Aetiologies of Leg Pain among Patients Presenting to a Vascular Surgery Clinic.

OBJECTIVE: To determine the frequency and pattern of different aetiologies of leg pain among patients visiting vascular surgery clinics. STUDY DESIGN: Cross-sectional study. Place and Duration of the Study: Vascular Surgery Clinics of the Aga Khan University Hospital, Karachi, Pakistan, between February 2021 and June 2023. METHODOLOGY: This study examined patients presenting with leg pain for the first time at vascular surgery clinics. The socio-demographic and clinical data including the clinical symptoms, physical examination findings, and management of leg pain were noted using a specially designed proforma. RESULTS: In a total of 142 patients (200 limbs), 82 (57.7%) were females and 60 (42.3%) were males, with a mean age of 46.8 ± 15.1 years. The patients' mean body mass index (BMI) was 30.2 ± 7.9 kg/m2. Ninety-one (64.1%) patients had a predominantly standing job compared to 51 (35.9%) patients who had a predominantly sitting job. The most common aetiology of leg pain was chronic venous insufficiency (CVI), diagnosed in 107 (53.5%) patients, followed by neurogenic pain [41 (20.5%)], musculoskeletal pain including knee osteoarthritis [30 (15.0%)], and arterial insufficiency [22 (11.0%)].  Conclusion: CVI followed by neuropathic pain was the leading cause of leg pain in vascular surgery clinics at a tertiary care hospital. KEY WORDS: Chronic venous insufficiency, Arterial insufficiency, Vascular surgery, Leg pain, Musculoskeletal pain, Neuralgia.

A short report on the current landscape of Artificial Intelligence (AI) in vascular surgery in Pakistan.

This study focuses on the current applications, potential, and challenges to Artificial Intelligence (AI) integration in vascular surgery with specific emphasis on its relevance in Pakistan. Despite the benefits of AI in vascular surgery, there is a substantial gap in its adoption in Pakistan compared to global standards. In our context with limited resources and a scarcity of vascular surgeons, AI can serve as a promising solution. It can enhance healthcare accessibility, improve diagnostic accuracy, and alleviate the workload on vascular surgeons. However, hurdles including the absence of a comprehensive vascular surgery database, a shortage of AI experts, and potential algorithmic biases pose significant challenges to AI implementation. Despite these obstacles, the study underscores the imperative for continued research, collaborative efforts, and investments to unlock the full potential of AI and elevate vascular healthcare standards in Pakistan.

High-Pressure Delivery of Oncolytic Viruses via Needle-Free Injection Preserves Therapeutic Activity.

Intratumoural delivery of oncolytic viruses (OVs) to solid tumours is currently performed via multiple percutaneous methods of needle injections (NI). In this study, we investigated the potential use of a novel delivery approach, needle-free injection (NFI), to administer OVs to subcutaneous tumours. The stability and genetic integrity of several RNA and DNA viruses exposed to high-pressure jet injectors were first evaluated in vitro. We demonstrate that replication competence and infectivity of the viruses remained unchanged after NFI, as compared to traditional NI. Using the oncolytic Vesicular Stomatitis Virus expressing luciferase (VSVΔ51-Luc) in the syngeneic CT26 subcutaneous tumour model, we show that NFI administration not only successfully delivers infectious particles but also increases the dissemination of the virus within the tumour tissues when compared to NI. Furthermore, mice treated with VSVΔ51-Luc by NFI delivery showed similar reduction in tumour growth and survival compared to those with needle-administered virus. These results indicate that NFI represents a novel approach to administer and potentially increase the spread of OVs within accessible solid tumours, highlighting its usefulness in virotherapy.

A systematic review of simulation training for lower extremity bypass procedures.

OBJECTIVES: Simulation is used across surgical specialties for skill enhancement. The choice and assessment method of a simulator varies across literature. In the age of endovascular approach, trainees have limited exposure to open lower limb bypass procedures which needs attention. This review aims to assess the utility of simulation training in lower limb bypass surgery using Kirkpatrick's model. METHODS: Using PRISMA statement, we included all the studies done on simulators in lower limb bypass surgical procedures for this systematic review. The primary outcome was to assess the effectiveness of different types of simulation used for lower limb bypass surgery using the Kirkpatrick's model for training evaluation. RESULTS: An initial search identified 295 articles out of which 7 articles were found to be eligible for this systematic review. A variety of simulators were used including cadavers and synthetic models. Most studies (n=5) found the use of simulation as an effective tool in achieving technical competence. All the five studies we found at level 2 on Kirpatrick's model evaluation. CONCLUSION: Most of the existing studies are at level 2 of Kirkpatrick's model which reflects learning changes in trainees after simulation. Feedback mechanism needs to be evolved where the improvement after simulation training can be gauged by its replication in clinical practice and improved patient care practices corresponding to the highest level of Kirkpatrick's model.

Axillary synovial sarcoma recurrence involving brachial plexus, a rare case report from Pakistan.

INTRODUCTION: Synovial sarcomas are rare tumors, and the incidence of axillary synovial sarcoma involving the brachial plexus has been reported as 2.9 % among all axillary soft tissue tumors. However, the recurrence of axillary synovial sarcomas has not been reported in literature. CASE PRESENTATION: A 36-years-old Afghan female presented in Karachi, Pakistan with a history of persistently increasing, recurrent, right axillary mass for 6 months. Initially diagnosed as a spindle-cell tumor on excision in Afghanistan, she had received ifosfamide and doxorubicin, but the lesion recurred. On examination, it was a 5 × 6 cm, hard mass palpable in right axilla. After radiological work-up and a multidisciplinary team discussion, she underwent complete excision of the tumor with successful preservation of brachial plexus. The final diagnosis was reported as monophasic synovial sarcoma FNCLCC Grade 3. DISCUSSION: Our patient presented with a recurrent right axillary synovial sarcoma that was involving the axillary neurovascular bundle and brachial plexus, which was initially diagnosed as a spindle cell sarcoma. Pre-operative core-needle biopsy was unable to provide a definitive diagnosis. MRI scan was useful in delineating the proximity of the neurovascular structures. Re-excision of the tumor was performed which is the mainstay of treatment for axillary synovial sarcomas, combined with radiotherapy depending on the disease grading, staging and patient factors. CONCLUSION: Axillary synovial sarcoma recurrence with involvement of the brachial plexus is an extremely rare presentation. Our patient was successfully managed through a multidisciplinary approach with complete surgical excision and preservation of the brachial plexus followed by adjuvant radiotherapy.

Hybrid Steel/NSM/GFRP System versus GFRP Wrapping for Upgrading RC Wall-like Columns.

Reinforced concrete (RC) wall-like columns are commonly employed in structures in Saudi Arabia. These columns are preferred by architects owing to their minimum projection in the usable space. However, they often need strengthening due to several reasons, such as the addition of more stories and increasing the live load as a result of changing the usage of the building. This research aimed to obtain the best scheme for the axial strengthening of RC wall-like columns. The challenge in this research is to develop strengthening schemes for RC wall-like columns, which are favored by architects. Accordingly, these schemes were designed so that the dimensions of the column cross-section are not increased. In this regard, six wall-like columns were experimentally examined in the event of axial compression with zero eccentricity. Two specimens were not retrofitted to be used as control columns, whereas four specimens were retrofitted with four schemes. The first scheme incorporated traditional glass fiber-reinforced polymer (GFRP) wrapping, while the second one utilized GFRP wrapping combined with steel plates. The last two schemes involved the addition of near-surface mounted (NSM) steel bars combined with GFRP wrapping and steel plates. The strengthened specimens were compared with regard to axial stiffness, maximum load, and dissipated energy. Besides column testing, two analytical approaches were suggested for computing the axial capacity of tested columns. Moreover, finite element (FE) analysis was performed for evaluating the axial load versus displacement response of tested columns. As an outcome of the study, the best strengthening scheme was proposed to be used by practicing engineers for axial upgrading of wall-like columns.

Autologous vein graft repair of mycotic innominate artery aneurysm: A case report.

INTRODUCTION: Innominate artery aneurysm (IAA) is an extremely rare fatal condition with an overall prevalence of less than 3 % of all supra-aortic artery aneurysms. These infrequent lesions usually present as an emergency and require challenging surgical procedures. CASE PRESENTATION: We report an interesting case of mycotic IAA in a 25 years old male patient. He was a known intravenous drug abuser having mycotic aneurysm arising from brachiocephalic artery with eccentric thrombus causing adjacent mass effect over the trachea. He underwent successful emergent surgical management of aneurysm with autologous vein graft using superficial femoral vein. Unfortunately, he died due to massive upper gastrointestinal bleeding leading to multi-organ failure after a prolonged post-operative course. CLINICAL DISCUSSION: Mycotic aneurysms of the IA are extremely rare with an overall incidence of 1-2.7 % cases of all IAA. Presentation of the IAA can be quite variable from asymptomatic to symptoms exhibiting mass effect over surrounding structures. Rupture of IAA can be fatal and can occur if not treated promptly. There are no current recommendations or guidelines for treatment and interventions in IAA. Surgical management involves complete excision of the aneurysm and then revascularization. CONCLUSION: Infected Innominate artery aneurysm is a rare surgical entity requiring early diagnosis, detailed investigation and prompt surgical management involving multidisciplinary team approach. Our case describes a relatively innovative approach to this scarce condition.

Perception and Validity of Online Formative Oral Assessment in Surgical Trainees: A Cross-Sectional Study.

BACKGROUND: Online oral assessments have been poorly studied in medical education. This study aims to assess the perception of the online oral assessment strategy for formative purposes. OBJECTIVE: To explore the perception of trainees and examiners on their experience of online oral assessment. METHODS: Online oral assessments were conducted using the Zoom platform (Zoom Video Communications, Inc., San Jose, California, United States) over a period of six days. Each candidate was examined by two examiners and formative feedback was provided at the same time. At the end of the course, participants were asked to fill out an online questionnaire regarding their perception of this online platform for oral assessment.  Results: A total of 192 participants were included in this study as examiners (n=48), candidates (n=53), and observers (n=91). The overall impression of the organization and accessibility of the model was found favorable with a generally lower degree of perceived anxiety in this format. Major limitations faced by participants included technical difficulties (n=84), linguistic issues (n=37), and failure to observe body language (n=38). Using the Joughin matrix, this model of online oral assessment was found as a fair and valid assessment tool with relatively low reliability. CONCLUSIONS: The online oral assessment model has been found to be a reliable and valid method of formative assessment. Further work could be done on this model to assess its potential for summative purposes.

Availability of Operative Surgical Experience and Supervision for Competency-Based Education: A Review of A General Surgery Program at A Tertiary Care Teaching Hospital in Pakistan.

BACKGROUND: In view of importance for competency-based education (CBE), we undertook a self-study to elicit the available operative surgical workload and supervision for residents in the general surgical residency program at the teaching hospital in Karachi. METHODOLOGY: This was a cross-sectional study spanning a 5-year period between January 2015 and December 2019. The numbers of surgical residents during this period were identified. Five procedures were selected as core general surgical procedures: incision and drainage of superficial abscess, laparoscopic appendectomy, laparoscopic cholecystectomy, open inguinal hernia repair, and perianal procedures. Trends of the number of residents per year and the numbers of procedures per year were determined. The mean number of core procedures per eligible resident during their entire training was calculated to represent potential operative surgical experience and were benchmarked. The ratio of the average number of residents rotating in general surgery per year to the number of attending surgeons was determined as a measure of available supervision. RESULT: The mean total number of general surgical residents per year was 31.2 (range 28-35). The numbers of core general surgical procedures were consistent over the years of study. Potential exposure of eligible residents to each core procedure during their entire training was: 19.5 cases for incision and drainage of superficial abscess; 89 cases for laparoscopic appendectomy; 113.6 for inguinal hernia repair, 267.5 for laparoscopic cholecystectomy and 64.5 for perianal procedures. The average yearly residents to full-time attending surgeons' ratio was 2.5. The workload of core general surgical procedures at AKUH was higher than the Accreditation Council for Graduate Medical Education (ACGME) recommended volumes for operative surgical experience for residents in the US. CONCLUSION: This method of assessing the potential of a surgical program for transitioning to CBE appears practical and can be generalized.

Role of simulation in open varicose veins surgery: A systematic review.

OBJECTIVE: To assess the types and effectiveness of simulators present for open varicose vein surgery. METHODS: The systematic review was conducted at The Aga Khan University Hospital Karachi and comprised studies published from 1st January 2000 to 30th June 2020 related to open varicose vein surgical procedures done on simulators. Databases searched were PubMed, Medline, Google Scholar, Cochrane and Scopus using appropriate key words. The primary outcome of the review was to assess the effectiveness of different types of simulators used for varicose vein surgery. RESULTS: Of the 286 articles found, 6(2%) were included. A variety of simulators ranging from animal models, homemade simulators and commercially designed models with high fidelity options had been used. Technical competence was the major domain assessed in most of the studies 5(83.3%), while 1(16.6%) study focussed on self-assessment. Blinding was done in 4(66.6%) studies for assessment purpose, and videorecording of the trainees' performance was done in 5(83.3%) studies. Most studies 4(66.6%) found the use of simulation to be an effective tool in achieving technical competence. CONCLUSION: The use of simulation in the training of surgical residents for open varicose vein surgery was found to be beneficial, but most studies were heterogeneous in terms of design, simulator types and study participants. This makes it difficult to establish the superiority of any one type of simulator over the rest. Further research is needed to develop and validate simulators in open varicose vein surgery procedures.

Barriers in surgical research: A perspective from the developing world.

Research in surgery has led to significant advances over the last century in terms of how medicine is practised in and outside the operating rooms today. Surgical research in the developed countries is responsible for most of this advancement, but it is often inapplicable in resource-limited settings in the developing world. Lower- and middle-income countries are in a unique position to take this work further, but they are limited by certain barriers. These barriers could broadly be classified under social and cultural, infrastructure, financial, ethical, and personal categories. These barriers are often not fully realised, but can potentially be addressed with concerted efforts to continue the advancement of medicine for everyone.

Validation of Task-Specific Rating Scale for Open Balloon Catheter Arterial Embolectomy: An Assessor-Blinded Quasi-Experimental Pilot Study.

Objective: To develop and validate a task-specific rating scale (TSRS) by comparing with the Global Rating Scale (GRS) for the evaluation of brachial artery embolectomy (BAE). Methods: Participants were divided into expert and novice groups who were oriented on the locally developed simulator model. The following day, an embolectomy procedure was performed independently by the participants and graded by two independent assessors using the GRS and TSRS. Validity was evaluated using Pearson's correlation coefficient (r), reliability by the interclass correlation coefficient (ICC), and agreement by Bland-Altman plots. A p-value <0.05 was considered significant. Results: Thirty-two participants were enrolled in this study. The overall TSRS was found to be a valid assessment tool (r=0.82; 95% confidence interval [CI]: 0.66, 0.91; p<0.001). Domain-specific analyses showed a moderate positive association between all domains (p<0.05), except for instrument handling (r=0.09; 95%CI: -0.27, 0.42; p=0.642). The ICC for overall scores showed excellent reliability for both instruments, GRS and TSRS, with values of 0.97 and 0.92, respectively. Conclusion: The TSRS was found to be a valid and reliable assessment tool for BAE; however, for some domains, such as instrument handling and time and motion, it has limited reliability.

Role of Simulated Training for Carotid Endarterectomy: A Systematic Review.

Vascular surgery trainees often do not get to perform carotid endarterectomy (CEA) directly on the patients as it requires meticulous surgical technique and has a high risk of procedure-related complications. Hence, the role of simulation in training future vascular surgeons becomes essential. This review aims to assess the types and utility of simulators available for CEA. In this systematic review, all the studies performed on CEA simulation were included. The purpose of this review was to assess different types of simulators and their usefulness for CEA. We identified 122 articles, of which 10 were eligible for review. A variety of simulators, ranging from animal models, virtual reality simulators and commercially designed models with high fidelity options were used. Technical competence was the major domain assessed in the majority of the studies (n=8), whereas four studies evaluated anatomical and procedural knowledge. Blinding was done in five studies for assessment purposes. The majority of studies (n=9) found the simulation to be an effective tool for achieving technical competence. This review shows the potential usefulness of simulation in acquiring technical skills and procedural acumen for CEA. The available literature is unfortunately too diverse to have a common recommendation.

Pharmacophore based drug design and synthesis of oxindole bearing hybrid as anticancer agents.

Dual TK inhibitors have shown significant clinical effects against many tumors, but with unmanageable side effects. Design approach and selectivity of these inhibitors plays substantial role in their potency and side-effects. Understanding the homology of binding sites in targeted receptors, and involvement of signaling proteins after the inhibition might help in producing less toxic but effective inhibitors. Herein, we designed benzylideneindolon-2-one derivatives based on homology modeling in binding sites of VEGFR-2 and EGFR receptors as dual- inhibitor potent anticancer compounds with high selectivity. The benzylideneindolon-2-one derivatives were found to possess conformational switch in form of oxindole, substituted at 2-benzimidazole. Within synthesized compounds, 5b was found most active in in-vitro enzyme inhibition assay against VEGFR-2 and EGFR with highest IC50 value of 6.81 ± 2.55 and 13.04 ± 4.07 nM, respectively. Interestingly, cytotoxicity studies revealed selective toxicity of compound 5b against proliferation of A-431 cell lines (over expressed VEGFR-2 and EGFR) with GI50 value of 0.9 ± 0.66 µM. However, the compounds showed mild to moderate activity in all other cancer cell line in the range of 0.2-100 µM. Further mode of action studies by flow cytometry and western blot on A-431 indicated that they work via apoptosis at S- phase following Bcl/Bax pathway, and cell migration via MMP9. 5b not only suppressed tumor growth but also improved vandetanib associated with weight loss toxicity. Moreover, 5b was found safer than sunitinib and erlotinib with LD50 of 500 mg/kg body weight. These results propose 5b as potential anti-tumor drug with safer profile of conventional inhibitors of VEGFR-2 and EGFR for solid tumors.

Hypoglossal Nerve Paraganglioma Depicting as Glomus Tumor of Neck.

INTRODUCTION: Paraganglioma are infrequent neuroendocrine tumors that are most commonly found in the carotid body, ganglia of the vagus, jugular and tympanic nerve. Very rarely they can involve other cranial nerves outside the cranial cavity, we present one such case of hypoglossal nerve paraganglioma in neck. CASE REPORT: A 48 years old male presented with 1-month history of right sided stroke and aphasia. Ultrasonography of neck revealed a highly vascular mass on the right side of the neck. CT angiogram confirmed a highly vascular mass arising above the carotid bifurcation. With the working diagnosis of Glomus tumor, he underwent right sided neck exploration, however, intra-operatively tumor was found to be arising from the hypoglossal nerve instead. Surgery was abandoned on basis of the available literature, with only 6 reported cases in the past 54 years. Patient had no immediate post op complications and was sent for cyber knife treatment. After completion of 5 cycles of cyber knife there was a total of 45% reduction in the size of the paraganglioma with the resolution of the patient's symptoms after a follow up of 6 months. CONCLUSION: Hypoglossal nerve paraganglioma is an uncommon tumor of the neck and can be misdiagnosed with the other tumors in this region especially chemodectoma and glomus tumor. The diagnostic criteria and appropriate treatment modalities have not been established due to the rare presentation hence hypoglossal paraganliomas should be kept in mind when Highly vascular neck mass is encountered.

Structural Variants at the BRCA1/2 Loci are a Common Source of Homologous Repair Deficiency in High-grade Serous Ovarian Carcinoma.

PURPOSE: The abundance and effects of structural variation at BRCA1/2 in tumors are not well understood. In particular, the impact of these events on homologous recombination repair deficiency (HRD) has yet to be demonstrated. EXPERIMENTAL DESIGN: Exploiting a large collection of whole-genome sequencing data from high-grade serous ovarian carcinoma (N = 205) together with matched RNA sequencing for the majority of tumors (N = 150), we have comprehensively characterized mutation and expression at BRCA1/2. RESULTS: In addition to the known spectrum of short somatic mutations (SSM), we discovered that multi-megabase structural variants (SV) were a frequent, unappreciated source of BRCA1/2 disruption in these tumors, and we found a genome-wide enrichment for large deletions at the BRCA1/2 loci across the cohort. These SVs independently affected a substantial proportion of patients (16%) in addition to those affected by SSMs (24%), conferring HRD and impacting patient survival. We also detail compound deficiencies involving SSMs and SVs at both loci, demonstrating that the strongest risk of HRD emerges from combined SVs at both BRCA1 and BRCA2 in the absence of SSMs. Furthermore, these SVs are abundant and disruptive in other cancer types. CONCLUSIONS: These results extend our understanding of the mutational landscape underlying HRD, increase the number of patients predicted to benefit from therapies exploiting HRD, and suggest there is currently untapped potential in SV detection for patient stratification.

Design, Synthesis, Molecular Docking, and Anticancer Evaluation of Pyrazole Linked Pyrazoline Derivatives with Carbothioamide Tail as EGFR Kinase Inhibitors.

BACKGROUND: The Epidermal Growth Factor Receptor (known as EGFR) induces cell differentiation and proliferation upon activation through the binding of its ligands. Since EGFR is thought to be involved in the development of cancer, the identification of new target inhibitors is the most viable approach, which recently gained momentum as a potential anticancer therapy. OBJECTIVE: To assess various pyrazole linked pyrazoline derivatives with carbothioamide for EGFR kinase inhibitory as well as anti-proliferative activity against human cancer cell lines viz. A549 (non-small cell lung tumor), MCF-7 (breast cancer cell line), SiHa (cancerous tissues of the cervix uteri), and HCT-116 (colon cancer cell line). METHODS: In vitro EGFR kinase assay, in vitro MTT assay, Lactate dehydrogenase release, nuclear staining (DAPI), and flow cytometry cell analysis. RESULTS: Compounds 6h and 6j inhibited EGFR kinase at concentrations of 1.66µM and 1.9µM, respectively. Furthermore, compounds 6h and 6j showed the most potent anti-proliferative results against the A549 KRAS mutation cell line (IC50 = 9.3 & 10.2µM). Through DAPI staining and phase contrast microscopy, it was established that compounds 6h and 6j also induced apoptotic activity in A549 cells. This activity was further confirmed by FACS using Annexin-V-FITC and Propidium Iodide (PI) labeling. Molecular docking studies performed on 6h and 6j suggested that the compounds can bind to the hinge region of ATP binding site of EGFR tyrosine kinase in a similar pose as that of the standard drug gefitinib. CONCLUSION: The potential anticancer activity of compounds 6h and 6j was confirmed and need further exploration in cancer cell lines of different tissue origin and signaling pathways, as well as in animal models of cancer development.

British Gynaecological Cancer Society (BGCS) cervical cancer guidelines: Recommendations for practice.

Cervix cancer in many countries is declining and screening programmes and immunisation will reduce the incidence in the next few decades. This guideline attempts to cover management of invasive disease reflecting diagnosis and imaging including new imaging and sentinel lymph node biopsies. Smaller volume disease is usually managed surgically whereas advanced disease is treated with (chemo)- radiation. It also includes discussion of fertility sparing procedures. Practices are changing frequently for all aspects of care usually in attempts to reduce complications and improve quality of life. The management of advanced disease is treated by chemotherapy and the use of newer agents is also discussed. Other sections discuss specialist situations such as cancer in pregnancy, rare cervical tumours, late effects and supportive measures and fertility preserving approaches.

3'-(4-(Benzyloxy)phenyl)-1'-phenyl-5-(heteroaryl/aryl)-3,4-dihydro-1'H,2H-[3,4'-bipyrazole]-2-carboxamides as EGFR kinase inhibitors: Synthesis, anticancer evaluation, and molecular docking studies.

Pyrazoline-linked carboxamide derivatives were designed, synthesized, and evaluated for potential epidermal growth factor receptor (EGFR) kinase inhibition, anticancer activity, and apoptotic and cardiomyopathy toxicity. Compounds 6m and 6n inhibit EGFR kinase at a concentration of 6.5 ± 2.91 and 3.65 ± 0.54 µM, respectively. Some of these compounds showed effects on proliferation, which were also then evaluated against four different human cancer cell lines, that is, MCF-7 (breast cancer), A549 (non-small-cell lung tumor), HCT-116 (colon cancer), and SiHa cells (cancerous tissues of the cervix uteri). The results showed that certain synthetic compounds showed significant inhibitor activity; compounds 6m and 6n were more cytotoxic than doxorubicin against A549 cancer cells, with IC50 values of 10.3 ± 1.07 and 4.6 ± 0.57 µM, respectively. Additionally, compounds 6m and 6n induced apoptosis in A549 cancer cells, as evidenced by 4',6-diamidino-2-phenylindole (DAPI) staining and phase-contrast microscopy. Potency to induce apoptosis by compound 6n was further confirmed by fluorescence-activated cell sorting using Annexin V-FITC and propidium iodide labeling. Compound 6n showed normal cardiomyocytes with no marked sign of pyknotic nuclei in cardiomyopathy and also normal histological appearance of the renal cortex when compared with that of control. Results of molecular docking studies suggested that compounds 6m and 6n can bind to the hinge region of the adenosine triphosphate-binding site of EGFR kinase, like the standard drug erlotinib. Therefore, the present study suggests that compounds 6m and 6n have potent in vitro antitumor activities against the human non-small-cell lung tumor cell line A549, which can be further explored in other cancer cell lines and in animal studies.