Adverse events of cell therapy clinical trials in human chronic spinal cord injury, a systematic review and meta-analysis.

Spinal cord injury is a lesion with high mortality and significant morbidities. After the primary injury, during six months, a cascade of secondary cellular and molecular events makes the lesion chronic. Recently, cell-based clinical trials as a new procedure have been gradually tested to improve the symptoms of patients. Each treatment method is associated with different adverse events. Based on the PRISMA flow diagram of the identified records, and after multistep screening, finally in 76 reviewed studies with 1633 cases and 189 controls, 64 types of adverse events in 12 categories were recorded in 45 studies. The most common adverse events were transient backache and meningism (90%) and cord malacia (80%). The cell therapy method in which the treatment was associated with more adverse events was Olfactory ensheathing cell and bone marrow mesenchymal stem cell combination therapy in 55%, and the adverse events were less with the embryonic stem cell in 2.33% of patients. In a meta-analysis, the total prevalence of adverse events in cell therapy was 19% and the highest pulled effect size belonged to urinary tract and localized adverse events. Also, the total prevalence of adverse events in 14 cell therapy methods was 18% and four cell types (neural stem cell, bone marrow hematopoietic stem cell, embryonic stem cell, and umbilical cord mesenchymal stem cell) had the most effect. None of the adverse events were reported on the 4 (life-threatening consequences) and 5 (death) grading scales. We concluded that the frequency of life-threatening adverse events following cell therapy clinical trials in chronic spinal cord injury patients is very scarce and can be ignored.

Systematic Review of Cell Therapy Efficacy in Human Chronic Spinal Cord Injury.

Spinal cord injury (SCI) is one of the most debilitating problems for humans. About 6 months after the initial injury, a cascade of secondary cellular and molecular events occurs and the primary damage enters the chronic phase. Current treatments are not curative. One of the new treatment methods is the use of cell therapy, which is gradually being tested in clinical trials to improve the symptoms of SCI patients. In this review article, we investigated the effect of different cell therapy trials in improving patients' symptoms and their paraclinical indicators. In the 72 final reviewed studies with 1144 cases and 186 controls, 20 scores were recorded as outcomes. We categorized the scores into seven groups. In upper extremity motor score, daily living function, trunk stability, postural hypotension, somatosensory evoked potential, and motor evoked potential scores, the bone marrow hematopoietic stem cell therapy had a more healing effect. In the International Association of Neurorestoratology SCI Functional Rating Scale, light touch score, bowel function, decreased spasticity, Visual Analog Scale, and electromyography scores, the bone marrow mesenchymal stem cell had more impact. The olfactory ensheathing cell had a greater effect on lower extremity motor score and pinprick scores than other cells. The embryonic stem cell had the greatest effect in improving the important score of the American Spinal Injury Association scale. Based on the obtained results, it seems that a special cell should be used to improve each symptom of patients with chronic SCI, and if the improvement of several harms is involved, the combination of cells may be effective. Impact statement Compared to similar review articles published so far, we reviewed the largest number of published articles, and so the largest number of cases and controls, and the variety of cells we examined was more than other published articles. We concluded that different cells are effective for improving the symptoms and paraclinical indicators of patients with chronic spinal cord injury. Bone marrow hematopoietic stem cell and bone marrow mesenchymal stem cell have had the higher overall mean effect in more scores (each in six scores). If the improvement of several harms is involved, the combination of cells may be effective.

Chilblain or perniosis-like skin lesions in children during the COVID-19 pandemic: A systematic review of articles.

COVID toes or chilblain-like skin lesions represent a widespread and specific skin presentation mostly in the feet that may be attributed to COVID-19 infection. They may last for several months. We conducted this study to investigate chilblain-like lesions in children during the COVID-19 pandemic, any predisposition, location, clinical course, and prognosis. We searched Google Scholar, Scopus, and Medline (PubMed) databases using the following keywords: "Coronavirus" OR "COVID-19" AND "Chilblains" OR "Pernio" OR "Perniosis" OR "Children" OR "Cutaneous" OR "skin." The inclusion criteria were: (a) Studies that described the specific vascular skin lesion. (b) Studies that included patients aged >1 month till 18 years. (c) Case reports, case series, retrospective or prospective cohort studies, case-control studies. A total of 28 articles were included. The total number of children with chiblain-like lesions (CLL) was 433. The mean age of children presenting CLL during the COVID-19 pandemic was estimated as 12.58 ± 2.15. Of note, 53.6% of them were male. The nasopharyngeal SARS-CoV-2 RT-PCR test and anti-SARS-CoV-2 antibodies were mostly negative for the virus. In conclusion, it is crucial to be familiar with various presentations of COVID-19 infection and their clinical significance to approach the earliest diagnosis, immediate treatment, estimate the prognosis, and finally isolate the patients to prevent spreading. Chilblain-like lesions as a possible cutaneous presentation of COVID-19 in children may last several months with the indolent course.

Assessment of the fitness of Cox and parametric regression models of survival distribution for Iranian breast cancer patients' data.

Factors affecting the time of survival after breast cancer (BC) diagnosis remain unknown. However, some of the prognostic factors have been identified. The aim of this study was to investigate the effects of biologic and socioeconomic factors on long-term survival of BC patients. This was a descriptive chart review and survey of all women with a confirmed diagnosis of BC registered in Shohada-e-Tajrish Cancer Research Center database from March 2004 to March 2015. The checklist of study consisted of biologic, demographic, reproductive, genetic, medical, and therapeutic information of patients. The minimum time of follow-up was 3 years and the maximum was 10 years. We then evaluated possible associations of these variables with BC survival using Cox and parametric regression models of survival analysis. The study population was 1276 BC patients. Their mean survival was 23 (range 1-120) months. Between the parametric models, Weibull regression model demonstrated the lowest Akaike information criterion and thus the best fit, and tumor size, number of lymph nodes, BC stage, educational level, and high-fat diet were significant in this model. Based on our findings, educational level, consumption of fat, and characteristics of tumor at the time of diagnosis (disease stage, tumor size, number of involved lymph nodes) are the most important prognostic factors affecting long-term survival of BC patients. We suggest that future studies assess the efficacy of possible interventions for these factors.

Relationship of Social Determinants of Health with the Three-year Survival Rate of Breast Cancer

Background: Social determinants of health are among the key factors affecting the pathogenesis of diseases. Considering the increasingly high prevalence of breast cancer and the association of social determinants of health with its occurrence, related morbidity and mortality and survival rate, this study sought to assess the relationship of three-year survival rate of breast cancer with social determinants of health. Materials and Methods: This cohort study was conducted on males and females presenting to the Cancer Research Center of Shohada-E-Tajrish Hospital from 2006 to 2010 with definite diagnosis of breast cancer. Data were collected via phone interviews. Kaplan-Meier and Cox regression was fitted using SPSS (version 18) and PH assumption was tested by STATA (version 11) software. Results: The study was performed on 797 breast cancer patients, aged 25-93 years with mean age of 54.66 (SD=11.86) years. After 3 years from diagnosing cancer 700 (87.8%) patients were alive and 97 (12.2%) patients were dead. Using log rank test, there was relationship between 3-year survivals with age, education, childhood residence, sibling, treatment type, and district were significant (p<0.05). Using Cox PH regression, 3-year survival was related to age, level of education, municipal district of residence and childhood condition (p<0.05). Conclusion: Social determinants of health such as childhood condition, city region residency, level of education and age affect the three-year survival rate of breast cancer. Future studies must focus on the effect of childhood social class on the survival rates of cancers, which have been paid less attention to.

Application of Cox and Parametric Survival Models to Assess Social Determinants of Health Affecting Three-Year Survival of Breast Cancer Patients.

Breast cancer is one of the most common causes of cancer mortality in Iran. Social determinants of health are among the key factors affecting the pathogenesis of diseases. This cross-sectional study aimed to determine the social determinants of breast cancer survival time with parametric and semi-parametric regression models. It was conducted on male and female patients diagnosed with breast cancer presenting to the Cancer Research Center of Shohada-E-Tajrish Hospital from 2006 to 2010. The Cox proportional hazard model and parametric models including the Weibull, log normal and log-logistic models were applied to determine the social determinants of survival time of breast cancer patients. The Akaike information criterion (AIC) was used to assess the best fit. Statistical analysis was performed with STATA (version 11) software. This study was performed on 797 breast cancer patients, aged 25-93 years with a mean age of 54.7 (±11.9) years. In both semi-parametric and parametric models, the three-year survival was related to level of education and municipal district of residence (P<0.05). The AIC suggested that log normal distribution was the best fit for the three-year survival time of breast cancer patients. Social determinants of health such as level of education and municipal district of residence affect the survival of breast cancer cases. Future studies must focus on the effect of childhood social class on the survival times of cancers, which have hitherto only been paid limited attention.

The Estimation of Survival Function for Colon Cancer Data in Tehran Using Non-parametric Bayesian Model.

BACKGROUND: Colon cancer is the third cause of cancer deaths. Although colon cancer survival time has increased in recent years, the mortality rate is still high. The Cox model is the most common regression model often used in medical research in survival analysis, but most of the time the effect of at least one of the independent factors changes over time, so the model cannot be used. In the current study, the survival function for colon cancer patients in Tehran is estimated using non-parametric Bayesian model. METHODS: In this survival study, 580 patients with colon cancer who were recorded in the Cancer Research Center of Shahid Beheshti University of Medical Sciences since April 2005 to November 2006 were studied and followed up for a period of 5 years. Survival function was plotted with non-parametric Bayesian model and was compared with the Kaplan-Meier curve. RESULTS: Of the total of 580 patients, 69.9% of patients were alive. 45.9% of patients were male and the mean age of cancer diagnosis was 65.12 (SD= 12.26) and 87.7 of the patients underwent surgery. There was a significant relationship between age at diagnosis and sex and the survival time while there was a non-significant relationship between the type of treatment and the survival time. The survival functions corresponding to the two treatment groups cross, in comparison with the patients who had no surgery in the first 30 months, showed a higher level of risk in the patients who underwent a surgery. After that, the survival probability for the patients undergoing a surgery has increased. CONCLUSION: The study showed that survival rate has been higher in women and in the patients who were below 60 years at the time of diagnosis.

Associations of Demographic and Socioeconomic Factors with Complete Treatment and Follow-up of Colon Cancer.

BACKGROUND: Cancer is the second cause of death in the world, and colon cancer is the third cause of death and is one of the most common cancers which will cure with early diagnosis, treatment and sufficient follow up. Assessing factors which affect this cancer is important for prolonging patient survival. Socioeconomic factors are among effective factors of cancer morbidity and mortality. Because mortality rates for colon cancers vary by socioeconomic characteristics, this study has been performed to recognize the relationship between socioeconomic factors with treatment and follow up of colon cancer. METHODS: This was a cross-sectional, descriptive study for patients with colon cancer registered in Cancer Research Center of Shahid Beheshti University of Medical Sciences from April 2005 to November 2006. Patients were selected randomly, and the study was conducted using questionnaires filled by interviewing the patients via phone (if a patient was dead, the questions were asked from their family members). Data analysis was done using SPSS (version 19) software. RESULTS: The study was performed on 520 colon cancer patients with age range of 23-88 years. The mean age of the patients was 63 (S.D.=11.8) and the median age was 64. Two hundred thirty seven (45.4%) patients were female and 283 (54.4%) were male. Using Chi-square test, age<60 (p=0.002) and female gender (p=0.034) had a significant correlation with complete treatment and there was a significant relationship between complete follow up and age<60 (p=0.037), academic education (p=0.02) and having insurance (p=0.021). Multiple logistic regression tests were used to evaluate concurrent effects of variables on treatment and follow up. Correlated variables to complete treatment include: age<60 (p=0.001), and female gender The Odds Ratio (OR) of completing treatment for patients under 60 years of age versus patients above 60 years was 3.13 (95% C.I. 1.55 to 6.34), and the OR of completing treatment for women versus men was 1.91(95% C.I. 1.33 to 2.74). Correlated variables to follow up were academic education ( ) and having insurance . The OR of cancer follow up in illiterate patients versus college-educated patients was 0.45 (95% C.I. 0.24 to 0.82), and the OR of cancer follow up in patients without insurance versus patients with health was 0.46 (95% C.I. 0.21 to 0.98). CONCLUSION: Age is a correlated factor on completing colon cancer treatment. Women have more complete colon cancer treatment than men. Academic education and having insurance were the most important factors among socioeconomic factors observed in a five-year follow up after treatment. As the population of the old is increasing, executing effective interventions to improve treatment and follow up procedures for old patients is of prime importance. It seems that increasing the insurance contribution in follow up measures may lead to increase in the regular follow up and may affect patients' survival.