Current practice of pre-operative assessment at a public sector hospital in Pakistan - a clinical audit.

Objective: To assess the practice of ordering unnecessary laboratory investigations by primary surgical teams. METHODS: The clinical audit was conducted from December 17, 2022, to January 15, 2023, at the Civil Hospital, Karachi, and comprised primary surgeons working in different surgical units who ordered laboratory investigations for patients as a part of preoperative assessment. Data was collected using a self-administered questionnaire. Data was analysed using SPSS 20. RESULTS: Of the 280 surgeons approached, 249(89%) responded. The units covered were General surgery 96(38.5%), Gynaecology 74(29.7%), Neurosurgery 5(2.0%), Ear, Nose and Throat 19(7.6%), Plastic surgery 15(6.02%), Paediatric surgery 13(5.2%), Vascular surgery 8(3.21%), Oromaxilofacial 9(3.61%), Opthalmology 6(2.4%), and Orthopaedics 4(1.60%).As part of baseline investigations, 244(98%) surgeons ordered complete blood count, 173(69.5%) ordered urea and creatinine, 229(92%) ordered viral markers, 197(78.7%) ordered fasting and random blood glucose, and 178(71.5%) focussed on cardiac fitness. Conclusion: A need was found to establish standard protocols for pre-surgery evaluation so that unnecessary investigations may be avoided.

Distinct genetic landscape and a low response to doxorubicin in a luminal-A breast cancer cell line of Pakistani origin.

BACKGROUND: Breast cancers exhibit genetic heterogeneity which causes differential responses to various chemotherapy agents. Given the unique demographic and genomic background in South Asia, genetic architecture in breast cancers is not fully explored. METHODS AND RESULTS: In this study, we determined the genetic landscape of our previously established luminal-A subtype breast cancer cell line (BC-PAK1), and compared it with a Caucasian origin MCF7 breast cancer cell line of the same molecular subtype. Deep whole-exome sequencing (100X) was performed from early passages of the primary cancer cells using the Illumina NextSeq500. Data analysis with in silico tools showed novel non-silent somatic mutations previously not described in breast cancers, including a frameshift insertion (p.Ala1591AlafsTer28) in CIC, and a frameshift deletion (p.Lys333LysfsTer21) in PABPC1. Five genes CDC27, PIK3CG, ARAP3, RAPGEF1, and EFNA3, related with cell cycle pathway (hsa04110), ErbB signaling pathway (hsa04012), Ras signaling pathway (hsa04014), and Rap1 signaling pathway (hsa04015) were found to have recurrent non-silent somatic mutations. Further, the major contribution of COSMIC signatures 3 (failure of DNA double-strand break repair by homologous recombination), and 12 (transcriptional strand-bias for T>C substitutions) was observed. Also, the somatic mutations landscape in BC-PAK1 was found to be different as compared to the MCF7 cell line. The unique genetic landscape of BC-PAK1 might be responsible for significantly reduced response to doxorubicin than the MCF7 cell line. CONCLUSION: This study presents a distinct genetic architecture in luminal-A breast cancer potentially responsible for differential response to chemotherapy. Further studies on large cohorts of breast cancer patients are suggested for implementation in personalized medicine.

Assessment of pattern for consumption and awareness regarding energy drinks among medical students.

BACKGROUND: Energy drink is a type of beverage which contains stimulant drugs chiefly caffeine and marketed as mental and physical stimulator. Coffee, tea, soft drinks and other caffeinated beverages are not considered as energy drinks. Purpose of our study was to evaluate the awareness of medical students regarding energy drinks and their pattern and reason of energy drinks consumption. METHODS: This was a cross sectional and observational study conducted during the period of January - December 2012 at four Medical Colleges (Dow Medical College, Sindh Medical College, Jinnah Medical College and Liaquat National Medical College) of Karachi, Pakistan. Over all 900 M.B.B.S students were invited to participate after taking written consent but viable questionnaire was submitted by 866 students, estimated response rate of 96%. All data was entered and analyzed through SPSS version 19. RESULT: Out of 866 participants, majority were females 614 (70.9%) and only 252 (28.5%) were males, with a mean age of 21.43 ± 1.51 years. Energy drinks users were 350 (42.89%) and non users were 516 (59.58%). Only 102 (29.3%) users and 159 (30.7%) non users know the correct definition of Energy drinks. Regarding awareness, mostly user and non users thought that usage of energy drinks had been on rise due to its usefulness in reducing sleep hours [users193 (43.9%), nonusers 247 (56.1%) (p < 0.05)], for studying or completing major projects [users184 (45.0%), nonusers 225 (55.0%) (p < 0.05)] and for refreshment purposes [users179 (44.9%), nonusers 220 (55.1%) (p < 0.05)]. Two main reasons of not using energy drinks by non-users were "awareness from its side effects" 247 (47.8%) and "have no specific reason" 265 (51.3%). Most common side effects reported by users were fatigue 111 (31.7%) and weight gain 102 (29.4%). CONCLUSION: In sum, the fact that despite serious side effects of weight gaining and fatigue, practice of consuming energy drinks is highly prevalent among medical students, particularly because they are ever ready to boost their energy level and reduce sleep hours due to stress of exams and projects. This warrants the creation of continued public health awareness about the appropriate use of caffeinated beverages, their potential benefits, side effects and correction of wrong perceptions.

Spectrum of prostatic lesions.

BACKGROUND: Prostate gland of male reproductive system is about the size of walnut and surrounds the urethra. Most frequently encountered diseases affecting prostate are Prostatitis, Benign prostatic hyperplasia and Prostatic cancer .Our objective of study was to evaluate the spectrum and correlation of prostatic lesions with presenting complaints of patient. METHODS: It was a cross-sectional study conducted in Pathology Department of Dow Medical College, Dow University of Health Sciences during the period of 1st January 2010 to December 2012. Pathology department of Dow Medical College collected specimens from both Civil Hospital and Lyari General Hospital Karachi, Pakistan. Specimens were taken through transurethral resection of prostate (TURP), simple prostatectomy and radical prostatectomy. A questionnaire was made and information including name, age, ward name of hospital, laboratory number, clinical diagnosis and symptoms were noted in it. Data was entered and analyzed through SPSS 19. RESULT: During the targeted months, 48 prostatic specimens were received with a mean age of 65.7 + -7.6 years. Common presenting complains were urinary retention in 23(47.9%) patients, followed by dribbling in 12(25%). Out of 48 patients, 42 have Benign Prostatic Hyperplasia and 6 have Prostatic Adenocarcinoma. Both Benign Prostatic Hyperplasia and Prostatic Adenocarcinoma were more prevalent in the age group of 60-70 years. CONCLUSION: Frequency of prostatic cancer is on the rise and measures should be taken for its early detection. Screening protocols and awareness programs need to be introduced. Screening programs should be focused on level of androgens and molecular pathogenesis.

Association of socioeconomic classes with diet, stress and hypertension.

OBJECTIVE: To evaluate the relationship between diet and socioeconomic conditions and find out the prevalence of stress and Hypertension in different socioeconomic classes. METHODS: A cross-sectional study was conducted from May 2010 to October 2011, 176 people from four different socio economic Strata (low class, low middle class, upper middle class, and high class) were selected, which were defined on the basis of monthly income. Complete dietary intake was assessed with the last 3 days' dietary record, dietary patterns and restrictions. Background information and Stress level were evaluated by a preformed questionnaire and blood pressure was taken with the aneroid manometer. RESULT: A total of 176 people were interviewed for diet, blood pressure and stress was measured. The High socioeconomic Stratum was found to have the highest number of people having hypertension 15 (27.8%), taking medications 21 (38.9%), 18 (33.3%) multi vitamin supplements, and with an overall lower calorie intake 1617.31 +/- 698.99 as compared to other strata. It also had the highest number of people who thought they were active 44 (81.5%). The High middle Socioeconomic Stratum was similar with the High class, in having the most hypertensive people 10 (27.8%) and they had least chance of developing stress related health illnesses 6 (16.7%). Individuals living below poverty line had the highest prevalence ratio of stress 16 (36.4%) and they were considered as least physically active 30 (68.2%). CONCLUSION: Highest frequency of Hypertension was in high class and high middle income group. The low class had the highest ratio of stress. There was a difference in type of food, but not much in calorie intake.

Bcr-Abl tyrosine kinase inhibitors- current status.

Bcr-Abl plays a central role in the development of chromosome positive leukaemia. Chronic Myeloid leukaemia occurs due to increase proliferation and resistance to apoptosis by Bcr-Abl positive cells. Imatinib (STI571) is the first drug in the family of Bcr-Abl tyrosine kinase inhibitors while Nilotinib (AMN107) and Dasatinib (BMS-345825) are second generation drugs that are intended to have less resistance and intolerance than imatinib. Ponatinib (AP24534) an orally active Bcr-Abl Tyrosine Kinase Inhibitor and Bafetinib (INNO-406) have efficacy against various point mutations in the Bcr-Abl kinase. 1, 3, 4 thiadiazole derivatives has also displayed moderate inhibitory action on both Abl and Src kinase family. However there are varieties of Bcr-Abl inhibitors but Nilotinib is still the frontline tyrosine kinase inhibitors.

Clinico- pathological profile of patients with breast diseases.

BACKGROUND: To evaluate the spectrum of breast diseases and their association with presenting complains of patients. METHODOLOGY: It was a cross sectional study conducted from 1st January 2010 - 30th December 2012. A total of 254 breast specimens of patients, who were admitted in Civil Hospital Karachi with breast complaints, were included. Specimens were collected either from mastectomy, lumpectomy or needle biopsy from the admitted patients. Informed written consent was taken from all the patients. All patients with primary breast diseases were included. Patients undergoing chemotherapy or with secondary breast disease and slides with insufficient specimen were excluded. All data was entered and analyzed through SPSS 19. RESULT: There were 254 breast lesions, histologically diagnosed in 3 year review period. The overall mean age of patients with breast lesion was 25.18, SD ± 11.73 with a wide age range of 12-74 years. Most common cases identified are benign 191(75.3%), followed by inflammatory 30(11.8%) and malignant lesions 30(11.8%). Most patients presenting with the complain of pain have diagnosis of fibroadenoma 24 (63.2%) while patient with complain of lump also have the most common diagnosis of fibroadenoma 147 (72.8%). CONCLUSIONS: Study shows that in Pakistani females, mostly encountered breast lesion was fibroadenoma. Due to lack of awareness breast diseases present lately. Awareness must be created among women to reduce the mortality and morbidity with breast lesions. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1037059088969395.

c-Met inhibitors.

c-Met is a receptor tyrosine kinase that encodes protein such as hepatocyte growth factor receptor (HGFR). Inappropriate activity of c-Met can cause wide variety of carcinomas. c-Met inhibitor are relatively new class of small molecules that inhibit the enzymatic activity of c-Met tyrosine kinase. Met inhibitors divided into two main classes: class I (SU-11274-like) and class II (AM7-like). The use of c-Met inhibitors with other therapeutic agents could be crucial for overcoming potential resistance as well as for improving overall clinical benefit. Met pathway inhibitors might be used in combination with other treatments, including chemo-, radio- or immunotherapy.