Effect of Melissa officinalis on Chemotherapy-Induced Peripheral Neuropathy in Cancer Patients: A Randomized Trial.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant cancer treatment side effect that can influence both quality of life and treatment course. Melissa Officinalis (MO), due to its high content of flavonoids, has antioxidant, anti-inflammatory, and neuroprotective properties.  Materials and Methods: The cancer patients diagnosed with CIPN attended a referral center in Sari (Iran). The hydroalcoholic extract of MO leaves was extracted by the maceration method. The control group received a placebo along with gabapentin as the standard treatment, and the intervention group received 500 mg Melissa officinalis 2 times daily for 3 months plus gabapentin. Patients were evaluated at the baseline and 3 months later, according to Common Terminology Criteria for Adverse Effects (CTCAE) and EORTC QLQ-C30 (Integrated System for Quality of Life Assessment).  Results: A total of 40 patients were considered as group D (intervention group), and 35 patients completed the study. Out of 40 subjects in the placebo group (P), 3 patients could not tolerate the drug due to gastrointestinal disturbances. The final values of CTCAE showed a statistically significant difference (p=0.010). Indicators related to the quality of life in both groups showed a significant improvement. In the intervention group, the pain perception and diarrhea experience were significantly reduced. Conclusion: Quality of life indicators were improved by prescribing gabapentin with and without Melissa officinalis. The addition of Melissa officinalis to the chemotherapy regimen may improve diarrhea and pain perception.

Evaluation of the therapeutic effect of Descurainia sophia (L.) Webb ex Prantl seed extract on hyperthyroidism: A double-blind placebo-controlled pilot clinical trial.

The seeds of Descurainia sophia (L.) Webb ex Prantl contain goitrogenic glucosinolates, such as gluconapin (3-butenyl glucosinolate). Because of the important role of iodine in the synthesis of thyroid hormones and the inhibitory activity of D. sophia on iodine uptake by the thyroid gland, this study aimed to determine the effects of D. sophia syrup on clinical and biochemical variables of thyrotoxicosis in hyperthyroid patients. In this randomized, double-blind trial, 10 newly diagnosed hyperthyroid female patients were randomly assigned to treatment with (1) methimazole (MMI) plus D. sophia capsules (350 mg/d) or (2) MMI plus placebo capsules. The primary outcomes were clinical and biochemical manifestations of hyperthyroidism after 60 days. Serum levels of FT3 and FT4 significantly decreased (5.9 ± 2.5 vs. 9.4 ± 5.9 and 29.1 ± 3.1 vs. 31.77 ± 3.7, respectively) and the serum thyroid-stimulating hormone (TSH) concentration significantly increased in the D. sophia group contrasted to the placebo group (4.7 ± 0.1 vs. 0.05 ± 0.02). Significant improvement in the thyrotoxicosis clinical symptoms was reported in the D. sophia group contrasted to the placebo group (p < .05). D. sophia can suppress plasma levels of FT3 and FT4 and may be useful as adjunctive therapy for hyperthyroidism.

Clinical uses and safety concerns of tyrosine kinase inhibitors with a focus on novel drugs: A narrative review.

Objective:To review the safety issues surrounding tyrosine kinase inhibitors (TKIs), specifically, hematological adverse effects, cardiovascular issues, renal adverse effects and nephrotoxicity, endocrine system adverse effects, concerns related to the reproductive system, dermatological and gastrointestinal adverse effects. Data Sources: A literature search was performed through Web of Science, PubMed, Google Scholar, Scopus, and the Food and Drug Administration. Data Summary: Several safety issues have been raised following the use of TKIs. Most TKIs show hematological side effects. Considering cardiovascular toxicities, as opposed to imatinib which is relatively safe, new-generation TKIs may be associated with severe cardiovascular side effects. Both acute and chronic renal failure were reported with TKIs such as gefitinib, imatinib, pazopanib, sorafenib, and sunitinib. Many endocrine adverse effects have been reported including hypercholesterolemia and hypertriglyceridemia (with lorlatinib) and thyroid dysfunction (with dasatinib). TKIs may interfere with fetus implantation, growth, and gonadal development. Females receiving TKIs and encountering unwanted pregnancy may have a normal pregnancy, miscarriage, or an abnormality in the fetus. Skin toxicity has been identified as the most debilitating adverse effect in patients receiving EGFR-TKI. Gastrointestinal side effects are common with TKIs. Diarrhea was the most frequently reported adverse effect of many TKIs. Conclusions: TKIs are increasingly taking up a critical role in the treatment of cancers due to their specific action toward malignant cells compared to conventional cytotoxic chemotherapy. Despite a dramatic improvement in the survival of patients with cancer following approval of TKIs, various early and late adverse effects were reported.

Amlodipine: Can act as an antioxidant in patients with transfusion-dependent ß-thalassemia? A double-blind, controlled, crossover trial.

BACKGROUND AND AIM: This study aimed to assess the antioxidant effects of amlodipine in transfusion-dependent ß-thalassemia (TDT) patients. METHODS: This crossover trial consisted of two sequences (AP and PA). In the AP sequence, nine cases received amlodipine 5 mg daily (phase I) and then were switched to placebo (phase II). In PA sequence, 10 patients took the placebo (phase I) and were shifted to amlodipine (phase II). The washout period was 2 weeks. The length of each phase was 6 months. Serum malondialdehyde (MDA, µmol/L), carbonyl (protein CO, µM/L), glutathione (GSH, nM/L), and total antioxidant capacity (TAC, µmol FeSO4/L) were measured in the beginning and at the end of phases I and II. The clinical significance was viewed as a minimum change difference of 5% for each outcome between amlodipine and placebo. RESULTS: Seventeen cases completed the study. According to the baseline MDA values, the adjusted Hedges's g for MDA was -0.59, 95% confidence interval [CI] -1.26 to 0.08. After controlling the baseline protein CO values, Hedges's g computed for protein CO was -0.11, 95% CI -0.76 to 0.55. The estimated values of the adjusted Hedges's g for GSH and TAC were also 0.26, 95% CI -0.40 to 0.91, and 0.42, 95% CI -0.24 to 1.09, respectively. The change difference for MDA was 8.3% (protein CO 2.2%, GSH 3.1%, and TAC 12.9%). CONCLUSION: Clinically, amlodipine therapy is an efficacious adjuvant treatment with conventional iron chelators for improving the levels of MDA and TAC in patients with TDT.

Can cytokines response play a role in the treatment of fatal leptospirosis?

Background: The northern coastal regions of Iran are endemic for leptospirosis which may range from a subclinical illness to a progressively fatal disease. There has been growing evidence that inflammatory markers play a significant role in the severity and prognosis of leptospirosis. This study aimed to investigate inflammatory cytokines in patients with leptospirosis. Methods: This descriptive-analytical prospective study was performed in 75 patients over 18 years old who had a positive microscopic agglutination test (MAT) titer from January to June 2019. SPSS software Version 20 was used for statistical analysis and the significance level was considered as p<0.05. Results: The patients' age enrolled in this study are from 21 to 75 years with a mean and standard deviation of 48.6±14.0. The male to female ratio in our participants was 54/21. Fever was the most common symptoms in 66 (88.0%) patients, followed by myalgia in 62 (82.7%) cases. The level of interleukin 10 was significantly higher in severe illness (P=0.003) and fatal cases (p<0.028) compared with recovered patients. The level of TNF-α level was also higher in the severe illness and Weil's syndrome compared with the mild kind (P=0.022). Conclusion: Our results showed that the levels of TNF-α and IL-10 significantly increased in severe leptospirosis. Also, IL-10 was significantly higher in fatal cases. The inhibition of IL-10 production might play an important role in decreasing the risk of fatal outcomes in leptospirosis.

Ifosfamide-induced acute kidney injury in a patient with leiomyosarcoma: A case report.

BACKGROUND: Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma that is derived from smooth muscles. Ifosfamide is in use for advanced metastatic LMS. CASE: A-44-years old woman with a chief complaint of pain in the epigastric area, itching, coughing, nausea, and vomiting was referred to the emergency department. Her medical history was LMS. She had taken Ifosfamide and mesna in her last chemotherapy. Seventy percent of her liver and her left kidney were removed 4 years ago to prevent the progress of the disease. Because of the increase in the level of creatinine and urea in the initial laboratory report, a Shaldon catheter was inserted for the patient, and she was under emergency dialysis for 3 h. In addition, during the six-day hospitalization period, dialysis was done two times. Finally, the patient was discharged with improved clinical tests accompanied by a twice-weekly dialysis order. CONCLUSION: Ifosfamide is metabolized into chloroacetaldehyde, which can cause acute kidney injury. Recovery from acute kidney injury may not always be perfect and can lead to some degree of chronic kidney disease. Opposite to hemorrhagic cystitis, mesna is not effective in preventing ifosfamide's nephrotoxicity and N-acetylcysteine may be effective in the prevention of this nephrotoxicity.

Aloe vera for Prevention of Acute Radiation Proctitis in Colorectal Cancer a Preliminary Randomized, Placebo-Controlled Clinical Trial.

OBJECTIVE: To examine the preventive effects of Aloe vera in colorectal cancer patients undergoing radiotherapy. MATERIAL AND METHOD: Twenty colorectal cancer patients, who received radiation, were randomized to receive Aloe vera 3% or placebo ointment, 1 g twice daily for 6 weeks. At weekly visits, acute radiation proctitis (ARP) was evaluated by Radiation Therapy Oncology Group and clinical presentation criteria as the primary endpoint. We also evaluated secondary endpoints of quality of life, psychosocial status, by applying Hospital Anxiety-Depression (HAD) Scale and laboratory measures of quantitative measurement of C-reactive protein (CRP) as a marker for systemic inflammation. RESULTS: There was a significant improvement in the symptom index (before treatment vs. after treatment with Aloe vera) for diarrhea (p = 0.029, median score: 0.5 vs. 0.001). The overall primary and secondary outcomes favored Aloe group, while the measures of toxicity did not achieve a statistical significant difference. The lifestyle score improved significantly with A. vera (p = 004), and they also had a lower depression score in HAD scale (p = 0.008). Furthermore, quantitative CRP decreased significantly during the course of treatment with Aloe vera. CONCLUSION: The use of topical formulation of Aloe vera 3% diminishes the severity of ARP in colorectal cancer patients.

Pharmacological Interventions for the Prevention and Treatment of Kidney Injury Induced by Radiotherapy: Molecular Mechanisms and Clinical Perspectives.

More than half of cancer patients need radiotherapy during the course of their treatment. Despite the beneficial aspects, the destructive effects of radiation beams on normal tissues lead to oxidative stress, inflammation, and cell injury. Kidneys are affected during radiotherapy of abdominal malignancies. Radiation nephropathy eventually leads to the release of factors triggering systemic inflammation. Currently, there is no proven prophylactic or therapeutic intervention for the management of radiation-induced nephropathy. This article reviews the biomarkers involved in the pathophysiology of radiation-induced nephropathy and its underlying molecular mechanisms. The efficacy of compounds with potential radioprotective properties on amelioration of inflammation and oxidative stress is also discussed. By outlining the approaches for preventing and treating this critical side effect, we evaluate the potential treatment of radiation-induced nephropathy. Available preclinical and clinical studies on these compounds are also scrutinized.

Efficacy and Safety of 0.25% Timolol Gel in Healing Split-Thickness Skin Graft Site.

As a common intervention among burn patients, skin graft has some risks such as infections and delay of wound healing. The aim of this study was to assess the efficacy and safety of topical 0.25% Timolol Gel (TG) in promoting wound healing in split-thickness skin graft donor sites. We conducted a double-blind, randomized clinical trial to assess re-epithelialization time, the level of pain based on the Visual Analog Scale (VAS), and the wound infection incidence. The scar status was also evaluated by the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). Totally, 64 patients were randomly assigned to the study groups. The two groups showed a significant difference in healing time (14.5 ± 3.2 vs. 11.5 ± 2.3 days, P < 0.001). No infection occurred in either group, and 3 cases of transplant rejection were observed in the placebo group. The VAS was significantly different on days 1, 2, 3, 4, and 7 (P < 0.05). In the third month, the results showed a significant difference in terms of VSS (P = 0.005). Topical TG, due to its favorable effects on wound healing and pain reduction, can be administered as a therapeutic agent in patients with a skin graft.

Malus domestica reduces chemotherapy-induced nausea and vomiting: A randomized double-blind placebo-controlled clinical trial.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is considered as the most common complications of chemotherapy which has a detrimental influence on the quality of life of patients with cancer. We assessed the efficacy of Apple (Malus domestica) syrup for reducing CINV. MATERIALS AND METHODS: This study was a randomized, double-blind, placebo-controlled trial carried out in a Hematooncology Clinic affiliated to Mazandaran University of Medical Sciences, Sari, Iran (from October 2017 to August 2018). Subjects were randomly allocated to receive apple syrup or placebo along with their previous antiemetic treatment and chemotherapy regimen, three times a day. Thirty-four patients received apple syrup (n = 16) or placebo (n = 18). Statistical analysis was conducted using SPSS software Version 21® (SPSS Inc., Chicago, IL, USA). A P < 0.05 indicated statistical significance. RESULTS: Both acute and delayed nausea grades were significantly lower in M. domestica syrup in comparison to placebo syrup (P = 0.001 and 0.001, respectively). The duration of nausea (P = 0.04) was lower in intervention group compared to placebo group. CONCLUSION: These findings demonstrated that M. domestica syrup can reduce the severity and duration of nausea in cancer patients who received chemotherapy.

A narrative review on adverse effects of dasatinib with a focus on pharmacotherapy of dasatinib-induced pulmonary toxicities.

Chronic myeloid leukemia (CML), a myeloproliferative disorder caused by the over activity of BCR-ABL1 (breakpoint cluster region-Abelson), has been successfully treated by Tyrosine kinase inhibitors (TKIs). While imatinib is known as the first-line treatment of CML, in some cases other TKIs including dasatinib, nilotinib, bosutinib, and ponatinib may be preferred. Dasatinib, a second-generation TKI, inhibits multiple family kinases including BCR-ABL, SRC family kinases, receptor kinases, and TEC family kinases. It is effective against most imatinib-resistant cases except T315I mutation. Despite the superiority of dasatinib in its hematologic and cytogenetic responses in CML compared to imatinib, its potentially harmful pulmonary complications including pleural effusion (PE) and pulmonary arterial hypertension (PAH) may limit its use. Appropriate management of these serious adverse reactions is critical in both improving the quality of life and the outcome of the patient. In this narrative review, we will scrutinize the pulmonary complications of dasatinib and focus on the management of these toxicities.

Pentoxifylline effects on hospitalized patients with COVID19: A randomized, double-blind clinical trial.

Pentoxifylline (PTX) has broad-spectrum properties such as anti-inflammatory, anticoagulant, and antiviral effects. The aim of this study was to evaluate the efficacy and safety of PTX in hospitalized patients with COVID-19. This double-blind, placebo-controlled randomized clinical trial was conducted on hospitalized patients with COVID-19. The recruited patients were randomly (1:1) assigned to the PTX group and the placebo group. The intervention group received PTX capsules at a dose of 400 mg three times a day for 10 days along with the national regimen, including interferon plus lopinavir/ritonavir and hydroxychloroquine. The primary outcome was the improvement of clinical scores. The secondary outcomes, on the other hand, were improvement in inflammatory and oxidative stress factors and hospital complications. From a total of 102 patients who met the inclusion criteria, 72 individuals completed the study and were analyzed. No significant differences were shown in demographics and baseline clinical characteristics. Clinical scores was not significant between the two groups (P = 0.31 and 0.07 for day 5 and 11, respectively). Although the mean serum levels of interleukin-6 (IL-6) and glutathione changed significantly after 5 days in the PTX group (P = 0.03 and p = 0.04), ICU admission, intubation, and hospital stay did not differ between the two groups. The results of our study did not show any superiority of PTX over placebo in improving the clinical outcomes of patients with COVID-19. Although PTX had a beneficial effect on IL-6 and showed an acceptable safety profile, it did not offer any clinical benefit for COVID-19 complications.

Efficacy and Safety of Adding Olanzapine to the Standard Preventive Regimen for Chemotherapy-induced Nausea and Vomiting in Children: A Randomized Double-blind Controlled Trial.

This study aimed to assess the additive value of olanzapine to a combination of ondansetron and dexamethasone to prevent chemotherapy-induced nausea and vomiting (CINV) in pediatric patients. A total of 40 patients between 4 to 18 years of age were enrolled in this randomized clinical trial. Both groups received a combination of ondansetron and dexamethasone, and 0.14 mg/kg olanzapine or matched placebo were administered for olanzapine and control groups, respectively. The primary end points were complete response and lack of nausea as far as three days after chemotherapy evaluated by the Common Terminology Criteria for Adverse Effects (CTCAE) v5.0 and the Multinational Association of Supportive Care in Cancer (MASCC) Anti-emesis Tool (MAT). Side effects of olanzapine were also analyzed. In patients receiving the standard regimen of ondansetron and dexamethasone, nausea was observed in 10.5% and 21% of patients according to MAT and CTCAE scales, respectively. In the olanzapine group, 37.5% (MAT scale) and 31.3% (CTCAE scale) of patients developed nausea. Complete response was observed in 84% (MAT scale) and 94.7% (CTCAE scale) of patients in the placebo group receiving ondansetron and dexamethasone. In comparison, it was observed in 87.5% (MAT scale) and 81.25% (CTCAE scale) for patients allocated to the olanzapine group. Neither acute nor delayed CINV was statistically different between placebo and olanzapine groups. The frequency of adverse effects was higher in the olanzapine group. Adding olanzapine to the standard regimen of CINV prophylaxis was only unhelpful in pediatric patients receiving moderately emetogenic chemotherapy but also associated with a higher rate of minor side effects.

Prediction of pharmacokinetic values of two various dosages of caffeine in premature neonates with apnea.

OBJECTIVES: Despite extensive caffeine use in preterm infants, the pharmacokinetics (PKs) data are limited because of the studies are complicated to do in these patients. This research was investigated the PK profile of two various dosages of caffeine in premature neonates. MATERIALS AND METHODS: The PK values of caffeine in premature neonates with Apnea were predicted by using all of computer-based simulation (Simcyp®), population-based PK, and modeling (P-Pharm®). We assayed the plasma levels of caffeine in two groups. The information was analyzed utilizing nonlinear mixed-effects modeling approach. The PK parameters were assessed simulating virtual clinical considers with subjects got 20 mg. kg-1 of caffeine in both groups, which was followed by a 5 mg. kg-1 once daily in Group 1 or 2.5 mg. kg-1 twice daily in Group 2. All statistical analysis was executed utilizing SSPS issue 19 and a P value of 0.05 was chosen significance. RESULTS: In the present study, the means CL, volume of distribution, and T1/2 of caffeine in preterm infants were 0.0476 L. h-1, 1.1081 L, 16.2284 h, respectively. Whereas our simulated means by Simcyp were 0.090 L. h-1, 1.841 L, and 14.653 h in Group 1 and 16.223 h in Group 2, respectively. CONCLUSIONS: There was overall good agreement between predicted and measured PK values in our study. This study provides an initial demonstration of Simcyp simulation advantage on anticipating of PK parameters.

Mometasone furoate nasal spray in the treatment of patients with COVID-19 olfactory dysfunction: A randomized, double blind clinical trial.

The aim of this study was to evaluate the usage of mometasone furoate nasal spray in the recovery of patients with severe microsmia or anosmia induced by COVID-19. This was a prospective clinical trial on non-hospitalized adult patients with COVID-19 (>18 years) who had severe microsmia or anosmia within two weeks. The subjects were randomly assigned to the mometasone furoate group (100 mcg twice daily) or sodium chloride group (0.9%); both groups also received olfactory training for 4 weeks. The primary outcome was the improvement of the olfactory score at the end of the study. Visual analog scale (VAS) and the University of Pennsylvania Smell Identification Test (UPSIT) were used to assess primary outcome. A total of 80 patients were recruited, 77 of them completed the study and were analyzed. There was no statistically significant difference in terms of demographics and baseline clinical characteristics. The olfactory scores (based on VAS) at weekly intervals showed a significant difference between the two groups (P:0.318, <0.001, <0.001, <0.001, respectively). The analyses also showed significant within-group differences from baseline. Nevertheless, the changes were not significant between the two groups (P: 0.444, 0.402, 0.267, 0.329). There was no significant difference between the two groups in terms of the UPSIT results (p > 0.239). However, a significant between-group difference was noted in the severity of loss of smell (P < 0.001). Compared to olfactory training, mometasone furoate nasal spray combination with olfactory training showed a higher improvement in severe chronic anosmia by COVID-19.

A double-blind, controlled, crossover trial of amlodipine on iron overload status in transfusion dependent ß-thalassemia patients.

BACKGROUND AND AIM: This study examined whether administration of amlodipine could improve myocardial iron loading status in patients with transfusion dependent ß-thalassemia (TDT), through a placebo-controlled, crossover study. METHODS: Amlodipine (5 mg, daily) or placebo were prescribed to all patients (n = 19) for 6 months, and after a 2-week washout period, patients were crossed over to the other group. The efficacy of amlodipine on iron loading was assessed by measuring myocardial T2*-weighted magnetic resonance imaging (MRI T2*, millisecond [ms]) and serum ferritin (ng/mL). RESULTS: Seventeen patients completed the study. The mean ± standard deviation [SD] of myocardial MRI T2* at baseline was 9.83 ± 2.67 ms Myocardial MRI T2* value rose to 11.44 ± 4.14 ms post amlodipine treatment in all patients. After placebo, myocardial MRI T2* value reached 10.29 ± 4.01 ms After controlling the baseline measures, Hedges's g for ferritin and myocardial MRI T2* outcomes were estimated 3.84 (95% confidence interval [CI] 2.68 to 4.97) and -1.80 (95% CI -2.58 to -0.10), respectively. CONCLUSION: Amlodipine might improve myocardial MRI T2* and serum ferritin level compared to placebo. However, larger clinical studies are needed to confirm the results.

Nanocurcumin as an Add-on to Antipsychotic Drugs for Treatment of Negative Symptoms in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study.

PURPOSE/BACKGROUND: It is well documented that one of the pathophysiological mechanisms of negative symptoms in patients with schizophrenia is hypofunction of N-methyl-d-aspartate receptors. This double-blind, placebo-controlled clinical trial was designed to assess the efficacy and safety of nanocurcumin as an adjuvant agent on psychotic symptoms, especially negative symptoms, in patients with chronic schizophrenia. METHODS/PROCEDURES: Fifty-six inpatients with stable chronic schizophrenia and predominant negative symptoms were randomized in a 1:1 ratio to nanocurcumin soft gel capsule (160 mg/d) and control groups, along with their antipsychotic regimen for 16 weeks. The efficacy of treatment was assessed by Positive and Negative Syndrome Scale, Calgary Depression Scale for Schizophrenia, Clinical Global Impressions-Severity, and Clinical Global Impressions-Improvement scales. Extrapyramidal symptoms were evaluated by Simpson-Angus Scale and Barnes Akathisia Rating Scale. Patients were assessed at baseline and weeks 4, 8, 12, and 16 after the medication started. FINDINGS/RESULTS: No significant differences were observed in demographic or clinical variables between both groups at baseline. The nanocurcumin group showed significantly greater improvement on the negative subscale (P = 0.05), the general psychopathology subscale (P < 0.001), the positive subscale (P = 0.004), total Positive and Negative Syndrome Scale (P < 0.001), Clinical Global Impressions-Severity (P < 0.001), and Clinical Global Impressions-Improvement scores (P < 0.001) in comparison with the control group at the endpoint. Extrapyramidal symptom rating scales and Calgary Depression Scale for Schizophrenia and frequency of other adverse effects were comparable between 2 groups. IMPLICATIONS/CONCLUSIONS: The present study indicates nanocurcumin as a safe and potential adjunctive treatment strategy for treatment of primary negative symptoms of schizophrenia.

Can Use of Silymarin Improve Inflammatory Status in Patients with ß-Thalassemia Major? A Crossover, Randomized Controlled Trial.

BACKGROUND: In ß-thalassemia major (ß-TM) patients, iron overload is one of the main causes of inflammation. This study investigated whether use of silymarin could improve inflammatory status in patients with ß-TM and iron overload, through a placebo-controlled, crossover study. METHODS: Silymarin (140 mg, 3 times a day) or placebo were prescribed to all patients (n = 82) for 12 weeks, and after a 2-week washout period, patients were crossed over to the other group. The efficacy of silymarin was assessed by measuring serum C-reactive protein (CRP) (mg/dL), interleukin (IL)-6 (pg/mL), and IL-10 (pg/mL). RESULTS: Sixty-nine patients completed the study. Data analysis showed that compared to the placebo, silymarin could decrease CRP, IL-6, and raise IL-10 significantly (the p values for all variables were <0.001). Cohen's d for CRP adjusted according to the baseline CRP value was -1.72, the 95% confidence interval (CI) -2.12 to -1.33. The adjusted Cohen's d equal to -1.12, 95% CI -1.48 to -0.76, and 0.78, 95% CI 0.43-1.12, were also estimated for IL-6 and IL-10, respectively. CONCLUSION: The results of the current study demonstrate that the combination of iron chelation therapy with silymarin can improve inflammatory status in patients with ß-TM in the clinical setting.

Clinical Effectiveness of a High Dose Versus the Standard Dose of Meropenem in Ventilator-associated Pneumonia Caused by Multidrugresistant Bacteria: A Randomized, Single-blind Clinical Trial.

BACKGROUND: Meropenem standard doses are based on the minimum inhibitory concentration of sensitive pathogens and the pharmacokinetic parameter of not critically ill patients. We compared the efficacy of high versus standard dose of meropenem in ventilator-associated pneumonia (VAP). ; Methods: 24 out of 34 eligible patients were randomized to receive meropenem 3 g q8h (high dose group, 11 patients) or 2 g q8h (standard-dose group, 13 patients) as a 3h infusion. The primary outcome was considered as clinical success that was defined as stable hemodynamic, improved sequential organ failure assessment (SOFA) score, stable or improved PaO2/FiO2 after 7 days. Sputum culture was taken before the intervention. ; Results: Clinical success rate was not significantly different between the high and standard-dose group (54.5% vs. 38.5%, P= 0.431). There was a significant difference in the reduction of clinical pulmonary infection score (CPIS) compared to a high dose to the standard group (P=0.038). SOFA score declined significantly in the high dose group throughout the study (P=0.006). A shorter duration of VAP treatment was recorded in the high dose group (P=0.061). We did not observe any significant adverse event related to meropenem. Acinetobacter spp. (34.8%), Klebsiella spp. (32.6%) and Pseudomonas aeruginosa (19.5%) isolated more frequently from sputum cultures. ; Conclusion: Treatment with the high dose of meropenem seems to be safe. However, it did not provide a significantly higher clinical success rate in comparison with the standard dose, but could be considered as an appropriate empirical treatment in patients with severe infection due to reduction in SOFA and CPIS. ; The trial protocol was registered with IRCT.ir (registration number IRCT2010010700 3014N19 in April 2018).