Enhancing Postgraduate Medical Education: Upscaling and Recognition of Pakistan's Training.

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Managing the Adverse Events Associated with Pembrolizumab and Lenvatinib Therapy in Endometrial Cancer.

Endometrial cancer (EC) is the most common gynaecological cancer. The combination of lenvatinib and pembrolizumab has exhibited efficacy as the second line treatment for advanced EC, with a significant benefit in terms of progression free survival (PFS) and overall survival, but the adverse events (AE) profile is complex. AEs associated with the treatment may represent a limitation to this combination. Here, we report the case of a 38-year-old female patient diagnosed with stage IV EC elsewhere, whose disease progressed after the first line of treatment and was referred to a specialised cacncer centre in Muscat, Oman, in 2021. We treated her with the combination of lenvatinib and pembrolizumab. During the course of the treatment, she developed hand-foot syndrome grade III and hypothyroidism grade II. The AEs were managed with supportive medications, dose interruptions, dose reductions and multidisciplinary care, which allowed the continuation of the treatment. The patient achieved a good partial response and an ongoing PFS of more than 12 months.

Clinicopathological Features and Outcomes of Endometrial Cancer: A single institution experience.

Objectives: This study aimed to report the demographic features, clinical presentation, pathological types and long-term outcomes of patients diagnosed with endometrial cancer (EC) in Oman. EC is the sixth most common cancer in women worldwide and the fifth most common cancer in women in Oman. Survival outcomes of EC have not been reported previously from Oman. Methods: This retrospective study was carried out on consecutive patients treated at the Sultan Qaboos University Hospital, Muscat, Oman, between 2008 and 2020. Survival was estimated using the Kaplan and Meier method. Results: A total of 50 patients with EC were included. The median age was 61 years (range: 31-86 years), and 72% of the patients had type I histology. Most patients were diagnosed with stage IA and IB EC (49% and 20%, respectively), and the majority had grade 1 or 2 tumours (40% and 34%, respectively). Overall, the 5-year survival and 10-year survival rates were estimated to be 70% and 56%, respectively. Weight (>75 kg) and body mass index (>30 kg/m2) were significantly associated with better survival. Tumour histology (type I versus type II or carcinosarcoma), grade (1 versus 2 versus 3) and stage (IA or IB versus II-IV) were associated with better overall survival (P = 0.007, P <0.0001 and P <0.0003, respectively). Patients diagnosed with EC with co-morbidities, other than obesity, had inferior survival compared to those without co-morbidities. Conclusion: Median age at presentation, histological sub-type, clinical stage and outcomes are comparable to the published literature. Almost two-thirds of the patients were obese. These data could be used as a benchmark for outcomes of EC in the region.

Artificial Intelligence and the Gartner Cycle: Time to Introduce in Undergraduate Medical Education.

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An Unusual Presentation of Choriocarcinoma in a Postmenopausal Woman: A case report.

Choriocarcinoma (CC) is a malignant neoplasm of the trophoblastic tissue, with a potential to metastasise to distant organs. Limited case of gestational CC develops after a long latent period. We report a 52-year-old postmenopausal woman who developed metastatic choriocarcinoma presumably of gestational origin, 8 years after the last pregnancy and 2 years after the last menstrual period. The patient was brought to the emergency room of a tertiary care centre in Muscat, Oman, in 2022 and was diagnosed with CC metastatic to the brain, spleen, lung and the kidney. The ß-human chorionic gonadotrophin level was found to be raised (1,292,867 mIU/mL). The International Federation of Gynecologic Oncology risk score was calculated to be 14 (very high risk). The patient was initially treated with whole-brain radiotherapy and splenic artery embolisation because of a hemoperitoneum. Afterwards the patient received systemic treatment using the standard EMA/CO regimen till complete serological remission.

Successful Treatment of a Case of Crescentic Glomerulonephritis in a Patient with Primary Peritoneal Carcinoma: A case report.

Crescentic glomerulonephritis has been associated with several solid tumour malignancies. Only a few cases of nephropathy have been reported in association with tubo-ovarian/peritoneal malignancies. We report a 55-year-old female patient who presented to a tertiary care centre, Muscat, Oman, in 2022. She developed combined immune complex-mediated glomerulonephritis and pauci-immune necrotising crescentic vasculitis simultaneously with the diagnosis of tubo-ovarian/peritoneal cancer. The baseline estimated glomerular filtration rate (eGFR) was 13 mL/min. The patient received two doses of rituximab and three doses of pulse corticosteroids, leading to significant improvement in renal function and the disappearance of her proteinuria. The eGFR improved to >60mL/min; her proteinuria gradually resolved after 10 weeks of treatment. She was then given a combination chemotherapy treatment for tubo-ovarian/peritoneal cancer leading to a normalisation of her CA-125 after three months of therapy.

Direct and Moderating Effects of Work Environment and Structural Empowerment on Job Stress and Job Satisfaction Among Nurses in Oman.

Objectives: This study aimed to explore the relationships between nurses' work environment, job stress and job satisfaction, along with the moderating effects of work environment and empowerment on the relationship between job stress and job satisfaction. Methods: A descriptive correlational design was utilised for this study. The study encompassed a convenience sample of 1,796 hospital nurses from the 11 governorates in Oman. Moreover, a self-report questionnaire that included a set of instruments was used to collect the data. Results: Nurses who perceived higher levels of job stress reported lower levels of satisfaction and empowerment and perceived their work environment as less favourable and supportive. The findings only confirmed the direct effects of work environment and empowerment on satisfaction, whereas no support was found for indirect or moderating effects. Furthermore, the hierarchical regression model showed that 46.5% of the variation in the level of job satisfaction was explained by the study variables. Conclusion: The results of this study demonstrate the importance of implementing strategies that empower staff, provide a supportive and positive work environment and tackle job stress to enhance levels of job satisfaction.

Evolution of the Management of Brain Metastases: A Bibliometric Analysis.

A systematic review of the published literature was conducted to analyze the management evolution of brain metastases from different cancers. Using the keywords "brain metastasis", "brain metastases", "CNS metastasis", "CNS metastases", "phase III" AND/OR "Randomized Controlled Trial" (RCT), relevant articles were searched for on the SCOPUS database. A total of 1986 articles were retrieved, published over a 45-year period (1977-2022). Relevant articles were defined as clinical studies describing the treatment or prevention of brain metastases from any cancer. Articles on imaging, quality of life, cognitive impairment after treatment, or primary brain tumors were excluded. After a secondary analysis, reviewing the abstracts and/or full texts, 724 articles were found to be relevant. Publications significantly increased in the last 10 years. A total of 252 articles (34.8%) were published in 12 core journals, receiving 50% of the citations. The number of publications in Frontiers in Oncology, BMC Cancer, and Radiotherapy and Oncology have increased considerably over the last few years. There were 111 randomized controlled trials, 128 review articles, and 63 meta-analyses. Most randomized trials reported on brain metastases management from unselected tumors (49), lung cancer (47), or breast cancer (11). In the last 5 years (2017 to 2022), management of brain metastasis has moved on from WBRT, the use of chemotherapy, and radio-sensitization to three directions. First, Radiosurgery or Radiotherapy (SRS/SRT), or hippocampal-sparing WBRT is employed to reduce radiation toxicity. Second, it has moved to the use of novel agents, such as tyrosine kinase inhibitors (TKI) and immune checkpoint inhibitors (ICI) and third, to the use of molecularly directed therapy such as TKIs, in asymptomatic low volume metastasis, obviating the need for WBRT.

The Prevalence and Patterns of Toxicity With Immune Checkpoint Inhibitors in Solid Tumors: A Real-World Experience From a Tertiary Care Center in Oman.

Introduction Immune checkpoint inhibitors (ICIs) have revolutionized the management of multiple cancers over the last decade. They work by employing the immune system and exhibiting activity over T cells resulting in immune upregulation. Despite their widespread use, they produce side effects that can limit their use. The immune-related adverse events (irAEs) can be sometimes significant. The irAEs caused by ICIs may occur at any time during the treatment and can vary in grade (G). We sought to study the prevalence and toxicity patterns of ICIs in Oman. Methods One hundred forty-one adult patients (≥18 years) who received at least one dose of nivolumab, pembrolizumab, atezolizumab, or durvalumab between 2016 and 2022 were included. The data were analyzed retrospectively using univariable and multiple-variable logistic regressions. The Wilcoxon rank-sum test and Cochran-Armitage trend test were also used to summarize the continuous and ordinal data. Results Out of the 141 patients, 80 patients (56.7%) received pembrolizumab, and 48 (34%) received nivolumab. Common irAEs included endocrine abnormalities, pneumonitis, and colitis. Thirty patients (21.3%) experienced varying irAE grade toxicity. Out of the 30, 23 patients (82%) developed grade 2 and 3 irAEs. Discussion Predictive analysis showed that male sex and lower hemoglobin (Hb) and bilirubin levels were all significant predictors (p < 0.05) when associated with irAE occurrence. The prevalence of irAEs was similar compared to other reports, literature reviews, or meta-analyses. Female sex has been mentioned previously also to be a predictive factor for endocrine-related toxicities.

Factors associated with millennial nurses' intention to pursue formal leadership roles: a cross-sectional study.

PURPOSE: This study aims to examine the level of intention to pursue formal nursing leadership roles among millennial nurses and to identify the different factors that may play a role in their intentions to pursue such roles. DESIGN/METHODOLOGY/APPROACH: This study used a multi-center, cross-sectional research design. Registered nurses born between 1980 and 2000 (n = 1,377) who worked in 23 acute care hospitals in Oman were included in this study. Data were analyzed using descriptive statistics and multiple linear regression. Data were collected between July 2019 and January 2020. FINDINGS: Nearly 70% of millennial nurses researched their intention for career advancement to assume nursing leadership responsibility. Factors associated with nurses' intention to pursue formal nursing leadership roles were the type of nursing degree held (having a bachelor of science in nursing degree), type of hospital facility affiliation (teaching hospital), previous leadership experience, structural empowerment (access to support, opportunity and resources), work satisfaction and job burnout. ORIGINALITY/VALUE: Millennial nurses, who represent the largest segment of the nursing workforce, have begun assuming nursing management and leadership roles; however, little is known about the factors affecting their intentions to pursue these roles. The findings of this study revealed different factors (both modifiable and nonmodifiable) influencing millennial nurses' intentions to pursue formal leadership roles.

Undergraduate research in medical schools in Pakistan: Relevance, Needs, and Importance.

Recent trends in medical education demand practicing physicians to be competent in playing multiple roles. Life-long learning skills underpinned by research & scholarly activity will enable them to play these roles adequately. Therefore, the introduction of structured training in research during early undergraduate years is pivotal. This would enable trainee physicians to develop essential skills; the institutions will grow in terms of visibility & ranking; the trainers and supervisors will be satisfied in terms of research productivity and, most importantly the patients will benefit in terms of improved clinical outcomes.

A Step towards Personalised Cancer Treatment in Lower Middle-income Countries (LMICS): Molecular Tumour Boards.

Tumour boards are meetings where physicians from various disciplines treating cancer patients meet to recommend evidence-based or the best possible treatment plan. These meetings have evolved with time and now, in every part of the world; site-specific multi-disciplinary tumour boards are established. These meetings are considered pivotal for improving patient outcomes. The advances in molecular and genetic knowledge and technique and their integration in treatment options have paved the way for multiple therapeutic options. However, the adoption of personalised treatment choices is associated with a huge financial burden, especially in low and middle-income countries (LMICs). A molecular tumour board can help to identify and suggest the most appropriate plan of management. Key Words: Molecular, Genetics, Personalised, Challenges.

The influence of nurse managers' authentic leadership style and work environment characteristics on job burnout among emergency nurses.

BACKGROUND: Emergency nurses experience excessive workloads and high job burnout. Limited evidence exists exploring the role of authentic leadership and nurse work environment on job burnout among emergency nurses. OBJECTIVE: To assess the influence of nurse managers' authentic leadership and nurse work environment on job burnout among emergency nurses. METHODS: A cross-sectional study was conducted among 160 emergency nurses working in six hospitals in the Sultanate of Oman. The Maslach Burnout Inventory, Authentic Leadership Questionnaire, and the Practice Environment Scale of the Nursing Work Index were used to assess study variables. RESULTS: Of the 233 distributed surveys, 160 emergency nurses responded resulting in a response rate of 69%. More than two thirds of emergency nurses (72.1%) reported high levels of burnout. Authentic leadership and a favorable work environment were significantly associated with lower job burnout. Nurse managers' transparency (ß = - 0.481, p = 0.031), ethical/moral conduct (ß = - .408, p = 0.043), managerial ability and support (ß = - 0.497, p = 0.018), and adequate staffing and resources (ß = -.068, p = 0.028) were all associated with lower job burnout. CONCLUSIONS: Results suggest the importance of providing effective leadership, adequate support to staff, maintaining optimum staffing and resources, and developing nurse managers' authentic leadership to reduce nurses' job burnout.

Determinants of Physicians' Job Satisfaction: A national multi-centre study from the Sultanate of Oman.

Objectives: This study aimed to examine and assess job satisfaction of physicians across several factors, such as quality of care, ease of practice, relationship with leadership and inter-professional collaboration. Methods: The data for this descriptive cross-sectional study were collected between July 2019 and January 2020. Participants provided demographic information and completed surveys related to physician job satisfaction and inter-professional collaboration. Multiple linear regressions were used to determine the relationship between overall job satisfaction and demographic features and inter-professional collaboration. Results: Out of the 396 physicians contacted, 354 responded (response rate: 89.4%). Results showed that out of the 354 physicians, 4.3% were not satisfied with their jobs, 36.5% expressed a moderate level of satisfaction and 59.2% were highly satisfied. There was no difference in the mean job satisfaction score among different groups of study participants, except for gender and the working grade (P <0.05). The overall job satisfaction rates were higher for the quality of care (mean = 3.93 ± 0.61) and ease of practice (mean = 3.89 ± 0.55) and lower for relationship with leadership (mean = 3.67 ± 0.86). Having a clinical postgraduate degree together with a PhD, a senior level of responsibility and good inter-professional relationship were associated with higher job satisfaction rates (P = 0.003 and 0.007, respectively). Conclusion: Overall, the job satisfaction rate was high. There was no difference among different groups of study participants, except for the working grade. Having a clinical postgraduate degree, a senior level of responsibility and good inter-professional relationship were associated with higher job satisfaction rates. The overall job satisfaction rates were higher for the quality of care and for ease of practice and lower for relationship with the leadership. Relationship with leadership is a modifiable factor and efforts at enhancing the physician-leadership relationship may lead to even higher satisfaction rates.

Predictors of Hypersensitivity Reactions to Platinum-Based Chemotherapy in a Tertiary Care Hospital in Oman: A case control study.

Objectives: This study aimed to estimate the prevalence and evaluate risk factors of hypersensitivity reactions (HSRs) to platinum-based compounds (PBCs) in cancer patients. PBCs play an important role in cancer therapy. However, one of the drawbacks of PBCs is the occasional occurrence of HSRs, which can lead to serious consequences. Methods: This retrospective case control study was conducted from January 2013 to December 2020 at Sultan Qaboos University Hospital, Muscat, Oman and included patients who received any PBC for the management of non-haematological cancers. Data regarding demographic characteristics and diseases and treatment details were collected from the hospital's electronic database. The data were quantitatively described and Student's t-test and Wilcoxon Mann-Whitney tests were used to detect significant differences. Results: A total of 38 cases and 148 matched controls were studied. The prevalence of HSRs to PBCs in the cohort of this study was 4.7% (95% confidence interval: 3.33-6.37%), higher with carboplatin compared with cisplatin and oxaliplatin. The female gender (P = 0.032), concomitant taxanes (P = 0.002) and concurrent radiation (P <0.001) were significant predictors of HSRs to PBCs. The majority of the reactions were of mild to moderate severity, and the rechallenge rate after HSR development was 13%. Conclusion: HSRs to PBCs impact therapy decisions and understanding the risk factors is important to improve treatment outcomes in cancer patients.

Epigenetic status of FBXW7 gene and its role in Ovarian cancer pathogenesis.

BACKGROUND: Chromatin immunoprecipitation (ChIP) analysis revealed that the FBXW7 gene and the long non-coding RNA (LINC01588) are potential candidates in epithelial ovarian cancer (EOC) pathogenesis. However, their exact role in EOC is not yet known. Thus, the present study sheds light on the impact of the mutations/ methylation status of the FBXW7 gene. MATERIALS AND METHODS: We used public databases to assess the correlation between mutations/ methylation status and the FBXW7 expression. Furthermore, we performed Pearson's correlation analysis between the FBXW7 gene and LINC01588. We performed gene panel exome sequencing and Methylation-specific PCR (MSP) in HOSE 6-3, MCAS, OVSAHO, and eight EOC patients' samples to validate the bioinformatics results. RESULTS: The FBXW7 gene was less expressed in EOC, particularly in stages III and IV, compared to healthy tissues. Furthermore, bioinformatics analysis, gene panel exome sequencing, and MSP revealed that the FBXW7 gene is neither mutated nor methylated in EOC cell lines and tissues, suggesting alternative mechanisms for FBXW7 gene regulation. Interestingly, Pearson's correlation analysis showed an inverse, significant correlation between the FBXW7 gene and LINC01588  expression, suggesting a potential regulatory role of LINC01588. CONCLUSION: Neither mutations nor methylation is the causative mechanism for the FBXW7 downregulation in EOC, suggesting alternative means involving the lncRNA LINC01588.

Durable Response to Pazopanib in a Patient with Fumarate Hydratase-Mutant Tubulocystic Renal Cell Carcinoma.

Tubulocystic carcinoma of the kidney (TC-RCC) is a rare renal tumor and has been recently included as a distinct entity in WHO classification of renal neoplasms. We report the case of a patient with metastatic tubulocystic RCC whose disease progressed through standard of care treatment for nonclear RCC. However, genetic analysis revealed a germline pathogenic variant of fumarate hydratase (FH) gene, and the patient had a sustained and durable response to pazopanib.

Identification and validation of a novel long non-coding RNA (LINC01465) in ovarian cancer.

Epithelial Ovarian Cancer (EOC) is a heterogeneous disease usually diagnosed at advanced stages. Therefore, early detection is crucial for better survival. Despite the advances in ovarian research, mechanisms underlying EOC carcinogenesis are not elucidated. We performed chromatin immunoprecipitation sequencing to identify genes regulated by E2F5, a transcription factor involved in ovarian carcinogenesis. Results revealed several putative candidate genes (115 protein-coding genes, 20 lncRNAs, 6 pseudogenes, and 4 miRNAs). A literature review and bioinformatics analysis of these genes revealed a novel lncRNA candidate (LINC01465) in EOC. We validated LINC01465 by quantifying its expression in EOC cell lines and selected OVSAHO and SKOV3 as a model with high LINC01465 levels. We silenced LINC01465 and performed proliferation, wound healing, invasion, and drug resistance assays. Knocking-down LINC01465 resulted in reduced migration, suggesting potential involvement in EOC. Furthermore, to identify the significance of LINC01465 in chemoresistance, we assessed the LINC01465 levels in A2780 S cells treated with malformin, which revealed higher LINC01465 expression as compared to untreated A2780S cells implying the involvement of LINC01465 in cell death. Thus, this study unraveled the repertoire of E2F5 regulated candidate genes and suggested a putative role of LINC01465 in malformin-induced cell death in EOC.

Addition of Gallic Acid Overcomes Resistance to Cisplatin in Ovarian Cancer Cell Lines.

OBJECTIVE: Ovarian cancer is one of the leading causes of cancer-related mortality in women, and is often associated with drug resistance. Therefore, finding effective drugs, including naturally derived compounds, is urgently needed. Herein, we aimed to test the anti-cancer potential of gallic acid monohydrate (GA) and its congeners on cisplatin-sensitive (A2780S), and resistant (A2780CP) ovarian cancer and normal ovarian (HOSE6-3) cell lines. METHODS: Cytotoxicity was assessed by AlamarBlue and CCK08 assays by exposing cells to different concentrations of cisplatin (0-21µg/mL), GA and its congeners (0-100µg/mL), and a combination of GA and cisplatin. Apoptosis was estimated by Hoechst stain and monitoring the relative RNA expression of the apoptotic effector caspase-3 using qRT-PCR. RESULTS: GA decreased cell viability in a concentration-dependent manner in all cell lines, with an IC50 of 19.39µg/mL (A2780S), 35.59 µg/mL (A2780CP), and 49.32µg/mL (HOSE6-3). GA displayed higher cytotoxicity than its congeners. An apoptotic rate estimation of approximately 20% and 30% was obtained in A2780S and A2780CP. While the cytotoxicity observed with cisplatin and GA was comparable, combining the two enhanced the cytotoxicity significantly, especially in the A2780CP cell line (p<0.05). CONCLUSION: These data suggest that GA may help overcome the resistance. Hence, the cytotoxic effects of GA, especially on chemo-resistant ovarian cancer cells merit further investigation.
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