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Systematic review and meta-analysis of the impact of deviations from a clinical pathway on outcomes following pancreatoduodenectomy

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World Journal of Clinical Cases 2021年第13期9卷 3024-3037页

作者： Monish Karunakaran pavan kumar jonnada Savio George Barreto Department of Gastrointestinal Surgery Gastrointestinal Oncologyand Bariatric SurgeryMedanta Institute of Digestive and Hepatobiliary SciencesGurgaon 122001HaryanaIndia Department of Liver Transplantation and Regenerative Medicine Medanta-The MedicityGurgaon 122001HaryanaIndia Surgical Oncology Kidwai Memorial Institute of OncologyBengaluru 560029KarnatakaIndia Division of Surgery and Perioperative Medicine Flinders Medical CenterBedford Park 5042South AustraliaAustralia College of Medicine and Public Health Flinders UniversityBedford Park 5042South AustraliaAustralia

BACKGROUND Enhanced recovery after surgery is steadily gaining importance in patients undergoing pancreatic surgery,including pancreatoduodenectomy(PD).While clinical pathways targeting enhanced-recovery can achieve their intended outcome in reducing length of stay,compliance to these pathways,and their relevance is poorly understood.The aim of this systematic review was to assess the impact of deviations from/non-compliance to a clinical pathway on post-PD outcomes.AIM To assess the impact of deviations from/non-compliance to a clinical pathway on post-PD outcomes.METHODS A systematic review of major reference databases was undertaken,according to preferred reporting items for systematic reviews and meta-analysis guidelines,between January 2000 and November 2020 relating to compliance with clinical pathways and its impact on outcomes in patients undergoing PD.A meta-analysis was performed using fixed-effects or random-effects models.RESULTS Eleven studies including 1852 patients were identified.Median overall compliance to all components of the clinical pathway was 65.7%[interquartile range(IQR):62.7%-72.3%]with median compliance to post-operative parameters of the clinical pathway being 44%(IQR:34.5%-52.25%).Meta-analysis using a fixed-effects model showed that≥50%compliance to a clinical pathway predicted significantly fewer post-operative complications[pooled odds ratio(OR):9.46,95%confidence interval(CI):5.00-17.90;P<0.00001]and a significantly shorter length of hospital stay[pooled mean difference(MD):4.32,95%CI:-3.88 to-4.75;P<0.0001].At 100%compliance which was associated with significantly fewer post-operative complications(pooled OR:11.25,95%CI:4.71-26.84;P<0.00001)and shorter hospital stay(pooled MD of 4.66,95%CI:2.81-6.51;P<0.00001).CONCLUSION Compliance to post-PD clinical pathways remains low.Deviations are associated with an increased risk of complications and length of hospital stay.Understanding the relevance of deviations to clinical pathways post-PD presents pancreatic surgeons with opportuniti

关键词： Outcomes Morbidity Mortality Quality Surgery Recovery

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Drug resistance mechanisms in cancers:Execution of prosurvival strategies

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Journal of Biomedical Research 2024年第2期38卷 95-121页

作者： pavan kumar Dhanyamraju Fels Cancer Institute of Personalized Medicine Lewis-Katz School of MedicineTemple UniversityPhiladelphiaPA 19140USA

One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.

关键词： cancer drug resistance mechanisms microRNAs treatment strategies

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Coupled multiphysical model for investigation of influence factors in the application of microbially induced calcite precipitation

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第6期16卷 2232-2249页

作者： Xuerui Wang pavan kumar Bhukya Dali Naidu Arnepalli Shuang Chen Gesellschaft für Anlagen-und Reaktorsicherheit(GRS)GGmbH Braunschweig38122Germany Department of Civil Engineering Indian Institute of Technology MadrasChennai600036India Federal Institute for Geosciences and Natural Resources(BGR) Hannover30655Germany

The study presents a comprehensive coupled thermo-bio-chemo-hydraulic(T-BCH)modeling framework for stabilizing soils using microbially induced calcite precipitation(MICP).The numerical model considers relevant multiphysics involved in MICP,such as bacterial ureolytic activities,biochemical reactions,multiphase and multicomponent transport,and alteration of the porosity and permeability.The model incorporates multiphysical coupling effects through well-established constitutive relations that connect parameters and variables from different physical fields.It was implemented in the open-source finite element code OpenGeoSys(OGS),and a semi-staggered solution strategy was designed to solve the couplings,allowing for flexible model settings.Therefore,the developed model can be easily adapted to simulate MICP applications in different scenarios.The numerical model was employed to analyze the effect of various factors,including temperature,injection strategies,and application scales.Besides,a TBCH modeling study was conducted on the laboratory-scale domain to analyze the effects of temperature on urease activity and precipitated calcium carbonate.To understand the scale dependency of MICP treatment,a large-scale heterogeneous domain was subjected to variable biochemical injection strategies.The simulations conducted at the field-scale guided the selection of an injection strategy to achieve the desired type and amount of precipitation.Additionally,the study emphasized the potential of numerical models as reliable tools for optimizing future developments in field-scale MICP treatment.The present study demonstrates the potential of this numerical framework for designing and optimizing the MICP applications in laboratory-,prototype-,and field-scale scenarios.

关键词： Multiphysics Microbially induced calcite precipitation(MICP) Coupled thermo-bio-chemo-hydraulic(TBCH) model OpenGeoSys(OGS) Influence factors

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Role of aberrant Sonic hedgehog signaling pathway in cancers and developmental anomalies

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The Journal of Biomedical Research 2022年第1期36卷 11-19页

作者： Trupti N.Patel pavan kumar Dhanyamraju School of Biosciences and Technology Vellore Institute of TechnologyVellore CampusVelloreTamil Nadu 632014India Department of Pharmacology Penn State University College of MedicineHersheyPA 17033USA Penn State Cancer Institute HersheyPA 17033USA.

Development is a sophisticated process maintained by various signal transduction pathways,including the Hedgehog(Hh)pathway.Several important functions are executed by the Hh signaling cascade such as organogenesis,tissue regeneration,and tissue homeostasis,among various others.Considering the multiple functions carried out by this pathway,any mutation causing aberrant Hh signaling may lead to myriad developmental abnormalities besides cancers.In the present review article,we explored a wide range of diseases caused by aberrant Hh signaling,including developmental defects and cancers.Finally,we concluded this mini-review with various treatment strategies for Hh-induced diseases.

关键词： cancer developmental anomaly hedgehog signal transduction drug treatment

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Melanoma therapeutics: a literature review

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The Journal of Biomedical Research 2022年第2期36卷 77-97页

作者： pavan kumar Dhanyamraju Trupti N.Patel Department of Pediatrics and Pharmacology Pennsylvania State University College of MedicineHersheyPA 17033USA School of Biosciences and Technology Vellore Institute of TechnologyVellore CampusVelloreTamil Nadu 632014India

Melanoma is a relentless type of skin cancer which involves myriad signaling pathways which regulate many cellular processes.This makes melanoma difficult to treat,especially when identified late.At present,therapeutics include chemotherapy,surgical resection,biochemotherapy,immunotherapy,photodynamic and targeted approaches.These interventions are usually administered as either a single-drug or in combination,based on tumor location,stage,and patients'overall health condition.However,treatment efficacy generally decreases as patients develop treatment resistance.Genetic profiling of melanocytes and the discovery of novel molecular factors involved in the pathogenesis of melanoma have helped to identify new therapeutic targets.In this literature review,we examine several newly approved therapies,and briefly describe several therapies being assessed for melanoma.The goal is to provide a comprehensive overview of recent developments and to consider future directions in the field of melanoma.

关键词： cancer melanoma intervention target resistance

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3D printing of bio-instructive materials:Toward directing the cell

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Bioactive Materials 2023年第1期19卷 292-327页

作者： Piotr Stanisław Zielinski pavan kumar Reddy Gudeti Timo Rikmanspoel Małgorzata Katarzyna Włodarczyk-Biegun Polymer Science Zernike Institute for Advanced MaterialsUniversity of GroningenNijenborgh 49747 AGGroningenthe Netherlands Biotechnology Centre The Silesian University of TechnologyB.Krzywoustego 844-100GliwicePoland

Fabrication of functional scaffolds for tissue engineering and regenerative medicine applications requires material systems with precise control over cellular performance.3D printing is a powerful technique to create highly complex and multicomponent structures with well-defined architecture and composition.In this review paper,we explore extrusion-based 3D printing methods(EBP,i.e.,Near Field Electrospinning(NFES),Melt Electrowriting(MEW),Fused Deposition Modeling(FDM),and extrusion bioprinting)in terms of their ability to produce scaffolds with bio-instructive properties.These material systems provide spatio-temporal guidance for cells,allowing controlled tissue regeneration and maturation.Multiple physical and biochemical cues introduced to the EBP scaffolds are evaluated in their ability to direct cell alignment,proliferation,differentiation,specific ECM production,and tissue maturation.We indicate that the cues have different impacts depending on the material system,cell type used,or coexistence of multiple cues.Therefore,they must be carefully chosen based on the targeted application.We propose future directions in bio-instructive materials development,including such concepts as metamaterials,hybrid living materials,and 4D printing.The review gathers the knowledge essential for designing new materials with a controlled cellular response,fabrication of advanced engineered tissue,and developing a better understanding of cell biology,especially in response to the biomaterial.

关键词： Tissue engineering Additive manufacturing Melt electrowriting 3D scaffold Cell differentiation Biomaterials

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Mathematical Modeling and Evaluation of Reliability Parameters Based on Survival Possibilities under Uncertain Environment

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Computer Modeling in Engineering & Sciences 2023年第3期134卷 1943-1956页

作者： Alhanouf Alburaikan Hamiden Abd El-Wahed Khalifa pavan kumar SeyedaliMirjalili Ibrahim Mekawy Department of Mathematics College of Science and ArtsQassim UniversityAl-Badaya51951Saudi Arabia Department of Operations Research Faculty of Graduate Studies for Statistical ResearchCairo UniversityGiza12613Egypt Division of Mathematics School of Advanced Science and LanguagesVIT Bhopal UniversitySehore466114India Centre for Artificial Intelligence Research and Optimization Torrens University AustraliaBrisbane4006Australia Department of Mathematics College of Science and ArtsQassim UniversityAr Rass6688Saudi Arabia YFL(Yonsei Frontier Lab) Yonsei UniversitySeoul03722Korea

In this article,mathematical modeling for the evaluation of reliability is studied using two methods.One of the methods,is developed based on possibility theory.The performance of the reliability of the system is of prime concern.In view of this,the outcomes for the failure are required to evaluate with utmost care.In possibility theory,the reliability information data determined from decision-making experts are subjective.The samemethod is also related to the survival possibilities as against the survival probabilities.The other method is the one that is developed using the concept of approximation of closed interval including the piecewise quadratic fuzzy numbers.In this method,a decision-making expert is not sure of his/her estimates of the reliability parameters.Numerical experiments are performed to illustrate the efficiency of the suggested methods in this research.In the end,the paper is concluded with some future research directions to be explored for the proposed approach.

关键词： Reliability function probabilistic function piecewise quadratic fuzzy numbers survival possibility failure rate possibility distribution state function closed interval approximation

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Neuroprotective effects of Alda-1 mitigate spinal cord injury in mice:involvement of Alda-1-induced ALDH2 activation-mediated suppression of reactive aldehyde mechanisms

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Neural Regeneration Research 2022年第1期17卷 185-193页

作者： Mushfiquddin Khan Fei Qiao pavan kumar S.M.Touhidul Islam Avtar K.Singh Jeseong Won Inderjit Singh Department of Pediatrics Medical University of South CarolinaCharlestonSCUSA Department of Pathology and Laboratory Medicine Medical University of South CarolinaCharlestonSCUSA Ralph H.Johnson VA Medical Center CharlestonSCUSA

Spinal cord injury(SCI)is associated with high production and excessive accumulation of pathological 4-hydroxy-trans-2-nonenal(4-HNE),a reactive aldehyde,formed by SCI-induced metabolic dysregulation of membrane lipids.Reactive aldehyde load causes redox alteration,neuroinflammation,neurodegeneration,pain-like behaviors,and locomotion deficits.Pharmacological scavenging of reactive aldehydes results in limited improved motor and sensory functions.In this study,we targeted the activity of mitochondrial enzyme aldehyde dehydrogenase 2(ALDH2)to detoxify 4-HNE for accelerated functional recovery and improved pain-like behavior in a male mouse model of contusion SCI.N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide(Alda-1),a selective activator of ALDH2,was used as a therapeutic tool to suppress the 4-HNE load.SCI was induced by an impactor at the T9–10 vertebral level.Injured animals were initially treated with Alda-1 at 2 hours after injury,followed by once-daily treatment with Alda-1 for 30 consecutive days.Locomotor function was evaluated by the Basso Mouse Scale,and pain-like behaviors were assessed by mechanical allodynia and thermal algesia.ALDH2 activity was measured by enzymatic assay.4-HNE protein adducts and enzyme/protein expression levels were determined by western blot analysis and histology/immunohistochemistry.SCI resulted in a sustained and prolonged overload of 4-HNE,which parallels with the decreased activity of ALDH2 and low functional recovery.Alda-1 treatment of SCI decreased 4-HNE load and enhanced the activity of ALDH2 in both the acute and the chronic phases of SCI.Furthermore,the treatment with Alda-1 reduced neuroinflammation,oxidative stress,and neuronal loss and increased adenosine 5′-triphosphate levels stimulated the neurorepair process and improved locomotor and sensory functions.Conclusively,the results provide evidence that enhancing the ALDH2 activity by Alda-1 treatment of SCI mice suppresses the 4-HNE load that attenuates neuroinflammation and neurodegeneration,promotes the neur

关键词： 4-hydroxy-trans-2-nonenal Alda-1 ALDH2 Basso Mouse Scale score functional recovery mitochondrial function neuroinflammation neuroprotection pain spinal cord injury

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Process-structure-property relationship for plasma-sprayed iron-based amorphous/crystalline composite coatings

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International Journal of Minerals,Metallurgy and Materials 2022年第1期29卷 144-152页

作者： Abhishek Pathak Biswajyoti Mukherjee Krishna Kant Pandey Aminul Islam pavan Bijalwan Monojit Dutta Atanu Banerjee Anup kumar Keshri Research and Development Unit Tata SteelJamshedpur 831001India Plasma Spray Coating Laboratory Metallurgical and Materials EngineeringIndian Institute of Technology PatnaBihta 801106India

This study explores the fabrication of Fe-based amorphous/crystalline coating by air plasma spraying and its dependency on the coating parameters(plasma power,primary gas flow rate,powder feed rate,and stand-off distance).X-ray diffraction of the coatings deposited at optimized spray parameters showed the presence of amorphous/crystalline phase.Coatings deposited at a lower plasma power and highest gas flow rate exhibited better density,hardness,and wear resistance.All coatings demonstrated equally good resistance against the corrosive environment(3.5wt%NaCl solution).Mechanical,wear,and tribological studies indicated that a single process parameter optimization cannot provide good coating performance;instead,all process parameters have a unique role in defining better properties for the coating by con-trolling the in-flight particle temperature and velocity profile,followed by the cooling pattern of molten droplet before impingement on the substrate.

关键词： Fe-based alloys amorphous alloys plasma spray coating mechanical corrosion and wear

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Functional and clinical outcome with modified lateral approach total hip arthroplasty in stiff hips with ankylosing spondylitis

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World Journal of Orthopedics 2022年第8期13卷 714-724页

作者： Mathew Kiran Jacob pavan kumar Reddy Roncy Savio Kuruvilla Chandy Viruthapadavil John Pradeep Mathew Poonnoose Anil Thomas Oommen Unit 2 Department of OrthopaedicsChristian Medical College HospitalVellore 632004India

BACKGROUND Ankylosing spondylitis at total hip arthroplasty(THA)has significant hip stiffness with flexion deformity,restricted mobility,and function.Range of movement(ROM)improvement with good functional outcome is seen following THA in these hips.The modified Hardinge approach without abductor compromise is helpful in these stiff hips with associated flexion deformity.AIM To assess improvement in ROM and functional outcomes with a modified lateral approach THA in ankylosing spondylitis with stiff hips.METHODS A total of 69 hips that underwent THA with a modified Hardinge approach in 40 patients were evaluated at a mean follow-up of 38.33 mo.All individuals ambulated with weight-bearing as tolerated and ROM exercises from the 1st postoperative day.Modified Harris hip score and ROM were assessed during follow-up.Quality of life assessments using the 36-item and 12-item short form health surveys were done along with clinical and functional outcomes at followup.SPSS 22.0 was used for statistical analysis.The correlation of ROM and functional score change was performed using Pearson’s correlation coefficient.RESULTS Sixty-nine hips with a significant decrease in ROM preoperatively with 32 clinically fused hips showed significant improvement in flexion range.The mean flexion in 69 hips improved from 29.35±31.38 degrees to 102.17±10.48 degrees.The mean difference of 72.82 with a P value<0.0001 was significant.In total,45 out of 69 hips had flexion deformity,with 13 hips having a deformity above 30 degrees.The flexion during the follow-up was below 90 degrees in 3 hips.Eleven hips had flexion of 90 degrees at follow-up,while the remaining 55 hips had flexion above 100 degrees.Modified Harris hip score improved from 17.03±6.02 to 90.66±7.23(P value<0.0001).The 36-item short form health survey at the follow-up indicated health status in 40 patients as excellent in 11,very good in 20,good in 5,fair in 3,and poor in 1.The mean mental health score was 84.10±11.58.Pain relief was good in all 69 hips.Altogether,28/40 patients

关键词： Ankylosing Spondylitis Stiff flexion deformity Harris hip score Hip range of movement 36-item short form health survey score Total hip arthroplasty modified Hardinge approach

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