Real-world utilization and acceptance of biosimilar bevacizumab in metastatic colorectal cancer in India

Background: To describe the patient characteristics and usage pattern of biosimilar bevacizumab for the treatment of metastatic colorectal cancer (mCRC) in India.Methods: This real-world, retrospective analysis included adult patients receiving biosimilar bevacizumab between April 2021 and March 2022.Results: A total of 1125 patients with mCRC who received biosimilar bevacizumab-based chemotherapy were included. The mean age at diagnosis was 57.8 years. Majority of the patients were males (71%) and belonged to the age groups of 41-76 years. The primary tumor site was right colon (52.6%) followed by left colon (29.2%) and rectum (17.3%), and tumor grade was reported as high in most (88.7%) of the patients. Majority of the patients received biosimilar bevacizumab-based chemotherapy as first-line therapy (61.3%), followed by second-line (31.9%) and third-line therapy (6.8%). In combination with biosimilar bevacizumab, FOLFOX (folinic acid, 5-fluorouracil, and oxaliplatin) was the most commonly administered chemotherapy regimen (42.9%), followed by CAPOX (capecitabine and oxaliplatin, 26.5%) and FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan, 22.8%).Conclusions: Biosimilar bevacizumab-based chemotherapy is being widely used in real‑world clinical setting in India for the management of patients with mCRC

Entomopathogenic fungi in Portuguese vineyards soils: suggesting a ‘Galleria-Tenebrio-bait method’ as bait-insects Galleria and Tenebrio significantly underestimate the respective recoveries of Metarhizium (robertsii) and Beauveria (bassiana)

Entomopathogenic fungi (EPF) are the natural enemies of insect-pests. However, EPF recoveries can be influenced by the soil habitat-type(s) incorporated and/or the bait-insect(s) used. Galleria mellonella (GM) as bait-insect, i.e. ‘Galleria-bait’, is arguably the most common methodology, which is sometimes used solely, to isolate EPF from soils. Insect baiting using Tenebrio molitor (TM) has also been employed occasionally. Here 183 soils were used to estimate the functional diversity of EPF in Portuguese Douro vineyards (cultivated habitat) and adjacent hedgerows (semi-natural habitat), using the TM bait method. Moreover, to study the effect of insect baiting on EPF recovery, 81 of these 183 soil samples were also tested for EPF occurrences using the GM bait method. Twelve species were found in 44.26% ± 3.67% of the total of 183 soils. Clonostachys rosea f. rosea was found in maximum soils (30.05% ± 3.38%), followed by Beauveria bassiana (12.57% ± 2.37%), Purpureocillium lilacinum (9.29% ± 2.14%) and Metarhizium robertsii (6.01% ± 1.75%). Beauveria pseudobassiana (P < 0.001), C. rosea f. rosea (P = 0.006) and Cordyceps cicadae (P=0.023) were isolated significantly more from hedgerows, highlighting their sensitivities towards agricultural disturbances. Beauveria bassiana (P = 0.038) and M. robertsii (P = 0.003) were isolated significantly more using GM and TM, respectively. Principal component analysis revealed that M. robertsii was associated both with TM baiting and cultivated habitats, however, B. bassiana was slightly linked with GM baiting only. Ecological profiles of B. bassiana and P. lilacinum were quite similar while M. robertsii and C. rosea f. rosea were relatively distant and distinct. To us, this is the first report on (a) C. cicadae isolation from Mediterranean soils, (b) Purpureocillium lavendulum as an EPF worldwide; and (c) significant recoveries of M. robertsii using TM over GM. Overall, a ‘Galleria-Tenebrio-bait method’ is advocated to study the functional diversity of EPF in agroecosystems

UNSTEADY FLOW THROUGH POROUS MEDIA PAST ON MOVING VERTICAL PLATE WITH VARIABLE TEMPERATURE IN THE PRESENCE OF INCLINED MAGNETIC FIELD

In this paper, we have investigated the motion of unsteady flow through porous media past on moving vertical plate with variable temperature in the presence of inclined magnetic field. The fluid considered is viscous, electrically conducting, incompressible, absorbing-emitting radiation in a non-scattering medium. The Laplace transform technique has been used to find the solutions for the velocity profile. The velocity profile has been studied for different parameters like Hartmann number, Prandtl number, thermal Grashof number and time. The effects of variable parameters to the velocity profiles are discussed graphically and the numerical values obtained for skin-friction has been tabulated

Glass capillary microfluidics for production of monodispersed poly (dl-lactic acid) and polycaprolactone microparticles: experiments and numerical simulations

Hypothesis: Droplet size in microfluidic devices is affected by wettability of the microfluidic channels. Three-dimensional countercurrent flow focusing using assemblies of chemically inert glass capillaries is expected to minimize wetting of the channel walls by the organic solvent. Experiments: Monodispersed polycaprolactone and poly(lactic acid) particles with a diameter of 18-150 μm were produced by evaporation of solvent (dichloromethane or 1:2 mixture of chloroform and toluene) from oil-in-water or water-in-oil-in-water emulsions produced in three-dimensional flow focusing glass capillary devices. The drop generation behaviour was simulated numerically using the volume of fluid method. Findings: The numerical results showed good agreement with high-speed video recordings. Monodispersed droplets were produced in the dripping regime when the ratio of the continuous phase flow rate to dispersed phase flow rate was 5-20 and the Weber number of the dispersed phase was less than 0.01. The porosity of polycaprolactone particles increased from 8 to 62% when 30 wt% of the water phase was incorporated in the organic phase prior to emulsification. The inner water phase was loaded with 0.156 wt% lidocaine hydrochloride to achieve a sustained drug release. 26 % of lidocaine was released after 1 h and more than 93 % of the drug was released after 130 h

Glass capillary microfluidics for production of monodispersed poly (dl-lactic acid) and polycaprolactone microparticles: experiments and numerical simulations

Hypothesis: Droplet size in microfluidic devices is affected by wettability of the microfluidic channels. Three-dimensional countercurrent flow focusing using assemblies of chemically inert glass capillaries is expected to minimize wetting of the channel walls by the organic solvent. Experiments: Monodispersed polycaprolactone and poly(lactic acid) particles with a diameter of 18-150 μm were produced by evaporation of solvent (dichloromethane or 1:2 mixture of chloroform and toluene) from oil-in-water or water-in-oil-in-water emulsions produced in three-dimensional flow focusing glass capillary devices. The drop generation behaviour was simulated numerically using the volume of fluid method. Findings: The numerical results showed good agreement with high-speed video recordings. Monodispersed droplets were produced in the dripping regime when the ratio of the continuous phase flow rate to dispersed phase flow rate was 5-20 and the Weber number of the dispersed phase was less than 0.01. The porosity of polycaprolactone particles increased from 8 to 62% when 30 wt% of the water phase was incorporated in the organic phase prior to emulsification. The inner water phase was loaded with 0.156 wt% lidocaine hydrochloride to achieve a sustained drug release. 26 % of lidocaine was released after 1 h and more than 93 % of the drug was released after 130 h

Development of novel drug formulation using microfluidic device

Poster introduction: Biosorbable poly(lactic acid) (PLA) microspheres have been used for controlled drug release, as ultrasound contrast agents, for cell cultivation in tissue engineering, fabrication of scaffolds, composite coatings, etc. Coherent PLA particles can be fabricated via single emulsion route. First, PLA is dissolved in a volatile organic solvent (DCM) and this solution is emulsified in an aqueous surfactant solution. In the next stage, the resultant droplets are solidified by evaporation of solvent. Porous PLA particles can be produced via W/O/W emulsion route, where first, an inner water phase is dispersed in a mixture of PLA and DCM in the presence of oil-soluble surfactant form a W/O emulsion. This emulsion is then dispersed drop-wise into an aqueous surfactant solution to form a W/O/W emulsion. W/O particles are formed by evaporation of DCM

Cross-species gene expression analysis of species specific differences in the preclinical assessment of pharmaceutical compounds

Animals are frequently used as model systems for determination of safety and efficacy in pharmaceutical research and development. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this cross-species methodology by investigating species specific differences of the peroxisome proliferatoractivator receptor (PPAR) a response in rat and human

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Effect of Soil Chemical Properties on the Occurrence and Distribution of Entomopathogenic Fungi in Portuguese Grapevine Fields

Entomopathogenic fungi (EPF) contribute to different ecosystem services. However, factors affecting their natural occurrences in soil remain poorly understood. In a previous study, 81 soil samples were subjected to insect baiting using Galleria mellonella and Tenebrio molitor to isolate EPF from Portuguese vine farms. Here, soils yielding any of the four common EPF, i.e., Beauveria bassiana, Purpureocillium lilacinum, Metarhizium robertsii, and Clonostachys rosea f. rosea, were correlated with their chemical properties. Beauveria bassiana was negatively affected by higher available P (p = 0.02), exchangeable K-ions (p = 0.016) and positively affected by higher soil pH_H2O (p = 0.021). High exchangeable K-ions inhibited P. lilacinum (p = 0.011) and promoted C. rosea f. rosea (p = 0.03). Moreover, high available K also suppressed P. lilacinum (p = 0.027). Metarhizium robertsii was inhibited by higher organic matter content (p = 0.009), higher C:N (p = 0.017), total N (p = 0.007), and exchangeable Mg-ions (p = 0.026), and promoted by higher exchangeable Na-ions (p = 0.003). Nonetheless, mean comparisons and principal component analysis suggested that higher soil pH and exchangeable Ca-ions have contrasting effects on EPF occurrences, as they promote B. bassiana and inhibit M. robertsii. Herbicides did not seem to affect EPF presence. Overall, this study is among the first reports on the effects of soil chemistry on EPF other than Metarhizium, and will facilitate biological pest management approaches