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Renal stones are the third most common problem affecting about 10% of global population. The management of nephrolithiasis has undergone a complete transformation since the 1980s. Percutaneous nephrolithotomy (PCNL) has established itself an effective and safe technique that delivers high stone-free rate as well as overall shorter treatment time. We aim to compare the outcome of mini-PCNL with standard-PCNL in patients presenting with renal stones. In all, 90 patients fulfilled the selection criteria and randomized into two groups. Group A underwent mini-PCNL whereas Group B underwent standard-PCNL. Pre-operative hemoglobin level was recorded. Duration of procedure as well as drop in hemoglobin level was also recorded. A kidney, ureter, and bladder (KUB) X-ray was performed to confirm the presence of of stone and stone-free status. The mean age of patients in mini-PCNL group was 43.11 years and in standard-PCNL group, it was 36.91 years. The mean stone size in patients of mini-PCNL group was 29.53 mm and 31.58 mm in standard-PCNL group. The mean duration of renal stone in mini-PCNL group was 1.91 years and that in standard-PCNL group 1.80 years. The mean operative time in mini-PCNL group was 59.56 min and 61.22 min in standard-PCNL group. The mean fall in hemoglobin in mini-PCNL group was 0.38 g/dL and that in standard-PCNL group 0.51 g/dL. In mini-PCNL group, stone clearance was observed in 42 (93.3%) patients, while in standard-PCNL group, it was observed in 45 (100%) patients. This difference was insignificant (P > 0.05). Mini-PCNL and standard-PCNL have no significant differences in terms of outcome, operative time, and stone clearance, although fall in hemoglobin level was less in mini-PCNL group, which showed less blood loss in this group, thereby making it a more appropriate method for renal stone removal.

Aim: Assessment of the consequences of arthroscopic repair of large and massive rotator cuffs. Study design: Retrospective analysis Place and duration: This study was conducted at Shaheed Zulifqar Ali Bhutto Medical University/PIMS Islamabad Pakistan from August 2020 to August 2021. Methodology: In the current study, 50 patients were included out of which 37 patients had large tears and 13 had massive tears which were repaired arthroscopically. Average follow up was of 32 months. Modified UCLA shoulder rating scale was used to evaluate the function, strength, range of motion and the pain before and after surgery. Results: Among the included 50 patients, 21 patients were female, and 29 were male. The range of their ages was between 41 and 76 years. The dominant extremity was affected in majority of patients. The average preoperative time of patients was 10 months. According to UCLA, 98% patients experienced satisfactory results, and only 1 patient had to undergo second surgery for the repair. Conclusion: The study concluded that arthroscopic repair of tears in rotator cuffs is the best technique which can be used for repairing large and massive tears in rotator cuff. Keywords: tears, outcome, arthroscopy, rotator cuff

Aim:To assess the potency of unilateral external fixation as a proper cure for tibial fractures. Study design: A retrospective longitudinal study Place and duration: This study was conducted at Pakistan Institute of Medical Sciences (PIMS) Islamabad Pakistan from August 2020 to August 2021. Methodology:Treatment of 225 tibial shaft fractures was done, in which closed fractures took 22 weeks and open 26 weeks for complete fusion. All fractures were fixed with AO fixator Results:Data of 210 patients was evaluated. Treatment of 225 tibial shaft fractures was done, in which closed fractures took 22 weeks and open 26 weeks for complete fusion. A total of 17 nonunion patients were observed while there were 22 delayed fusions, 5 malunion, 59 pin infections, and 4 osteomyelitis, 43 patients went through the re-operation process. Conclusion:Four patients had fat embolism while pulmonary embolism was present in six and venous thrombosis in 15 patients. The ultimate treatment in 88.0% of patients was external fixation. If there is a no formation of callus formation, reoperation should be carried out so unilateral external fixation is the preferred treatment for tibial fractures. Keywords: External Fixation, Tibial Diaphyseal Fractures, treatment

SummaryHead and neck cancer is the sixth leading cause of cancer across the globe and is significantly more prevalent in South Asian countries, including Pakistan. Prediction of pathological stages of cancer can play a pivotal role in early diagnosis and personalized medicine. This project ventures into the prediction of different stages of head and neck squamous cell carcinoma (HNSCC) using prioritized DNA methylation patterns. DNA methylation profiles for each HNSCC stage (stage-I-IV) were used to extensively analyze 485,577 methylation CpG sites and prioritize them on the basis of the highest predictive power using a wrapper-based feature selection method, along with different classification models. We identified 68 high-power methylation sites which predicted the pathological stage of HNSCC samples with 90.62 % accuracy using a Random Forest classifier. We set out to construct a protein-protein interaction network for the proteins encoded by the 67 genes associated with these sites to study its network topology and also undertook enrichment analysis of nodes in their immediate neighborhood for GO and KEGG Pathway annotations which revealed their role in cancer-related pathways, cell differentiation, signal transduction, metabolic and biosynthetic processes. With information on the predictive power of each of the 67 genes in each HNSCC stage, we unveil a dynamic stage-course network for HNSCC. We also intend to further study these genes in light of functional datasets from CRISPR, RNAi, drug screens for their putative role in HNSCC initiation and progression.

Protein-Protein Interaction (PPI) networks can be useful scaffolds for the integration of whole cell multi-omics datasets that can aid significantly in drug discovery research. This study aims to use domain-domain interaction (DDI) data to produce high resolution protein interaction networks with enhanced topological insights for head and neck squamous cell carcinoma as well as the more well studies, triple negative breast cancer (TNBC). An extensive literature review identified 65 driver genes for HNSCC and 19 genes for TNBC which collectively had 557 and 316 protein domains. Eventually, 343/557 and 191/316 domains had well-annotated somatic mutations reported in COSMIC. PPI networks were created using BioGrid and STRING data and the top two hubs in PPI networks were TP53 for HNSCC and EGFR for TNBC, while the top two hubs in DDI networks were PF12796 (NOTCH) and PF07714 (EGFR) for HNSCC and TNBC networks, respectively. The top nodes in the densest sub-clusters based on module analysis in PPI networks were ERBB4, MET and NOTCH1 for HNSCC, and FGFR1, AR, and EGFR for TNBC. For DDI networks, the top nodes in the densest subcluster for HNSCC were PF06816 (NOTCH1-3), while for TNBC PF07714 domains from FGFR1, ERBB2 and EGFR were the top nodes. Our preliminary results re-emphasize the significance of NOTCH, EGFR and TP53, and their domains, in cancer networks. Next, we attempted to decipher potential candidates for drug repurposing and were able to map 20 out of the 31 FDA approved cancer drugs against proteins within our HNSCC network. EGFR was revealed as a hub gene in both HNSCC and TNBC networks with most of the therapies designed against the PF07714 kinase domain of EGFR. PF07714 is also a common domain in ERBB4, EPHA2, MAP2K1 and MET, and was targeted by different drugs in other cancer types. Next, we attempt to undertake an in vitro drug screen of all candidates against HNSCC cell lines to validate our in silico findings. Citation Format: Maryam Shah, Arsalan Riaz, Faisal Khan. Higher-resolution protein interaction networks for precision medicine: A case for drug repurposing in head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6338.

Oro-pharyngeal squamous cell carcinoma (OPSCC) cases are rising worldwide specifically among young individuals with risk factors including smoking and alcohol. HPV infection specifically the subtype HPV16 is a significant risk factor in the initiation and progression of OPSCC, more prevalent in the western part of the world. This study carries out a computational analysis using protein interactions between HPV16 proteins and protein products of key OPSCC and Oral Squamous Cell Carcinoma (OSCC) cancer genes, which aims to investigate the influence of HPV16 on OPSCC and OSCC in terms of protein-protein interactions (PPIs).We created a protein interaction network of HPV16 and human proteins followed by retrieval of mutated genes in OPSCC and OSCC from online databases including COSMIC, cBioPortal and the GDC Portal, along with literature mining. We used MCODE and ClueGo tools for cluster and enrichment analysis, respectively. Drug candidates against the common interacted proteins were found using drug databases like PanDrugs and CLUE Repurposing. After annotating the HPV16-Human PPI network with proteins encoded by genes found to be mutated in both cancers, 31 proteins in OPSCC and 17 proteins in OSCC were in direct interaction with the viral proteins especially, E5, E6, and E7. The immediate network (of first neighbors only) appeared to be sparse, but after looking at the broader HPV16-Human network we found 5 highly connected modules, 4 of which were dominated by proteins encoded by genes mutated in OPSCC as compared to OSCC, indicating the influence of HPV16 on OPSCC. Based on module integrity and topological characteristics we identified 4 significant candidates for HPV16-driven OPSCC i.e. MYC, CREBBP, PML, and RB1 which are significantly enriched in cancer pathways. In the South Asian countries, Epstein Bar Virus type 1 (EBV-1) is a more prevalent risk factor for virus-driven Head and Neck Squamous Cell Carcinoma (HNSCC) as compared to HPV-16, however, knowledge regarding the EBV induced OPSCC and OSCC is scarce. We created a protein interaction network for EBV1 and Human proteins to analyze the topological characteristics especially of proteins encoded by genes mutated in HNSCC using the same methodology and we identified 5 candidate proteins i.e. EP300, CUL3, RB1, DDB1, and CREBBP for further in vitro validation. Citation Format: Arsalan Riaz, Yusra Ilyas, Faisal Khan. Differential analysis of HPV16-human and EBV1-human protein interaction networks to identify new protein candidates in head and neck squamous cell carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6323.

Head and neck cancer is the most incident and prevalent cancer in men in South Asian countries, especially Pakistan. Prediction of pathological stages of cancer can play a critical role in early diagnosis and personalized medicine. This project ventures into the prediction of different stages of head and neck squamous cell carcinoma (HNSCC) using prioritized DNA methylation patterns. DNA methylation profiles for each HNSCC stage (stage-I-IV) were used to extensively analyze 485,577 methylation CpG sites and prioritize them on the basis of the highest predictive power using a wrapper-based feature selection method, along with different classification models. We identified 68 high-power methylation sites which predicted the pathological stage of HNSCC samples with 90.62% accuracy using a Random Forest classifier. We set out to construct a protein-protein interaction network for the proteins encoded by the 67 genes associated with these sites to study its network topology and also undertook enrichment analysis of nodes in their immediate neighborhood for GO and KEGG Pathway annotations revealing their role in cancer-related pathways, cell differentiation, signal transduction, metabolic and biosynthetic processes. With information on the predictive power of each of the 67 genes in each HNSCC stage, we unveil a dynamic stage-course network for HNSCC that evolves over the course of the four cancer stages. We intend to further study these genes in light of functional datasets from CRISPR, RNAi, drug screens for their putative role in HNSCC initiation and/or progression. Citation Format: Arsalan Riaz, Faisal Khan. Dynamic, stage-course protein interaction network using high power CpG sites in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6322.

Background: Urinary stone disease or nephrolithiasis is the third most common disease of the urinary tract is major health issue due to its high prevalence, occurrence and recurrence. The hallmark of a stone that obstructs the ureter or renal pelvis is excruciating, intermittent pain that radiates from the flank to the groin or to the inner thigh. Stone size influences the rate of spontaneous stone passage. Objective: To compare the efficacy (frequency of stone free patients) at one week after extracorporeal shock wave lithotripsy (ESWL) and ureterorenoscopic (URS) manipulation for proximal ureteric stone (10 – 15 mm size) Material & Methods: Study Design: Randomized control trial Setting: Department of Urology, KRL Hospital Islamabad Duration: 6 months i.e. 18-11-2019 to 18-5-2020 Data collection: After meeting the inclusion criteria 100 patients were enrolled and were divided into 02 groups. One group treated with ESWL and other with URS. Then procedures were done. Follow-up was noted after one week in stone clinic. All the data was collected on pre-designed proforma. Results: The average age of the patients was 39.71±10.17 years. The efficacy in ESWL group was noted in 68% cases while in URS group the efficacy was achieved in 76% cases (p-value>0.05). Male were 3 times at higher risk as compared to females. Conclusion: This study concluded that both ESWL and URS are statistically equally effective in terms of frequency of stone free patients at one week for proximal ureteric stone (10 – 15 mm size). Keywords: Proximal Ureteric Stone, extracorporeal shock wave lithotripsy, ureterorenoscopic, manipulation

Urinary stone disease or nephrolithiasis, the third most common disease of the urinary tract, is a major health issue due to its high prevalence, occurrence, and recurrence. The hallmark of a stone that obstructs the ureter or renal pelvis is excruciating, intermittent pain that radiates from the flank to the groin or to the inner thigh. Stone size influences the rate of spontaneous stone passage.Our aim was to compare the efficacy & the frequency of stone-free patients after intervention at 1 week after extracorporeal shock wave litho-tripsy (ESWL) and ureterorenoscopic (URS) manipulation for proximal ureteric stone (10–15 mm size).This randomized control trial was done in the department of Urology, KRL Hospital Islamabad from 18th Nov 2019 to 18th May 2020. After meeting the inclusion criteria, 100 patients were enrolled and were divided into two groups. The first group was treated with ESWL and the other with URS. Then, procedures were done. Follow-up was noted after 1 week in the stone clinic.The average age of the patients was 39.71 ± 10.17 years. Efficacy in the ESWL group was found in 68% cases while in the URS group, efficacy was noticed in 76% cases (P > 0.05). Male patients were three times at a higher risk of recurrence as compared to females.This study concluded that both ESWL and URS are equally effective statistically in terms of the frequency of stone-free patients at 1 week for proximal ureteric stone (10–15 mm size).

Recent studies have suggested that fractional flow reserve (FFR) measurement can be avoided by using similar ranges of baseline mean coronary pressure (Pd) to mean aortic pressure (Pa) ratio (0.88-0.95). Further studies have suggested that too many significant coronary stenoses are misclassified based on these ranges. We hypothesized that with a certain range of baseline Pd/Pa, 100% positive predictive value (PPV) and negative predictive value (NPV) can be achieved to avoid misclassification.We retrospectively evaluated the pressure tracings of 555 consecutive intermediate coronary stenotic lesions that had undergone FFR measurement in the cardiac catheterization laboratory of a tertiary-care center. The baseline Pd/Pa was manually measured and correlated with final FFR. The operating test characteristics were calculated using an abnormal FFR of ≤0.80 as the criterion standard for the presence of hemodynamic, significant coronary stenosis.The area under the receiver-operating characteristics curve of baseline Pd/Pa for predicting FFR was 0.89, very similar to published results for instantaneous wave-free ratio and Pd/Pa. However, a significant number of lesions were mischaracterized (ie, using a baseline Pd/Pa of ≤0.88 to0.95, there were 22 misclassifications, with 6 false-positive and 16 false-negative results). At a Pd/Pa of ≤0.86, 100% PPV was achieved, and 100% NPV was achieved at1.00.A baseline Pd/Pa of ≤0.86 is associated with a PPV of 100%, which can avoid the misclassification errors seen in prior studies. This provides a more clinically useful application of baseline Pd/Pa.

Prior studies have evaluated baseline Pd/Pa (mean coronary artery/mean aorta pressure) ratio as well as iFR (instantaneous wave-free ratio obtained during entire period of diastole) to predict fractional flow reserve (FFR) ≤0.8. Since most of the flow occurs during diastole, we hypothesized a