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Background and Objective: A delayed presentation of benign breast diseases may lead to a therapeutic challenge when they enlarge enormously or become multiple. Aim of this study was to evaluate the factors leading to delayed presentation of benign breast lumps. Methods: This cross-sectional study was conducted at Madinah Teaching Hospital and Allied Hospital, Faisalabad from January 2019 to October 2021. One hundred and forty five female patients were selected by non-probability purposive sampling. Patients with large size (>5cm) or multiple benign breast lumps were included. An interview was conducted using structured questionnaire translated in Urdu. Factors leading to delayed presentation and social impact scale for stigma were evaluated. Results: Patients had a mean age of 26.52 ± 6.90 years. The average delay of seeking medical care was 8.48 ± 8.41 months. Factors leading to delayed presentation were; lack of knowledge n=112 (77.2%) and parda (religious issues) n=112 (77.2%), followed by poverty n=109 (75.2%), and fear of cancer n=90 (62.1%). All the sub-scales of stigma, i.e., social rejection, financial insecurity, internalized shame and social isolation were high in late presenters, though, only financial insecurity was significantly high in late presenters (p=0.03). Conclusion: Lack of awareness, socioeconomic factors and disease related stigma were the main factors related to delayed presentation in young females with benign breast diseases. Addressing these factors may improve timely diagnosis and management of delayed and challenging cases. doi: https://doi.org/10.12669/pjms.39.1.6647 How to cite this: Saleem S, Tariq S, Tariq S, Irfan S, Javed F. Factors leading to delayed and challenging presentation of benign breast lumps in young females. Pak J Med Sci. 2023;39(1):---------. doi: https://doi.org/10.12669/pjms.39.1.6647 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective: To compare the efficacy of paramedian and midline approach for spinal block in elderly, in terms of success rate and number of attempts required by either approach. Study Design: Randomized Controlled Trial. Setting: Department of Anaesthesia, Madina Teaching Hospital Faisalabad. Period: January 2018 to December 2019. Material & Method: 120 elderly ASA I-III patients scheduled to undergo lower abdominal or limbs; general or orthopaedic surgery were randomly divided into two equal groups A and B of sixty patients. Patients were assigned into groups by lottery method. Group A patients were supposed to receive spinal block by midline approach while group B patients were planned to receive spinal block by paramedian approach. Results: It was observed that success rate was significantly high in group B, 98.3% as compared to group A, 80%, (p value 0.001). The number of attempts were significantly less in group B in comparison to group A (p-value 0.0001). Conclusion: The paramedian approach for spinal block in elderly patient’s offers ease of administration and a higher success rate as compared to midline approach.

Objective: To compare the effects of intraincisional and intraperitoneal infiltration of local anaesthetic to relieve early postoperative pain in laparoscopic cholecystectomy. Study Design: Randomized Control Trial. Setting: Department of Anaesthesia and Surgery, Madinah Teaching Hospital Faisalabad. Period: July 2017 to March 2018. Material & Methods: A sample of 100 patients with American Society of Anaesthesiologists Physical status (ASA) I and II, undergoing laparoscopic cholecystectomy were selected using simple random sampling technique. Patients were randomly assigned into groups A and B. Group A patients received intraperitoneal infiltration of 20 ml solution of 0.25% bupivacaine and group B patients received intraincisional infiltration of 20 ml solution of 0.25% bupivacaine. Results: Demographic characteristics were not significantly different in both groups. Our study showed that Group A patients had better pain relief as compared to group B patients. Visual analogue score (VAS) for pain relief at 0, 3,6,12 and 24 hours was statistically different in both groups. The requirement of rescue analgesia between group A and B was found to be12% and 38% which is statically significant (p value 0.003). Conclusion: intraperitoneal infiltration of Bupivacaine offers better postoperative pain relief after laparoscopic cholecystectomy and is associated with less analgesic requirement in early postoperative period.

Congenital cataract is causing one-third of blindness worldwide. Congenital cataract is heterogeneous in its inheritance patterns. The current study is aimed to explore the unknown genetic causes underlying congenital cataracts.Blood samples from affected and normal individuals of n = 25 Pakistani families identified with congenital cataracts were collected. Genomic DNA was extracted and Sanger sequencing was performed to identify novel pathogenic variants in the FYCO1 (MIM#607182) gene. Later structural bioinformatics tools and molecular dynamics simulations were performed to analyze the impact of these variants on protein structure and function.Sanger sequencing resulted in the identification of a novel splice site mutation (NM_024513.3: c.3151-29_3151-7del) segregating in an autosomal recessive manner. This novel variant was confirmed to be absent in the n = 300 population controls. Further, bioinformatics tools revealed the formation of a mutant protein with a loss of the Znf domain. In addition, we also found a previously known (c.4127 T C; p.Leu1376Pro) mutation in four families. We also report a novel heterozygous variant (c.3419G A; p.Arg1140Gln) in another family.In conclusion, we report a novel deletion (NM_024513.3: c.3151-29_3151-7del) in one family and a frequent homozygous missense mutation (c.4127 T C; p.Leu1376Pro) in four Pakistani families. The current research highlights the importance of autophagy in lens development and maintaining its transparency.

Objectives: To determine the oncological outcome of different types of phyllodes tumour (PT) and to analyze the impact of radiotherapy on outcome. Study Design: Experimental study. Setting: Madina Teaching Hospital, Faisalabad, Pakistan. Period: April 2015 to April 2020. Material & Methods: Female patients diagnosed as phyllodes tumour of breast were included and classified into benign, borderline and malignant PT according to WHO criteria. Borderline and malignant PT were further divided into 2 groups; Group A (Surgery alone) and Group B (Surgery + Radiotherapy). Oncological outcome based on local recurrence, distant metastasis and overall survival rate among different types of phyllodes tumour and those patients who received or not received radiotherapy was assessed. Results: In 5 years, 29 patients of phyllodes tumour were studied. 15 (51.7%) patients had benign, 8 (27.6%) malignant and 6 (20.7%) borderline tumour. Mean age of our patients was 39.5 years (range: 25-55 years).The disease free survival rate was 82.8% (100% for benign, 83.4% for borderline and 50% for malignant PT). Malignant histotype and tumour size >6cm were significantly associated with recurrence (p

Study Design: Sectional study. Setting: Madina Teaching Hospital Faisalabad. Period: July 2018 to June 2019. Material & Methods: A sample of 107 patients was selected using non-probability purposive sampling out of all the patients presenting with acute appendicitis. Study population was divided into Groups A and B, former undergoing appendectomy within 8 hours of admission and later undergoing surgery more than 8 hours after admission. Spinal and general anesthesia was used and both Laparoscopic and open surgical techniques were employed. Results: Out of total 107 patients, 62 (57.94%)were placed in group A and 45 (42.06%) in group B. Age and gender related distribution in both groups were similar. 5 patients in group A had perforated appendix and 3 patients in Group B were found to have perforated appendix. The difference between incidence of perforation between the two groups was not statistically significant. Conclusion: in-hospital delay before appendectomy does not significantly increase the risk of perforation in uncomplicated acute appendicitis.

Oral squamous cell carcinoma (OSCC) is the most prevalent subtype of head and neck cancers that has a disproportionately high incidence and mortality in developing countries in South-Central Asia, including Pakistan. The standard treatment for OSCC generally consists of surgery combined with radiotherapy or chemotherapy; however, the overall survival rates have not improved, and only ~50% of patients survive the disease. Therefore, identifying and validating new drug targets can provide new therapeutic options for improved treatment and better prognosis for OSCC patients. The present study aimed to develop an organoid model from patient-isolated primary tumour cells and determine their drug sensitivity profile coupled with mutational analysis. New combinations of targeted drugs with synergistic activity in oral cancer cells were identified through high-throughput screening followed by validation of their activity in oral cancer cells in 2D monolayer and 3D organoid cultures. Results indicate a synergistic activity of proteasome (PR-171) and survivin (YM155) inhibitors in all tested patient-derived tumour cells and four oral cancer cell lines. Moreover, chitosan-based nanocapsules harboring these drugs showed therapeutic efficacy comparable to free drug combinations, indicating a potential for efficient and targeted delivery. Next-generation sequencing data identified missense mutations in eleven cancer-related genes that encode BRAF, EGFR, KRAS, NRAS, HRAS, MEK1, PIK3CA, PTEN, NOTCH1, TP53 and TERT. The ongoing research aims to correlate the drug sensitivity data with the mutational profile of patient-derived tumour cells to find novel targets. In conclusion, we have developed 3D organoids from patient-derived primary tumours and utilized them to validate the synergistic combination between screen-identified proteasome and survivin inhibitors. Our preclinical study provides a rationale for further evaluation of the novel drug combination in vivo and in clinical settings. Citation Format: Muhammad Furqan, Iffat Aleem, Muhammad Tahseen, Raza Hussain, Asif Loya, Muhammad Tariq Mahmood, Philippe Gautier, Kevin Myant, Saira Saleem, Amir Faisal. Proteasome and survivin inhibitors synergize to inhibit the growth of oral cancer organoids. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4940.

BACKGROUND & OBJECTIVE: Laparoscopic cholecystectomy (LC) following Endoscopic retrograde cholangiopancreatography (ERCP) is associated with an increased risk of complications. ERCP is associated with increased incidence of complications during LC. Surgery may be performed in same anesthesia with ERCP or up to 6 weeks later. We aimed to determine the benefits of performing LC within 72hrs of ERCP. METHODOLOGY: After institutional ethical approval this prospective cross-sectional study was performed at Madinah Teaching Hospital Faisalabad from April 2019 to June 2020. By performing convenience sampling, all patients undergoing LC after uneventful ERCP in our hospital were included. Study population was divided based on interval between ERCP and Cholecystectomy; Group-A had LC within 72hrs of ERCP, Group B had LC in same hospital stay after 72hrs and Group-C patients were discharged after ERCP and readmitted for LC. Data was collected using custom designed questionnaire, tabulated using Microsoft Excel 2016 and subjected to statistical tests to compare outcomes. Primary outcome was incidence of complications, while operative time, hospital stay and cost were considered as secondary outcomes. p-value of

Objectives: Oncoplastic breast surgery (OBS) is a revolutionary approach for managing breast cancer. This manuscript aimed to assess the oncological and cosmetic outcomes of OBS in breast cancer. Study Design: Descriptive, prospective study. Setting: Department of Surgery, Madina Teaching Hospital, Faisalabad. Period: January 2018 to June 2019. Material & Methods: Females with invasive breast cancer having 5-6 cm tumour size, Locally advanced tumour after chemotherapy, single tumour and patients < 70 years were included; while patients with fixed tumours, high tumour to breast size ratio, multiple axillary lymph nodes, metastatic cancer & patient’s choice for mastectomy were excluded. Oncological outcome was assessed by; Margin involvement, time lag for chemotherapy, local recurrence and distant metastasis. Cosmetic outcome was detected by score given by patient and an independent surgeon. Results: Thirty two female patients underwent OBS. Mean age of patients was 46.56 yr (SD =10.23). Six patients (18.8%) had central tumors. 3 patients were post neoadjuvant chemotherapy. In 28 patients volume displacement (VD) surgery; while in 4 patients volume replacement (VR) using different flaps like LICAP flap were done. Oncological outcome showed positive margin in one case only, in all other cases clear margins were found. Chemotherapy start time varied from 3 to 8 weeks after surgery (Mean=31.3 days). Delayed time was associated with high BMI and diabetes (P

The aim of the study is to identify cornulin (CRNN) protein expression associated with advancement of tongue squamous cell carcinoma (TSCC). A comparison of addictive (containing potential carcinogens) versus non-addiction causative agents was expected to allow detection of differences in CRNN expression associated with TSCC. Bespoke tissue microarrays (TMAs) were prepared and immunohistochemistry (IHC) performed to determine the changes in CRNN expression in epithelial cells of node-negative (pN-), node-positive (pN+) TSCC and non-cancer patients’ oral tissues. TMAs were validated by performing IHC on whole diagnostic tissues. Chi-square test or Fisher’s-exact tests were used to establish significant expression differences. Analogous analyses were performed for biomarkers previously associated with TSCC, namely collagen I alpha 2 (COL1A2) and decorin (DCN) to compare the significance of CRNN. Keratinisation and its level (low, extensive) were studied in relation to CRNN so that the extent of squamous differentiation could better be assessed. IHC immunoreactive score (IRS) clustered the patients based on weak/moderate (Low (IRS ≤ +3)) or strong (High (IRS ≥ +4)) expression groups. A low expression was observed in a larger number of patients in control proteins COL1A2 (77.3%), DCN (87.5%) and target protein CRNN (52.3%), respectively. Low CRNN expression was observed in TSCC where nodes were involved (pN+: mean 1.4 ± 2.1) (p = 0.248). Keratinisation (%) was low (0% ≤ 50%) in 42.2% and extensive (1% ≥ 50.0%) in 57.8% patients. In conclusion, our study suggested that Low CRNN expression was associated with grade and lymph node metastasis in TSCC. CRNN expression is independent of addiction, however potentially carcinogenic addictive substances might be aiding in the disease progression.

The key intention of this review is to summarize the different studies which relate the genome-diet interactions with future perspectives of exploring an insight into the well defined functions of diverse micronutrients and other dietary components that play a vital task in defining the early developmental patterns of an organism. Human fetus development is a complex process that is totally dependent on the dietary components which interact with the genes to regulate the different proliferation and differentiation stages. We want to explore those complex interactions that lay hidden between micro-nutrients and gene expressions but are means of the apparent changes of a phenotype of an individual. Along with this the review will also perceive some basics of development of certain diseases as well, due to these complex genome-diet interactions thus leading to refine the dietary outlines for maternal and prenatal develop- mental stages in future. Research has also shown that genome-diet interactions are very complex as without proper nutrients the end result is the genome instability which may lead to chronic diseases, developmental defects and certain types of cancer.