Prognostic parameters of luminal A and luminal B intrinsic breast cancer subtypes of Pakistani patients.

BACKGROUND: Prognosis of breast cancer and success of therapeutic interventions largely rely on the clinico-pathologic and biological characteristics of the tumor and vary due to the heterogeneous nature of breast cancers. The aim of this study was to determine the frequency and prognostic parameters of luminal breast cancers in our population to devise targeted and personalized therapeutic regimens tailored to the needs of the loco-regional population. METHODS: A retrospective cross-sectional study including 1951 cases of primary breast cancer treated at Liaquat National Hospital Karachi was conducted during the year 2011-2016. The clinico-pathologic characteristics were observed and semiquantitative immunohistochemical analysis was performed to study the luminal subtypes A and B. The cross-tabulated statistics of the observed characteristics were performed between the two subtypes. The significance level of each characteristic was estimated utilizing the chi-square test. RESULTS: Luminal cancers comprised 62.7% of the total number of cases diagnosed with breast cancers in the study period. Out of these 1224 cases of luminal cancers, 845 cases (69%) were luminal B, while 379 (31%) cases were of luminal A. Luminal B cancers were significantly more common in younger age groups as compared to luminal A cancers. Comparison of the two subtypes of luminal breast cancers revealed significant differences. Luminal B cancers were associated with higher grade (26% grade III in luminal B compared to 8% in luminal A), micropapillary histology, and high frequency of nodal metastasis (54 vs. 43%). CONCLUSIONS: Luminal B comprised the most frequent subtype of breast cancer in our study and they were found more constantly in a younger age group. Moreover, they were associated with adverse clinico-histologic parameters like higher grade and nodal metastasis. Therefore, we suggest that, despite lack of widespread availability of molecular studies in our setup, IHC-based typing should be done in every case of breast cancer to individualize therapy.

Antimicrobial Susceptibility Of Intra-Abdominal Infection Isolates From A Tertiary Care Hospital In Karachi.

BACKGROUND: Intra-abdominal infections are associated with significant morbidity and mortality. The most frequent pathogens involved are the gastrointestinal flora which can cause poly-microbial infections. Microbiological diagnosis is required to determine the aetiology and antimicrobial susceptibility of the organisms involved. Prompt initiation of antimicrobials is essential for improving patient's outcome. Knowledge of local trends of antimicrobial resistance in nosocomial isolates is essential for empiric therapy. METHODS: A total of 190 clinical isolates collected from intra-abdominal infections during July 2013 to July 2014 were included in the study. Organism identification and Antimicrobial sensitivity testing using standard biochemical tests and CLSI recommended criteria was carried out. RESULTS: Of the total 190 isolates from abdominal infection sources 52% were from fluid sources (peritoneal & ascitic fluid), 41% were from gall bladder and 6.5% were from other abdominal sources. E. coli (46.8%) was the most frequently isolated gram negative and Enterococcus (13.1%) was the most frequently isolated gram positive organism. Carbapenem (imipenem) was the most active agent against enterobacteraceae exhibiting, 94.4% and 91.3% sensitivity against E. coli and Klebsiella respectively. While vancomycin was the most active agent against gram positive organisms. Eighty-four percent of the Enterococci isolated were sensitive to vancomycin. Most isolates exhibited resistance to one or more antibiotics. CONCLUSIONS: Continuous evolution of antimicrobial resistance patterns in bacteria necessitates updating of local data on antimicrobial susceptibility profiles to ensure the safety and efficacy of pathogen specific antimicrobial therapies.

Concurrent Obsessive-Compulsive Symptoms in Patients With Schizophrenia: A Retrospective Study From a Tertiary Care Centre in Sindh, Pakistan.

INTRODUCTION: The present study aimed to evaluate the proportion of concurrent symptoms of obsessive-compulsive symptoms (OCSs) among patients with schizophrenia. METHODS: A retrospective study was undertaken at the Department of Psychiatry, Jinnah Postgraduate Medical Center, Sindh, Pakistan between 1st March 2019 and 1st April 2020. All cases with diagnosed schizophrenia irrespective of gender, age, or ethnicity were eligible for the study. We excluded patients with acute psychosis due to isolated substance use disorder or any organic brain disease. The medical records for each patient were retrieved from the departmental database. Sociodemographic factors including age, gender, ethnicity, and presence of OCSs and other psychiatric comorbidities were recorded in a predefined pro forma. The presence of OCSs was noted by the attending psychiatrist during history taking as positive or negative. RESULTS: A total of 139 patients were included. A predominance of the male gender was noted. There were 63 (45.3%) patients with concurrent OCSs. Out of the total patients, 42 (66.67%) males and 21 (33.33%) females had OCSs. A total of 28 (44.44%) patients between 31 and 45 years of age had OCSs. Out of the 63 patients with OCSs, 36 (57.14%) had a history of substance abuse (p = 0.471). In the study, 17 (26.98%) Balochi and 19 (30.16%) Pashtuns had OCSs. However, the difference was statistically insignificant. CONCLUSION: In conclusion, OCSs were frequent in patients with schizophrenia, according to the current study. We discovered that males, individuals between the ages of 18 and 30 years, Balochis, Pashtuns, and those with a history of substance abuse were more likely to have OCSs. However, the difference was not statistically significant.

Perceptions, Practices, and Challenges Regarding Menstrual Hygiene Among Women in Karachi, Pakistan: A Comparison Between General Population and Healthcare Workers.

Background Menstruation is a natural physiological phenomenon, yet considered a stigmatized subject, particularly in low- and middle-income countries like Pakistan. It is seldom discussed openly, leading to flow of incorrect and incomplete knowledge. The resultant unhealthy practices not only affect the health of the menstruator but can also contribute to considerable psychosocial stress. Menstrual hygiene management (MHM) is an important facet, which is associated with a variety of practices and beliefs in different parts of the world, some of which may not be correct. Identifying these poor methods is necessary in order to rectify them. Hence, our study aimed at determining the level of knowledge, beliefs, and practices pertaining to menstruation in the general female populace of Karachi. Healthcare workers have a potential role in the dissemination of authentic knowledge and practices. Therefore, we assessed and compared the accuracy and reliability of the aforementioned parameters in them and the need for an educational intervention. Methods A descriptive, cross-sectional study was conducted on females visiting the Gynecologic and Obstetrics Outpatient Department (OPD), and healthcare workers employed at Dr. Ruth K. M. Pfau Civil Hospital Karachi and Dow University Hospital Ojha. Using non-probability convenience sampling, a self-structured questionnaire was used to collect data from 353 respondents over a duration of three months from October 2019 to January 2020. Data was tabulated in Statistical Package for the Social Sciences (SPSS) version 24.0 (IBM Corp., Armonk, NY, US). In accordance with the objectives of the study, descriptive analysis was performed, and data was presented in the form of frequencies and percentages.  Results Of the 353 participants, 176 were from the general population and 177 were healthcare workers. At menarche, only 28.4% of the general population and 29.4% of healthcare workers had an idea of menses and proper placement of absorbent. Significantly lower number of females from the general population were found to be aware of tampons and menstrual cups (15.9% and 11.4% respectively) as compared to healthcare workers. For both groups, the source of knowledge was mostly their mother. The study showed that 77.8% of the general population and 66.1% of healthcare workers avoided bathing on certain days during menses, with the most common reason being that "it causes irregular flow". As compared to healthcare workers, a significantly higher number of women from the general population had restrictions of activity (53.4%) and avoided washing of groin area during menstruation (31.2%). Majority of women from the general population mentioned that they were scared when they menstruated for the first time. The most common absorbent used by respondents was pads, followed by cloth. The data showed 64.2% of females from the general population and 28.8% of healthcare workers abstained from eating certain foods. Seeking treatment for gynecological issues was not widespread among respondents. Conclusion Our study demonstrated insufficient menstrual knowledge, and consequent incorrect practices in the female population of Karachi. Destigmatizing menstruation and educating women and young girls is indispensable to overcoming this gap. At the same time, reinforcing the availability of MHM products is long overdue and is a crucial milestone towards facilitation of MHM for the women of Pakistan.

Clinical and prognostic profile of Her2neu positive (non-luminal) intrinsic breast cancer subtype: comparison with Her2neu positive luminal breast cancers.

OBJECTIVE: Her2neu receptor is proto-oncogene which can be over-expressed in both luminal and non-luminal breast cancers. In the present study, we aimed to compare the prognostic and predictive factors like tumor grade, T-stage, N-stage and ki67 index in Her2neu intrinsic breast cancer subtype with Her2neu over-expressed luminal breast cancers. RESULTS: 801 (41%) cases were Her2neu positive; out of which, 418 cases (52.2%) showed ER positivity and thus were classified as Her2neu positive luminal cancers whereas 383 cases (47.8%) were ER and PR negative and therefore were labeled as intrinsic Her2neu subtype (non-luminal). Her2neu positive (non-luminal) cancers were significantly associated with higher grades and Ki67 proliferative index compared to Her2neu positive luminal cancers. On the other no significant association was noted in T-stage and N-stage. We found a high frequency of her2neu positivity in our studied population of breast cancer. Moreover, association of her2neu positive (non-luminal) breast cancers with higher grade and ki67 index indicates a predictive value of ER/PR positivity in her2neu positive breast cancers. On the other hand, lack of association with respect to T and N stage, signifies no prognostic benefit of ER/PR in her2neu positive breast cancers.

Clinicopathologic features of invasive metaplastic and micropapillary breast carcinoma: comparison with invasive ductal carcinoma of breast.

OBJECTIVES: The aim of this study was to determine the frequency of metaplastic breast carcinoma and invasive micropapillary carcinoma in our population and also to compare the clinico-pathologic features of metaplastic breast carcinoma and invasive micropapillary carcinoma with invasive ductal carcinoma, not otherwise specified (IDC, NOS). RESULTS: 86.9% of the cases were identified as ductal carcinoma, NOS, while 2.2% were metaplastic and 0.76% cases were micropapillary carcinoma. Metaplastic carcinomas were found to be of higher grade as compared to IDC, NOS as 81% of metaplastic carcinoma were grade III compared to 35% IDC, NOS. 79% of metaplastic carcinoma were ER negative and 86% were PR negative, respectively as compared to ductal carcinoma NOS, which were 40% ER negative and 54% were PR. Similarly, 86.7% micropapillary cancers were ER positive and 73.3% were PR positive. Moreover, 66.7% micropapillary carcinoma showed nodal metastasis and 77.8% showed lymphovascular invasion, which was significantly higher than that of IDC, NOS micropapillary and metaplastic carcinomas accounts for less than 2 and 1% of the breast cancer burden in our population and highly correlates with poor prognosis parameters therefore, require more intensive management in our population.

Promotion of spinal cord regeneration by neural stem cell-secreted trimerized cell adhesion molecule L1.

The L1 cell adhesion molecule promotes neurite outgrowth and neuronal survival in homophilic and heterophilic interactions and enhances neurite outgrowth and neuronal survival homophilically, i.e. by self binding. We investigated whether exploitation of homophilic and possibly also heterophilic mechanisms of neural stem cells overexpressing the full-length transmembrane L1 and a secreted trimer engineered to express its extracellular domain would be more beneficial for functional recovery of the compression injured spinal cord of adult mice than stem cells overexpressing only full-length L1 or the parental, non-engineered cells. Here we report that stem cells expressing trimeric and full-length L1 are indeed more efficient in promoting locomotor recovery when compared to stem cells overexpressing only full-length L1 or the parental stem cells. The trimer expressing stem cells were also more efficient in reducing glial scar volume and expression of chondroitin sulfates and the chondroitin sulfate proteoglycan NG2. They were also more efficient in enhancing regrowth/sprouting and/or preservation of serotonergic axons, and remyelination and/or myelin sparing. Moreover, degeneration/dying back of corticospinal cord axons was prevented more by the trimer expressing stem cells. These results encourage the view that stem cells engineered to drive the beneficial functions of L1 via homophilic and heterophilic interactions are functionally optimized and may thus be of therapeutic value.