Characteristics of salt contents in soils under greenhouse conditions in China

Abstract

Greenhouse cultivation is expanding in China due to high production efficiency and greater economic benefits. Although the accumulation of soil salinity and nutrients has been observed in greenhouse cultivation areas, the linkage between soil salinity, soil major ions, and farm practices is not clear in China. Few studies have examined soil salinity accumulated in soil layers; thus, a broad investigation is needed in order to understand the potential causes of soil salinity in greenhouse soil. In this study, a short review was given to show the salt contents and the major ion under greenhouse conditions in China. Then, we analyzed a total of 132 soil samples from different parts of China in terms of their soil major ions and nutrient components and investigated the relevant farm practices. Based on survey data from three different types of cultivation areas (open farmland, plastic greenhouses, and multispan greenhouses), we found that cultivation in both greenhouse types resulted in a significant increase in salt content and a decrease in soil pH values, a pattern not shown in open farmland. The linkage between soil salinity and cultivation type was confirmed by soil salinity classification. The proportion of each ion in the soil salt differs significantly between the different management methods, but the variation range of the main ions ranged from − 23.3 to 225.6% for multispan greenhouses and − 22.6 to 430.5% for plastic greenhouses. In addition, the salt source in greenhouses is not unique to those methods, suggesting that different growing practices cause the differences in ion concentration. Removing greenhouse covers during the rainy season can avoid further accumulations of salt, but the subsequent rinsing of soil can lead to the deeper salt accumulations. In addition, increasing salt content may lead to decreasing pH once the natural salt balance is altered. These results show that the soil salinization produced by greenhouse cultivation cannot be ignored.

https://ift.tt/2rAnzn6

Monitoring haemodynamic response to fluid-challenge in ICU: Comparison of pressure recording analytical method and oesophageal Doppler

BACKGROUND The ability of the pressure recording analytical method (PRAM) in tracking change in cardiac output (ΔCO) after a fluid challenge in ICU needs to be evaluated with the most contemporary comparison methods recommended by experts. OBJECTIVE Our objective was to report the trending ability of PRAM in tracking ΔCO after a fluid challenge in ICU and to compare this with oesophageal Doppler monitoring (ODM). DESIGN Prospective, observational study. SETTING Hôpital Lariboisière and Hôpital Européen George Pompidou, Paris, France, from April 2016 to December 2017. PATIENTS Critically ill patients admitted to ICU with monitoring of CO monitored by ODM and invasive arterial pressure. INTERVENTION ΔCO after fluid challenge was simultaneously registered with ODM and PRAM connected to the arterial line. MAIN OUTCOME MEASURE Polar statistics (mean angular bias, radial limits of agreement and polar concordance rate) and clinical concordance evaluation (error grid and clinical concordance rate). Predictors of bias were determined. RESULTS Sixty-eight fluid challenge were administered in 49 patients. At the time of fluid challenge, almost all were mechanically ventilated (99%), with 85% receiving norepinephrine. Admission diagnosis was septic shock in 70% of patients. Patients had a Sequential Organ Failure Assessment score of 10 [7 to 12] and a median Simplified Acute Physiology Score II of 61 [49 to 69]. Relative ΔCO bias was 7.8 (6.3°) with radial limits of agreement of ±41.7°, polar concordance rate 80% and clinical concordance rate 74%. ΔCO bias was associated with baseline bias (P = 0.007). Baseline bias was associated with radial location of the arterial line (P = 0.03). CONCLUSION When compared with ODM, PRAM has insufficient performance to track ΔCO induced by fluid challenge in ICU patients. Baseline bias is an independent predictor of trending bias. TRIAL REGISTRATION IRB 00010254-2016-033. Correspondence to Romain Barthélémy, MD, Department of Anaesthesia, Burn, and Critical Care, Saint-Louis Lariboisière University Hospital, AP-HP, 2 Rue Ambroise Paré, 75475 Paris Cedex 10, France E-mail: romain.barthelemy@aphp.fr Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (https://ift.tt/2ylyqmW). © 2018 European Society of Anaesthesiology

https://ift.tt/2LdQJ4P

Comparison of rocuronium requirement in children with continuous infusion versus intermittent bolus: A randomised controlled trial

BACKGROUND Minimising rocuronium administration during paediatric surgery helps to reduce the incidence of residual muscular blockade. OBJECTIVE To determine whether intermittent bolus injection (Bolus group) or continuous infusion (group) requires the lesser amount of rocuronium. DESIGN A prospective, randomised, single-blind controlled trial. SETTING A single university hospital from March to June 2017. PATIENTS Sixty-six children undergoing general anaesthesia. INTERVENTIONS Dose of rocuronium for maintenance of muscle relaxation in either Bolus or continuous infusion group. Train-of-four (TOF) count of two was maintained during surgery. When TOF count reached three, 0.1 mg kg−1 of rocuronium was administered in Bolus group or infused at an increased rate of 0.1 mg kg−1 h−1 in continuous infusion group. MAIN OUTCOME MEASURES Primary outcome was the dose of rocuronium given (μg kg−1 min−1). The recovery time from the TOF count four to TOF 0.7 (RT0.7), and 0.9 (RT0.9) were recorded. All adverse events were recorded up to 30 min after extubation. RESULTS Mean (SD) rocuronium dose in the Bolus group was 6.1 (0.9), [95% confidence interval (95% CI) 5.7 to 6.4] μg kg−1 min−1 and 4.9 (1.0), (95% CI 4.6 to 5.3) μg kg−1 min−1 in the continuous infusion group (P = 0.001). RT0.7 was 24.0 (13.7), 95% CI 19.3 to 28.7) min in the Bolus group, and 25.7 (16.0), (95% CI 20.2 to 31.2) min in the continuous infusion group (P = 0.73). RT0.9 was 30.7 (17.1), (95% CI 24.9 to 36.5) min in the Bolus group, and 30.0 (17.6), (95% CI 24.0 to 36.0) min in the continuous infusion group (P  = 0.91). The incidence of adverse events was not significantly different between two groups. CONCLUSION In children undergoing general anaesthesia, the dose of rocuronium given by continuous administration was less than that with intermittent bolus. TRIAL REGISTRATION ClinicalTrials.gov (identifier: NCT03060707). Correspondence to Hee-Soo Kim, MD, PhD, Department of Anaesthesiology and Pain Medicine, College of Medicine, Seoul National University, #101 Daehak-ro, Jongno-gu, 03080, Seoul, Republic of Korea Tel: +82 2 2072 3659; fax: +82 2 747 5639; e-mail: dami0605@snu.ac.kr © 2018 European Society of Anaesthesiology

https://ift.tt/2C8BSFU

Orthostatic intolerance following hip arthroplasty: Incidence, risk factors and effect on length of stay a prospective cohort study

BACKGROUND Early postoperative mobilisation is important for enhanced recovery, but can be hindered by orthostatic intolerance, characterised by dizziness, nausea, vomiting, feeling of heat, blurred vision and ultimately syncope. Although the incidence of orthostatic intolerance following total hip arthroplasty has been identified, few studies have yet investigated potential risk factors for developing orthostatic intolerance after hip arthroplasty. OBJECTIVES The aim of this study was to assess the incidence of orthostatic intolerance on the first postoperative day after total hip arthroplasty, potential predisposing risk factors for developing orthostatic intolerance and its effect on length of stay. DESIGN A prospective observational study. SETTING Tertiary hospital, Auckland, New Zealand, May to September 2015. PATIENTS One hundred and seventeen consecutive patients undergoing unilateral total hip arthroplasty. Patients were excluded if they had revision surgery. MAIN OUTCOME MEASURES Incidence of orthostatic intolerance during mobilisation on the first postoperative day. Significant peri-operative risk factors for developing orthostatic intolerance were identified using logistic regression. Length of stay was compared between orthostatic intolerant and orthostatic tolerant patients using the Mann–Whitney U-test. RESULTS On the first postoperative day, 22% of patients failed mobilisation due to orthostatic intolerance. Factors independently associated with orthostatic intolerance were female sex; OR (95% CI), 3.11 (1.01 to 9.57), postoperative use of gabapentin; OR 3.55 (1.24 to 10.15) and high peak pain levels (≥5/10) during mobilisation; OR 4.05 (1.30 to 12.61). Overall, 78% of patients were correctly identified. The model was more accurate at predicting those who would not get orthostatic intolerance (89% correct), compared with those who did have orthostatic intolerance (39% correct). Length of stay was longer in patients with orthostatic intolerance (P = 0.019). CONCLUSION Orthostatic intolerance is common after total hip arthroplasty. Optimising pain control prior to mobilisation and limiting gabapentin use may modify the risk of developing postoperative orthostatic intolerance. Although personalised recovery pathways appear attractive, at present, the ability to predict at-risk individuals is still limited. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. https://ift.tt/OBJ4xP Correspondence to Dr David A. Rice, Health and Rehabilitation Research Institute, Auckland University of Technology, Private Bag 92006, Auckland 1142, New Zealand E-mail: david.rice@aut.ac.nz Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (https://ift.tt/2ylyqmW). © 2018 European Society of Anaesthesiology

https://ift.tt/2LbkNhp

Use of tracheal ultrasound combined with clinical parameters to select left double-lumen tube size: A prospective observational study

BACKGROUND Left double-lumen tubes (LDLTs) are used in thoracic surgery to allow one-lung ventilation. Their size is usually chosen on the basis of clinical parameters (height, sex). Double-lumen endobronchial tubes are frequently undersized/oversized, risking tube displacement or tracheal trauma. A correlation between ultrasound tracheal diameter and left main bronchus dimension has been demonstrated. OBJECTIVES We hypothesised that the insertion of undersized/oversized double-lumen tubes is frequent when the size is selected using standard criteria, and that the use of ultrasound to estimate tracheal diameter may help to reduce the frequency of insertion of oversized tubes. DESIGN Two-step prospective observational study. SETTING The operating room of a French University hospital from January 2016 to February 2017. PATIENTS We enrolled 102 and 50 consecutive patients undergoing elective thoracic surgery in Steps 1 and 2 (males 63.7 and 60.0%, age 63 (13) and 63 (11) years, height 170 (13) and 169 (9) cm, respectively). INTERVENTION In Step 1, the size of the LDLT inserted was selected on the basis of clinical parameters. Ultrasound data about tracheal diameter were collected to determine cut-off points associating height and tracheal diameter. Cut-off values for ultrasound tracheal diameter were applied retrospectively to test their capability to reduce the insertion rate of oversized tube. In Step 2, the LDLT size was chosen according to the determined combined cut-off values. MAIN OUTCOME MEASURE LDLT size was considered adequate if the bronchial cuff volume required for isolation of the lung (i.e. no difference between inspiratory and expiratory lung volumes) was 0.5 to 2.5 ml of air; undersized and oversized tubes required more than 2.5 ml and less than 0.5 ml, respectively. RESULTS In Step 1, LDLT size was appropriate/undersized/oversized in 40 (39.2%)/23 (22.6%)/39 (38.6%) of patients. Cut-off values derived from ultrasound measurements would have reduced the use of oversized tubes by 20.6% (P 

https://ift.tt/2C7dynz

Impact of Nasoseptal Flap Harvest Technique on Olfaction Following Endoscopic Transsphenoidal Pituitary Surgery

Conditions:   Pituitary Tumor;   Surgery;   Olfactory Nerve Injuries
Intervention:   Procedure: Electrocautery versus scalpel
Sponsor:   St. Michael's Hospital, Toronto
Not yet recruiting

https://ift.tt/2EfV99D

Comparison of Aramchol Concentrations With Once or Twice Daily Dosing

Condition:   Healthy
Intervention:   Drug: Aramchol
Sponsors:   Galmed Pharmaceuticals Ltd;   Hammersmith Medicines Research (HMR);   Analyst Research Laboratories;   Diamond PV Services Ltd
Not yet recruiting

https://ift.tt/2EeGyeO

Irinotecan-based Triplet (FOLFOXIRI) as Perioperative Treatment in Resectable Gastric and Gastroesophageal Junction Adenocarcinoma.

Condition:   Resectable Gastric and Gastroesophageal Junction Adenocarcinoma
Interventions:   Drug: Fluorouracil;   Drug: Oxaliplatin;   Drug: Irinotecan
Sponsor:   Lund University Hospital
Not yet recruiting

https://ift.tt/2EuaaFG

Anti-liver cancer effect and the mechanism of arsenic sulfide in vitro and in vivo

Abstract

Purpose

This study aimed at investigating the anti-tumor effect of arsenic sulfide (As₂S₂) against liver cancer both in vivo and in vitro and to elucidate its underlying mechanisms.

Methods

Cell viability of the human hepatocellular carcinoma cell lines SMMC-7721, BEL-7402, HepG2 were measured by CCK-8 assay. The effects of As₂S₂ on cell proliferation and apoptosis of SMMC-7721 cells were investigated using Calcein-AM and PI staining, Hoechst 33258 staining, crystal violet staining, and JC-1 staining. Cell cycle and Annexin V/PI assay were analyzed via flow cytometry. The expression of apoptosis-related proteins, phosphorylation of PI3K and AKT were detected by Western blotting. H22-bearing mice model was established to evaluate the anti-tumor effect of As₂S₂ in vivo. HE staining, PCNA was observed via immunohistochemistry, and TUNEL assay was used to assess the anti-proliferation and pro-apoptotic effects of As₂S₂.

Results

As₂S₂ significantly inhibited the growth of human hepatoma cells SMMC-7721, BEL-7402 and HepG2. As₂S₂ inhibited cell proliferation effectively by inducing G0/G1 cell cycle arrest in SMMC-7721 cells. As₂S₂ could increase Bax/Bcl-2 ratio, decrease mitochondrial membrane potential, promote the release of cytochrome c, increase the levels of cleaved caspase-3 and PARP, indicating that As₂S₂ induced apoptosis in SMMC-7721 cells via mitochondrial-mediated apoptosis pathway. Further research showed that As₂S₂ inhibited the PI3K/AKT signaling pathway leading to apoptotic cell death. In addition, As₂S₂ significantly inhibited tumor growth in H22-bearing mice and induced apoptosis by deactivating PI3K/AKT pathway, which was consistent with the in vitro results.

Conclusion

These findings suggested that As₂S₂ could induce apoptosis of liver cancer cells in vitro and in vivo, which was related to PI3K/AKT-mediated mitochondrial pathway and may provide a novel promising therapeutic agent for liver cancer treatment.

https://ift.tt/2PxzAU3

Cannabinoids: Potential Role in Inflammatory and Neoplastic Skin Diseases

Abstract

The endocannabinoid system is a complex and nearly ubiquitous network of endogenous ligands, enzymes, and receptors that can also be stimulated by exogenous compounds such as those derived from the marijuana plant, Cannabis sativa. Recent data have shown that the endocannabinoid system is fully functional in the skin and is responsible for maintaining many aspects of skin homeostasis, such as proliferation, differentiation, and release of inflammatory mediators. Because of its role in regulating these key processes, the endocannabinoid system has been studied for its modulating effects on both inflammatory disorders of the skin and skin cancer. Although legal restrictions on marijuana as a Schedule I drug in the USA have made studying cannabinoid compounds unfavorable, an increasing number of studies and clinical trials have focused on the therapeutic uses of cannabinoids. This review seeks to summarize the current, and rapidly expanding field of research on the broad potential uses of cannabinoids in inflammatory and neoplastic diseases of the skin.

https://ift.tt/2GdoaFG

Basic chemical peeling—superficial and medium-depth peels

Publication date: Available online 11 December 2018

Source: Journal of the American Academy of Dermatology

Author(s): Kachiu C. Lee, Carlos G. Wambier, Seaver L. Soon, J.Barton Sterling, Marina Landau, Peter Rullan, Harold J. Brody, International Peeling Society(IPS)

Abstract

Chemical peeling, or chemexfoliation, has been used for centuries to improve signs of ultraviolet light-induced sun damage. Over the last 30 years, the science behind chemical peeling has evolved, increasing our understanding of the role of peeling ingredients and treatment indications. The depth of peels is directly related to improved results and to the number of complications that can occur. Key principles for superficial and medium depth peeling are discussed, as well as appropriate indications for these treatments.

Chemical peeling is the controlled wounding of the epidermis and dermis for medical and aesthetic improvement. Although the use of chemical peels dates to ancient Egyptian times, our understanding of the science behind chemical peeling is still evolving.1 Recent scientific studies investigating the histologic and long-term effects of peels provide data to support the clinical observations. This first part of the two-part chemical peels CME discusses superficial and medium depth peels, with a description of the histological effects and treatment indications of these peels.

https://ift.tt/2QoWDpv

Tezepelumab, an anti-TSLP monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: A randomized phase 2a clinical trial

Publication date: Available online 12 December 2018

Source: Journal of the American Academy of Dermatology

Author(s): Eric L. Simpson, Jane R. Parnes, Dewei She, Sarah Crouch, William Rees, May Mo, René van der Merwe

Abstract

Background

Tezepelumab (AMG 157/MEDI9929), a first-in-class monoclonal antibody, targets thymic stromal lymphopoietin, a cytokine implicated in atopic dermatitis (AD) pathogenesis.

Objective

Evaluate efficacy and safety of tezepelumab in adults with moderate to severe AD.

Methods

In this phase 2a study (NCT02525094), 113 patients were randomized 1:1 to subcutaneous tezepelumab 280 mg or placebo every 2 weeks, plus Class 3 topical corticosteroids (TCS). The primary endpoint was the Week-12 response rate for a ≥50% reduction in Eczema Area and Severity Index (EASI50). Secondary endpoints including EASI75, Investigator's Global Assessment, Scoring of Atopic Dermatitis (SCORAD) 50, SCORAD75, pruritus numeric rating and 5-D itch scales, and exploratory endpoints (including EASI90) were assessed at Week 12, and Week 16 (post hoc).

Results

A numerically greater percentage of tezepelumab plus TCS-treated patients achieved EASI50 (64.7%) versus placebo plus TCS (48.2%; P = .091). Numerical improvements over placebo were demonstrated for Week 12 secondary and exploratory endpoints, with further improvements at Week 16. Treatment-emergent adverse events were similar between treatment groups.

Limitations

Greater than expected response rates in placebo-treated patients were possibly attributable to TCS.

Conclusion

Although not statistically significant, numerical improvements over placebo for all Week 12 endpoints were demonstrated, with greater Week 16 responses.

https://ift.tt/2QvEsi5

Access to Dermatology Services at Free Medical Clinics, A Nationwide Cross-sectional Survey

Publication date: Available online 12 December 2018

Source: Journal of the American Academy of Dermatology

Author(s): Victoria Madray, Sarvani Ginjupalli, Osama Hashmi, Richard W. Sams, J.Aaron Johnson, Benjamin Stoff

https://ift.tt/2RZovNO

Happy Holidays

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Season's Greetings

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Gemcitabine and metabolite pharmacokinetics in advanced NSCLC patients after bronchial artery infusion and intravenous infusion

Abstract

Purpose

We investigated the safety, pharmacokinetics, and efficacy of gemcitabine administered via bronchial artery infusion (BAI) and IV infusion in advanced NSCLC patients.

Methods

Patients were eligible if they had received at least two prior cytotoxic chemotherapy regimens. Gemcitabine was administered via BAI as 600 mg/m² on day one of cycle one, followed by IV as 1000 mg/m² on day eight of cycle one, and IV on days one and eight of all subsequent cycles. Pharmacokinetics for gemcitabine and dFdU metabolite in plasma, and dFdCTP active metabolite in peripheral blood mononuclear cells (PBMC) were evaluated. Intensive pharmacokinetic sampling was performed after BAI and IV infusions during cycle one.

Results

Three male patients (age range 59–68 years) were evaluated. All patients responded with stable disease or better. One PR was observed after cycle three, and the remaining had SD. C_max (mean ± SD) following BAI for gemcitabine, dFdCTP, and dFdU were 7.71 ± 0.13, 66.5 ± 40.6, and 38 ± 6.27 µM and following IV infusion, 17 ± 2.36, 50.8 ± 3.61, and 83.2 ± 12.3 µM, respectively. The AUCinf (mean ± SD) following BAI for gemcitabine, dFdCTP, and dFdU were 6.89 ± 1.2, 791.1 ± 551.2, and 829.9 ± 217.8 µM h and following IV infusion, 12.5 ± 3.13, 584 ± 86.6, and 1394.64 ± 682.2 µM h, respectively. The AUC and Cmax of dFdCTP after BAI were higher than IV. The median OS was 6.27 months. No grade 3 or 4 toxicity was observed. The most common side effects were all grade ≤ 2 involving nausea, vomiting, rigor, thrombocytopenia, and anemia.

Conclusions

Systemic exposure to dFdCTP was higher after BAI than IV in two out of three patients.

https://ift.tt/2BfYdzl

Predicting the appropriate size of the uncuffed nasotracheal tube for pediatric patients: a retrospective study

Abstract

Objectives

The selection of an appropriate size of tracheal tube is important for airway management. For nasotracheal intubation, passing the nasal cavity should be taken into account for the selection of tube size. The aim of this study was to investigate the selection of appropriate size of nasotracheal tube in pediatric patients retrospectively.

Materials and methods

The 1–12-year patients underwent dental procedures under general anesthesia intubated nasotracheally. The correlation between height, age, weight, the tracheal diameters at C6, C7, Th2 on the chest X-ray, and actually performed tube sizes were calculated. In addition, we compared the relationships between the predicted tube size and actually the intubated tube size.

Results

The tube sizes intubated actually were between 4.0 and 6.0-mm ID. The formula by height could be most suitable for tube size. The correspondence rates for the tube with 4.5- and 5.0-mm ID were 78% and 53%. When they were predicted as 5.5- or 6.0-mm ID, 0.5 mm smaller size tube were intubated actually; 56% and 70%. When the predicted tube size was 4.0-mm ID, 0.5 mm larger size tube was intubated actually; 66%.

Conclusions

The formula by height could be most suitable for the selection of size for pediatric nasotracheal intubation. When the predicted tube size was 5.5 or 6.0-mm ID, 0.5 mm smaller size should be chosen at first. In the case of 4.0-mm ID, 0.5 mm larger size should be chosen for first trial.

Clinical relevance

The present data indicate that the selection of nasotracheal tube using the formula by height might be useful.

https://ift.tt/2GeB862

Effects of neonicotinoids on the emergence and composition of chironomids in the Prairie Pothole Region

Abstract

The use of neonicotinoid pesticides is widespread throughout agricultural regions, including the Prairie Pothole Region of North America. The occurrence of these pesticides to the abundant adjacent wetlands can result in impacts on nontarget insects, and cascading effects through wetland ecosystems. In the current study, field-based mesocosms were used to investigate the effects of multiple pulses of the neonicotinoid imidacloprid on the emergence and chironomid community composition, in an effort to simulate episodic rain events to Prairie Pothole Wetlands. Sediments from two local wetlands were placed into the mesocosm tanks and three imidacloprid pulses added, each 1 week apart at nominal concentrations of 0.2, 2.0, and 20 μg/L. Overall, a significant decrease in the emergence of adult chironomids was observed within the 2.0 μg/L and greater concentrations, with the subfamilies Chironominae and Tanypodinae showing a greater sensitivity than the members of the subfamily Orthocladiinae. The chironomid community also had a dose-related response, followed by a recovery of the community composition near the end of the experiment. Our results provide additional evidence that repeated pulses of imidacloprid may have effects on chironomids and other sensitive aquatic insects living within Prairie Pothole Wetlands, resulting in reduced food availability. We stress the need for continued monitoring of US surface waters for neonicotinoid compounds and the continuation of additional experiments looking into the impacts on aquatic communities.

https://ift.tt/2SIubeK

Clinical outcomes of oral metronomic vinorelbine in advanced non-small cell lung cancer: correlations with pharmacokinetics and MDR1 polymorphisms

Abstract

Purpose

This study investigated correlations of the clinical outcomes of oral metronomic vinorelbine (VNR) with VNR pharmacokinetics and MDR1 polymorphisms.

Methods

Eighty-two patients with metastatic non-small cell lung cancer (NSCLC) unfit for standard chemotherapy were treated with VNR at the oral doses of 20–30 mg every other day or 50 mg three times a week. They had a performance status (PS) ≤ 3, were > 70-year-old and drug-naïve or cisplatin-pretreated. MDR1 2677G > T and 3435C > T polymorphisms were analysed and blood concentrations of VNR and desacetyl-VNR (dVNR: active metabolite) assayed. Overall survival (OS), treatment duration and drug-related toxicity were the main endpoints.

Results

Median OS and treatment duration were 27 weeks (range 1.3–183) and 15 weeks (range 1.3–144), respectively. OS was directly correlated with the duration of VNR treatment and number of therapy lines after VNR treatment (multiple linear regression: adjusted r² = 0.71; p < 0.00001). Neither MDR1 genotypes nor VNR/dVNR concentrations predicted OS. VNR blood levels were positively correlated with platelet counts (r² = 0.12; p = 0.0036). Patients who had long-term benefit (treated for ≥ 6 month without toxicity) showed lower VNR concentrations than those who had not. Twelve patients stopped therapy due to grade 3–4 toxicity. Toxicity was associated with blood concentrations of VNR ≥ 1.57 ng/mL and dVNR ≥ 3.04 ng/mL, but not with MDR1 polymorphisms.

Conclusions

Neither pharmacokinetic nor pharmacogenetic monitoring seem useful to predict OS. On the other hand, high VNR and dVNR blood levels were associated with severe toxicity.

https://ift.tt/2PAHqMC

Season Greetings

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com