Design, Synthesis, Anti-Tubercular Evaluation and Teratogenicity Studies of Furanyl Pyrazolo[3,4-b] Quinoline-5-Ones.

We have synthesized novel pyrazolo-quinoline analogues (P1-10) in an effort to create newer antitubercular drugs against the rising bacterial resistance. NMR, IR and ESI-MS spectra were utilized to characterize the synthesised compounds. The antitubercular activity of the target compounds was evaluated against Mycobacterium tuberculosis. Six derivatives (P1-6) displayed very significant activity at 1.6 µg/mL concentration and were found to be more active than pyrazinamide standard. Thus, as per the drug susceptibility results the MIC value could be considered between 1.6 and 0.8 µg/mL. In addition, all the synthesised compounds were subjected to molecular docking studies against specific protein, Enoyl acyl carrier protein reductase (InhA) in complex with N-(4-methylbenzoyl)-4-benzylpiperidine, PDB ID: 2NSD. Among all the compounds the most effective compounds were found an Autodock score of 11.6 and 11.2 against 2NSD, respectively. Further, Zebrafish larvae have been used to test the teratogenicity of the synthesised compounds. There were no indications of abnormalities with (P2), (P4), (P5), (P6), and (P10) at 0.5 µM. Supplementary Information: The online version contains supplementary material available at 10.1134/S1068162023010053.

Predictors of adjuvant treatment for pancreatic adenocarcinoma at the population level.

BACKGROUND: In the present study, we aimed to describe, at the population level, patterns of adjuvant treatment use after curative-intent resection for pancreatic adenocarcinoma (pcc) and to identify independent predictors of adjuvant treatment use. METHODS: In this observational cohort study, patients undergoing pcc resection in the province of Ontario (population 13 million) during 2005-2010 were identified using the provincial cancer registry and were linked to administrative databases that include all treatments received and outcomes experienced in the province. Patients were defined as having received chemotherapy (ctx), chemoradiation (crt), or observation (obs). Clinicopathologic factors associated with the use of ctx, crt, or obs were identified by chi-square test. Logistic regression analyses were used to identify independent predictors of adjuvant treatment versus obs, and ctx versus crt. RESULTS: Of the 397 patients included, 75.3% received adjuvant treatment (27.2% crt, 48.1% ctx) and 24.7% received obs. Within a single-payer health care system with universal coverage of costs for ctx and crt, substantial variation by geographic region was observed. Although the likelihood of receiving adjuvant treatment increased from 2005 to 2010 (p = 0.002), multivariate analysis revealed widespread variation between the treating hospitals (p = 0.001), and even between high-volume hepatopancreatobiliary hospitals (p = 0.0006). Younger age, positive lymph nodes, and positive surgical resection margins predicted an increased likelihood of receiving adjuvant treatment. Among patients receiving adjuvant treatment, positive margins and a low comorbidity burden were associated with crt compared with ctx. CONCLUSIONS: Interinstitutional medical practice variation contributes significantly to differential patterns in the rate of adjuvant treatment for pcc. Whether such variation is warranted or unwarranted requires further investigation.

The Australian and New Zealand Audit of Surgical Mortality-birth, deaths, and carriage.

OBJECTIVE: This article outlines the formation of the Australian and New Zealand Audit of Surgical Mortality (ANZASM) and describes its objectives, governance, functioning and challenges. BACKGROUND: A nationwide audit of surgical mortality provides an overview of the leading causes of death in patients who require surgical care. It identifies system or process errors, trends in deficiency of care and helps develop strategies to reduce deaths in the surgical arena. METHODS: A standardized tool is used to systematically collect data after every surgical death. Patient details are reviewed by a peer surgeon (and in certain cases a second) to identify issues with patient management and hospital processes. The treating surgeon is then offered confidential feedback and alternate views on patient management. RESULTS: From January 2009 to December 2012, 19,096 deaths were reported to the ANZASM. Eighty-six percent of the audited deaths occurred in patients requiring an emergency admission. Significant criticism of patient care was reported in 13% of cases with 16% of clinical issues perceived to be preventable. Western Australia, which first began the audit process, has shown a 30% reduction in surgical deaths. CONCLUSIONS: Nationwide mortality audits are a useful and worthwhile exercise. Recommendations identified in the audit reports direct educational workshops and seminars to address these issues. They allow Departments of Health to make informed decisions in their hospitals. Through this model, and the lessons learnt, we would encourage other countries planning to set up their own audits to follow a similar concept.

A population-based study of the epidemiology of pancreatic cancer: a brief report.

OBJECTIVE: Administrative data are used to describe the pancreatic cancer (pcc) population. The analysis examines demographic details, incidence, site, survival, and factors influencing mortality in a cohort of individuals diagnosed with pcc. METHODS: Incident cases of pcc diagnosed in Ontario between 1 January 2004 and 31 December 2011 were extracted from the Ontario Cancer Registry. They were linked by encrypted health card number to several administrative databases to obtain demographic and mortality information. Descriptive, bivariate, and survival analyses were conducted. RESULTS: During the period of interest, 9221 new cases of pcc (4548 in men, 4673 in women) were diagnosed, for an age-adjusted standardized annual incidence in the range of 8.6-9.5 per 100,000 population. Mean age at diagnosis was 70.3 ± 12.5 years (standard deviation). Five-year survival was 7.2% (12.8% for those <60 years of age and 3.6% for those >80 years of age). Survival varied by sex, older age, rural residence, lower income, site of involvement in the pancreas, and presence of comorbidity. CONCLUSIONS: The mortality rate in pcc is exceptionally high. With an increasing incidence and a mortality positively associated with age, additional support will be needed for this highly fatal disease as demographics in Ontario continue to trend toward a higher proportion of older individuals.

Aberrant expression of metastasis-inducing proteins in ectopic and matched eutopic endometrium of women with endometriosis: implications for the pathogenesis of endometriosis.

BACKGROUND: Endometriosis is a metastatic disease without obvious tumorigenesis. Expression of S100P, S100A4, osteopontin (OPN) or anterior gradient homologue 2 (AGR2) proteins can induce metastasis but fail to induce tumorigenesis per se. We now explore whether this group of metastasis-inducing proteins (MIPs) are associated with the pathogenesis of endometriosis. METHODS: Eutopic endometrial biopsies were taken from 73 women (35 fertile women without endometriosis and 38 women with surgically diagnosed endometriosis). Ectopic endometriotic lesions were collected from eight of the women with endometriosis. The expression of MIPs at the cellular level was evaluated by immunohistochemistry and the presence of these proteins in the endometrial tissues was verified by western blotting and their gene expression was confirmed by RT-PCR. RESULTS: All four MIPs were immunolocated in the endometrium of control women and S100P, AGR2 and OPN showed a cyclical variation. Proliferative phase eutopic endometrium of both groups showed a similar staining pattern for all MIPs, whereas secretory phase endometrium showed a differential expression between controls and cases. The secretory phase endometrial immunostaining of controls showed weak stromal and perivascular AGR2, and decreased stromal and glandular S100P. In contrast, immunostaining for all MIPs was increased in the late secretory endometrial samples of women with endometriosis and intense immunostaining was seen for S100A4 in the stroma (P< 0.05) and for S100P (P< 0.001) and AGR2 (P< 0.0001) in both glands and stroma (P< 0.001). All active peritoneal endometriotic lesions showed strong immunostaining for each of the MIPs studied. CONCLUSIONS: We propose that these MIPs enhance endometrial cell invasiveness and contribute to the establishment of ectopic endometriotic deposits after retrograde menstruation.

Management of colorectal cancer liver metastasis in a patient with immune thrombocytopaenia.

Immune thrombocytopaenia (ITP) was referred to previously as idiopathic thrombocytopaenic purpura and is usually of autoimmune or viral aetiology. Colorectal cancer liver metastasis with concomitant ITP is rare and only three cases have been reported in the English literature. Adverse effects of adjuvant chemotherapy may aggravate ITP. The sequencing of chemotherapy, operation for the primary and liver metastasis, and a decision on splenectomy is important. We present our experience in the management of a 52-year-old man who, having undergone anterior resection one year earlier for carcinoma of the rectum, presented with liver metastasis and ITP. He underwent splenectomy with hepatectomy prior to chemotherapy.

Benign biliary papillomatosis in a patient with a choledochal cyst presenting as haemobilia: a case report.

Biliary papillomatosis is a rare condition usually detected on imaging or postoperative histopathology. It may be asymptomatic or present with features of cholangitis. We report the management of a patient presenting with haemobilia.