Stage Migration for Upper Tract Urothelial Cell Carcinoma

IntroductionUpper tract urothelial carcinomas (UTUCs) account for 5% to 10% of urothelial cancers. The phenomenon of stage migration in tumors has been evident with increased use and higher resolution of cross-sectional imaging. Using the National Cancer Database, we analyzed trends in stage at presentation and overall survival for UTUCs.Patients and MethodsWe analyzed UTUCs in the renal pelvis or ureter from 2004 to 2016. Pathologic tumor stage data were available for 71.3% of patients and clinical tumor staging were available for 28.7% of patients. Five-year overall survival was analyzed comparing patients between 2004-2007 and 2008-2011. Tumor stage was categorized as early (0-1), intermediate (2-3), or late (4) for survival analyses. Linear regression and Kaplan-Meier analyses were utilized.ResultsA total of 37,210 renal pelvic and 23,200 ureteral origin UTUC cases were evaluated. Stage migration toward stage 0 and stage 4 was observed. There was a significant increase in proportion of stage 0 Ta/Tis (22.8%-33.4%, R² = 0.86, P < .001) and stage 4 (22.3%-26.4%, R² = 0.57, P = .003) disease for renal pelvic tumors, and a significant decrease in stages 1, 2, and 3. For UTUCs of ureteral origin, diagnosis at stage 0 Ta/Tis (37.6%-44.7%, R² = 0.53, P = .005) and stage 4 (10.9%-14.6%, R² = 0.63, P = .001) increased significantly, with significant reductions in stage 1 and 2. There was no difference in 5-year overall survival for ureteral or renal pelvic UTUCs for patients during 2004-2007 versus 2008-2011 when stratified by early, intermediate, or late stage.ConclusionThere is a stage migration toward stage 0 and stage 4 disease for UTUC. Five-year survival data from 2004 to 2011 remained stable across early, intermediate, and late stage groups.     

Medicinal Plants Used for Treatment of Diabetes by the Marakh Sect of the Garo Tribe Living in Mymensingh District,Bangladesh

Diabetes mellitus is an endocrinological disorder arising from insulin deficiency or due to ineffectiveness of the insulin produced by the body. This results in high blood glucose and with time, to neurological, cardiovascular, retinal and renal complications. It is a debilitating disease and affects the population of every country of the world. Around 200 million people of the world suffer from this disease and this figure is projected to rise to 300 million in the coming years. The disease cannot be cured with allopathic medicine as the drugs used do not restore normal glucose homeostasis and moreover have side-effects. On the other hand, traditional medicinal practitioners of various countries claim to cure diabetes or at least alleviate the major symptoms and progression of this disease through administration of medicinal plants. The Garos are an indigenous community of Bangladesh, who still follow their traditional medicinal practices. Their traditional medicinal formulations contain a number of plants, which they claim to be active antidiabetic agents. Since observation of indigenous practices have led to discovery of many modern drugs, it was the objective of the present study to conduct a survey among the Marakh sect of the Garos residing in Mymensingh district of Bangladesh to find out the medicinal plants that they use for treatment of diabetes. It was found that the tribal practitioners of the Marakh sect of the Garos use twelve medicinal plants for treatment of diabetes. These plants were Lannea coromandelica, Alstonia scholaris, Catharanthus roseus, Enhydra fluctuans, Terminalia chebula, Coccinia grandis, Momordica charantia, Cuscuta reflexa, Phyllanthus emblica, Syzygium aqueum, Drynaria quercifolia, and Clerodendrum viscosum. A review of the scientific literature demonstrated that almost all the plants used by the Garo tribal practitioners have reported antidiabetic and/or antioxidant properties and have enormous potential for possible development of new and efficacious antidiabetic drugs.     

Reasons for migration among medical students from Karachi

CONTEXT: The subject of economic migration among health care professionals has received intense attention. However, the aetiology of this migration has not been rigorously evaluated in Pakistan. Such knowledge can potentially influence health care and academic policies. Our current study proposes to quantify the relative contributions of various personal, professional and economic variables among final-year medical students in Karachi. METHODS: A self-administered structured questionnaire using a 10-point scale was developed and piloted among Karachi medical students. Additional open-ended questions were included to allow us to capture information not otherwise covered in the questionnaire. SPSS software was used for data entry and analysis. RESULTS: Over 95% of Aga Khan University (AKU) and over 65% of Baqai University (BU) final-year medical students intend to proceed abroad for their postgraduate training. The 2 most important factors behind this intent as pointed out by the students are poor salary structure (AKU mean score 8.94 +/- 1.73, BU mean score 7.14 +/- 2.6) and poor quality of training in the home country (AKU mean score 9.20 +/- 1.20, BU mean score 8.68 +/- 2.03). Other interesting factors captured through the open-ended questions were the poor work environment and lack of rigor in teaching of residents in domestic university hospitals. Over 50% of final-year medical students cited these issues as major reasons behind their decision to migrate.     

From UVs to metastases: modeling melanoma initiation and progression in the mouse

Cutaneous malignant melanoma is highly invasive and capable of metastasizing to distant sites where it is typically resistant to available therapy. While striving to prevent or eradicate melanoma, researchers have two significant advantages not shared by those working on many other cancers. The main environmental etiological agent, UV radiation, is known and melanocytic lesions are excisable for molecular analysis from most stages. Yet knowledge about how UV initiates melanoma has been insufficient to achieve prevention, and the understanding of metastatic mechanisms has been inadequate to reduce mortality. Here, we review the value of melanoma mouse models, focusing on these critical early and late stages.     

Toward a clinical protocol for assessing rod, cone, and melanopsin contributions to the human pupil response

PURPOSE. To better understand the relative contributions of rod, cone, and melanopsin to the human pupillary light reflex (PLR) and to determine the optimal conditions for assessing the health of the rod, cone, and melanopsin pathways with a relatively brief clinical protocol. METHODS. PLR was measured with an eye tracker, and stimuli were controlled with a Ganzfeld system. In experiment 1, 2.5 log cd/m(2) red (640 ± 10 nm) and blue (467 ± 17 nm) stimuli of various durations were presented after dark adaptation. In experiments 2 and 3, 1-second red and blue stimuli were presented at different intensity levels in the dark (experiment 2) or on a 0.78 log cd/m(2) blue background (experiment 3). Based on the results of experiments 1 to 3, a clinical protocol was designed and tested on healthy control subjects and patients with retinitis pigmentosa and Leber's congenital amaurosis. RESULTS. The duration for producing the optimal melanopsin-driven sustained pupil response after termination of an intense blue stimulus was 1 second. PLR rod- and melanopsin-driven components are best studied with low- and high-intensity flashes, respectively, presented in the dark (experiment 2). A blue background suppressed rod and melanopsin responses, making it easy to assess the cone contribution with a red flash (experiment 3). With the clinical protocol, robust melanopsin responses could be seen in patients with few or no contributions from the rods and cones. CONCLUSIONS. It is possible to assess the rod, cone, and melanopsin contributions to the PLR with blue flashes at two or three intensity levels in the dark and one red flash on a blue background.     

The potential application of zoledronic acid as anticancer therapy in patients with non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) is frequently characterized by metastases to bone. Bisphosphonates have demonstrated efficacy in reducing the risk of skeletal-related events in cancer patients with bone metastases, including those with NSCLC. Zoledronic acid (ZA) is one of the most potent bisphosphonates and is approved for the first-line treatment of patients with multiple myeloma and bone metastases from solid tumors. Recent preclinical and clinical data suggest that ZA may also have direct and indirect anticancer effects. Several preclinical studies have provided insight into the potential mechanisms responsible for the anticancer activity of ZA, including inhibiting farnesyl pyrophosphate or geranylgeranyl pyrophosphate and activation of immune-mediated anticancer response by γδ T cells. In patients with NSCLC, ZA has been shown to reduce vascular endothelial growth factor levels with a direct correlation to clinical response. Clinical studies in this setting have shown that ZA may also provide a survival benefit and prolong time to progression. Ongoing studies are evaluating the efficacy of ZA for anticancer activity and prevention of bone metastases. Bisphosphonates, particularly ZA, are generally well tolerated and may likely offer an adjunct therapeutic option for patients with NSCLC.     

How we developed a bioethics theme in an undergraduate medical curriculum

The 5-year undergraduate medical curriculum at Aga Khan University integrates basic sciences with clinical and community health sciences. Multimodal strategies of teaching and learning, with an emphasis on problem-based learning, are utilized to equip students with knowledge, skills, behaviours, attitudes and values necessary for a high-calibre medical graduate. Bioethics teaching was introduced in the medical curriculum in 1988 and has since undergone several changes. In 2009, a multidisciplinary voluntary group began review of undergraduate bioethics teaching and invested over 350 man-hours in curricular revision. This involved formulating terminal objectives, delineating specific objectives and identifying instructional methodologies and assessment strategies appropriate for the contents of each objective. Innovative strategies were specially devised to work within the time constraints of the existing medical curriculum and importantly, to increase student interest and engagement. The new bioethics curriculum is designed to be comprehensive and robust, and strives to develop graduates who, in addition to being technically skilled and competent, are well-versed in the history and philosophy of ethics and bioethics and are ethical in their thinking and practice, especially in the context of a developing country like Pakistan where health indicators are among the worst in the region, and clinical practices are not effectively regulated to ensure quality of care.