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Objective Triple-negative breast cancer (TNBC) represents an aggressive and prognostically poor variant of breast cancer. Over the years, detailed research has been conducted and published in Western literature. However, there lacks a detailed account of TNBC cases from the perspective of a low-volume institution. This study aims to assess the clinical features of TNBC, as well as their prognostic implications in a tertiary care centre. Methods and materials This prospective observational study took place at a tertiary health centre for two years, spanning from 2021 to 2023. The study aimed to investigate various clinicopathological and epidemiological parameters, thereby highlighting the shortcomings in the existing knowledge about the subject in the context of a low-volume centre, as well as additional contributing factors in developing countries like India. A group of 150 participants diagnosed with TNBC through biopsy and immunohistochemistry and >40 years of age were included in the study. Patients who tested positive for hormonal receptors and who refused to give consent for participation were excluded from the study. The study subjects were categorized according to their clinical TNM (cTNM) stage and eventually segregated into two primary heads, namely pre-surgery chemotherapy with breast-conserving surgery (BCS) after a good response, or modified radical mastectomy (MRM) upfront. Important demographic details, including age, socioeconomic status, and education, were also recorded. A comprehensive follow-up assessment post-treatment was performed to detect early recurrence. After data collection, the recurrence rates were correlated with the TNBC status to establish the aggressiveness of the cancer. Statistical analysis of the data was done using the Statistical Package for Social Sciences (SPSS) -16version software. Results The average age of the 150 participants in the study was 52.21 years (SD±4.89 years). The highest recorded age was 64 years, while the lowest recorded age was 45 years. In the study, it was observed that 41% of the participants diagnosed with TNBC had stage III disease, whereas 33.5% had stage I disease, 22% had stage IV disease and 3.6% had stage II disease. A total of 27.5% of individuals with TNBC exhibited metastases in various anatomical sites, whereas the other 72.5% did not show any signs of metastasis. Conclusion Triple-negative breast cancer has earned its position as a unique subtype of breast cancer due to its unusual molecular characteristics, aggressive behavior, limited treatment options, and poor prognosis. The lower per-capita income and limited knowledge pertaining to this variant, along with the absence of more specific treatment options, contribute to the already high levels of morbidity and mortality associated with this illness. To effectively address this unique and very virulent ailment and customize our strategies, it is imperative to do further comprehensive investigations, thereby enabling us to deliver the highest quality of medical attention to individuals afflicted by this pathology.
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OBJECTIVE: To evaluate the accuracy of the modified CT severity index (MCTSI) in predicting the severity of acute pancreatitis and to prognosticate the clinical outcomes. METHODS AND MATERIALS: The study was conducted at a tertiary health center between January 2021 and June 2023. A total of 150 consecutive patients with clinical/laboratory features suggestive of acute pancreatitis were included in the study and underwent a contrast-enhanced CT scan within 24 hours of admission. Based on their MCTSI score, these patients had conservative or surgical/endoscopic treatment. Clinical outcomes were assessed in terms of recovery, development of complications, or death. The receiver operating characteristic curve and descriptive statistics were computed to determine the sensitivity and specificity. The data were analyzed using SPSS version 16 software (SPSS Inc., Chicago, IL), and an attempt was made to evaluate the accuracy of MCTSI in predicting these clinical outcomes. RESULTS: The mean age of patients in our study was 49.21 ± 11.02 years. Out of the 150 included patients, 103 were men and 47 were women. Compared to 11.68% of severe acute pancreatitis patients who died, 88.32% recovered. The area under the curve was determined as 0.865, based on which the MCTSI score predicted acute pancreatitis clinical outcome with 64% sensitivity and 92% specificity. The MCTSI demonstrated value in predicting clinical outcomes with a p-value of 0.043 ± 0.012 (p < 0.05) in the recovered patients while p = 0.032 ± 0.012 for patients who succumbed. The p-value for MCTSI in predicting complications was p = 0.0012 ± 0.0008 (p < 0.05). CONCLUSION: Our study was able to demonstrate the high level of accuracy of the MCTSI score in predicting complications and clinical outcomes, especially in patients with severe acute pancreatitis. The MCTSI serves as a valuable asset in the preliminary evaluation of acute pancreatitis, thereby facilitating appropriate management.
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Development of a series of highly kinome-selective spleen tyrosine kinase (Syk) inhibitors with favorable druglike properties is described. Early leads were discovered through X-ray crystallographic analysis, and a systematic survey of cores within a selected chemical space focused on ligand binding efficiency. Attenuation of hERG ion channel activity inherent within the initial chemotype was guided through modulation of physicochemical properties including log D, PSA, and pKa. PSA proved most effective for prospective compound design. Further profiling of an advanced compound revealed bacterial mutagenicity in the Ames test using TA97a Salmonella strain, and subsequent study demonstrated that this mutagenicity was pervasive throughout the series. Identification of intercalation as a likely mechanism for the mutagenicity-enabled modification of the core scaffold. Implementation of a DNA binding assay as a prescreen and models in DNA allowed resolution of the mutagenicity risk, affording molecules with favorable potency, selectivity, pharmacokinetic, and off-target profiles.
