Effect of l-arginine compared to placebo on sexual function in women with major depressive disorder: a randomized controlled trial.

BACKGROUND: While some evidence suggests that l-arginine may improve sexual function and alleviate depression, it has not been investigated in women with depression to assess both its effects on the depression and sexual function concurrently. METHODS: Patients who had received a diagnosis of major depressive disorder, as determined by predetermined inclusion and exclusion criteria, were enrolled in this triple-blind clinical trial. Patients were divided into two groups: group A, received L-arginine 1 gram twice daily, and group B, received a placebo for four weeks. They were evaluated at baseline, after four and eight weeks with the Hamilton Depression Rating Scale (HDRS), and Rosen's questionnaire or Female Sexual Function Index (FSFI). RESULTS: A decrease in the severity of depression was observed in all patients, which was determined due to Hamilton's questionnaire (P-value < 0.001). During the time in group A, FSFI increased. Based on the FSFI questionnaire, they had improvement in some domains, including the lubrication index and orgasm index, which significantly changed in the eighth week compared to the baseline (P-value < 0.05). However, these two indicators did not change statistically significantly compared to the placebo group. CONCLUSION: L-arginine supplementation can improve sexual function, particularly lubrication and orgasm, and mood in women with depression, with minimal side effects observed. Additional research is necessary to validate these results by examining the effects of higher dosages, extended durations, and larger populations of depressed patients. TRIAL REGISTRATION: Iranian Registry of Clinical Trial: IRCT20100127003210N26.

All about blinatumomab: the bispecific T cell engager immunotherapy for B cell acute lymphoblastic leukemia.

INTRODUCTION: B cell acute lymphoblastic leukemia-lymphoma (B-ALL) accounts for approximately 75% of ALL cases and is observed in children and adults. Recent advances in disease diagnosis, stratification and prognostication have led to a better characterization of different subgroups of ALL. Notwithstanding the significant improvement in the complete remission rate of B-ALL, patients with minimal residual disease (MRD) and relapsed/refractory (R/R) settings suffer from poor outcomes. HYPOTHESIS: However, novel therapies, such as agents targeting tyrosine kinases or the CD20 molecule, combination therapies and improved supportive care, have changed the treatment landscape of B-ALL. METHOD AND RESULTS: Meanwhile, blinatumomab has been FDA-approved for MRD-positive or R/R B-ALL patients. Blinatumomab is a bispecific T cell engager containing the CD3 and CD19 that recognize domains redirecting cytotoxic T cells to lyse B cells. Promising outcomes, including long-term overall survival and improved MRD-negative response rates, have been reported in patients who received this drug. Adding blinatumomab to new ALL regimens seems promising for achieving better outcomes in poor prognosis B-ALL patients. Nevertheless, the neurotoxicity and cytokine release syndrome are the two major adverse events following the blinatumomab therapy. CONCLUSION: This review summarizes the function and effectiveness of blinatumomab in R/R and MRD positive B-ALL patients. Furthermore, blinatumomab's positive and negative aspects as a novel therapy for B-ALL patients have been briefly discussed.

Post-hematopoietic stem cell transplantation relapse: Role of checkpoint inhibitors.

Background and Aims: Despite the revolutionary effects of hematopoietic stem cell transplantation (HSCT) in treating hematological malignancies, post-HSCT relapse is considered a critical concern of clinicians. Residual malignant cells employ many mechanisms to evade immune surveillance and survive to cause relapse after transplantation. One of the immune-frustrating mechanisms through which malignant cells can compromise the antitumor effects is misusing the self-limiting system of immune response by overexpressing inhibitory molecules to interact with the immune cells, leading them to so-called "exhausted" and ineffective. Introduction of these molecules, known as immune checkpoints, and blocking them was a prodigious step to decrease the relapses. Methods: Using keywords nivolumab, pembrolizumab, and ipilimumab, we investigated the literature to figure out the role of the immune checkpoints in the HSCT setting. Studies in which these agents were administrated for relapse after transplantation were reviewed. Factors such as the interval from the transplant to relapse, previous treatment history, adverse events, and the patients' outcome were extracted. Results: Here we provided a mini-review discussing the experiences of three immune checkpoints, including nivolumab, pembrolizumab, and ipilimumab, as well as the pros and cons of using their blockers in relapse control after HSCT. In conclusion, it seems that CI therapy seems effective for this population. Future investigations may provide detailed outlook of this curative options.

Highlighting the interaction between immunomodulatory properties of mesenchymal stem cells and signaling pathways contribute to Graft Versus Host Disease management.

Background Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) has been increasingly used as a therapeutic approach for hematological malignancies. Several potential strategies have been developed for treating or preventing allo-HSCT complications, specifically graft-versus-host disease (GVHD). GVHD could significantly affect the morbidity and mortality of patients after allo-HSCT. Curative treatment and prophylaxis regimens for GVHD could reduce GVHD incidence and improve survival rate. Among these therapeutic strategies, mesenchymal stem cell (MSCs) mediated immunomodulation has been explored widely in clinical trials. MSCs immunomodulation ability in GVHD correlates with the interactions of MSCs with innate and adaptive immune cells. However, signaling pathways responsible for MSCs' impact on GVHD regulation, like JAK/STAT, NOTCH, MAPK/ERK, and NFκß signaling pathways, have not been clearly described yet. This review aims to illuminate the effect of MSCs-mediated immunomodulation in GVHD management after allo-HSCT representing the role of MSCs therapy on signaling pathways in GVHD. Conclusion MSCs could potentially modulate immune responses, prevent GVHD, and improve survival after allo-HSCT. Previous studies have investigated different signaling pathways' contributions to MSCs immunoregulatory ability. Accordingly, targeting signaling pathways components involved in MSCs related GVHD regulation is proven to be beneficial.

All about blinatumomab: the bispecific T cell engager immunotherapy for B cell acute lymphoblastic leukemia

ABSTRACT Introduction: B cell acute lymphoblastic leukemia-lymphoma (B-ALL) accounts for approximately 75% of ALL cases and is observed in children and adults. Recent advances in disease diagnosis, stratification and prognostication have led to a better characterization of different subgroups of ALL. Notwithstanding the significant improvement in the complete remission rate of B-ALL, patients with minimal residual disease (MRD) and relapsed/refractory (R/R) settings suffer from poor outcomes. Hypothesis: However, novel therapies, such as agents targeting tyrosine kinases or the CD20 molecule, combination therapies and improved supportive care, have changed the treatment landscape of B-ALL. Method and results: Meanwhile, blinatumomab has been FDA-approved for MRD-positive or R/R B-ALL patients. Blinatumomab is a bispecific T cell engager containing the CD3 and CD19 that recognize domains redirecting cytotoxic T cells to lyse B cells. Promising outcomes, including long-term overall survival and improved MRD-negative response rates, have been reported in patients who received this drug. Adding blinatumomab to new ALL regimens seems promising for achieving better outcomes in poor prognosis B-ALL patients. Nevertheless, the neurotoxicity and cytokine release syndrome are the two major adverse events following the blinatumomab therapy. Conclusion: This review summarizes the function and effectiveness of blinatumomab in R/R and MRD positive B-ALL patients. Furthermore, blinatumomab's positive and negative aspects as a novel therapy for B-ALL patients have been briefly discussed.

Errors in preparation and administration of intravenous medications in the intensive care unit of a teaching hospital: an observational study.

OBJECTIVE: To determine the frequency of medication errors that occurred during the preparation and administration of IV drugs in an intensive care unit. SETTING: The study was conducted in a 12-bed intensive care unit of one of the largest teaching hospitals in Tehran. DESIGN: Data were collected over 16 randomly selected days at different medication round times, between July and September 2006. A trained observer accompanied nurses during intravenous (IV) drug rounds. Medication errors were recorded during the observation times of IV drug administration and preparation. Drugs with the highest rate of use in the intensive care unit (ICU) were selected. Details of the process of preparation and administration of the selected drugs were compared to an informed checklist which was prepared using reference books and manufacturers' instructions. RESULTS: We observed a total of 524 preparations and administrations. The calculated number of opportunities for error was 4040. The number of errors identified were 380/4040 (9.4%). Of those, 33.6% were related to the preparation process and 66.4% to the administration process. The most common type of error (43.4%) was the injection of bolus doses faster than the recommended rate. Amikacin was involved in the highest rate of error (11%) among all the selected medications. It was found that the IV rounds conducted at 9:a.m. had the highest rate of error (19.8%). No significant correlation was found between the rate of error and the nurses' age, sex, qualification, work experience, marital status, and type of working contract (permanent or temporary). CONCLUSIONS: Since our system is devoid of a well-organized reporting system, errors are not detected and consequently not prevented. Administrators need to take the initiative of developing systems that guarantee safe medication administration.