Mesenchymal neoplasms with NTRK and other kinase gene alterations

Kinase alterations are increasingly recognised as oncogenic drivers in mesenchymal tumours. Infantile fibrosarcoma and the related renal tumour, congenital mesoblastic nephroma, were among the first solid tumours shown to harbour recurrent tyrosine kinase fusions, with the canonical ETV6::NTRK3 fusion identified more than 20 years ago. Although targeted testing has long been used in diagnosis, the advent of more robust sequencing techniques has driven the discovery of kinase alterations in an array of mesenchymal tumours. As our ability to identify these genetic alterations has improved, as has our recognition and understanding of the tumours that harbour these alterations. Specifically, this study will focus upon mesenchymal tumours harbouring NTRK or other kinase alterations, including tumours with an infantile fibrosarcoma-like appearance, spindle cell tumours resembling lipofibromatosis or peripheral nerve sheath tumours and those occurring in adults with a fibrosarcoma-like appearance. As publications describing the histology of these tumours increase so, too, do the variety kinase alterations reported, now including NTRK1/2/3, RET, MET, RAF1, BRAF, ALK, EGFR and ABL1 fusions or alterations. To date, these tumours appear locally aggressive and rarely metastatic, without a clear link between traditional features used in histological grading (e.g. mitotic activity, necrosis) and outcome. However, most of these tumours are amenable to new targeted therapies, making their recognition of both diagnostic and therapeutic import. The goal of this study is to review the clinicopathological features of tumours with NTRK and other tyrosine kinase alterations, discuss the most common differential diagnoses and provide recommendations for molecular confirmation with associated treatment implications.     

„Gesagt ist nicht gehört,gehört ist nicht verstanden“ – Therapiezieleinschätzung aus Sicht von PatientInnen in der Radiologie

Die Onkologie - Trotz Aufklärungsgespräch durch den behandelnden Arzt wird häufig eine große Diskrepanz hinsichtlich der Therapiezieleinschätzung zwischen Arzt- und...     

Emerging Viral Infections Causing Anterior Uveitis

Purpose: To review the systemic and ocular manifestations of specific emergent viral infectious diseases relevant to the ophthalmologist with particular emphasis on anterior uveitis

Methods: Review of literature.

Results: Arboviral diseases are among the most important emergent and resurgent human infections, occurring mostly in tropical and subtropical zones, but appearing in virtually all regions of the world as a result of climate change, travel, and globalization. Arboviral infections are transmitted to humans by the bite of hematophagous arthropods, mainly mosquitoes. Systemic disease may range from asymptomatic to life-threatening. A wide variety of ocular manifestations, including uveitis, has been reported in association with these emerging viral diseases. Numerous viruses other than arboviruses also have been recently recognized as a potential cause of uveitis.

Conclusions: Proper clinical diagnosis of any emerging infectious disease is based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. The diagnosis is usually confirmed by detection of virus-specific DNA or antivirus antibodies in serum.     

Short-term outcomes of patients with neovascular exudative AMD: the effect of COVID-19 pandemic

Graefe's Archive for Clinical and Experimental Ophthalmology - To estimate the impact of delayed care during the coronavirus disease 2019 (COVID-19) pandemic on the outcomes of patients with...     

Use of a Checklist During Observation of a Simulated Cardiac Arrest Scenario Does Not Improve Time to CPR and Defibrillation Over Observation Alone for Subsequent Scenarios

Theory: Immersive simulation is a common mode of education for medical students. Observation of clinical simulations prior to participation is believed to be beneficial, though this is often a passive process. Active observation may be more beneficial. Hypotheses: The hypothesis tested in this study was that the active use of a simple checklist during observation of an immersive simulation would result in better participant performance in a subsequent scenario compared with passive observation alone. Methods: Medical students were randomized to either passive or active (with checklist) observation of an immersive simulation involving cardiac arrest prior to participating in their own simulation. Performance measures included time to cardiopulmonary resuscitation (CPR) and time to defibrillation and were compared between first and second scenarios as well as between passive and active observers. Results: Seventy-nine simulations involving 232 students were conducted. Mean time to CPR was 18 seconds (SD = 11.6) for those using the checklist and 24 seconds (SD = 15.8) for those who observed passively (M difference = 6 seconds), t(35) = 1.46, p =.153. Time to defibrillation was 94 seconds (SD = 26.4) for those using the checklist and 92 seconds (SD = 23.8) for those who observed passively (M difference = –2 seconds), t(38) =.21, p =.837. Time to CPR was 24 seconds (SD = 15.8) for passive observers and 31 seconds (SD = 21.0; M difference = 7 seconds), t(35) = 1.13, p =.265, for their first scenario counterparts. Time to CPR was 18 seconds (SD = 11.6) for active observers and 36 seconds (SD = 26.2; M difference = 18 seconds), t(24) = 2.81, p =.010, for their first scenario counterparts. Time to defibrillation was 92 seconds (SD = 23.8) for passive observers and 125 seconds (SD = 32.2; M difference = 33 seconds), t(33) = 3.63, p =.001, for their first scenario counterparts. Time to defibrillation was 94 seconds (SD = 26.4) for the active observers and 132 seconds (SD = 52.9; M difference = 38 seconds), t(28) =.46, p =.008, for their first scenario counterparts. Conclusions: Observation alone leads to improved performance in the management of a simulated cardiac arrest. The active use of a simple skills-based checklist during observation did not appear to improve performance over passive observation alone.     

COVID‐19 and maternal and child food and nutrition insecurity: a complex syndemic

Globally, the COVID‐19 pandemic has already led to major increases in unemployment and is expected to lead to unprecedented increases in poverty and food and nutrition insecurity, as well as poor health outcomes. Families where young children, youth, pregnant and lactating women live need to be protected against the ongoing protracted pandemic and the aftershocks that are very likely to follow for years to come. The future wellbeing of the vast majority of the world now depends on reconfiguring the current ineffective food, nutrition, health, and social protection systems to ensure food and nutrition security for all. Because food, nutrition, health, and socio‐economic outcomes are intimately inter‐linked, it is essential that we find out how to effectively address the need to reconfigure and to provide better intersecoral coordination among global and local food, health care, and social protection systems taking equity and sutainability principles into account. Implementation science research informed by complex adaptive sytems frameworks will be needed to fill in the major knowledge gaps. Not doing so will not only put the development of individuals at further risk, but also negatively impact on the development potential of entire nations and ultimately our planet.     

Oncocytic Schneiderian papilloma in a young adult: a rare diagnosis

The oncocytic Schneiderian papilloma (OSP) is a rare neoplasm of the nose and paranasal sinuses. The majority of the approximately twenty patients reported in the literature with this papilloma have been over the age of fifty at the time of diagnosis. The 33-year-old woman reported here is the youngest patient with this lesion to date. The OSP should be considered in the work-up of all unilateral nasal polypoid lesions. This lesion's propensity for recurrence and its documented association with synchronous malignant disease warrant surgical excision by en bloc resection of the lateral nasal wall, with corresponding careful microscopic evaluation of all excised tissue.     

Association of Hypoalbuminemia on the First Postoperative Day and Complications Following Esophagectomy

Objective Changes in serum albumin may reflect systemic immunoinflammation and hypermetabolism in response to insults such as trauma and sepsis. Esophagectomy is associated with a major metabolic stress, and the aim of this study was to determine if the absolute albumin level on the first postoperative day was of value in predicting in-hospital complications. Methods A retrospective study of 200 patients undergoing esophagectomy for malignant disease at St. James Hospital between 1999 and 2005 was performed. Patients who had pre and postoperative (days 1, 3, and 7) serum albumin levels measured were included in the study. Patients were subdivided into three postoperative albumin categories <20 g/l, 20–25 g/l, >25 g/l. Logistic regression analysis was performed to calculate the odds of morbidity and mortality according to the day 1 albumin level. Results Patients with an albumin of less than 20 g/l on the first postoperative day were twice as likely to develop postoperative complications than those with an albumin of greater than 20 g/l (54 vs 28% respectively, p < 0.011). Correspondingly, these patients also had a significantly higher rate of Adult Respiratory Distress Syndrome (22 vs 5%, p < 0.001), respiratory failure (27 vs 8%, p < 0.01) and in-hospital mortality (27 vs 6% (p < 0.001). On multivariate logistic regression analysis, day 1 albumin level was independently related to postoperative complications (odds ratios, 0.89: 95%; confidence intervals, 0.83–0.96; p < 0.005). In addition, albumin <20 g/l on the first postoperative day was associated with the need for further surgery and a return to ICU. Conclusion Serum albumin concentration on the first postoperative day is a better predictor of surgical outcome than many other preoperative risk factors. It is a low cost test that may be used as a prognostic tool to detect the risk of adverse surgical outcomes.