Is oral nano-curcumin formulation a safe and effective measure for preventing cisplatin-induced nephrotoxicity in cancer patients?

Nephrotoxicity is one of the most important complications in cancer patients under treatment with cisplatin-containing regimens. Curcumin, as the most important active component of Curcuma longa, is an antioxidant and anti-inflammatory compound. In this clinical trial, we assessed the preventive effect of nano-curcumin oral formulation against cisplatin-induced nephrotoxicity in cancer patients. In this triple-blind clinical trial 30 cancer patients on cisplatin were randomly included in the treatment group, receiving nano-curcumin 40 mg capsules (n = 15) or the placebo group (n = 15) twice a day during four chemotherapy courses. Kidney function was measured at the beginning of the study and then at the end of each course of chemotherapy. There was no significant difference in acute kidney injury occurrence rate and creatinine and blood urine nitrogen serum levels between the treatment and placebo groups at the end of each chemotherapy course (P value >0.05). Just at the end of the first course, the difference was close to significant (P = 0.055). We also found no difference in mortality and recurrence rate in an average 30-month follow-up. Nano-curcumin in the prescribed dose and duration was not effective in preventing cisplatin-induced nephrotoxicity in cancer patients in comparison with the placebo. Further studies with larger sample size using different doses and duration of nano-curcumin are recommended.

Albumin: a comprehensive review and practical guideline for clinical use.

PURPOSE: Nowadays, it is largely accepted that albumin should not be used in hypoalbuminemia or for nutritional purpose. The most discussed indication of albumin at present is the resuscitation in shock states, especially distributive shocks such as septic shock. The main evidence-based indication is also liver disease. In this review, we provided updated evidence-based instruction for definite and potential indications of albumin administration in clinical practice, with appropriate dosing and duration. METHODS: Data collection was carried out until November 2023 by search of electronic databases including PubMed, Google Scholar, Scopus, and Web of Science. GRADE system has been used to determine the quality of evidence and strength of recommendations for each albumin indication. RESULTS: A total of 165 relevant studies were included in this review. Fluid replacement in plasmapheresis and liver diseases, including hepatorenal syndrome, spontaneous bacterial peritonitis, and large-volume paracentesis, have a moderate to high quality of evidence and a strong recommendation for administering albumin. Moreover, albumin is used as a second-line and adjunctive to crystalloids for fluid resuscitation in hypovolemic shock, sepsis and septic shock, severe burns, toxic epidermal necrolysis, intradialytic hypotension, ovarian hyperstimulation syndrome, major surgery, non-traumatic brain injury, extracorporeal membrane oxygenation, acute respiratory distress syndrome, and severe and refractory edema with hypoalbuminemia has a low to moderate quality of evidence and weak recommendation to use. Also, in modest volume paracentesis, severe hyponatremia in cirrhosis has a low to moderate quality of evidence and a weak recommendation. CONCLUSION: Albumin administration is most indicated in management of cirrhosis complications. Fluid resuscitation or treatment of severe and refractory edema, especially in patients with hypoalbuminemia and not responding to other treatments, is another rational use for albumin. Implementation of evidence-based guidelines in hospitals can be an effective measure to reduce inappropriate uses of albumin.

Prevention of colistin-induced neurotoxicity: a narrative review of preclinical data.

Polymyxin E or colistin is an effective antibiotic against MDR Gram-negative bacteria. Due to unwanted side effects, the use of this antibiotic has been limited for a long time, but in recent years, the widespread of MDR Gram-negative bacteria infections has led to its reintroduction. Neurotoxicity and nephrotoxicity are the significant dose-limiting adverse effects of colistin. Several agents with anti-inflammatory and antioxidant properties have been used for the prevention of colistin-induced neurotoxicity. This study aims to review the preclinical studies in this field to prepare guidance for future human studies. The data was achieved by searching PubMed, Scopus, and Google Scholar databases. All eligible pre-clinical studies performed on neuroprotective agents against colistin-induced neurotoxicity, which were published up to September 2023, were included. Finally, 16 studies (ten in vitro and eight in vivo) are reviewed. Apoptosis (in 13 studies), inflammatory (in four studies), and oxidative stress (in 14 studies) pathways are the most commonly reported pathways involved in colistin-induced neurotoxicity. The assessed compounds include non-herbal (e.g., ascorbic acid, rapamycin, and minocycline) and herbal (e.g., curcumin, rutin, baicalein, salidroside, and ginsenoside) agents. Besides these compounds, some other measures like transplantation of mitochondria and the use of nerve growth factor and mesenchymal stem cells could be motivating subjects for future research. Based on the data from experimental (in vitro and animal) studies, a combination of colistin with neuroprotective agents could prevent or decrease colistin-induced neurotoxicity. However, well-designed randomized clinical trials and human studies are essential for demonstrating efficacy.

The evaluation of atorvastatin as an adjunct to fluconazole for the anti-fungal prophylaxis in acute myeloid leukemia: a multicenter, triple-blinded, randomized clinical trial.

The development of invasive fungal infections (IFIs) is a serious complication in acute myeloid leukemia (AML) patients who undergo an induction to remission chemotherapy. Given the increased mortality in AML patients with IFI despite prophylaxis, we need to address this problem. Statins have traditionally been employed in clinical settings as agents for reducing lipid levels. Nonetheless, recent investigations have brought to light their antifungal properties in animals, as well as in vitro studies. The objective of this study was to assess the effectiveness of atorvastatin when added to the routine IFI prophylaxis regimen in patients diagnosed with AML. A randomized, multicenter, triple-blind study was conducted on 76 AML patients aged 18-70, who received either placebo or atorvastatin in addition to fluconazole. Patients were followed for 30 days in case of developing IFIs, patient survival, and atorvastatin- related adverse drug reactions. Data were analyzed with SPSS version 26.0. A level of significance of 0.05 was utilized as the threshold for all statistical tests. The data were analyzed by adjusting for the effect of age, regarding that there was a significant difference between the two groups, and showed that atorvastatin reduced the development of both probable and proven IFI (based on EORTC/MSGERC criteria) compared to placebo. IFI-free survival was also significantly better in the atorvastatin group. The incidence of developing aspergillosis did not differ between the two groups. No serious adverse events related to atorvastatin were observed. The present investigation has substantiated the antecedent in vitro and animal research on the fungicidal impact of statins and has suggested the need for additional research involving larger sample sizes and an extended duration of follow-up. Trial registration: This study was registered on the Iranian registry of clinical trials as IRCT20210503051166N1 (Date of confirmation 2021.05.03).

Evaluation of silver sulfadiazine 1%-cerium nitrate 2.2% cream efficacy and safety in moderate to severe burn patients: a single-blind randomized clinical trial.

BACKGROUND: Burn injury is a major global health crisis. Topical antimicrobials such as silver sulfadiazine (SSD) are commonly used for superficial burn wounds. SSD has a broad-spectrum antimicrobial activity and also anti-inflammatory property, but also suffers from some limitations. Therefore, some studies suggest to add cerium nitrate (CN) to SSD, as an immunomodulatory and tanning agent with antitoxic properties, but its effect on patients' mortality, length of hospital stay, and bacterial colonization is contraversial. OBJECTIVES: In this research, we evaluated the efficacy and safety of SSD 1%+CN 2.2% cream in patients with moderate to severe burn. MATERIAL AND METHODS: Twenty-two patients who fulfilled the inclusion criteria randomly were assigned to the intervention (n=7) or control (n=15) group and received SSD 1%+CN 2.2% or SSD cream 1% respectively, once daily until the complete re-epithelization or prepration of the burned skin for grafting. Intesity of pain, re-epithelialization time, required interventions, laboratory and clinical findings and final outcome were recorded. RESULTS: There was no significant difference in re-epithelialization time between the treatment and control groups (P>0.05). The same findings were reported about the required interventions and laboratory and clinical parameters. However, the final outcome and the pain score on third day were significantly better in the treatment group (P=0.017). On the other hand, all patients in the treatment group needed graft surgery. CONCLUSION: Use of SSD 1%+CN 2.2% cream did not significantly improve re-epithelization time or infection occurrence and patients' pain, but also increased graft surgery rate in comparison with SDD 1% cream in moderate to severe burns.

Cost-effectiveness and budget impact analysis of lisdexamfetamine versus methylphenidate for patients under 18 with attention-deficit/hyperactivity disorder in Iran.

BACKGROUND: Lisdexamfetamine (LDX) and Methylphenidate (MPH) are stimulant agents that have been shown to provide significant benefits in the management of attention-deficit/hyperactivity disorder (ADHD) in patients. AIM: This study aimed to assess the cost-effectiveness and the budget impact of LDX compared to MPH as the first-line treatment for ADHD. METHODS: A one-year cost-effectiveness analysis (CEA) was conducted to compare the effects of LDX and MPH in reducing disease symptoms and patient costs and improving quality of life (QoL) from a social perspective. Clinical data were obtained using the EQ-5D questionnaire. In contrast, economic data were sourced from the official website of the Iranian Food and Drug Association (FDA), the national book of tariffs, and specific questionnaires designed to evaluate patients' direct and indirect costs. 197 patients were included in the study, including individuals who sought psychiatric evaluation at a hospital in Mashhad and those who obtained ADHD medications from governmental pharmacies. The cost-effectiveness of the study medicine was assessed using the decision tree method, and the results were presented as the Incremental Cost-Effectiveness Ratio (ICER). Deterministic Sensitivity Analysis (DSA) and Probabilistic Sensitivity Analysis (PSA) were performed to assess the robustness of the findings. Additionally, a Budget Impact Analysis (BIA) was conducted over five years, considering three different scenarios, to evaluate the financial implications of incorporating LDX into the national pharmaceutical system. RESULTS: The ICER for LDX therapy compared to MPH was estimated at USD 264.28 (with an incremental cost of USD 54.9, incremental effectiveness of 0.208, and Quality-Adjusted Life Years (QALYs) gained of 0.765). The PSA indicated a 0.994% probability of LDX being cost-effective, considering a threshold of USD 2450 per QALY. Furthermore, the DSA revealed that the acquisition cost of LDX influenced the model's sensitivity. The BIA demonstrated that incorporating LDX into Iran's healthcare system would result in a financial burden of approximately $368,566 in the first year, representing an additional cost of $11,154 compared to the non-availability of this medicine and the use of previous medications. It is projected that by 2027, the financial burden of treating ADHD with LDX will reach approximately USD 443,879 over five years, amounting to an increase of $71,154 compared to the absence of this medicine. CONCLUSION: From a social perspective, the inclusion of LDX in the treatment regimen for ADHD is associated with higher costs and an increased financial burden. However, based on our analysis, LDX appears to be a cost-effective choice for managing ADHD in Iran when compared to MPH.

The efficacy of colchicine as an adjunct therapy in non-hospitalized COVID-19 patients: A randomized placebo-controlled trial.

BACKGROUND: The therapeutic potential of oral colchicine administration may help combat COVID-19 infection due to reduced disease severity and mortality risk. OBJECTIVE: This randomized trial aimed to assess the effect of colchicine treatment on the inflammatory and hematologic markers as well as clinical features in non-hospitalized patients with mild-to-moderate COVID-19 disease. METHODS: In the present placebo-controlled randomized trial, 80 non-hospitalized COVID-19 patients were enrolled and followed for 14 days. Subjects randomly received oral colchicine or placebo tablets once a day for two weeks. The fever and cough clinical signs, as well as C-reactive protein (CRP) and lymphopenia, were evaluated through the follow-up. RESULTS: No significant between-group differences were observed in terms of the duration of clinical symptoms, CRP, and lymphopenia at 0, 7, and 14 days of intervention. Although the proportion of participants with fever, cough, positive CRP, and lymphopenia was higher reduced in the colchicine group than the placebo during treatment, no significant differences were found between groups. Due to no adverse effects detected in this trial, colchicine therapy was well-tolerated and safe. CONCLUSION: Our findings revealed that colchicine adjuvant therapy had no beneficial effect on clinical and para-clinical parameters in non-hospitalized COVID-19 patients during 14 days of intervention. The present trial does not support colchicine as a potential treatment against COVID-19 disease.

The efficacy of medicinal plant preparations in the alleviation of radiodermatitis in patients with breast cancer: A systematic review of clinical trials.

Radiodermatitis in breast cancer patients varies from mild irritation to life-threatening lesions. Several studies suggest a role for topical corticosteroid ointments in the treatment of radiodermatitis. Yet, to avoid the adverse effects of corticosteroids, many authors recommend the use of topical herbal products instead. The therapeutic role of herbal treatments has yet to be fully understood. This systematic review evaluates the role of topical or oral herbal medicines in radiodermatitis prevention and treatment. A systematic search of four databases (Embase, PubMed, Web of Science, and Scopus) was performed without language and time restrictions from their inception until April 2023. The bibliographies of potential articles were also searched manually. Studies evaluated and compared the effects of herbal preparations with the control group, on dermatitis induced by radiotherapy for breast cancer. The Cochrane risk of bias tool was used to assess the included studies. Thirty-five studies were included in the systematic review. Studies which used herbal drugs including topical and oral formulations were evaluated. Herbal monotherapy and combination therapy were reported, and their effects on radiodermatitis were explained in the systematic review. In conclusion, henna ointments, silymarin gel, and Juango cream were reported to reduce the severity of radiodermatitis. These agents should be considered for radiodermatitis prophylaxis and treatment. The data on aloe gel and calendula ointment were conflicting. Further randomized controlled trials of herbal medications and new herbal formulations are required to determine their effects on breast cancer radiodermatitis.

Preventive and therapeutic use of herbal compounds against doxorubicin induced hepatotoxicity: a comprehensive review.

Doxorubicin (DOX) is associated with numerous acute and chronic dose-related toxicities including hepatotoxicity. This adverse reaction may limit the use of other chemotherapeutic agents with hepatic excretion, and so, its prevention is an important issue. The aim of this study was to conduct a comprehensive review of in vitro, in vivo and human studies regarding the protective effects of synthetic and naturally-occurring compounds against DOX-induced liver injury. The search was conducted in Embase, PubMed, and Scopus databases using the following keywords: "doxorubicin," "Adriamycin," "hepatotoxicity," "liver injury," "liver damage," and "hepatoprotective," and all articles published in English were included without time restriction. Forty eligible studies to the end of May 2022 finally were reviewed. Our results demonstrated that all of these drugs, except acetylsalicylic acid, had considerable hepatoprotective effects against DOX. In addition, none of the studied compounds attenuated the antitumor efficacy of DOX treatment. Silymairn was the only compound which is assessed in human studies and showed promising preventive and therapeutic effects. Altogether, our results demonstrated that most of compounds with antioxidant, anti-apoptosis, and anti-inflammatory properties are efficacious against DOX-induced hepatotoxicity and may be considered as a potential adjuvant agent for prevention of hepatotoxicity in cancer patients, after fully been assessed in well-designed large clinical trials.

Silymarin as a preventive or therapeutic measure for chemotherapy and radiotherapy-induced adverse reactions: a comprehensive review of preclinical and clinical data.

PURPOSE: Thus far, silymarin has been examined in several studies for prevention or treatment of various chemotherapy or radiotherapy-induced adverse reactions. In this review, we try to collect all available human, animal, and pre-clinical data in this field. METHODS: The search was done in Scopus, PubMed, Medline, and systematic reviews in the Cochrane database, using the following keywords: "Cancer," "Chemotherapy," "Radiotherapy," "Mucositis," "Nephrotoxicity," "Dermatitis," "Ototoxicity," "Cardiotoxicity," "Nephrotoxicity," "Hepatotoxicity," "Reproductive system," "Silybum marianum," "Milk thistle," and "Silymarin" and "Silybin." We included all relevant in vitro, in vivo, and human studies up to the date of publication. RESULTS: Based on 64 included studies in this review, silymarin is considered a safe and well-tolerated compound, with no known clinical drug interaction. Notably, multiple adverse reactions of chemotherapeutic agents are effectively managed by its antioxidant, anti-apoptotic, anti-inflammatory, and anti-immunomodulatory properties. Clinical trials suggest that oral silymarin may be a promising adjuvant with cancer treatments, particularly against hepatotoxicity (n = 10), nephrotoxicity (n = 3), diarrhea (n = 1), and mucositis (n = 3), whereas its topical formulation can be particularly effective against radiodermatitis (n = 2) and hand-foot syndrome (HFS) (n = 1). CONCLUSION: Further studies are required to determine the optimal dose, duration, and the best formulation of silymarin to prevent and/or manage chemotherapy and radiotherapy-induced complications.

Evaluation of serum nitric oxide synthase levels in patients with coronary slow flow based on corrected TIMI frame count.

Introduction: The coronary slow flow phenomenon (CSFP) finding in angiography is characterized by the delayed filling of the terminal vessels without significant epicardial coronary disease. The endothelium performs a vital role in cardiovascular homeostasis by releasing vasoactive substances. Endothelial cells produce nitric oxide (NO) as one of these essential compounds. Three isoforms of nitric oxide synthase (NOS) are endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), and induced nitric oxide synthase (iNOS). We aimed to determine the role of NOS in the development of CSFP as the first human study. Material and methods: A total of 129 patients who met the inclusion criteria were enrolled in the study. The patients were classified into five groups based on the results of coronary angiography: Group 1 without coronary artery disease (CAD) and without CSF, group 2 without CAD and with CSF, group 3 with CAD (< 50%) and without CSF, group 4 with CAD (50-90%) and without CSF, and group 5 with CAD and CSF. The serum level of NOS was determined in the participants. Coronary flow was quantified in patients with CSFP using the corrected TIMI frame count (CTFC) method, and the correlation between the levels of this biomarker and CTFC was investigated. Results: In this study, the NOS serum levels were not significantly correlated with the mean CTFC. Since the total amount of NOS was measured as a result of 3 isoforms of this enzyme, the lack of correlation could be related to increased iNOS level and decreased eNOS concentration. Conclusions: These results should be confirmed by more human studies.

Availability and affordability of anticancer medicines in Iran based on WHO/HAI standard survey methods.

PURPOSE: Cancer is the second leading cause of death in the world after cardiovascular disease. The present study aimed to investigate the affordability and physical access to chemotherapy drugs among patients with one of the three common cancers of the breast, stomach, and colon in the city of Mashhad, Iran, in 2021. METHODS: This was a descriptive cross-sectional study. Twenty drug stores including two public and 18 privates in Mashhad were evaluated. Data was collected by consistent stay in the drug stores or pharmacies. For each oncology medicine, selling price, lowest general price, and availability were investigated. Three approaches have been experimented to calculate the affordability of anticancer medicines in this study. RESULTS: Out of 28 studied medicines from public and private drug stores, 15 (53.5%) received very low, 8 (28.5%) relatively high, and 2 (7%) high access scores. The generic docetaxel brand's ultra-drug and trastuzumab (AryoTrust) were the most available drugs, but the doxorubicin (Ebewe), oxaliplatin (Mylan), and trastuzumab (Herceptin) were not available to the individuals with cancer. Also, the first approach (based on income decile) indicated that insured patients from all income deciles were able to pay the costs of the lowest price drugs of the DCF drug regimen, and if the patients were insured and belonged to the ninth income decile, they had the financial ability to buy drugs at the lowest price of the FLO drug regimen. CONCLUSION: Unaffordability of cancer medicines can lead to treatment abandonment and increase inequality in access to healthcare services. Therefore, this requires immediate attention of policy makers to be planned in order to ensure to reducing the costs of medicines for patients and increasing patient access to anticancer medicines.

The effect of concomitant use of Colony-Stimulating factors on bleomycin pulmonary toxicity - A systematic review and meta-analysis.

BACKGROUND: Changes in the incidence of bleomycin pulmonary toxicity (BPT) as a result of adding colony-stimulating factors (CSF) to bleomycin regimens has been investigated in numerous studies. We performed a systematic review and meta-analysis to assess the outcomes of these studies. METHODS: A systematic search was performed using Pubmed, Scopus, Web of Science, and Embase on April 2021. Studies evaluating the incidence of BPT in patients receiving bleomycin with and without CSF were included. In addition, meta-analysis was performed by pooling odds ratios using R. RESULTS: Out of 340 obtained records, our qualitative and quantitative analysis included 3234 and 1956 patients from 22 and 14 studies, respectively. The quantitative synthesis showed that addition of CSF significantly increased the risk of BPT incidence (OR = 1.82, 95 % CI: 1.37-2.40, p < 0.0001; I2 = 10.7 %). Subgroup analysis did not show any association between continent, bleomycin dose, cancer type, type of study, and pulmonary function test with BPT incidence. CONCLUSION: This systematic review and meta-analysis showed that co-administration of CSF with bleomycin increases the incidence of BPT. The physicians need to consider this finding while deciding the best strategy for this cohort of patients.

Atorvastatin Efficacy in the Management of Mild to Moderate Hospitalized COVID-19: A Pilot Randomized Triple-blind Placebo- controlled Clinical Trial.

BACKGROUND: Statins are first-line lipid-lowering agents with tolerable adverse reactions, low cost, and high availability worldwide. The potent anti-inflammatory, antioxidant, anti-thrombotic and immunomodulatory effects of statins propose them as an option against COVID-19 infection. OBJECTIVE: In this randomized triple-blind placebo-controlled clinical trial, we have investigated the atorvastatin efficacy in the management of mild to moderate hospitalized COVID-19 patients. METHODS: In this study, 52 mild to moderate hospitalized COVID-19 patients who fulfilled the inclusion criteria were allocated to the treatment group to receive 40 mg atorvastatin orally once daily for two weeks (n=26) or the placebo group (n=26). Patients' symptoms and laboratory investigations were assessed at baseline and during the follow-up period. We also evaluated the duration of hospitalization and supplemental oxygen therapy as endpoints. RESULTS: After 14-day of follow-up, the oxygen saturation (SaO2) was significantly higher, and the serum high sensitivity C-reactive protein (hs-CRP) level was lower in the treatment group compared to the placebo group. Moreover, at the end of the followup in the treatment group, the lymphocyte count was higher, and the duration of symptom resolution was shorter but not significant. Additionally, in the treatment group, the length of supplemental oxygen therapy and hospitalization duration were meaningfully shorter. Our results revealed that the mortality rate was almost twice higher in the placebo group compared to the treatment group, without any significant adverse drug reaction. CONCLUSION: Atorvastatin significantly reduces supplemental oxygen need, hospitalization duration, and serum hs-CRP level in mild to moderate hospitalized COVID-19 patients.

Antibiotic use during the first 6 months of COVID-19 pandemic in Iran: A large-scale multi-centre study.

WHAT IS KNOWN AND OBJECTIVE: Although antibiotics are ineffective against viral infections, epidemiological studies have revealed that the COVID-19 pandemic resulted in the overuse of antibiotics and disruption of antimicrobial stewardship programmes. We investigated the pattern of antibiotic use during the first 6 months of the COVID-19 pandemic in Iran. METHODS: A multi-centre retrospective study was designed to investigate the use of 16 broad-spectrum antibiotics in 12 medical centres. The rate of antibiotic use was calculated and reported based on the Defined Daily Dose (DDD) per 100 hospital bed-days. The bacterial co-infection rate was also reported. RESULTS AND DISCUSSION: Totally, 43,791 hospitalized COVID-19 patients were recruited in this study. It was found that 121.6 DDD of antibiotics were used per 100 hospital bed-days, which estimated that each patient received approximately 1.21 DDDs of antibiotics every day. However, the bacterial co-infections were detected only in 14.4% of the cases. A direct correlation was observed between the rate of antibiotic use and mortality (r[142] = 0.237, p = 0.004). The rate of antibiotic consumption was not significantly different between the ICU and non-ICU settings (p = 0.15). WHAT IS NEW AND CONCLUSION: In this study, widespread antibiotic use was detected in the absence of the confirmed bacterial coinfection in COVID-19 patients. This over-consumption of broad-spectrum antibiotics may be associated with increased mortality in hospitalized COVID-19 patients, which can be an alarming finding.

Skin ulcers as a complication of short-term use of phenazopyridine in an old man: A case report.

INTRODUCTION: Phenazopyridine is an azo dye, which exerts local anesthetic or analgesic action on urinary tract mucosa through an unknown mechanism. Besides its common complications including orange discoloration of the urine and gastrointestinal problems, it may have rare side effects like hemolytic anaemia, methemoglobinemia, renal failure, and skin changes. We reported a paraplegic man with skin ulcers on scretom and right foot after about 3 days of phenazopyridine use CASE REPORT: A 62-year-old man presented with flesh shaped deep ulcers in lower parts of the body. He declared that at first a bluish discoloration was developed in the lower extremities and scrotum skin after use of eight phenazopyridine tablets (200 mg) and then these lesions turned to blisters and ulcers and they were prurient. The patient underwent sonography and CT-angiography; however, no pathologic findings were found. He just received losartan for many years as past drug history. According to the history, a delayed drug hypersensitivity reaction was suspected and the patient wounds healed after using special type of dressings and antibiotic therapy regarding positive wound cultures. CONCLUSION: Phenazopyridine severe skin changes are hardly reported. We described a case who experienced severe skin reactions and ulcers following phenazopyridine use not related to other complications including renal dysfunction, methemoglobinemia, and hemolytic anemia.

Evaluation of the efficacy of oral nano-silymarin formulation in hospitalized patients with COVID-19: A double-blind placebo-controlled clinical trial.

Considering the outbreak pandemic of Coronavirus Disease 2019 (COVID-19), the lack of effective therapeutic strategies for the management of this viral disease, and the increasing evidence on the antiviral potential of silymarin, this study aimed to investigate the effectiveness of silymarin nanomicelles on the symptom's resolution time, laboratory parameters, and liver enzymes in patients with COVID-19. The participants were assigned to the nano-silymarin (n = 25) (receiving SinaLive soft gel, containing 70 mg silymarin as nanomicelles) or placebo groups (n = 25) three times daily for two weeks. Patients' symptoms and laboratory findings were assessed at baseline and during the follow-up period (one week and one month after the beginning of the treatment). No significant differences were observed between the two groups in terms of symptoms resolution time, laboratory parameters, and hospitalization duration (p > 0.05). However, the alanine aminotransferase level decreased significantly in the treatment group, compared to the placebo group (p < 0.001). Concomitant use of dexamethasone and remdesivir with silymarin might make the effects of silymarin on the improvement of patients' condition unclear. Further clinical trials are recommended with diverse dosages and larger sample sizes.

Saffron nephroprotective effects against medications and toxins: A review of preclinical data.

Toxin and drug-induced nephrotoxicity (DIN) account for about 25% of all acute kidney injury cases and are associated with morbidity and increased utilization of healthcare services. No approved preventive compound is available for DIN. Saffron (Crocus sativus) has important biological properties like antioxidant and anti-inflammatory effects. The protective effects of saffron and its main constituents in different tissues including the brain, heart, liver, kidney, and lung have been confirmed against some toxic materials or drugs in animal studies. This review covers all aspects of saffron's preventive and therapeutic effects against toxins and DIN including proposed mechanism of action, dosing schedule, and effects on renal biomarkers and histological changes. PubMed, Embase, Scopus, and Web of Science databases were searched by these search terms: "saffron" OR "Crocus sativus" OR "crocetin" OR "crocin "OR "safranal" AND "Drug induced nephrotoxicity" OR "Renal Injury" OR "Kidney Injury" OR "Nephrotoxicity". All 25 relevant in vitro and in vivo studies up to the date of publication were included. Promising protective effects were reported particularly on aminoglycosides, cisplatin, and ethanol. Saffron and its constituents significantly prevented biochemical and histopathological changes, mediating via antioxidant, anti-apoptosis, and anti-inflammatory effects. Despite success in animal models, no human study is available in this field and further well-designed clinical trials are necessary for better judgment.

Personality traits of patients with multiple sclerosis and their correlation with anxiety and depression levels: A cross-sectional case-control study.

OBJECTIVE: Multiple sclerosis is a chronic demyelinating disease of the central nervous system that can cause severe disability and impair the quality of life (QoL). METHODS: In the current cross-sectional, case-control study, we investigated personality traits, anxiety and depression levels, in 101 patients in the case group and 202 individuals as a control group. The personality traits of the participants were collected via the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI) questionnaire. We evaluated the level of anxiety and depression based on the Hospital Anxiety and Depression Scale questionnaire. RESULTS: Our study showed in patients with disease duration above 1 year, the rates of agreement (29.78), anxiety (8.83), and depression level (6.39) were significantly higher than the control group (27.19, 6.47, and 4.97, respectively). Although patients with disease duration below 1 year showed a higher level of agreement and conscientiousness (29.65 and 34.35, respectively) than controls (26.6 and 30.86, respectively). The level of anxiety and depression in patients with a disability index above 4.5 was significantly higher than patients with a disability index below 1. Patients with a disability index below 1 showed a higher rate of extraversion and agreement and conscientiousness (31.47, 31.53, and 35.07, respectively) than controls (25.5, 26.23, and 3033, respectively). In addition, patients with a disability index above 4.5 showed a higher level of agreement (35.64), conscientiousness (35.5), anxiety (9.64), and depression (7.5) than controls (25.96, 30.71, 6.96, and 4.71, respectively). CONCLUSIONS: In conclusion, anxiety and depression levels were much higher among MS patients compared with controls and the severity of these conditions correlate with the score of the disability index. Therefore, a complete comprehension of these conditions by the neurologist could be vital in improving patients' QoL and increasing compliance and adherence to pharmacological therapy.

Topical henna and curcumin (Alpha®) ointment efficacy for prevention of capecitabine induced hand-foot syndrome: A randomized, triple-blinded, placebo-controlled clinical.

PURPOSE: In this clinical trial, we evaluated Alpha® ointment efficacy in prevention of capecitabine induced hand-foot syndrome (HFS) in patients with gastrointestinal or breast cancers, for the first time. METHODS: During this pilot, randomized, triple-blinded, placebo-controlled clinical trial, the effect of Alpha® ointment (Lawsonia inermis 3 g and Curcuma longa 0.15 g/ 30 g) was assessed. It was applied on the palms and the soles, two times daily starting at the first day of chemotherapy for 4 consecutive courses. The severity of HFS was assessed at the end of the chemotherapy courses based on World Health Organization (WHO) scale and scored between 0-4. RESULTS: Ninety eligible patients were included randomly in the treatment or placebo group. Median WHO HFS grade was not significantly different between the two groups, during the follow-up period (P > 0.05). In the weekly assessment, the scores increased meaningfully in both the placebo and treatment groups, but there was a delay in HFS occurrence and deterioration in Alpha ointment group based on post hoc analysis. CONCLUSION: Administration of Alpha® ointment containing henna and curcumin could not significantly prevent capecitabine induced HFS during 4 courses of treatment, but can somewhat delay its occurrence in patients with gastrointestinal or breast cancer.