Chemo-immune cell therapy by intratumoral injection of adoptive NK cells with capecitabine in gastric cancer xenograft model.

Introduction: Gastric cancer is one of the most commonly known malignancies and is the fifth cancer-related death globally. Whereas natural killer (NK) cells play a critical role in tumor elimination; therefore, adoptive NK cell therapy has become a promising approach in cancer cytotherapy. Hence, this study investigated the chemo-immune cell therapy in MKN-45 derived xenograft gastric cancer model. Methods: Three groups of animals have received the following treatments separately: activated NK cells, capecitabine, the combination of capecitabine and activated NK cells, and one was considered as the control group. Morphometric properties of tumor samples were evaluated at the end of the study. NK cells infiltration was evaluated by immunohistochemistry (IHC) of hCD56. Mitotic count and treatment response was assessed by hematoxylin and eosin (H&E) staining. The proliferation ratio to apoptosis was determined by IHC assessment of Ki67 and caspase 3. Results: The results indicated that the NK cell therapy could effectively decrease the mitotic count in pathology assessment, but the tumor was not completely eradicated. In combination with metronomic chemotherapy (MC) of capecitabine, NK cell therapy demonstrated a significant difference in tumor morphometric properties compared to the control group. The proliferation ratio to apoptosis was also in line with pathology data. Conclusion: Although NK cell therapy could effectively decrease the mitotic count in vivo, the obtained findings indicated lesser potency than MC despite ex vivo activation. In order to enhance NK cell therapy effectiveness, suppressive features of the tumor microenvironment and inhibitory immune checkpoints blockade should be considered.

Cardiovascular diseases in patients after hematopoietic stem cell transplantation: Systematic review and Meta-analysis.

BACKGROUND: Hematopoietic Stem Cell Transplantation (HSCT), is performed to treat many malignancies such as autologous or allogenic. Despite the success of this method in treating patients, - sometimes some HSCT recipients face problems such as cardiovascular complications. Therefore, this systematic review and meta-analysis aimed to evaluate the prevalence of cardiovascular complications in post-transplant patients. METHOD: In order to review the published studies, we examined PubMed, MEDLINE, Cochrane Library, Scopus, and web of science databases from the beginning to the end of January 2022, and we used tools by the Newcastle-Ottawa Scale to evaluate the quality of the studies. RESULT: In this study, 37 articles were included in the meta-analysis and 30,957 patients were examined. Also, the mean age of patients was 35.37 years. Based on the results of the meta-analysis, the prevalence of cardiovascular disease (CVD), was 16.84%. In addition, other complications related to CVD which include Arrhythmias, Congestive Heart Failure (CHF), Hypertension, stroke, and mortality were examined in patients who had hematopoietic stem cell transplantation and the resulting amounts were 3.91%, 3.66, 17.71, 0.22%, and 1.53%, respectively. CONCLUSION: This study showed that the prevalence of cardiovascular disease after hematopoietic stem cell transplantation is high and needs special attention.

Cardioprotective effects of dapsone against doxorubicin-induced cardiotoxicity in rats.

PURPOSE: It has been supposed that cardiac toxicity of doxorubicin is due to its production of free radicals and inflammatory cytokines. Dapsone, an antibiotic drug which is the principal in a multidrug regimen for the treatment of leprosy, is a sulfone with anti-inflammatory and antioxidant immunosuppressive properties. Therefore, we designed this study to investigate the possible effects of dapsone on doxorubicin-induced cardiotoxicity. METHODS: Male rats were administrated doxorubicin (2.5 mg/kg) and dapsone (1, 3, 10 mg/kg) intraperitoneally six times in 2 weeks. Then electrocardiographic (ECG) parameters (QRS complexes, RR and QT intervals) alternation, papillary muscle contraction and excitation, and histopathological changes were assessed. Also, the heart tissue levels of malondialdehyde (MDA) as oxidant factor and superoxide dismutase (SOD) as antioxidant enzyme, tumor necrosis factor-alpha (TNF-α) and serum level of CK-MB were analyzed. RESULTS: Administration of dapsone with doxorubicin significantly reversed alterations induced by doxorubicin in serum levels of CK-MB, ECG parameters, papillary muscle contractility and excitation. Furthermore, the measurement of MDA, SOD and TNF-α tissue level indicated that dapsone significantly reduced oxidative stress and inflammation. These findings were consistent with histopathological analysis. CONCLUSION: Dapsone exerts cardioprotective effects on doxorubicin-induced cardiotoxicity through its anti-inflammatory and antioxidant mechanism.

Management of colon and rectal cancers during COVID-19 pandemic: A clinical guideline (TUMS-CRC-CoV19 Guideline).

Background: In a resource-demanding COVID-19 pandemic, guidelines can free up health care resources needed for providing better care to those with COVID-19 and other patients. This study was performed to design a guideline to manage patients with colorectal cancers during the COVID-19pandemic. Methods: To design this guideline, major topics and headings of colon and rectal cancers (CRC) were selected and included. Based on the extent of COVID-19 infection in the community and availability of hospital resources, the guideline has been designed for 2 major COVID-19 phases. Several multidisciplinary discussion sessions were held to review the comments of experts, finalize the data, and write the guideline. Results: This guideline has been prepared in 2 main COVID-19 phases of the community/hospital. Phase A refers to the condition where a large number of COVID-19 patients are admitted to the hospital, but limited surgical ICU beds and facilities are still accessible. In phase B, many people are affected by COVID-19, and all hospital resources are allocated for COVID 19 patients. In phase A, 4 major groups are discussed, including malignant and suspicious colorectal polyps, colon cancers, rectal cancers, and recurrent cancers. The approach to emergent cases, including obstruction, bleeding, and perforation, will be presented in phase B. Conclusion: This guideline is a comprehensive instruction on the approach to colorectal cancers during the COVID-19 pandemic that covers the major topics of colon and rectal cancers in detail.

Inhibitor development in patients with congenital factor VII deficiency, a study on 50 Iranian patients.

: Congenital factor VII (FVII) deficiency is a rare bleeding disorder with an estimated prevalence of 1 per 500 000 in the general population. On-demand replacement therapy is the main therapeutic choice in patients with congenital FVII deficiency. Inhibitor formation against exogenous FVII is very rare and can cause challenges in the management of the disorder. The present study was conducted to assess the prevalence of FVII inhibitor in 50 patients with congenital FVII deficiency under on-demand or prophylaxis treatment by recombinant activated FVII. All patients with confirmed congenital FVII deficiency were assessed for inhibitor development in regular intervals. Inhibitor titer was determined by a modified Nijmegen-Bethesda assay. The study results were analyzed by SPSS software. Among all cases, two patients (4%) developed an FVII inhibitor. Case 1 was a 14-year-old boy with severe FVII deficiency (FVII activity <1%) with regular prophylaxis. The patient was a high-responder with high-titer FVII inhibitor (170 Bethesda Unit). This patient, who had a history of intracranial hemorrhage, had undergone brain surgery three times. The second patient was a 70-years old man with on-demand therapy that also developed a high-titer inhibitor (10 Bethesda Unit). This patient had experienced easy bruising and endured a few surgeries for his brain tumor and, finally, succumbed to the disease. Although the inhibitor formation is a rare phenomenon, it may result in a significant challenge to manage the affected patients.

Spiritual Care Training for Mothers of Children with Cancer: Effects on Quality of Care and Mental Health of Caregivers.

BACKGROUND: The purpose of this study was to explore the effectiveness of a spiritual care training package in maternal caregivers of children with cancer. MATERIALS AND METHODS: This study was a quasi-experimental study with pretest and posttest design consisting of a sample of 42 mothers of children diagnosed as having cancer. Participants were randomly assigned to either an experimental or a control group. The training package consisted of seven group training sessions offered in a children's hospital in Tehran. All mothers completed the Spirituality and Spiritual Care Rating Scale (SSCRS) and the Depression, Anxiety and Stress Scale (DASS-21) at pre and post test and after a three month follow up. RESULTS: There was significant difference between anxiety and spiritual, religious, Personalized care and total scores spiritual care between the intervention and control groups at follow-up (P<0.001).There was no statistically significant difference in stress and depression scores between the intervention and the control groups at follow-up. CONCLUSIONS: Findings show that spiritual care training program promotes spirituality, personalized care, religiosity and spiritual care as well as decreasing anxiety in mothers of children with cancer and decreases anxiety. It may be concluded that spiritual care training could be used effectively in reducing distressful spiritual challenges in mothers of children with cancer.

The effects of intervention based on supportive leadership behaviour on Iranian nursing leadership performance: a randomized controlled trial.

AIMS: To assess the effects of a workshop on supportive leadership behaviour (SLB) on the performance of head nurses, using a randomized controlled trial design. BACKGROUND: The effect of transformational leadership on SLB in nursing management is emphasised. METHODS: A total of 110 head nurses working at university hospitals were included randomly in two control and intervention groups. The head nurses in the intervention group participated in supportive leadership training, but the control group did not. Performance in supportive leadership was assessed with a validated instrument, which six subordinates used to assess their head nurse (n = 731). RESULTS: There was a significant difference in SLB scores from baseline to the 3 month follow-up (P < 0.0001). Moreover, the post-intervention scores were significantly higher in the intervention group, compared with the control group (P < 0.0001). The results showed that in the intervention group, the effect sizes were greater for males (50%) than for females (36%) and greater for married participants (42%) than for single participants (37%). CONCLUSION: The workshop on supportive leadership behaviour, particularly the interactive multifaceted training, improved the leadership performance of the head nurses who participated in this study. IMPLICATIONS FOR NURSING MANAGERS: Health policy decision makers should apply SLB, which is a significant leadership style, to improve the outcomes in other groups of health-care management, such as physicians. Future studies are needed to investigate the effects of such workshops in longer periods of follow up.

Liver function and anemia pathogenesis in Iranian traditional medicine.

BACKGROUND: Nutritional deficiency, bleeding, and inflammation are three main causes of anemia. On the other hand, erythropoietin (EPO) production, iron availability, and a healthy bone marrow are essential for erythropoiesis. Recently, recombinant human erythropoietin (rhEPO) has been used to treat the patients already taking iron supplements. In Iranian traditional medicine literature, much has been written about anemia and its treatment. OBJECTIVES: This study aimed to review Iranian traditional medicine theories in the treatment of anemia. MATERIALS AND METHODS: In the present study, authors have attempted to find the etiology and pathogenesis of anemia in Iranian traditional Medicine Literature and the views of ancient physicians in this field. RESULTS: Our findings proved that Iranian traditional medicine defined anemia as blood humor production dysfunction, which is caused by several reasons mainly hepatic dysfunction. Thus, liver is supposed to be the most important organ in this regard. This will make considering hepatoprotective medicines in anemia even in patients with non-hepatic problems. CONCLUSIONS: The article presents the relation between anemia and liver dysfunction viewed by Iranian traditional medicine as an important finding in designing a treatment plan. Despite the new findings on the evaluation of liver function (i.e. laboratory tests), it seems that further studies for earlier evaluation of liver function in anemia are highly required.

Comparing live lecture, internet-based & computer-based instruction: A randomized controlled trial.

BACKGROUND: Comparing computer and internet based instruction with traditional giving lecture would provide enough evidence to identify best teaching practice. In this study, we compared lecture, interactive internet based and computer based learning regarding medical students' knowledge acquisition and satisfaction in teaching pathophysiology of hematology and oncology. METHODS: Eighty four medical students were randomized into three groups and an identical faculty member conducted the instructions through the above mentioned methods. Students' knowledge was assessed one week before and immediately after the interventions by pre and posttest. Students' satisfaction was assessed using a validated 5-point Likert scale. RESULTS: The results showed that students' satisfaction was significantly higher in interactive internet based group than other ones (p=0.05). There were a significant increase between pre and posttest scores in all groups (p=0.000). We used ANCOVA to compare score changes in the study groups, with posttest scores as the dependent factor and pretest scores as covariate and knowledge acquisition was significantly higher in interactive internet based group than other two groups (p=0.026). CONCLUSION: The study showed that although interactive internet based instruction is a difficult and time consuming method, it is recommended to integrate this method to medical curricula.

Upregulation of CD200 is associated with Foxp3+ regulatory T cell expansion and disease progression in acute myeloid leukemia.

Immunosuppression in acute myeloid leukemia (AML) is an important mechanism of tumor escape. CD200, as an immunosuppressive molecule, is overexpressed in some hematological malignancies and it has also been shown to be an independent prognostic factor in AML. In the current study, simultaneous CD200 expression and Foxp3(+) regulatory T cell levels were investigated in Iranian patients with AML by flow cytometry. We also assessed the effect of CD200-CD200R blockade on Th1 and T-reg cytokine production and T cell proliferation in autologous AML- and monocyte-DC mixed lymphocyte reactions (MLRs). ELISA assay was performed to detect IL-2, IL-12, IFN-γ, IL-10, and TGF-ß production in MLR supernatants. Expression of Foxp3, IL-10, and TGF-ß mRNAs in MLRs were detected by real-time PCR. Our results demonstrated significant overexpression of CD200 (P = 0.001) in association with higher frequencies of Foxp3(+) T cells in AML patients (r = 0.8, P < 0.001). Blocking of CD200-CD200R interaction demonstrated a significant decrease in TGF-ß and IL-10 expression in AML-DC MLRs and a significant increase in IL-12 and IFN-γ expression in monocyte-DC MLRs. Elevated T cell levels with lower Foxp3 intensity was also shown in CD200-CD200R-blocked MLRs. Expression of IL-10 mRNA declined significantly only in AML-DC MLRs where CD200-CD200R interaction was blocked and the same result was observed for TGF-ß and Foxp3 mRNA in both AML- and monocyte-DC MLRs. These data present a significant role for CD200 in suppressing anti-tumor immune response through stimulation of regulatory mechanisms in AML patients and suggest that CD200 may have a prognostic value in this malignancy and its blockade may be used as a target for AML immunotherapy.