RETRACTED: Godugu et al. Anti-Cancer Activities of Thyrointegrin αvß3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma. Cancers 2021, 13, 2780.

The journal retracts the article, "Anti-Cancer Activities of Thyrointegrin αvß3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma" [...].

Comparison of Perioperative Pregabalin and Duloxetine for Pain Management After Total Knee Arthroplasty: A Double-Blind Clinical Trial.

Background: Chronic residual pain after total knee arthroplasty (TKA) is one of the challenges of postoperative pain management. Duloxetine, by controlling neuropathic pain, and pregabalin, by affecting nociceptors, can effectively manage postoperative pain. Objectives: This study aimed to compare the effect of perioperative oral duloxetine and pregabalin in pain management after knee arthroplasty. Methods: In this clinical trial, 60 patients scheduled for TKA under spinal anesthesia were randomly assigned to one of three groups A (pregabalin 75 mg), B (duloxetine 30 mg), and C (placebo). Drugs were administered 90 minutes before, 12, and 24 hours after surgery. The visual analog scale (VAS) score for pain, the first analgesic request time, postoperative analgesic consumption (i.v. paracetamol), and WOMAC score six months after surgery were recorded. Results: The VAS score and analgesic consumption 48 hours after TKA in groups A and B significantly decreased compared to the placebo (P < 0.05). The first analgesic request time was longer in groups A and B than in group C (P < 0.05). While the differences were statistically significant, they are most likely not clinically significant. The WOMAC score before and six months after arthroplasty did not differ between the groups (P > 0.05). Conclusions: Perioperative oral pregabalin and duloxetine similarly reduce pain and the need for analgesic consumption within 48 hours after TKA but do not affect knee mobility status.

Assessment of thyme honey oral gel for the prevention of adriamycin and cyclophosphamide chemotherapy-induced oral mucositis in patients with breast cancer.

PURPOSE: Oral mucositis (OM) is a common complication of cancer treatment that has an impact on a patient's quality of life and the outcome of cancer therapy. This trial evaluated the effect of thyme honey oral gel for the prevention of chemotherapy-induced OM. METHODS: One hundred ten breast cancer patients who received their first cycle of chemotherapy with adriamycin (60 mg/m2) and cyclophosphamide (600 mg/m2) were randomly recruited into two groups: group A were patients who followed general oral hygiene recommendations and rinsing saline 3 times a day, and group B were patients with similar protocol but supplied with our formulated oral gel to be applied 2 to 4 times a day. Patients were assessed by the World Health Organization (WHO) oral mucositis grading scales and self-assessment daily questionnaire. RESULTS: The use of thyme honey was associated with diminishing incidence of OM grade ≥ 2 (95% CI, 0.12 to 0.90; P = 0.030), duration of OM (- 3.36 days; 95% CI, - 5.50 to - 1.22; P = 0.037) and delayed occurrence of OM grade ≥ 2 (95% CI, 0.10 to 0.80; P = 0.017). CONCLUSION: Thyme honey can be considered as a prophylactic agent for OM and decrease the severity of its symptoms. TRIAL REGISTRATIONS: This protocol was registered at the Iranian Registry of Clinical Trials: registration number IRCT201506063106N25, on June 12, 2015; approved by the institutional review board at the Deputy of Research, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran; and approved by the Ethics Committee of Medical Researches of Pharmaceutical Sciences Branch of Islamic Azad University, Tehran, Iran-reference number 5936, on August 17, 2014.

Correction: Godugu et al. Anti-Cancer Activities of Thyrointegrin αvß3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma. Cancers 2021, 13, 2780.

In the original publication [...].

Effects of Anticancer Agent P-bi-TAT on Gene Expression Link the Integrin Thyroid Hormone Receptor to Expression of Stemness and Energy Metabolism Genes in Cancer Cells.

Chemically modified forms of tetraiodothyroacetic acid (tetrac), an L-thyroxine derivative, have been shown to exert their anticancer activity at plasma membrane integrin αvß3 of tumor cells. Via a specific hormone receptor on the integrin, tetrac-based therapeutic agents modulate expression of genes relevant to cancer cell proliferation, survival and energy metabolism. P-bi-TAT, a novel bivalent tetrac-containing synthetic compound has anticancer activity in vitro and in vivo against glioblastoma multiforme (GBM) and other types of human cancers. In the current study, microarray analysis was carried out on a primary culture of human GBM cells exposed to P-bi-TAT (10-6 tetrac equivalent) for 24 h. P-bi-TAT significantly affected expression of a large panel of genes implicated in cancer cell stemness, growth, survival and angiogenesis. Recent interest elsewhere in ATP synthase as a target in GBM cells caused us to focus attention on expression of genes involved in energy metabolism. Significantly downregulated transcripts included multiple energy-metabolism-related genes: electron transport chain genes ATP5A1 (ATP synthase 1), ATP51, ATP5G2, COX6B1 (cytochrome c oxidase subunit 6B1), NDUFA8 (NADH dehydrogenase (ubiquinone) FA8), NDUFV2I and other NDUF genes. The NDUF and ATP genes are also relevant to control of oxidative phosphorylation and transcription. Qualitatively similar actions of P-bi-TAT on expression of subsets of energy-metabolism-linked genes were also detected in established human GBM and pancreatic cancer cell lines. In conclusion, acting at αvß3 integrin, P-bi-TAT caused downregulation in human cancer cells of expression of a large number of genes involved in electron transport and oxidative phosphorylation. These observations suggest that cell surface thyroid hormone receptors on αvß3 regulate expression of genes relevant to tumor cell stemness and energy metabolism.

Therapeutic effects of turmeric topical cream in vitiligo: A randomized, double-blind, placebo-controlled pilot study.

BACKGROUND: Vitiligo is an autoimmune and acquired disease characterized by the destruction of epidermal melanocytes leading to depigmentation of the skin. Although vitiligo is a common disease, there is not a definite cure and conventional therapies can lead to serious adverse effects. Turmeric has been widely studied for its anti-inflammatory, antioxidant, and anti-cell proliferation, while it is a cost-benefit and available treatment for a variety of diseases. AIMS: The aim of this study was to evaluate the efficacy of topical turmeric cream on vitiligo's lesion appearance including size and repigmentation. PATIENTS/METHODS: Following the screening, 30 patients were enrolled according to inclusion criteria. The patients received training to apply turmeric and placebo cream at the specified side of their body twice a day for 4 months. Patients were evaluated at the baseline and at monthly intervals to access possible side effects. Lesion size, vitiligo area scoring index (VASI), vitiligo noticeability scale (VNS), and physician global assessment (PGA) were evaluated at the baseline and after four months to compare the changes induced by turmeric and placebo cream. RESULTS: Twenty-four patients completed the trial. Applying turmeric cream reduced the size of lesions and improved lesion's appearance significantly compared to the placebo group (p < 0.001), and also, patient's satisfaction score was higher following applying turmeric cream compared to placebo (p < 0.05). CONCLUSIONS: Turmeric cream can be used as an alternative remedy or adjuvant therapy in mild to moderate vitiligo lesions and in those who cannot tolerate the adverse effects of conventional therapies.

Solvent-free microwave extraction: an eco-friendly and rapid process for green isolation of essential oil from lemongrass.

The extraction of lemongrass essential oil (LGEO) using large quantities of solvents makes this extraction a hazardous and environmentally unfriendly procedure. Our aim was to find a suitable method for the improvement of its extraction and its quality. Solvent-Free Microwave Extraction (SFME) is a combination of dry distillation and microwave heating. SFME of LGEO was compared with conventional extraction hydrodistillation (HD). SFME is quicker than conventional HD. An extraction time of 15 min with SFME provided a yield of 0.6% comparable with that obtained after 120 min using HD. The composition of these oils revealed that the main components obtained with HD and SFME were both geranial (59.93% vs 44.59%, respectively). The quality of lemongrass is determined by its citral content, and a higher amount of citral was present in SFME oil (74%) in comparison with HD oil (60%). SFME is a green and a promising technology for the extraction of essential oils.

Current Strategies in Pain Regimens for Robotic Urologic Surgery: A Comprehensive Review.

Context: Robotic surgery is becoming the most common approach in minimally invasive urologic procedures. Robotic surgery offers less pain to patients because of smaller keyhole incisions and less tissue retraction and stretching of fascia and muscular fibers. Tailored pain regimens have also evolved and allowed patients to feel minimal to no discomfort after robotic urologic surgery, allowing in parallel better surgical outcomes. This study aims to analyze the most current pain regimens in robotic urologic surgery and to evaluate the most current pain protocols and corresponding outcomes. Evidence Acquisition: A literature review was performed of published manuscripts utilizing Pubmed and Google Scholar on pain protocols for patients undergoing robotic urologic surgery. Results: Multimodal analgesia is gaining ground in robotic urologic surgery. Regional analgesia includes four major modalities: Neuroaxial analgesia, intercostal blocks, tranvsersus abdominis plane blocks, and paravertebral blocks. Each approach has a different injection site, region of analgesia coverage, and duration of coverage depending upon local anesthesia and/or adjuvant utilized with advantages and disadvantages that make each modality unique and efficacious. Conclusions: Robotic urologic surgery has offered the advantage of smaller incisions, faster recovery, less postoperative opioid consumption, and better surgical outcomes. Neuraxial, intercostal, transversus abdominis plane, and quadratus lumborum blocks are the best and most adopted approaches which offer optimal outcomes to patients.

Impact of rapid correction of vitamin D deficiency in asthmatic patients.

BACKGROUND: Asthma is one of the most common chronic diseases, which is a growing public health concern worldwide. In recent years, there has been an increasing number of interests in the relationship between vitamin D level and asthma control. Hence, the objective of this study was to assess the effect of high doses of vitamin D3 injection on asthmatic patient's respiratory condition and quality of life. METHODS: This was a single arm, before and after interventional study involving 18 patients with moderate to severe asthma. Spirometry test, St George's respiratory questionnaire (SGRQ) and serum vitamin D assay were performed. Subjects with 25-hydroxyvitamin D3 (25-(OH) D3) < 20 ng/ml were deemed deficient (n = 18) and received 2 intramuscular injections of vitamin D3 300,000 IU at monthly intervals consecutively. RESULTS: The mean changes of forced expiratory volume in the first second (FEV1) were significantly different in subjects who received vitamin D3 injections (p = 0.008). Also, the mean changes in FEV1/forced vital capacity ratio (FEV1/FVC) were significant (p < 0.001) as well as maximum expiratory flow between 25% and 75% of FVC (MEF25-75) (p = 0.001). Interestingly, improvement in clinical parameters of SGRQ was also observed with significant differences in total score (p = 0.001). Naturally, serum vitamin D levels were increased in our patients following the injections (p < 0.001). CONCLUSIONS: Our findings suggest that screening for serum 25-(OH) D3 deficiency is important in asthmatic patients and correction of this deficiency with high doses of vitamin D3 injection may lead to improvement in pulmonary function, symptoms and quality of life (QOL).

Anti-Cancer Activities of Thyrointegrin αvß3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma.

Integrin αvß3 receptors are overexpressed in different tumors and their associated neovascularization and hence, represent a potential cancer target. We previously synthesized a high affinity thyrointegrin αvß3, P4000-bi-TAT (tetrac derivative), with potent anticancer properties. However, the long polydisperse PEG conjugate showed large scaleup and analytical/bioanalytical issues. Hence, in the present study, we synthesized a mono versus bi-triazole tetrac with discrete monodisperse PEG, which provided improvement in scaleup and bioanalysis. In the present study, we compared binding affinity and anticancer activates with a smaller PEG size (P1600-bi-TAT, Compound 2) and the removal of one TAT molecule (P1600-m-TAT, Compound 3) versus P4000-bi-TAT, Compound 1. The results of the selectivity and affinity of TATs showed greater affinity to integrin αvß3. The xenograft weights and tumor cell viabilities were decreased by >90% at all doses compared to the control (ON Treatment, *** p < 0.001) in cells treated with Compounds 1, 2, and 3 in U87-Luc-treated mice. The in vivo luminescent signals of U87-luc cells reflect the proliferation and distribution of tumor cells in the animals and the maximum intensity corresponding to the maximum tumor cells that the animals could tolerate. We found that the three thyrointegrin αvß3 antagonists exhibited optimal therapeutic efficacy against U87 or primary glioblastoma cells. Biological studies showed that decreasing the PEG linker size (1600 vs. 4000) or having mono-TAT or bi-TAT had no significant impact on their αvß3 binding affinity, anti-angiogenesis, or overall anti-cancer efficacy.

Evaluation of Adherence to Antiemetic Treatment Guidelines in Patients With Chemotherapy-Induced Nausea and Vomiting in Teaching Hospitals in Tehran.

The present study evaluated adherence to antiemetic guidelines for prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) in four tertiary university teaching hospitals in Tehran. This prospective observational study enrolled 382 adult patients on chemotherapy at oncology centers affiliated to medical universities located in Tehran. Patients were followed up during their chemotherapy cycles. Risk factors related to CINV were evaluated, and information on antiemetic prescribing patterns was gathered using direct interview and patient medical records. Guideline adherence was found to be low; however, 81.3% of the patients experienced chemotherapy without CINV. Low frequency of adherence to the guidelines in prescription patterns does not mean that prescription patterns were very different. Indeed, some drugs were added to base guideline recommendation regiments, since in high and moderate emetogenic chemotherapy categories, some novel antiemetics recommended by international guidelines are not yet included in Iranian pharmacopeia. It was shown that two drug classes were added as a common practice, namely, H1/H2 antagonists and dopamine receptor antagonist (metoclopramide). Statistically significant differences were found between antiemetic prescribing patterns of physicians and chemotherapy regimen category (aspect of emetogenic potential) (p < 0.001). The most commonly prescribed regimen in the minimal-emetic-risk category and the low-emetic-risk category was reported to be the combination of corticosteroids, 5HT3, and H1/H2 antagonists, 33% and 66.1% respectively. Moreover, corticosteroids +5HT3 and H1/H2 antagonists + NK1 antagonist were found to be the most frequently prescribed regimen in the moderate-emetic-risk category (39.7%) and high-emetic-risk category (41.8%). Antiemetic prescribing patterns were not completely compatible with the guidelines in moderate and high emetogenic chemotherapy categories. Differences were detected in two states of over- and undertreatment. The present study confirmed low level of adherence of antiemetic prescribing patterns with international guidelines. However, it could not be proved that high levels of adherence with the guidelines result in reduction of CINV incidence. Complete success in CINV control cannot be achieved only by adherence to the established guidelines as novel antiemetics recommended by the guidelines have not been included in the Iranian pharmacopeia as yet. The authors do recommend implementation of strategies for increasing guideline-compliant prescriptions with the aim of improving patients' outcomes. We also suggest that policymakers in healthcare system point more critically to overprescribing as an issue of concern.

A New Eucalyptol-Rich Lavender (Lavandula stoechas L.) Essential Oil: Emerging Potential for Therapy against Inflammation and Cancer.

BACKGROUND/AIM: natural products are a potential source for drug discovery and development of cancer chemoprevention. Considering that drugs currently available for the treatment of inflammatory and cancer conditions show undesirable side effects, this research was designed to evaluate, for the first time, the in vitro anticancer activity of Algerian Lavandula stoechas essential oil (LSEO) against different cancer cell lines, as well as its in vitro and in vivo topical and acute anti-inflammatory properties. MATERIALS AND METHODS: the LSEO was extracted by steam distillation, and chemical composition analysis was performed using gas chromatography. The main compounds identified in LSEO were oxygenated monoterpenes, such as 1,8-Cineole (61.36%). LSEO exhibited a potent anti-inflammatory activity using the xylene-induced mouse ear edema model. RESULTS: LSEO (200 and 20 mg/kg) was able to significantly reduce (p < 0.05) the carrageenan-induced paw edema with a similar effect to that observed for the positive control. Topical application of LSEO at doses of 82 and 410 mg/kg significantly reduced acute ear edema in 51.4% and 80.1% of the mice, respectively. Histological analysis confirmed that LSEO inhibited the skin inflammatory response. Moreover, LSEO was tested for its antitumor activity against different cancer cell lines. LSEO was found to be significantly active against human gastric adenocarcinoma (AGS), Melanoma MV3, and breast carcinoma MDA-MB-231 cells, with median inhibitory concentration (IC50) values of 0.035 ± 0.018, 0.06 ± 0.022 and 0.259 ± 0.089 µL/mL, respectively. Altogether, these results open a new field of investigation into the characterization of the molecules involved in anti-proliferative processes. CONCLUSION: We suggest that LSEO, with 1,8-Cineole as the major active component, is a promising candidate for use in skin care products with anti-inflammatory and anticancer properties. The results of this study may provide an experimental basis for further systematic research, rational development, and clinical utilization of lavender resources.

An Observational Study of QTc Prolongation in Critically Ill Patients: Identification of Incidence and Predictors.

AIMS: Despite the importance of abnormal QTc interval values in intensive care unit (ICU) patients, there is a paucity of information on this topic. The current study was designed to identify the incidence and predictors of QTc prolongation in medical (M), surgical (S), and emergency (E) ICUs. MATERIALS AND METHODS: A prospective observational study was conducted for 6 months. Patients more than 18 years old who admitted to MICU, SICU, and EICU were included in the study. Electrocardiogram (ECG) was taken on day 1, 3, and 5 of ICU admission. The QTc intervals >460 ms in male and >470 ms in female and increased >60 ms above baseline were considered QTc prolongation. Comparative analysis was done between two groups of patients (normal vs prolonged QTc). Logistic regression models were carried out to determine the predictors of QTc prolongation. RESULTS: Incidence of QTc prolongation was 6.5, 9.8, and 15.7% on day 1, 3, and 5 of ICU admission, respectively. On day 1, the history of alcohol addiction and the reason of ICU admission were associated with a prolonged QTc. A significant association was demonstrated between administration of azithromycin and QTc prolongation on day 3. High serum creatinine and hospitalization in EICU were predictors of QTc prolongation on day 5 of ICU admission. CONCLUSION: The QTc prolongation is relatively common among patients admitted to ICUs and its incidence increases with increasing length of hospital stay. Predictors of QTc prolongation may be affected by the duration of ICU admission. Physicians should consider these predictors particularly before prescribing QTc-prolonging drugs. HOW TO CITE THIS ARTICLE: Farzanegan B, Hosseinpoor Z, Baniasadi S, Seyyedi SR, Rajabi M. An Observational Study of QTc Prolongation in Critically Ill Patients: Identification of Incidence and Predictors. Indian J Crit Care Med 2020;24(4):270-275.

Dual Targeting of Norepinephrine Transporter (NET) Function and Thyrointegrin αvß3 Receptors in the Treatment of Neuroblastoma.

Therapeutic targeting of the norepinephrine transporter (NET) function with benzylguanidine (BG), conjugated with the high-affinity thyrointegrin αvß3 antagonist triazole tetraiodothyroacetic acid, TAT, via noncleavable bonding to poly(ethylene glycol) (PEG400) (P) might allow for effective treatment options in neuroblastoma. BG-P-TAT is a dual-targeting agent, targeting the NET function and the thyrointegrin αvß3 receptors that are overexpressed in neuroblastoma and other neuroendocrine tumors. Various cancer cells and actively dividing tumor-endothelial cells express the thyrointegrin αvß3 receptors. In this work, the novel compound BG-P-TAT was synthesized and evaluated in the neuroblastoma SK-N-FI cell line for improved targeting and to offer a new strategy for patients with neuroblastoma. BG-P-TAT demonstrated significant suppression of neuroblastoma tumor progression, growth, and viability in a dose-dependent manner. In conclusion, BG-P-TAT represents a potential lead candidate for the treatment of neuroblastoma and other neuroendocrine tumors.

Magnesium Sulfate and Clonidine; Effects on Hemodynamic Factors and Depth of General Anesthesia in Cesarean Section.

BACKGROUND: Making stable hemodynamic and also durable unawareness is a daily challenge in the setting of general anesthesia in women who undergo surgical delivery of neonate and have limitations to receive opioids derivatives. OBJECTIVES: We aimed to evaluate the effects of magnesium sulfate and clonidine on hemodynamic changes and depth of anesthesia and in mentioned mothers and also in neonatal APGAR index. METHODS: Current randomized, double-blind controlled trial study was conducted among a total of 360 pregnant females (38 - 41 weeks of gestation) who underwent elective cesarean section. Participants were randomly divided into three drug-receiving groups (equal 120 members): magnesium sulfate (30 mg/kg), clonidine (3 µg/kg), and placebo (0.9% NaCl). Patients' blood pressure, heart rate, cerebral state index (CSI) in specific time zones, and also late 24-hour recall were recorded. The CSI is an electroencephalographic monitoring method helping to assess the depth of anesthesia. Neonatal parameters, including APGAR score and umbilical venous blood sampling, were measured. RESULTS: Mean patients' age was 28 ± 4.5. A significant decreasing and stabilizing effect of magnesium sulfate and clonidine on hemodynamic parameters (blood pressure and heart rate) was revealed (P < 0.001). Evidence implied on deeper anesthesia (lower CSI) among drug receivers comparing to placebo (P < 0.001). None of the participants experienced a late 24-hour recall postoperatively. All neonates were healthy, and no decrease was reported in APGAR score at minutes 1 and 5. Umbilical blood gas analysis showed no signs of acidosis and/or hypoxemia. CONCLUSIONS: Adjuvant administration of either magnesium sulfate or clonidine is associated with hemodynamic stability and favorable unawareness in the setting of elective surgical delivery.

The efficacy and safety of permethrin 2.5% with tea tree oil gel on rosacea treatment: A double-blind, controlled clinical trial.

BACKGROUND: Rosacea is a chronic skin condition that typically affects the face and it results in redness and inflammation. The main risk factors of this disease are Demodex folliculorum, living in the pilosebaceous units. AIMS: To evaluate the efficacy and safty of permethrin 2.5% in combination with tea tree oil (TTO) topical gel versus placebo on Demodex density (Dd) and clinical manifestation using standard skin surface biopsy (SSSB) in rosacea patients. PATIENT/METHODS: In this double-blind, randomized clinical trial, 47 papulopustular rosacea patients were enrolled, with 35 patients finishing the 12 weeks of treatment. Each patient used permethrin 2.5% with TTO on one side of the face and a placebo on the other, twice daily for 12 weeks. SSSB, photography and clinical rosacea scores according to National Rosacea Society, as well as adverse drug reaction (ADRs) were reported at the baseline, 2nd, 5th, 8th, and 12th weeks. RESULTS: A total of 47 patients were enrolled with papulopustular rosacea, and 35 patients finished the study. The effects of permethrin 2.5% with TTO gel on mite density were significant at week 5, 8, 12 (P value = .001). Clinical features and global assessments showed papules, pustules and nontransient erythema had improvement in drug group after 12 weeks (P values <.05). The improvement of burning and stinging and dry appearance was greater than the placebo gel (P value <.05). Itching in placebo group was significantly more than other group (P value = .002). CONCLUSION: Administration of permethrin 2.5% with TTO gel demonstrated good efficacy and safety in rosacea. This topical gel inhibited the inflammatory effects of rosacea and reduced Demodex mite.

Drug interactions and creatinine levels are associated with QTc prolongation in intensive care units: a prospective, observational study.

Background Prolongation of the QTc interval may lead to life threatening arrhythmias. QTc prolongation is common in intensive care unit (ICU) patients. The objectives of this study were to identify the role of drug-drug interactions (DDIs) and other predictors (age, sex, cardiovascular diseases, and electrolyte abnormalities) in life threatening QTc prolongation in patients admitted to medical (M), surgical (S) and emergency (E) ICUs. Methods This prospective, observational study included patients above the age of 18 years who were admitted to SICU, EICU, and MICU at a tertiary respiratory referral center. Electrocardiogram (ECG) monitoring was performed during the first 5 days of ICU admission. Risk factors and DDIs which were anticipated to be associated with the prolongation of the QTc interval were assessed for all patients. Results Two hundred patients were included in the study. QTc prolongation occurred in 10.7% of patients and the majority of patients presenting with QTc prolongation had creatinine levels above 1.3 mg/dL during their 5 days of ICU admission. Incidence of pharmacodynamic (PD) DDIs was significantly higher in patients with QTc prolongation vs. other patients. Creatinine levels above 1.3 mg/dL and PD DDIs were associated with QTc prolongation during 5 days of ICU admission. Conclusions High serum creatinine and PD DDIs can increase the risk of QTc prolongation in patients admitted to the ICU. QTc interval measurements should be performed prior to initiation or after starting any drug that is associated with QT prolongation, specifically in patients with the known risk factors.

Oral calcitriol in hematopoietic recovery and survival after autologous stem cell transplantation: a randomized clinical trial.

BACKGROUND: Calcitriol, the active metabolite of vitamin D, is an essential regulator in the hematopoiesis and immunity. However, knowledge revealing its influence on the immune and hematologic reconstitution after hematopoietic stem cell transplantation (HSCT) in clinical trials is very limited. OBJECTIVES: The effects of calcitriol on short-term and long-term hematopoietic recovery, relapse-free survival (RFS) and overall survival (OS) in multiple myeloma, Hodgkin's and non-Hodgkin's lymphoma following autologous peripheral blood HSCT were assessed. METHODS: Eighty patients (age: 18-68 years) in complete remission were allocated 1:1 to two groups by balanced block randomization. Calcitriol 0.25 µg or placebo capsule was administered three times daily from transplantation to day 30. Absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and platelet count (PC) were determined daily from transplantation to day 30. White blood cell count (WBC), PC, and hemoglobin concentration (HC) of days 180 and 365 were extracted from clinic files. A thorough examination for oral mucositis (OM) was completed daily during hospital stay. Adverse drug reactions (ADRs) as well as two-year RFS and OS were evaluated. RESULTS: Median time to ANC engraftment (≥0.5 × 103/µl: 10.0 vs. 11.0 days; P = 0.98) and PC engraftment (≥20.0 × 103/µl: both 14.0 days; P = 0.58) was similar between groups. However, the median time to ALC recovery was significantly shorter in the calcitriol group (≥0.5 × 103/µl: 13.0 vs. 20.0 days; P < 0.001). Moreover, ALC recovery rates on day 15 (≥0.5 × 103/µl: 82.1% vs. 42.5%; P < 0.001) and on day 30 (≥1.0 × 103/µl: 91.7% vs. 57.5%; P = 0.001) was significantly higher with calcitriol. WBC, PC, and HC on days 180 and 365 were not significantly different between groups. None of the OM indices were modulated by calcitriol. All the ADRs were non-serious and mild, possibly or unlikely related to the intervention. In a median of 29 months follow-up, RFS was significantly better in the calcitriol group (77.0%, SE = 7.0% vs. 59.0%, SE = 8.0%; P = 0.03), albeit the OS was not affected (87.0%, SE = 5.0% vs. 92.0%, SE = 4.0%; P = 0.72). CONCLUSION: Calcitriol could improve ALC recovery and RFS as a safe option post-HSCT. Graphical abstract Oral calcitriol 0.25 µg three times daily from transplantation to day 30 improved lymphocytes recovery and two-year relapse-free survival as a safe option in 80 patients of autologous hematopoietic stem cell transplantation in comparison with placebo.