Background
Transplant recipients have an elevated risk of cancer because of immunosuppressive medications used to prevent organ rejection, but to the authors’ knowledge no study to date has ...comprehensively examined associations between transplantation status and mortality after a cancer diagnosis.
Methods
The authors assessed cases in the US general population (N=7,147,476) for 16 different cancer types as ascertained from 11 cancer registries. The presence of a solid organ transplant prior to diagnosis (N=11,416 cancer cases) was identified through linkage with the national transplantation registry (1987‐2014). Cox models were used to examine the association between transplantation status and cancer‐specific mortality, adjusting for demographic characteristics and cancer stage.
Results
For the majority of cancers, cancer‐specific mortality was higher in transplant recipients compared with other patients with cancer. The increase was particularly pronounced for melanoma (adjusted hazard ratio aHR, 2.59; 95% confidence interval 95% CI, 2.18‐3.00) and cancers of the breast (aHR, 1.88; 95% CI, 1.61‐2.19), bladder (aHR, 1.85; 95% CI, 1.58‐2.17), and colorectum (aHR, 1.77; 95% CI, 1.60‐1.96), but it also was increased for cancers of the oral cavity/pharynx, stomach, pancreas, kidney, and lung as well as diffuse large B‐cell lymphoma (aHR range, 1.21‐1.47). Associations remained significant after adjustment for first‐course cancer treatment and generally were stronger among patients with local‐stage cancers for whom potentially curative treatment was provided, including patients with melanoma (aHR, 3.82; 95% CI, 2.94‐4.97) and cancers of the colorectum (aHR, 2.77; 95% CI, 2.07‐3.70), breast (aHR, 2.08; 95% CI, 1.50‐2.88), and prostate (aHR, 1.60; 95% CI, 1.12‐2.29), despite the lack of an association for prostate cancer overall.
Conclusions
For multiple cancer types, transplant recipients with cancer appear to have an elevated risk of dying of their cancer, even after adjustment for stage and treatment, which may be due to impaired immunity.
The number of solid organ transplant recipients has increased within the last 10 years, with nearly 35,000 transplantations reported to have occurred in the United States in 2017. Although solid organ transplantation is life‐saving, recipients have an elevated risk of many types of cancer, and for multiple cancer types, transplant recipients with cancer appear to have an elevated risk of dying of their cancer, even after adjustment for stage of disease and treatment, which may be due to impaired immunity.
The intrinsic mechanisms that link extracellular signalling to the onset of neural differentiation are not well understood. In pluripotent mouse cells, BMP blocks entry into the neural lineage via ...transcriptional upregulation of inhibitor of differentiation (Id) factors. We have previously identified the major binding partner of Id proteins in pluripotent cells as the basic helix-loop-helix (bHLH) transcription factor (TF) E2A. Id1 can prevent E2A from forming heterodimers with bHLH TFs or from forming homodimers. Here, we show that overexpression of a forced E2A homodimer is sufficient to drive robust neural commitment in pluripotent cells, even under non-permissive conditions. Conversely, we find that E2A null cells display a defect in their neural differentiation capacity. E2A acts as an upstream activator of neural lineage genes, including
and
, and as a repressor of Nodal signalling. Our results suggest a crucial role for E2A in establishing neural lineage commitment in pluripotent cells.
CONTEXT Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Because most prior research has concerned kidney recipients, large studies ...that include recipients of differing organs can inform cancer etiology. OBJECTIVE To describe the overall pattern of cancer following solid organ transplantion. DESIGN, SETTING, AND PARTICIPANTS Cohort study using linked data on solid organ transplant recipients from the US Scientific Registry of Transplant Recipients (1987-2008) and 13 state and regional cancer registries. MAIN OUTCOME MEASURES Standardized incidence ratios (SIRs) and excess absolute risks (EARs) assessing relative and absolute cancer risk in transplant recipients compared with the general population. RESULTS The registry linkages yielded data on 175 732 solid organ transplants (58.4% for kidney, 21.6% for liver, 10.0% for heart, and 4.0% for lung). The overall cancer risk was elevated with 10 656 cases and an incidence of 1375 per 100 000 person-years (SIR, 2.10 95% CI, 2.06-2.14; EAR, 719.3 95% CI, 693.3-745.6 per 100 000 person-years). Risk was increased for 32 different malignancies, some related to known infections (eg, anal cancer, Kaposi sarcoma) and others unrelated (eg, melanoma, thyroid and lip cancers). The most common malignancies with elevated risk were non-Hodgkin lymphoma (n = 1504; incidence: 194.0 per 100 000 person-years; SIR, 7.54 95% CI, 7.17-7.93; EAR, 168.3 95% CI, 158.6-178.4 per 100 000 person-years) and cancers of the lung (n = 1344; incidence: 173.4 per 100 000 person-years; SIR, 1.97 95% CI, 1.86-2.08; EAR, 85.3 95% CI, 76.2-94.8 per 100 000 person-years), liver (n = 930; incidence: 120.0 per 100 000 person-years; SIR, 11.56 95% CI, 10.83-12.33; EAR, 109.6 95% CI, 102.0-117.6 per 100 000 person-years), and kidney (n = 752; incidence: 97.0 per 100 000 person-years; SIR, 4.65 95% CI, 4.32-4.99; EAR, 76.1 95% CI, 69.3-83.3 per 100 000 person-years). Lung cancer risk was most elevated in lung recipients (SIR, 6.13 95% CI, 5.18-7.21) but also increased among other recipients (kidney: SIR, 1.46 95% CI, 1.34-1.59; liver: SIR, 1.95 95% CI, 1.74-2.19; and heart: SIR, 2.67 95% CI, 2.40-2.95). Liver cancer risk was elevated only among liver recipients (SIR, 43.83 95% CI, 40.90-46.91), who manifested exceptional risk in the first 6 months (SIR, 508.97 95% CI, 474.16-545.66) and a 2-fold excess risk for 10 to 15 years thereafter (SIR, 2.22 95% CI, 1.57-3.04). Among kidney recipients, kidney cancer risk was elevated (SIR, 6.66 95% CI, 6.12-7.23) and bimodal in onset time. Kidney cancer risk also was increased in liver recipients (SIR, 1.80 95% CI, 1.40-2.29) and heart recipients (SIR, 2.90 95% CI, 2.32-3.59). CONCLUSION Compared with the general population, recipients of a kidney, liver, heart, or lung transplant have an increased risk for diverse infection-related and unrelated cancers.
This viewpoint examines the impact of COVID-19 travel bans and remote education on the global health education of students from high-income countries (HIC) and low- and middle-income countries (LMIC) ...and explores potential opportunities for strengthening global health education based upon more dispersed and equitable practices. Global health is unique in the opportunities it can offer to students during the pandemic if programs can manage and learn from the pandemic's many challenges. Global health educators can: shift to sustainable remote engagement and mobilize resources globally to facilitate this; collaborate with partners to support the efforts to deal with the current pandemic and to prepare for its next phases; partner in new ways with health care professional students and faculty from other countries; collaborate in research with partners in studies of pandemic related health disparities in any country; and document and examine the impact of the pandemic on health care workers and students in different global contexts. These strategies can help work around pandemic travel restrictions, overcome the limitations of existing inequitable models of engagement, and better position global health education and face future challenges while providing the needed support to LMIC partners to participate more equally.
Introduction: Integrated teaching helps the students to understand the concepts well and conceptualise the subject well. Clinical cases introduced in the first year are interesting and stimulative ...for the student but may overwhelm and confuse the student. Aim: To know the perception and acceptance of integrated teaching among the first year MBBS students which include multiple case scenarios. Materials and Methods: This educational research is a cross-sectional observational study involving first year medical students in Ramaiah Medical College, Bangalore. Study was conducted for a period of one year (August 2018 to June 2019). Horizontal integration of a system in the first year MBBS subjects were done. This was followed by an interactive session conducted by a Clinician basically comprising of multiple case scenarios on the particular system. The sessions focussed on integration of basic medical science subjects and their application in the case scenarios. Six organ-systems were similarly covered. The integrated sessions involved in-class discussions of the clinical cases and were designed, implemented and moderated by two faculties (clinicians and basic science faculty). Collected data were entered into MS Excel, and analysis was done using SPSS software. The students’ feedback regarding the perception of integrated teaching was collected on the Five point likerts scale using a validated questionnaire and analysed. Results: The number of students included in the study was 140. About 135 (96.4%) of the students felt that integrated teaching using multiple case scenarios motivates them to learn in a better way. About 133 (95%) of students felt that integrated teaching helps them to understand concepts well, stimulates the critical thinking. About 136 (97.14%) of students felt that integrated teaching helped them to understand the topic in a holistic way. Conclusion: The students felt that the integrated teaching using multiple case scenarios enhanced their perception and comprehension of the diseases and helped them to understand the relevance of application of pre-clinical knowledge in clinicalpractise.
Abstract Background: The term “brain tumor” refers to a diverse group of neoplasms that originate in intracranial tissues and the meninges and range in malignancy from benign to aggressive. The ...epidermal growth factor receptor (EGFR) is expressed at high levels in a variety of cancers, suggesting a role in cancer etiology. Phosphatase and tensin homolog (PTEN) deleted from chromosome 10 is one of the most essential tumor suppressor genes, and it is frequently altered in brain, breast, kidney, lung, and uterine malignancies. Many people with brain malignancies have PTEN gene abnormalities. Brain tumors have proved challenging to treat, largely owing to the biological characteristics of these cancers, which often conspire to limit progress. The present study aimed to analyze the expression of EGFR and PTEN in different types of brain tumor. Methods: Tumor samples were collected. Immunohistochemistry (IHC) analysis, Western blot, and RNA expression analysis were performed to check the receptor expression . Results: IHC analysis showed the expression of EGFR in patients with meningioma, CP angle tumor, and pituitary adenoma, but no expression of PTEN was observed. In glioma, the expression of both the receptors was observed. RNA expression of PTEN was similar to control, and significantly higher expression of EGFR was observed in patients with CP angle tumor, pituitary adenoma, and meningioma. Higher expression of PTEN and EGFR was observed in glioma samples. In the present study, we have also observed the expression of EGFR, p-AKT, and p-STAT 3 in the tumor tissue samples, but no expression of PTEN was observed in CP angle, meningioma, and pituitary adenoma. Expression of both PTEN and EGFR was observed in glioma samples. Conclusion: Thus, EGFR and PTEN involved in brain tumors can be considered targets for therapeutic purposes.
Triple Negative Breast Cancer (TNBC) is defined by a lack of expression of the steroid hormone receptors (oestrogen and progesterone), and the human epidermal growth factor receptor-2 (HER-2). It is ...characterized by distinct molecular, histological and clinical features. It is a high risk breast cancer that lacks the benefit of a specific therapy. Our study was aimed at pathologically illustrating triple-negative breast carcinoma and at evaluating the expression of the Epidermal Growth Factor Receptor (EGFR) ,cytokeratin 5/6 (CK 5/6) and Ki-67 among triple-negative breast cancer cases. Further, we aimed to probe whether triple-negative phenotype could be a surrogate marker for the basal phenotype and to correlate the expression of the basal markers (CK 5/6 and EGFR) with the clinico-pathological prognostic parameters.
The expression of EGFR, CK 5/6 and Ki-67 were studied by immunohistochemistry (IHC) in 50 triple-negative breast cancer cases.
A statistical analysis was implemented by using the SPSS version 20.0. The Chi-square test was conducted to assess the relationship between the immunohistochemical markers and other variables. The Fischer exact test was used when the expected cell counts were less than 5.
The women with triple-negative breast cancer were younger, with the adverse pathological characteristics of a high tumour grade, tumour necrosis, frequent nodal metastases and high proliferation. 37 (74%) of the 50 triple-negative breast carcinomas showed the expression of the basal markers (EGFR and /or CK 5/6). We observed a statistically significant association between the basal marker expression and the presence of tumour necrosis.
The triple-negative breast cancers in our population harbour adverse pathobiological features and a five marker immunohistochemical panel can be reliably used to define the basal-like cancers. The "Triple-negative" status cannot be used as a surrogate for the "basal marker expression".
Child abuse is a serious criminal act against children in our country and punishable according to protection of children from sexual offenses act 2012. No one agency has the ability to respond ...completely to the abuse. Hence a multidisciplinary team approach was developed in India. Aim is to narrate the collaborative effort among the multiple disciplines in a general hospital to deliver child protection services and explore the barriers to integrate psychiatric services.
Methodology: Members of the team were recruited from different disciplines and trained by experts. A mission statement, protocol to assess the victims and provide treatment was formulated as an algorithm. The barriers to psychiatric treatment among the stakeholders were analyzed using framework method of qualitative analysis. Results (After 20 months) the unit received 27 referrals in 20 months, 24 females, and 3 males. Age of the victims was between 8 months and 17 years. Two cases found to be physically abused. Penetrative sexual abuse was found in 23 cases, pregnant victims were 4. Most referrals were by police, trafficking found in 6 cases.
Discussion: It was possible to provide multidisciplinary care to the victims and families. Recurrent themes of barriers to psychiatric treatment were stigma, victim blaming; focus on termination of pregnancy, minimization of abuse in males by stakeholders. Conclusion is collaboration needs more effort to integrate psychiatric services but can minimize the reduplication of services.
Receptor rearrangement upon ligand binding (induced fit) is a major stumbling block in docking and virtual screening. Even though numerous studies have stressed the importance of including protein ...flexibility in ligand docking, currently available methods provide only a partial solution to the problem. Most of these methods, being computer intensive, are often impractical to use in actual drug discovery settings. We had earlier shown that ligand-induced receptor side-chain conformational changes could be modeled statistically using data on known receptor-ligand complexes. In this paper, we show that a similar approach can be used to model more complex changes like backbone flips and loop movements. We have used p38 MAPK as a test case and have shown that a few simple structural features of ligands are sufficient to predict the induced variation in receptor conformations. Rigorous validation, both by internal resampling methods and on an external test set, corroborates this finding and demonstrates the robustness of the models. We have also compared our results with those from an earlier molecular dynamics simulation study on DFG loop conformations of p38 MAPK, and found that the results matched in the two cases. Our statistical approach enables one to predict the final ligand-induced conformation of the active site of a protein, based on a few ligand properties, prior to docking the ligand. We can do this without having to trace the step-by-step process by which this state is arrived at (as in molecular dynamics simulations), thereby drastically reducing computational effort.
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