Hypertensive Crisis Associated with Serotonin Syndrome Following Linezolid Administration: Report of Two Cases.

INTRODUCTION: Serotonin syndrome is a potentially life-threatening condition that can occur as a result of the therapeutic use of serotonergic medications or drug interaction. In this study, we describe two cases of serotonin syndrome-associated hypertensive crisis following linezolid use. CASE PRESENTATION: The first patient was a 52-year-old female who was admitted due to a diabetic foot infection and pneumonia associated with a decreased consciousness level. Serotonin syndrome occurred 24 hours after starting the linezolid use. Resistant hypertension was the main hemodynamic finding. It could not be controlled with amlodipine, valsartan, prazosin, and nitroglycerin infusion. Resistant hypertension and other symptoms of serotonin syndrome were resolved about 48 hours after discontinuation of linezolid use. The second case was a man with a history of kidney transplant, diabetes, and hypertension. He was admitted to the ICU due to severe COVID-19 broad-spectrum antibiotics [linezolid, cefepime], and remdesivir was initiated. Following intubation, continuous infusion of fentanyl was used for sedation. Within 24 hours after fentanyl and linezolid initiation, severe agitation, eye clonus, hyperreflexia, hypertension [160-186 /90-110 mmHg], and tachycardia [>100/min] were noted. With the possible diagnosis of serotonin syndrome, fentanyl was discontinued, and morphine was initiated. The patient's symptoms improved 48 hours after discontinuation of fentanyl. CONCLUSION: Both of the patients had a history of controlled hypertension. However, serotonin syndrome occurred following the use of linezolid and concomitant/recent use of serotonergic agents. A thorough evaluation of the patient's medical history and current situation can help clinicians prevent this syndrome in critically ill patients.

Methotrexate-induced Severe Pancytopenia in a Patient with Rheumatoid Arthritis: A Case Report and Review of Literature.

Toxicity associated with low doses of methotrexate (MTX) is low, but it may be fatal. Bone marrow suppression and mucositis are among the common side effects of low dose MTX toxicity. Different risk factors have been reported for toxicities associated with low doses of MTX, including accidental use of higher doses, renal dysfunction, hypoalbuminemia, and polypharmacy. In this paper, we present a female patient who had mistakenly used 7.5 mg of MTX daily instead of the same dose of MTX on Thursday and Friday. She was presented with mucositis and diarrhea to the emergency department. Moreover, we searched the databases Scopus and PubMed for available studies and case reports on toxicities associated with MTX dosing errors. The most frequently observed toxicities included gastrointestinal lesions, nausea, vomiting, skin lesions, and bone marrow suppression. Leucovorin, hydration, and urine alkalinization were among the most frequently used treatments. Finally, we summarize the data on the toxicities of low doses of MTX in different diseases.

Hypertension medication from guidelines to practice: A cohort study in western Iran.

PURPOSE: Hypertension (HTN) is one of the most common risk factors for non-communicable chronic diseases. The aim of the current study is to evaluate the prescribing patterns of antihypertensive medications in Kermanshah Province, west of Iran. METHODS: The Ravansar Non-Communicable Diseases (RaNCD) cohort study is the first Kurdish community-based study; subjects' age ranged from 35 to 65 years. In order to examine the use of medications to control blood pressure, participants were asked to bring all prescribed medications to the study center. Treatments were compared with 2013 European Society of Hypertension (ESH)/European Society of Cardiology (ESC) Guidelines for the management of arterial HTN. RESULTS: From a total of 10 040 participants in RaNCD cohort, 1575 (15.7%) individuals were hypertensive, of whom, 1271 (80.7%) people were aware of their condition. From 1153 (73.20%) people under treatment, 840 (72.8%) had their HTN properly controlled. The most common medications used to treat HTN were losartan (27.5%), metoprolol (14.3%), and captopril (11.9%). Regardless of type of treatment, 49.3% of all patients have received the medication for l 6 ≥ years. The most commonly used drugs were ß-blockers and angiotension receptor blockers as 620 (31.0%) and 612 (30.6%), respectively. Multivariable analysis showed that female gender, those receive ≥3 antihypertensive agents, and using preferred combinations were associated with a better blood pressure control. In addition, the probability of hypertension control was less likely with increasing duration of treatment (i.e >6 years) and in obese patients with ≥35 kg/m2 . CONCLUSIONS: Even though adherence to the international guidelines was acceptable, improvements can be made for better control of HTN. Therefore, it is imperative to educate healthcare professionals on improving their selection of antihypertensive medications and combination therapy for hypertensive patients.

Evaluation of Crocin Effect on Contrast-Induced Nephropathy Following Coronary Angiography or Angioplasty: A Randomized Controlled Trial.

Contrast-induced nephropathy (CIN) is the third cause of hospital-acquired acute kidney injury. The CIN prophylactic strategies adopted to date, although not highly efficient, are mostly based on antioxidant activity and hydration therapy. This study was designed and conducted to evaluate crocin's efficacy in the prevention of CIN in chronic kidney disease (CKD) patients undergoing coronary angiography/angioplasty. In this randomized clinical trial, a total of 110 eligible CKD stage 3 patients requiring contrast agent administration for coronary angiography/angioplasty were enrolled and randomly assigned to either crocin (n = 57) or control (n = 53) group. The patients in both groups received standard hydration therapy; nevertheless, in the crocin group, the patients were also orally administered three consecutive oral doses of 30 mg crocin tablets 1 day before up to 1 day after contrast media (CM) exposure. The primary endpoint was CIN incidence defined as an increase in serum creatinine (SrCr) level by ≥ 0.3 mg/dL or any change in urinary neutrophil gelatinase-associated lipocalin (NGAL) from the baseline within 48 hours of CM exposure. During 4 months, 130 patients were recruited. The mean age of the patients was 65.62 ± 9.05 years, and the majority of them were male (64.54%). The SrCr in the crocin group did not significantly increase within 48 hours of angiography/angioplasty. The changes in the urinary NGAL level were not significant in both groups. The CIN incidence was significantly lower in the crocin group than in the control group (1.75% and 13.2%; P = 0.028). Crocin administration plays an important nephron-protective role in the prevention of CIN.

Antimicrobial safety considerations in critically ill patients: part II: focused on anti-microbial toxicities.

INTRODUCTION: Antibiotic prescription is a challenging issue in critical care settings. Different pharmacokinetic and pharmacodynamic properties, polypharmacy, drug interactions, and high incidence of multidrug-resistant microorganisms in this population can influence the selection, safety, and efficacy of prescribed antibiotics. AREAS COVERED: In the current article we searched PubMed, Scopus and Google Scholar for neurotoxicities, hematologic toxicity and fluid stewardship in intensive care units. EXPERT OPINION: Critically ill patients who receive antimicrobial agents should be monitored for neurological, hematologic toxicities especially seizure, thrombocytopenia, and clostridioides infections. Other toxicities including QTc prolongation, electrolyte disturbances, liver enzyme elevation, and infusion-related reactions were being considered. Other changes, including fluid overload, hypoalbuminemia, augmented renal clearance, increased cardiac outputs in septic shock, and acute kidney injury, may influence treatment efficiency and patient outcome.

Antimicrobial safety considerations in critically ill patients: part I: focused on acute kidney injury.

INTRODUCTION: Antibiotic prescription is a challenging issue in critical care settings. Different pharmacokinetic and pharmacodynamic properties, polypharmacy, drug interactions, and high incidence of multidrug-resistant microorganisms in this population can influence the selection, safety, and efficacy of prescribed antibiotics. AREAS COVERED: In the current article, we searched PubMed, Scopus, and Google Scholar for estimating renal function in acute kidney injury, nephrotoxicity of commonly used antibiotics, and nephrotoxin stewardship in intensive care units. EXPERT OPINION: Early estimation of kidney function with an accurate method may be helpful to optimize antimicrobial treatment in critically ill patients. Different antibiotic dosing regimens may be required for patients with acute kidney injury. In many low-resource settings, therapeutic drug monitoring is not available for antibiotics. Acute kidney injury may influence treatment effectiveness and patient outcome.

Measured versus estimated creatinine clearance in critically ill patients with acute kidney injury: an observational study.

BACKGROUND: Acute kidney injury (AKI) commonly occurs in critically ill patients. Estimation of renal function and antibiotics dose adjustment in patients with AKI is a challenging issue. METHODS: Urinary creatinine clearance was measured in a 6-hour urine collection from patients with acute kidney injuries. The correlations between different formulas including the modified Cockcroft-Gault, modification of diet in renal disease, chronic kidney disease-epidemiology collaboration, Jelliffe, kinetic-glomerular filtration rate (GFR), Brater, and Chiou formulas were considered. The pattern of the prescribed antimicrobial agents was also compared with the patterns in the available resources. RESULTS: Ninety-five patients with acute kidney injuries were included in the research. The mean age of the participants was 63.11±17.58 years old. The most patients (77.89%) were in stage 1 of AKI according to the Acute Kidney Injury Network criteria, followed by stage 2 (14.73%) and stage 3 (7.36), respectively. None of the formulations had a high or very high correlation with the measured creatinine clearance. In stage 1, Chiou (r=0.26), and in stage 2 and 3, kinetic-GFR (r=0.76 and r=0.37) had the highest correlation coefficient. Antibiotic over- and under-dosing were frequently observed in the study. CONCLUSIONS: The results showed that none of the static methods can predict the measured creatinine clearance in the critically ill patients. The dynamic methods such as kinetic-GFR can be helpful for patients who do not receive diuretics and vasopressors. Further studies are needed to confirm our results.

Remdesivir-Associated Significant Bradycardia: A Report of Three Cases.

Recently, remdesivir was approved by the United States Food and Drug Administration for patients with Coronavirus disease 2019 (COVID-19). We herein describe 3 patients with COVID-19 who showed significant bradycardia and QTc prolongation after remdesivir administration. Bradycardia did not respond to atropine treatment in 2 of the patients, one of whom received theophylline and the other required a temporary pacemaker. Fortunately, the patients' heart rate and rhythm returned to normal after the discontinuation of remdesivir, albeit it lengthened their hospital stays. Careful monitoring during remdesivir infusion may decrease the risk of adverse cardiovascular side effects.

Analysis of QTc Interval during Levofloxacin Prescription in Cardiac Patients with Pneumonia.

BACKGROUND: Medications induced QT prolongation could cause ventricular arrhythmia, torsade de pointes, and death. OBJECTIVE: The purpose of this study was to evaluate the magnitude of QTc interval prolongation as a result of levofloxacin treatment in patients admitted to cardiology wards. METHODS: This was a cross-sectional study conducted in the coronary care units and general wards of the Imam Ali Heart Hospital in Kermanshah, Iran. The QTc interval was determined at baseline and after 72 hours of levofloxacin administration. Changes in the QTc interval before and after the levofloxacin prescription were determined. RESULTS: The mean age of recruited patients was 63.26 ± 14.56 years. More than 80% of patients who received levofloxacin experienced QTc prolongation. The QTc interval was increased significantly after levofloxacin administration (15.68 ± 26.84 milliseconds) (p<0.001). These changes remained significant after excluding medications with QTc lengthening properties (p<0.001). CONCLUSION: Treatment with levofloxacin in patients with heart disease increases the risk of QT prolongation.

Efficacy and safety of Achillea wilhelmsii C. Koch capsules on symptom severity and quality of life in patients with irritable bowel syndrome: a randomized, placebo-controlled clinical trial.

Background Irritable bowel syndrome (IBS) is one of the most common digestive diseases. The aim of this clinical trial was to determine the effectiveness of Achillea wilhelmsii C. Koch on the symptom severity and quality of life (QOL) in patients with IBS. Methods The patients were randomized into two groups of 45 each. The QOL and symptom severity of the patients were evaluated at baseline and at completion of the treatments by means of IBS-QOL and IBS severity index. Results The mean severity of clinical symptoms in the Achillea wilhelmsii C. Koch receiving groups before and after the treatment was 282.56 ± 103.57 and 178.06 ± 88.40, and in the placebo group was 265.93 ± 93.56 and 197.74 ± 106.26, respectively. The mean QOL in the Achillea wilhelmsii C. Koch receiving group before and after treatment was 51.49 ± 11.98 and 50.44 ± 13.39 and in the placebo group was 60.71 ± 11.97 and 58.39 ± 11.67, respectively. In both groups, there was a significant difference in the recovery rate in each group (p<0.05). However, the mean difference between the two groups before and after intervention was not significantly different (p>0.05). Also, no patient reported any adverse events during the trial. Although the symptom severity and QOL in both groups were improved compared to those before intervention, there was no significant difference between the two groups. Conclusion It is recommended to conduct future studies with larger sample size and longer treatment periods, and also investigate the efficacy on the IBS subtypes, separately.

Urine ratio of neutrophil gelatinase-associated lipocalin to creatinine as a marker for early detection of cisplatin-associated nephrotoxicity.

INTRODUCTION: Cisplatin is a widely used chemotherapeutic agent with a major side effect of nephrotoxicity. Delayed increase in serum creatinine after cisplatin injection makes serum creatinine not to be an ideal marker for early detection of cisplatin nephrotoxicity. Recently several new biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) have been proposed for early detection of acute kidney injury (AKI). This study assessed kinetic of urine NGAL-creatinine ratio in patients who received cisplatin-containing chemotherapy. MATERIALS AND METHODS: Patients with a glomerular filtration rates greater than 45 mL/min who received cisplatin-containing chemotherapy were included. Urine creatinine and NGAL concentrations were measured before cisplatin infusion and 6, 24, 48, and 72 hours after cisplatin administration. To minimize hydration effects, urine NGAL levels were adjusted according to urine creatinine. RESULTS: Twenty-four patients were assessed. According to the Acute Kidney Injury Network criteria, 2 patients (8%) experienced cisplatin-associated AKI. The median increases in urine NGAL-creatinine ratio  were 335% (interquartile range, 320% to 350%) in the patients with AKI and 100% (interquartile range, 73% to 190%) in those without AKI (P = .02) during the first 24 hours after cisplatin administration. A urine NGAL-creatinine ratio greater than 26.9 ng/mg 24 hours after cisplatin infusion had a sensitivity of 86% and a specificity of 50% to detect cisplatin-associated nephrotoxicity. CONCLUSIONS: Urine NGAL-creatinine ratio significantly increased in patients with cisplatin-associated AKI. Urine NGAL-creatinine ratio within the first 24 hours after cisplatin infusion may better predict cisplatin-associated nephrotoxicity than serum creatinine level.

Colistin: efficacy and safety in different populations.

This article reviews mechanisms, incidences, risk factors and preventive modalities of colistin toxicity as well as colistin use in special populations and through special routes. All clinical studies that examined the pharmacokinetic/pharmacodynamic, efficacy and side effects of colistin in the management of multidrug-resistant organisms in different patient population including pediatrics, adults, obese, critically ill, burn or cancer patients with any route of drug administration were considered. Compared with older recommended doses, current dosing approach improves cure rate without significant increase in the rate of colistin-induced nephrotoxicity. Efficacy and safety of high doses of colistin should be considered in the future studies. Also comparing efficacy and safety of different doses of aerosolized colistin and defining the appropriate dose in different populations is another open area of future researches.

Effect of Silymarin Administration on Cisplatin Nephrotoxicity: Report from A Pilot, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

Despite several introduced preventive modalities, cisplatin nephrotoxicity remains a clinical problem. Some in vitro and in vivo studies have addressed the protective effects of silymarin against cisplatin nephrotoxicity. This study evaluated the effects of silymarin administration on cisplatin nephrotoxicity as the first human study. During this pilot, randomized, double-blinded, placebo-controlled clinical trial, the effect of oral silymarin 420 mg daily in three divided doses starting 24-48 h before the initiation of cisplatin infusion and continuing to the end of three 21-day cisplatin-containing chemotherapy courses on cisplatin-induced renal electrolytes wasting and kidney function were assessed. Cisplatin-associated acute kidney injury (AKI) occurred in 8% of the patients. Urine neutrophil gelatinase-associated lipocalin to urine creatinine ratio (NGAL/Cr) and urinary magnesium and potassium wasting increased significantly after cisplatin infusion in both groups. Significant positive correlation was found between cumulative dose of cisplatin and urine NGAL/Cr after three courses of cisplatin infusion. Incidence of AKI and the magnitude of urinary magnesium and potassium wasting did not differ between silymarin and placebo groups. No adverse reaction was reported by silymarin administration. Prophylactic administration of conventional form of silymarin tablets could not prevent cisplatin-induced urine electrolyte wasting or renal function impairment.

The efficacy of Achilles millefolium topical gel along with intralesional injection of glucantime in the treatment of acute cutaneous leishmaniasis major.

BACKGROUND: Leishmaniasis is still one of the endemic parasitic infections in many countries comprising Iran. During the past decades, several medical and surgical approaches have been applied and studied to achieve the best option to treat the cutaneous leishmaniasis in Iran and the world. This study was carried out to evaluate the effect of topical Achilles millefolium in conjunction with intralesional glucantime on acute cutaneous leishmanial lesions. MATERIALS AND METHODS: sixty patients with confirmed acute cutaneous leishmaniasis were recruited in the study. Patients were randomly allocated into two groups to receive twice daily topical gel of Achilles millefolium 5% (containing 5% poly phenol) (group A) or placebo (group B) for four weeks along with weekly injection of intralesional Glucantime. RESULTS: There was no significant difference between the two groups according to age, gender, and duration of the disease. Also, there was no significant difference in complete and relative cure rates between the two groups (P = 0.35) using Visual Analog Scale (VAS). Application site reactions were occurred in 12 patients including redness in 8 cases in group-A and 2 cases in group-B, severe itching in one case in group-A and increasing wound secretion in another case in group-A (P = 0.014). CONCLUSIONS: Given the result of the present study, there is no significant difference in cure rates of lesions between yarrow and placebo topical gels as an adjuvant drugs with intralesional glucantime in treatment of acute cutaneous leishmanial lesions.

Potential renoprotective effects of silymarin against nephrotoxic drugs: a review of literature.

Drug-induced nephrotoxicity (DIN) accounts for up to sixty percent of hospital acquired acute kidney injury. Several efforts have been made to reduce drug-induced renal damage; however, DIN remains a matter of concern, with substantial impact on patients and the health system. Silymarin is a drug that has been used for many years in alternate and modern medicine for treating hepatic diseases. Its antioxidant, anti-inflammatory and anti-apoptotic effects make it an interesting herbal medicine, and these properties have implicated this compound as a potential renoprotective agent. Based on the findings from animal studies, this review concluded that silymarin might exert significant protective or ameliorative effects against drug-induced kidney disease, especially against cisplatin-induced renal damage. Whether the protective administration of silymarin could be an effective clinical pharmacological strategy to prevent DIN is a question that remains to be answered in clinical trials.

Pyuria as a screening test for detection of urinary tract infection in patients on long-term hemodialysis.

INTRODUCTION. This study was conducted to evaluate the sensitivity and specificity of pyuria detection in centrifuged urine samples of patients on hemodialysis, and its relationship with urinary tract infection. MATERIALS AND METHODS. Clean-catch midstream urine samples of 90 hemodialysis patients (34 women and 56 men) were obtained and divided into two parts for examination of urine sediment and urine culture. Pyuria was defined as the presence of more than 10 leukocytes per high-power field of microscope. RESULTS. Ninety patients with a mean age of 52.8 ± 14.2 and a mean period of dialysis of 3.3 ± 2.3 years were studied. Forty-five participants had pyuria and only 16 (35.5%) of them had a positive urine culture for infection. Pyuria and urinary tract infection were present in 52.9% and 29.4% of the women and 48.2% and 10.7% of the men, respectively. The sensitivity and specificity of pyuria screening for urinary tract infection was 100% and 61.8%, respectively. The positive and negative predictive values were 35.5% and 100%, respectively. CONCLUSIONS. In patients on hemodialysis, because of the low specificity and positive predictive values, samples with positive pyuria should be cultured to confirm urinary tract infections.