3.14 vs. 5.92, P < 0.001). Furthermore, while better control of the foveal thickness was achieved (P < 0.001), vision improvement was similar to that achieved with standard therapy (P > 0.05). If confirmed in larger studies, the findings of this interventional case series could provide a strategy to control neovascular age-related macular degeneration with fewer intraocular bevacizumab injections by co-administering a well-known oral agent-doxycycline.

Does bone marrow-derived mesenchymal stem cell transfusion prevent antisperm antibody production after traumatic testis rupture?

OBJECTIVE: To determine whether transfusion of mesenchymal stem cells (MSCs) could prevent humoral immune response and autoimmunization against sperms after traumatic testis rupture. METHODS: Immunomodulatory properties of MSCs have been evaluated by a prospective cohort on 50 adult BALB/c mice. In each interventional arms of study, controlled testis rupture and surgical repair were exerted. In addition to tissue repair, single dose of 5×10(5) MSCs labeled by green fluorescent protein was delivered intravenously to 20 cases (cell therapy group). After euthanizing, seroconversion of antisperm antibody (ASA) was compared between 2 interventional groups as response of humoral immune system. Lung and testis tissues were examined for green fluorescent protein-positive cells to assess whether presence of stem cells is correlated with seroconversion rates. RESULTS: Six cases had been lost during the study. Fourteen of 16 mice in cell therapy control group formed ASA (87.5%) but 6 of 18 mice (33.3%) in cell therapy group were immunized and formed ASA (P=.002). Transplanted cells were traced in lungs of 55% (n=10) of cell therapy group and none were found in trauma site. Small volume of mice blood was our main limitation to trace seroconversion or quantitative measurement of ASA in each case. CONCLUSION: In this in vivo model of autoimmune infertility, bone marrow-derived MSC transfusion showed immunosuppressive effects on antibody production. Considering immunomodulatory properties of MSCs even in allogeneic settings, novel clinical application should be investigated further.