Spectrum of germline pathogenic variants using a targeted next generation sequencing panel and genotype-phenotype correlations in patients with suspected hereditary breast cancer at an academic medical centre in Pakistan.

BACKGROUND: Breast cancer is the most common malignancy in women, affecting over 1.5 million women every year, which accounts for the highest number of cancer-related deaths in women globally. Hereditary breast cancer (HBC), an important subset of breast cancer, accounts for 5-10% of total cases. However, in Low Middle-Income Countries (LMICs), the population-specific risk of HBC in different ethnicities and the correlation with certain clinical characteristics remain unexplored. METHODS: Retrospective chart review of patients who visited the HBC clinic and proceeded with multi-gene panel testing from May 2017 to April 2020. Descriptive and inferential statistics were used to analyze clinical characteristics of patients. Fisher's exact, Pearson's chi-squared tests and Logistic regression analysis were used for categorical variables and Wilcoxon rank-sum test were used for quantitative variables. For comparison between two independent groups, Mann-Whitney test was performed. Results were considered significant at a p value of < 0.05. RESULTS: Out of 273 patients, 22% tested positive, 37% had a VUS and 41% had a negative genetic test result. Fifty-five percent of the positive patients had pathogenic variants in either BRCA1 or BRCA2, while the remaining positive results were attributed to other genes. Patients with a positive result had a younger age at diagnosis compared to those having a VUS and a negative result; median age 37.5 years, IQR (Interquartile range) (31.5-48). Additionally, patients with triple negative breast cancer (TNBC) were almost 3 times more likely to have a positive result (OR = 2.79, CI = 1.42-5.48 p = 0.003). Of all patients with positive results, 25% of patients had a negative family history of breast and/or related cancers. CONCLUSIONS: In our HBC clinic, we observed that our rate of positive results is comparable, yet at the higher end of the range which is reported in other populations. The importance of expanded, multi-gene panel testing is highlighted by the fact that almost half of the patients had pathogenic or likely pathogenic variants in genes other than BRCA1/2, and that our test positivity rate would have only been 12.8% if only BRCA1/2 testing was done. As the database expands and protocol-driven referrals are made across the country, our insight about the genetic architecture of HBC in our population will continue to increase.

The Modified Alternate Healthy Eating Index-2010 and Breast Cancer Risk among Women from Karachi, Pakistan.

OBJECTIVE: To determine any relationship of diet with breast cancer risk. METHODS: The case-control study was conducted at Aga Khan University Hospital and the Karachi Institute of Radiation and Nuclear Medicine, Karachi, from February 2015 to July 2017, and comprised of cases with a confirmed diagnosis of breast cancer and healthy controls. Data was collected using the Alternate Healthy Eating Index 2010, which was modified according to the particular cultural patterns of diet in the Pakistani population. Data was analysed using SPSS 21. RESULTS: Of the 1124 subjects, 374(33.3%) were breast cancer cases and 750(66.7%) were controls. High intake of grains, both whole and refined including white rice, was associated with breast cancer (odds ratio: 2.53; 95% confidence interval: 1.69-3.79; p<0.001). There was no association of breast cancer with Alternate Healthy Eating Index 2010 score (odds ratio: 1.85; 95% confidence interval: 0.61-1.17; p=0.291). CONCLUSIONS: There was found a need for awareness of a healthy diet based on more of whole grains and brown rice replacement with refined grains and white rice, respectively. Limiting refined carbohydrate intake might be a useful public health message and may reduce breast cancer incidence in the long term.

Meaningful in-training and end-of-training assessment: The need for implementing a continuous workplace-based formative assessment system in our training programs.

Objectives: To analyze the systems and tools involved in assessment of skill procurement and demonstrating workplace skills in postgraduate medical training. Methods: This cross-sectional survey was carried out by enrolling trainee doctors currently working in Medical, Surgical, Dental and Allied specialties of the country by sending a validated and piloted questionnaire through email. Data collection was done from 20th April to 20th May 2021. Data was analysed using SPSS v. 21.0. Results: A total of 351 completed responses were received from 10 major cities of the country. Multiple aspects of entry-into-training, in-training and end-of-training evaluation showed poor correlation with the required training goals. A comparison of assessment for entry-into-supervised training (FCPS-I) versus independent practice (FCPS-II) showed a dismal situation regarding assessing affective skills like leadership, teamwork, coping with pressure and self-awareness. The concept of maintaining portfolios was completely alien to the trainees and the assessment tools used for demonstrating workplace skills were outdated. The lack of a continuous, periodic and balanced assessment (65%); detailed feedback (61.5%); fair exams (59%); variability in scoring system (58%) and professionalism of the examiners (57.5%) were the most frequently selected perceived flaws in the assessment system by the participants. Conclusion: There are multiple lacunae regarding competency-based assessment systems in our training programs and a massive scope for improvement. Assessment systems should be implemented as continuous process of learning, self-reflection, feedback and revalidation throughout the training tenure at regular and multiple points.

Concentration and Localization of Fe and Zn in Wheat Grain as Affected by Its Application to Soil and Foliage.

Nutritional status of people can be improved by enhancing zinc (Zn) and iron (Fe) content in cereals used as staple mainly in poor resource countries. Zinc and Fe were applied through soil and foliage in a study to biofortify wheat grains. Foliar application of both micronutrients increased the growth and grain vigor as compared to soil application and control. Also, foliar application significantly enhanced Zn and Fe concentration in grain pre-dominantly localized in aleurone layer. Exogeneous application of Fe and Zn was found beneficial for plant growth and enhanced Fe and Zn concentrations in grain, however aleurone layer and embryonic region of the grain showed higher accumulations than that in endosperm. Therefore, understanding of physiological and molecular pathways for uptake and localization of Fe and Zn in wheat grains need to be critically examined to improve their concentration in grain to achieve the biofortification targets.

Knowledge and clinical practices of medical doctors regarding nutrition in cirrhosis patients - A multicentre study from Pakistan.

OBJECTIVE: To determine the nutritional knowledge and clinical practices of physicians regarding nutrition in cirrhosis patients. METHODS: This multi-centre cross-sectional knowledge and practice study was conducted at Pak Emirates Military Hospital, Rawalpindi, Bahria Town International Hospital, Rawalpindi, and District Headquarter Hospital, Mandi Bahauddin, Pakistan, from January to March 2020, and comprised physicians working in wards, out-patient and emergency departments. Data was collected through interviews using a self-generated structured questionnaire. Correct responses were scored 1 and incorrect ones as 0, with a maximum possible score of 13. Data was analysed using SPSS 16. RESULTS: Of the 92 participants, 52(56.5%) were males, while the overall mean age was 28.3±4years and mean years in service 3.7±3 years. The mean score obtained was 5.8±2.1. Of the total, 33(35.9%) physicians had received formal nutritional training, 27(29.3%) were giving regular nutritional counselling and 48(52.2%) wrongly believed in the implementation of restricted diets. A large number of participants incorrectly considered salt 61(66.3%), water 49(53.2%) and lipids/oils 24(26%) to be avoided in ascites. Mean knowledge scores varied significantly for physicians dealing with cirrhosis patients on a daily basis (p<0.001) and those who had received formal training (p=0.003). CONCLUSIONS: The nutritional knowledge of physicians regarding cirrhosis was found to be sub-optimal.

Persistent post-surgical pain following breast cancer surgery: An observational study in a tertiary care hospital.

OBJECTIVE: To determine the frequency of persistent pain in patients after breast cancer surgery, and to assess the distribution and characteristics of pain in such patients. METHODS: The prospective observational single cohort study was conducted at the Department of Anaesthesiology and in the Breast Clinic of the Department of Surgery, Aga Khan University Hospital, Karachi, from August 2016 to January 2017, and comprised adult female patients with biopsy-proven carcinoma of breast who were scheduled for elective definitive breast cancer surgery. The patients were followed up for up to three months post-surgery and those with persistent pain were followed up for six months post-operation. Data was analysed using SPSS 19. RESULTS: Of the 120 patients, 26(21.7%) developed persistent post-surgical pain for up to three months, while in 17(14.2%) patients, the pain continued for up to six months after the operation. Among those with persistent post-surgical pain, 11(42.3%) had burning pain, 10(38.5%) had throbbing pain, 3(11.5%) had numbness and 2(7.7%)had mixed character of pain. Also, 11(42.3%)patients developed pain at more than one site including axilla, chest wall, upper arm and surgical scar area, and the site of pain in majority patients 15(57.7%) was axilla. CONCLUSION: The incidence of persistent pain following breast cancer surgery was found to be 21.7%.

Cultural Barriers for Women in Surgery: How Thick is the Glass Ceiling? An Analysis from a Low Middle-Income Country.

BACKGROUND: This study aimed to highlight cultural barriers faced by surgeons pursuing a surgical career faced by surgeons at a tertiary care hospital in Pakistan. As more females opt for a surgical career, barriers faced by female surgeons are becoming increasingly evident, many of which are rooted in cultural norms. In Pakistan, a predominantly Muslim-majority, low middle-income country, certain societal expectations add additionally complexity and challenges to existing cultural barriers. METHODS: A cross-sectional survey was administered via e-mail to the full-time faculty and trainees in the Department of Surgery at the Aga Khan University Hospital, Karachi, Pakistan, from July 2019 to November 2019. RESULTS: In total, 100 participants were included in this study, with the majority being residents (55.6%) and consultants (33.3%). 71.9% of female surgeons felt that cultural barriers towards a surgical career existed for their gender, as compared to 25.4% of male surgeons (p < 0.001). 40.6% of females reported having been discouraged by family/close friends from pursuing surgery, as compared to only 9.0% of males (p < 0.001). Moreover, a greater percentage of females surgeons were responsible for household cooking, cleaning and laundry, as compared to male surgeons (all p < 0.001). Lastly, 71.4% of female surgeons felt that having children had hindered their surgical career, as compared to 4.8% of males (p < 0001). CONCLUSION: Our study shows that significant cultural barriers exist for females pursuing a surgical career in our setting. Findings such as these emphasize the need for policy makers to work towards overcoming cultural barriers.

Vitamin D and bone metabolism in breast cancer patients in Karachi, Pakistan.

Breast cancer is one of the common types of malignancy worldwide and in Pakistan. The heterogeneous disease itself and its complex treatment leads to various bone-affecting complications that make breast cancer patients more vulnerable to bone fractures. Vitamin D deficiency among these women worsens the condition and promotes breast cancer growth. Thus, the purpose of the study was to assess serum levels of 25-hydroxyvitamin D (25OHD) and bone markers in women suffering from breast cancer. Serum levels of 25OHD, alkaline phosphatase (ALP), bone specific ALP, calcium (Ca), phosphorus (P), magnesium (Mg), albumin (Alb) and beta carboxyl terminal collagen crosslink (ß-CTx) were analyzed in 201 histological diagnosed patient volunteers from breast cancer clinic. Vitamin D insufficiency was present among the total study population and deficiency was particularly observed among women with metastases. These patients had significantly increased serum levels of ß-CTx and bone specific ALP when compared with the non-metastatic group. No significant difference was observed in other biochemical parameters. A weak correlation between serum levels of 25OHD and ß-CTx was observed. Therefore, monitoring of serum levels of 25OHD and bone markers at the time of diagnosis and during the course of treatment will endeavor a better overall health status.

Report- Immunological study of different fraction of wheat proteins.

Wheat allergy specifically refers to the adverse reaction involving IgE antibody to one or more protein fraction of wheat such as albumin, globulin, gliadin and glutenin (gluten). The majority of IgE-mediated reactions to wheat involve albumin and globulin fraction while gluten (gliadin & glutenin) also cause allergy (Celiac disease). Allergic reactions to wheat may be caused by ingestion of wheat containing foods or inhalation of flour (Bakers asthma). The present study was an effort to explore the antibody response of different proteins present in wheat. ELISA results revealed that the antibody response for albumin varied from 0.92-1.78, whereas, for globulin ranged from 1.39-1.60. Antibody response against glutenin and gliadin ranged from 0.57-1.05 and 0.98-1.95 respectively, among the different varieties of wheat. All the tested wheat varieties showed the significant difference antibody response against the different fractions of protein.

Harmonic scalpel versus electrocautery dissection in modified radical mastectomy: a randomized controlled trial.

PURPOSE: To test the hypothesis that the use of a harmonic scalpel increases operative time but results in less estimated blood loss, postoperative pain, drainage volume, and duration of surgery, as well as fewer complications, such as flap necrosis, seroma, and surgical site infection (SSI), than electrocautery. METHODS: This parallel-group, single-institution blinded randomized controlled trial was conducted at the department of surgery of our institute between April 2010 and July 2011. Women undergoing modified radical mastectomy were randomly allocated to either harmonic dissection (n = 76) or electrocautery (n = 76). RESULTS: Both the groups were comparable for baseline variables with age of 50.5 ± 12.2 and 48.5 ± 14.5 years in the harmonic and electrocautery groups, respectively. Harmonic dissection yielded better outcomes compared to electrocautery with lower estimated blood loss (100 ± 62 vs. 182 ± 92, p < 0.001), less drain volume (631 ± 275 ml vs. 1035 ± 413 ml, p < 0.001), fewer drain days (12 ± 3 vs. 17 ± 4, p < 0.001), less seroma formation (21.3 vs. 33.3 %, p = 0.071), and less postoperative pain [median (interquartile range) 2 (2-2) vs. 3 (3-4), p < 0.001], whereas mean operative time (191 ± 44 vs. 187 ± 36 min, p = 0.49) and SSI (0 vs. 4 %, p = 0.122) did not differ. On multivariable Cox regression analysis, harmonic dissection was associated with lower risk of significant postoperative pain [adjusted relative risk 0.028 (95 % confidence interval (CI) 0.004-0.2)] and overall complications [adjusted relative risk 0.47, (95 % CI 0.26-0.86)]. On multiple linear regression, duration of drains in the harmonic dissection group was 4.5 days less than electrocautery (r2 = 0.28, ß = 11.8, p < 0.001). CONCLUSIONS: The harmonic scalpel significantly reduces postoperative discomfort and morbidity to the patient without increasing operating time. We thus recommend preferential use of harmonic dissection in modified radical mastectomy. (ClinicalTrials.gov NCT01587248).

Single-cell m6A mapping in vivo using picoMeRIP-seq.

Current N6-methyladenosine (m6A) mapping methods need large amounts of RNA or are limited to cultured cells. Through optimized sample recovery and signal-to-noise ratio, we developed picogram-scale m6A RNA immunoprecipitation and sequencing (picoMeRIP-seq) for studying m6A in vivo in single cells and scarce cell types using standard laboratory equipment. We benchmark m6A mapping on titrations of poly(A) RNA and embryonic stem cells and in single zebrafish zygotes, mouse oocytes and embryos.

Streptomyces as a promising biological control agents for plant pathogens.

Plant diseases caused by pathogenic microorganisms in agriculture present a considerable obstacle, resulting in approximately 30-40% crop damage. The use of conventional techniques to manage these microorganisms, i.e., applying chemical pesticides and antimicrobials, has been discovered to have adverse effects on human health and the environment. Furthermore, these methods have contributed to the emergence of resistance among phytopathogens. Consequently, it has become imperative to investigate natural alternatives to address this issue. The Streptomyces genus of gram-positive bacteria is a potentially viable natural alternative that has been extensively researched due to its capacity to generate diverse antimicrobial compounds, such as metabolites and organic compounds. Scientists globally use diverse approaches and methodologies to extract new bioactive compounds from these bacteria. The efficacy of bioactive compounds in mitigating various phytopathogens that pose a significant threat to crops and plants has been demonstrated. Hence, the Streptomyces genus exhibits potential as a biological control agent for combating plant pathogens. This review article aims to provide further insight into the Streptomyces genus as a source of antimicrobial compounds that can potentially be a biological control against plant pathogens. The investigation of various bioactive compounds synthesized by this genus can enhance our comprehension of their prospective utilization in agriculture.

Synthesis of novel 3-hydroxy-2-naphthoic hydrazones as selective chemosensors for cyanide ions.

The development of an effective and selective chemosensor for CN- ions has become the need of the hour due to their hazardous impact on the environment and humans. Herein, we report the synthesis of two novel chemosensors, IF-1 and IF-2 based on 3-hydroxy-2-naphthohydrazide and aldehyde derivatives that have shown selective sensing of CN- ions. IF-2 exhibited exclusive binding with CN- ions that is further confirmed by the binding constant value of 4.77 × 104 M-1 with a low detection limit (8.2 µM). The chemosensory potential is attributed to deprotonation of the labile Schiff base center by CN- ions that results in a color change from colorless to yellow as visible by the naked eye. Accompanying this, a DFT study was also performed in order to find the interaction between the sensor (IF-1) and its ions (F-). A notable charge transfer from 3-hydroxy-2-naphthamide to 2,4-di-tert-butyl-6-methylphenol, was indicated by the FMO analysis. The QTAIM analysis revealed that in the complex compound, the strongest pure hydrogen-hydrogen bonding was observed between H53 and H58, indicated by a ρ value of +0.017807. Due to its selective response, IF-2 can be successfully used for making test strips for the detection of CN- ions.

The RNA m6A landscape of mouse oocytes and preimplantation embryos.

Despite the significance of N6-methyladenosine (m6A) in gene regulation, the requirement for large amounts of RNA has hindered m6A profiling in mammalian early embryos. Here we apply low-input methyl RNA immunoprecipitation and sequencing to map m6A in mouse oocytes and preimplantation embryos. We define the landscape of m6A during the maternal-to-zygotic transition, including stage-specifically expressed transcription factors essential for cell fate determination. Both the maternally inherited transcripts to be degraded post fertilization and the zygotically activated genes during zygotic genome activation are widely marked by m6A. In contrast to m6A-marked zygotic ally-activated genes, m6A-marked maternally inherited transcripts have a higher tendency to be targeted by microRNAs. Moreover, RNAs derived from retrotransposons, such as MTA that is maternally expressed and MERVL that is transcriptionally activated at the two-cell stage, are largely marked by m6A. Our results provide a foundation for future studies exploring the regulatory roles of m6A in mammalian early embryonic development.

Knowledge attitude and practices among urban women of Karachi, Pakistan, regarding breast cancer.

OBJECTIVE: To determine the knowledge,attitudes and practices of urban women regarding breast cancer and its available screening modalities. METHODS: The cross-sectional, questionnaire-based, descriptive study was conducted in the urban population of Karachi in November 2010. Female attendants (n=373) visiting a tertiary care centre and four of its urban outreach centres during the study period were administered a questionnaire. The answers were then scored with regard to their knowledge. Frequencies and percentages were computed through SPSS 17, and analysis of variance was used to confirm significance. RESULTS: Of the 373 participants with a mean age of 32.4+/-10.9 years, 293 (78.6%) were married, and 257 (69%) were housewives. The education level was considerably high; with 214 (57.4%) graduates. The mean score for knowledge of risk factors was 2.84 out of a total of 13; which was significantly associated with marital status and income. Age > 40 years, education level, income and employment status were also significantly associated with higher mean screening awareness scores. Nearly 182 (48.8%) had heard about Breast Self Examination and 142 (38%) knew how to perform one. However, only 97 (25.9%) regularly performed such an exam. Almost all 3621 (97%) women wanted more media awareness campaigns regarding the issue. CONCLUSION: There is a real need for comprehensive health education programmes focusing on breast cancer awareness in Pakistan.

Concordance Between Clinical and Pathological Response Assessment After Neo-Adjuvant Chemotherapy in Patients With Invasive Lobular Carcinoma.

Background Neo-adjuvant chemotherapy (NAC) is frequently administered in breast carcinoma patients. The clinical response to NAC guides further treatment. The pathological response is not only an independent prognostic factor, but it also guides further treatment and prognosis. Objectives The aim of our study was to find the degree of concordance between clinical and pathological response assessments after NAC in Invasive lobular Carcinoma (ILC) cases by using World Health Organization (WHO) criteria and different pathological systems, respectively. We also tried to identify any useful parameter of clinical assessment that could better correlate with pathologic assessment and provide a better estimation of residual tumor. Methods This retrospective study was conducted on 26 ILC tumors diagnosed in 24 patients who were treated with NAC followed by surgical resection between January 2009 and December 2020. Medical records and microscopy glass slides were reviewed for clinical and pathological response assessments, respectively. Results The pre-treatment tumor area ranged from 1.8-255 cm2 and the mean±SD was 52.2±66.8 cm2. After NAC, complete clinical response was observed in four (15.3%) cases. The clinically assessed mean tumor area significantly reduced from 52.2±66.8 cm2 to 17.2±22.6 cm2 (p-value<0.001). The pathologically assessed mean tumor area (27.4±24.1 cm2) didn't differ significantly from the clinically assessed mean tumor area (17.2±22.6 cm2) (p-value=0.114). Pathologically, the majority of the cases showed partial response, and a complete pathological response was achieved in only two (7.7%) cases. The concordance rates between clinical assessment by the WHO method and pathological assessment of the breast using the Sataloff method, Miller-Payne (MP) system, Residual Cancer Burden system, and Chevallier method were 26.7%, 15.8%, 9%, and 3.5%, respectively, with insignificant p-values. Percentage reduction in clinical size and percentage reduction in tumor cellularity differed significantly (p-value=0.038). Conclusion Clinical response assessment provides a less accurate estimation of residual disease, as it shows poor concordance with pathological assessment using different assessment systems/methods.

Preoperative Ultrasound-guided Core Biopsy of Axillary Nodes for Staging of Clinically Negative Axilla in Breast Cancer Patients - A Pilot Study.

Objective The aim of the current study is to determine the feasibility and accuracy of ultrasound-guided core biopsy for staging the axilla in clinically node-negative patients with invasive breast cancer. Introduction Historically, in breast cancer patients, axillary lymph node dissection was performed to stage axilla. Because of the high morbidity of axillary lymph node dissection, sentinel lymph node biopsy (SLNB) became the standard of care in patients with clinically node-negative breast cancer. However, SLNB is expensive, time consuming, can cause morbidity and can be complicated by seroma formation, sensory nerve injury, lymphedema, etc. Many centers rely on the availability of frozen section on sentinel lymph nodes to avoid a second procedure with the accuracy of procedure ranging from 73 to 96%, however, the availability of frozen section is limited in our part of the world. Pre-operative identification of axillary node positivity in patients with clinically negative nodes by ultrasound imaging of the axilla would allow one-stage axillary clearance and can decrease the need for SLNB from 21% to 70%. The aim of the present study is to determine the accuracy and feasibility of ultrasound-guided core biopsy to stage the axilla in clinically node-negative breast cancer patients, comparing with final histopathology as gold standard. Material & methods This was a non-randomized, prospective interventional study, done at Radiology Department of Aga Khan University Hospital. All patients diagnosed with breast cancer (histologically proven) with clinically negative axilla and ipsilateral positive axillary ultrasound were included. These patients underwent axillary lymph node core biopsy. If the result was negative they were subjected to SLNB. Histopathology result was taken as gold standard. Results The sensitivity of ultrasound-guided core biopsy was 88%, specificity 100%, positive predictive values (PPV) 100%, negative predictive values (NPV) 89.28%, diagnostic accuracy 94%. Conclusion In conclusion, the present study demonstrated high accuracy of ultrasound-guided axillary lymph node core biopsy in breast cancer patients with clinically node-negative axilla. Positive core biopsy results can thus obviate the need for sentinel lymph node biopsy and allow breast surgeons to directly proceed to axillary lymph node dissection.

Patient Delay in Breast Cancer Diagnosis in Two Hospitals in Karachi, Pakistan: Preventive and Life-Saving Measures Needed.

PURPOSE: Patients with breast cancer in Pakistan commonly present with advanced disease. The objectives of this study were to evaluate the frequency and length of delays in seeking medical consultation and to assess the factors associated with them. METHODS: Four hundred ninety-nine patients with newly diagnosed breast cancer were enrolled and interviewed over the period from February 2015 to August 2017. Information on sociodemographic factors, delay to medical consultation, stage of breast cancer at presentation, and tumor characteristics of the breast cancer were collected through face-to-face interviews and medical file review. RESULTS: The mean (standard deviation) age of patients with breast cancer was 48.0 (12.3) years. The mean (standard deviation) patient delay was 15.7 (25.9) months, with 55.2% of women detecting a breast lump but not seeking a medical consultation because of a lack of awareness about the significance of the lump. A total of 9.4% of the women decided to seek treatment initially using complementary and alternative medicine and traditional treatment; 9.4% of the women presented to a health care provider with a breast lump but no action was taken, and they were wrongly reassured about the lump without mammography or biopsy. For 26% of the women, the delay in presentation was caused by anxiety, fears and misconceptions regarding diagnosis and treatment, and other social factors including possible adverse effects on their relationship with their husband. Multivariable analysis showed a strong association of lower socioeconomic status (odds ratio [OR], 8.11 [95% CI, 2.46 to 26.69]) and late stage of breast cancer (OR, 4.83 [95% CI, 1.74 to 13.39]) with a patient delay of ≥ 3 months. CONCLUSION: Patient delay is a serious problem in Pakistan. There is an urgent need for intensive and comprehensive breast cancer education that addresses the myths and misconceptions related to breast cancer.

A multicenter case control study of association of vitamin D with breast cancer among women in Karachi, Pakistan.

BACKGROUND: The prevalence of vitamin D inadequacy and breast cancer are both high among women living in Karachi, Pakistan. METHODS: A matched case control study was conducted in two hospitals of Karachi, Pakistan to evaluate the association of vitamin D (serum 25-hydroxyvitamin D) concentrations, vitamin D supplementation and sun exposure with breast cancer among Pakistani women. A total of 411 newly diagnosed histologically confirmed primary breast cancer cases were enrolled and 784 controls, free of breast and any other cancers, were matched by age (year of birth ± 5 years), residence in the same geographic area and study site. Information was collected on sociodemographic history, history of vitamin D supplementation, past medical and obstetrical history, family history of breast cancer, sun exposure history, histopathology reports and anthropometric measurement and venous blood was collected to measure serum 25-hydroxyvitamin D (25(OH)D) concentration. RESULTS: Compared to patients with sufficient serum vitamin D (>30 ng/ml), women with serum vitamin D deficiency (<20ng/ml), had a higher risk of breast cancer (OR = 1.65, 95%CI: 1.10, 2.50). Women with history of vitamin D supplementation one year prior to enrollment, had significant protective effect against breast cancer (OR = 0.32, 95% CI: 0.24, 0.43). CONCLUSIONS AND RECOMMENDATION: Serum vitamin D deficiency was associated with increased risk of breast cancer, while vitamin D supplementation was associated with decreased risk of breast cancer. In Pakistani women, where vitamin D deficiency is common, raising and maintaining serum vitamin D at population level is a safe and affordable strategy. It may play a role in reducing the incidence of both vitamin D deficiency and breast cancer, particularly among poor women where the breast cancer mortality is highest due to limited resources for early detection, diagnosis, and treatment. The effects of vitamin D with regard to breast cancer risk in Karachi Pakistan should be further evaluated.

Gender discrimination against female surgeons: A cross-sectional study in a lower-middle-income country.

INTRODUCTION: Although gender discrimination and bias (GD/bias) experienced by female surgeons in the developed world has received much attention, GD/bias in lower-middle-income countries like Pakistan remains unexplored. Thus, our study explores how GD/bias is perceived and reported by surgeons in Pakistan. METHOD: A single-center cross-sectional anonymous online survey was sent to all surgeons practicing/training at a tertiary care hospital in Pakistan. The survey explored the frequency, source and impact of GD/bias among surgeons. RESULTS: 98/194 surgeons (52.4%) responded to the survey, of which 68.4% were males and 66.3% were trainees. Only 19.4% of women surgeons reported 'significant' frequency of GD/bias during residency. A higher percentage of women reported 'insignificant' frequency of GD/bias during residency, as compared to males (61.3% vs. 32.8%; p = 0.004). However, more women surgeons reported facing GD/bias in various aspects of their career/training, including differences in mentorship (80.6% vs. 26.9%; p < 0.005) and differences in operating room opportunities (77.4% vs. 32.8%; p < 0.005). The source was most frequently reported to be co-residents of the opposite gender. Additionally, a high percentage of female surgeons reported that their experience of GD/bias had had a significant negative impact on their career/training progression, respect/value in the surgical team, job satisfaction and selection of specialty. CONCLUSION: Although GD/bias has widespread impacts on the training/career of female surgeons in Pakistan, most females fail to recognize this GD/bias as "significant". Our results highlight a worrying lack of recognition of GD/bias by female surgeons, representing a major barrier to gender equity in surgery in Pakistan and emphasizing the need for future research.