Mesenchymal stem cell-released oncolytic virus: an innovative strategy for cancer treatment.

Oncolytic viruses (OVs) infect, multiply, and finally remove tumor cells selectively, causing no damage to normal cells in the process. Because of their specific features, such as, the ability to induce immunogenic cell death and to contain curative transgenes in their genomes, OVs have attracted attention as candidates to be utilized in cooperation with immunotherapies for cancer treatment. This treatment takes advantage of most tumor cells' inherent tendency to be infected by certain OVs and both innate and adaptive immune responses are elicited by OV infection and oncolysis. OVs can also modulate tumor microenvironment and boost anti-tumor immune responses. Mesenchymal stem cells (MSC) are gathering interest as promising anti-cancer treatments with the ability to address a wide range of cancers. MSCs exhibit tumor-trophic migration characteristics, allowing them to be used as delivery vehicles for successful, targeted treatment of isolated tumors and metastatic malignancies. Preclinical and clinical research were reviewed in this study to discuss using MSC-released OVs as a novel method for the treatment of cancer. Video Abstract.

Combination therapy with nivolumab (anti-PD-1 monoclonal antibody): A new era in tumor immunotherapy.

Immune checkpoint inhibitors (ICIs) targeting programmed cell death-1 (PD-1 or CD279) have noticeably improved the treatment landscape of advanced cancer patients. Nivolumab, the most well-known genetically engineered anti-PD-1 monoclonal antibody (mAb), promotes anti-tumor immunity and shows excellent capability for treating various cancers, particularly lung cancer, renal cancer, and melanoma. Systemic administration of nivolumab could inspire durable therapeutic responses not typically seen with traditional cytotoxic anti-cancer agents. However, nivolumab monotherapy is ineffective in 60-70 percent of patients. The mechanisms leading to both primary and acquired resistance to PD-1/PD-L1 inhibition are varied and multifactorial. Recently, the rationality of adding other conventional therapies such as chemo-radiotherapy and targeted therapies such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and VEGF/VEGFR inhibitors to nivolumab has strongly been verified. These regimens overcome cancer resistance and thus boost nivolumab efficacy in cancer patients. Herein, we discuss the current status of the combination therapy with nivolumab in cancer patients, with a particular focus on the recent clinical reports.

Association of Polyunsaturated Fatty Acid Intake on Inflammatory Gene Expression and Multiple Sclerosis: A Systematic Review and Meta-Analysis.

The health benefits of omega-3 fatty acid (FA) supplementation on inflammatory gene expression (IGE) and multiple sclerosis (MS) are becoming more evident. However, an overview of the results from randomized controlled trials is lacking. This study aimed to conduct a meta-analysis to evaluate the effect of omega-3 fatty acid intake on MS (based on the criteria of the Expanded Disability Status Scale (EDSS)) and inflammatory gene expression (IGE). A search was conducted of PubMed, EMBASE, and Web of Science for cohort studies published from the inception of the database up to May 2022 that assessed the associations of omega-3 polyunsaturated fatty acids (n-3 PUFAs), docosahexaenoic acid (DHA), α-linolenic acid (ALA), and eicosapentaenoic acid (EPA) with EDSS and inflammatory gene expression (peroxisome proliferator-activated receptor gamma (PPAR-γ), tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8)) outcomes. For the highest vs. lowest comparison, the relative risk (RR) estimates with a 95% confidence interval (CI) were pooled using the random-effect model. In total, 13 cohort studies with 1353 participants were included in the meta-analysis during periods of 3 to 144 weeks. A significant inverse relationship was found between DHA and EDSS scores (RR: 1.05; 95% CI: 0.62, 1.48; p < 0.00001). Our results also showed that omega-3 FAs significantly upregulated the gene expression of PPAR-γ (RR: 0.95; 95% CI: 0.52, 1.38; p < 0.03) and downregulated the expression of TNF-α (RR: −0.15; 95% CI: −0.99, 0.70; p < 0.00001) and IL-1 (RR: −0.60; 95% CI: −1.02, −0.18; p < 0.003). There was no clear evidence of publication bias with Egger's tests for inflammatory gene expression (p = 0.266). Moreover, n-3 PUFAs and EPA were not significantly associated with EDSS scores (p > 0.05). In this meta-analysis of cohort studies, blood omega-3 FA concentrations were inversely related to inflammatory gene expression (IGE) and EDSS score, which indicates that they may hold great potential markers for the diagnosis, prognosis, and management of MS. However, further clinical trials are required to confirm the potential effects of the omega-3 FAs on MS disease management.

The effectiveness of skin allografts in survival rate of patients with major burns.

BACKGROUND: Burns are still one of the most prevalent injuries in the world. Allograft is in high demand as a biological dressing for any superficial open wounds, not just burn victims. Skin allograft is the gold standard for treating burns in people who do not have enough skin to cover all of the injured areas of their bodies. Studies have shown that skin allografts are superior to topical antimicrobial dressings in partial thickness burns and can reduce complications and length of hospital stay in burn patients. However, to the best of our knowledge very few studies have investigated these results in our country. The aim of the current study is to evaluate and report the outcomes of skin allograft on burn patient survival in Iran. METHOD: This prospective clinical trial study was performed on patients admitted to the burn center of Imam Khomeini Hospital in Tehran between July 15, 2017 and April 27, 2021. The control group consisted of patients admitted to the burn ward who were not undergoing skin allografts. This group was matched with the case group in terms of sex, age, and percentage of burns. We compared the outcome of the study was the duration of hospitalization, and status of patients at discharge. The study protocol was approved by Iranian Registry of Clinical Trials (IRCT) under the code of IRCT2016112431074N1 (https://fa.irct.ir/trial/24517). RESULT: Overall, 112 patients in the case group and 224 patients in the control group were studied. The length of hospital stay in the case group (41.13±11.7) was considerably longer than the control group (24.6±12.1) (P<0.001), but the mortality rate in the two groups was not statistically different (P=0.633). The average survival time of case group (53 days, 95% CI=45-56) was higher than the control group (49 days, 95% CI=39-58) (P=0.012). Number of allograft usage (OR=0.038, 95% CI=0.142-0.945) and also Age (OR=1.03, 95% CI=1.005-1.070) were predictors of death. CONCLUSION: Although the use of skin allografts in large burns (more than 50%) reduced mortality in burn patients, their use in burns less than 50% has not been effective in reducing patient mortality. Due to the limited access to this valuable product, its use in burns less than 50% should be done with caution and, due to the limited access to skin allografts in most burn centers in Iran, patients with extensive burns (more than 50%) should be used as a priority.

Predictive value of number and volume of demyelinating plaques in treatment response in patients with multiple sclerosis treated with INF-B.

BACKGROUND: Multiple Sclerosis (MS) is an autoimmune, inflammatory disease of the central nervous system. Magnetic resonance imaging (MRI) findings are associated with disease clinical activity and response to treatment. This study aimed to evaluate the future value of plaque number and volume in MRI as radiological criteria in determining the treatment response to INF-B in patients with MS. METHODS: This is a cross-sectional study performed in 2016-2021 in Iran on patients with the newly diagnosed (less than one year) relapsing-remitting MS. Brain MRI was taken for all patients. The number and volumes of the MS plaques were evaluated from FLAIR images by the two radiologists. Patients were treated with INF-B1a with a dosage of 12 million units equal to 44 micrograms subcutaneously, three times per week. Patients were visited monthly by neurologists to examine their clinical status. After one year, the brain MRI was conducted with the similar characteristics to the beginning of the study, and the number and volume of MS plaques were measured again. RESULTS: The study population consisted of 33 males and 90 females with a mean age of 28.37 ± 6.29 years. The mean Expanded Disability Status Scale (EDSS) of the patients was 3.16 ± 0.23 at the beginning of the study. The specificity for a 50% reduction in the number and volume of plaques as two separate criteria was the same and equal to 100%. The sensitivity of the number and volume of plaques were 65.5% and 90.6%, respectively. In addition, considering 10% as the cut-off point of the number of plaques, the sensitivity of the number of plaques as a criterion was equal to the sensitivity of the plaque volume. CONCLUSION: The results of this study showed that imaging criteria provide a more objective tool for evaluating the effectiveness of treatment. These findings indicate that the number and volume of plaques could be two reliable MRI imaging criteria for assessing therapy response. The number of plaques was less accurate than the volume of plaques.

Effects of Mindfulness-Based Stress Reduction on Blood Pressure, Mental Health, and Quality of Life in Hypertensive Adult Women: A Randomized Clinical Trial Study.

Background: Hypertension is one of the most important causes of cardiovascular diseases. Patients with hypertension have a lower quality of life. We aimed to evaluate the effects of mindfulness meditation on blood pressure, mental health, and quality of life in patients with hypertension. Methods: This randomized clinical trial was performed in 2019 in Isfahan. Eighty adult women with Stage I or II hypertension were included and assigned randomly to 2 groups: 12 weeks of mindfulness-based stress reduction (MBSR) and routine care. At baseline and 1 week after the end of the intervention, blood pressure, stress, depression, anxiety, and quality of life of the studied participants were measured using the Depression, Anxiety, and Stress Scale-21 (DASS-21) and 36-Item Short Form Survey (SF-36) questionnaires. The data were analyzed using the independent t-test, the paired t-test, and the MANCOVA test. Results: After the intervention, the mean systolic and diastolic blood pressures decreased significantly in the intervention group compared with the baseline (142.82±11.01 mmHg vs 133.7±510.43 mmHg for systolic pressure and 86.12±8.24 mmHg vs 79.15±6.26 mmHg for diastolic pressure) and the control group (140.18±14.27 mmHg vs 142.15±10.23 mmHg for systolic pressure and 84.62±9.22 vs mmHg 88.51±8.54 mmHg for diastolic pressure; P=0.001). There was also a significant increase in quality of life, stress, anxiety, and depression scores in the intervention group (P<0.05). Conclusion: The 12-week MBSR program resulted in a significant reduction in the mean systolic and diastolic blood pressures and improvement in mental health and different aspects of quality of life.

Correlations and diagnostic tools for metabolic syndrome (MetS) and chronic obstructive pulmonary disease (COPD).

BACKGROUND: Regarding the importance of obesity in patients with chronic obstructive pulmonary disease (COPD), we aimed to evaluate of correlation between metabolic syndrome (MetS) and COPD. METHODS: In this cross-sectional study, 96 patients with COPD were evaluated. This study was conducted in 2016-2018. The severity of COPD was determined by Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017 criteria. We investigated the correlations between MetS with COPD and possible diagnostic tools. RESULTS: Of all COPD patients, 86.5% had MetS, and the means of waist circumference, fasting blood glucose, systolic and diastolic blood pressure, body mass index, and triglyceride in patients with MetS were significantly higher than the patients without MetS (P < 0.05). We showed that forced expiratory volume in 1 second (FEV1) with a 37% cutoff had 92.8% and 69.2% sensitivity and specificity, respectively (area of the curve: 0.51, 0.31-0.71). CONCLUSION: MetS is prevalent among COPD and FEV1 could be considered as important diagnostic tool for COPD.

Comparison of therapeutic effects of statins and aloe vera mouthwash on chemotherapy induced oral mucositis.

BACKGROUND: Chemotherapy induced oral mucositis is a common problem among patients with cancer. Different therapeutic agents have been evaluated to prevent or treat the disease. Here we aimed to compare therapeutic effects of atorvastatin and aloe vera mouthwash on chemotherapy induced oral mucositis. METHODS: 120 patients with large intestine and gastric cancer who were treated with 5-fluorouracil (FOLFOX4) for the first time were entered and randomized into 3 groups. Group 1 received tablets of atorvastatin 10 mg daily until 2 weeks after chemotherapy sessions plus placebo mouthwash. Group 2 received aloe vera mouthwash plus placebo tablets and group 3 received placebo mouthwash and placebo tablets until 2 weeks after chemotherapy sessions. Severity of mucositis was assessed using world health organization (WHO) indexes. Based on this method, mucositis is divided into 4 grades. This study was approved by Iranian Registry of Clinical Trials (IRCT) with the code of: IRCT20201203049585N1 (https://fa.irct.ir/trial/54037). RESULTS: Analysis of the incidence of mucositis among patients showed that in placebo group, 50% of patients experienced grade 2 to 4 mucositis. In group 1, 9 patients (22.5%) had grade 2 mucositis and 6 patients (15%) had grade 3 mucositis and 4 patients (10%) had grade 4 mucositis. In group 2, only 1 patient (2.5%) was diagnosed with grade 2 mucositis. These data showed no significant differences between group 1 and group 3 (P=0.674), but the therapeutic results of group 2 were significantly better than those of group 3 (P=0.042) and group 1 (P=0.036). CONCLUSION: We showed that treatments with aloe vera mouthwash could be an effective choice in prevention of mucositis for patients undergoing chemotherapy. There are also much to discover about effects of aloe vera mouthwash on this disease.

Short term results of stapled versus conventional hemorrhoidectomy within 1 year follow-up.

BACKGROUND: Conventional hemorrhoidectomy is still used for patients but a variety of less invasive treatments are also developed. Stapled hemorrhoidectomy is known as a beneficial technique. Here we aimed to evaluate and compare the results of stapled hemorrhoidectomy with conventional methods in patients who require hemorrhoidectomy. METHODS: This study was performed on 120 patients with stage 3 or 4 hemorrhoids. Mean resting pressure (MRP) and mean squeezing pressure (MSP) were measured before surgeries. Patients were then randomized into 2 groups of 60 patients. Group 1 underwent stapled hemorrhoidectomy and group 2 underwent conventional hemorrhoidectomy. The pain of patients was also determined using the visual analogue scale (VAS) for each patient 1, 2 and 3 days after the surgeries. Patients were then followed for 1 month after surgeries for evaluating the surgical outcomes, MRP and MSP. In terms of recurrence, they underwent clinical and anoscopic re-examination at least once in the next 6 months and 12 months after interventions. RESULTS: We showed that both MRP and MSP did not change significantly in both groups after interventions (P>0.05). We also observed a significant decline in the pain of both groups (P<0.001) and also a significantly lower pain in group 1 (P<0.05). Our data showed that patients in group 1 required less analgesic after procedures (P=0.001). Evaluation of recurrence rate 6 and 12 months after interventions showed that patients who underwent stapled hemorrhoidectomy had a significant higher recurrence rate within 12 months compared to the other group (P=0.003). CONCLUSION: Stapled hemorrhoidectomy is a safe and effective method that is associated with lower pain, hospitalization duration and no significant complications within 1 year follow-up. But on the other hand, this surgical method was associated with a higher recurrence rate.

Comparison of opponensplasty techniques in isolated low median nerve palsy.

BACKGROUND: Thumb opposition is a critical operation of thumb. Median nerve palsy interferes with a large number of ordinary activities such as opposition. Opponensplasty for low median nerve injury is performed with various techniques. The purpose of this study is to compare tendon transfer techniques of Riordan and Burckhalter. METHODS: This study was a clinical trial performed on 120 patients who underwent Opponensplasty. Patients with traumatic low nerve palsy were divided into two equal groups of Riordan and Burckhalter operation. Demographic information, functional status, Kapandji score, and Pulp pinching method were recorded and compared for all patients 3 months and 8 months after surgery. FINDINGS: Performance status, Kapandji score and Pulp pinching tests showed significant improvements in both groups after surgeries. The changes in pressure between the thumb and fifth finger were significantly greater in the Burckhalter method compared with Riordan method (P<0.05). The incidence of complications was significantly higher in the Riordan group (P=0.01). CONCLUSION: According to the present study, there was no differences between Burckhalter and Riordan methods in terms of opposition recovery, although Burckhalter's opponensplasty had better therapeutic results. Postoperative complications were also less in the Burckhalter method.