Clinico-pathological factors associated with radioiodine refractory differentiated thyroid carcinoma status.

PURPOSE: Risk factors for developing radioiodine refractory thyroid cancer (RAIR-TC) have rarely been analyzed. The purpose of the present study was to find clinical and pathological features associated with the occurrence of RAIR-disease in differentiated thyroid cancers (DTC) and to establish an effective predictive risk score. METHODS: All cases of RAIR-DTC treated in our center from 1990 to 2020 were retrospectively reviewed. Each case was matched randomly with at least four RAI-avid DTC control patients based on histological and clinical criteria. Conditional logistic regression was used to examine the association between RAIR-disease and variables with univariate and multivariate analyses. A risk score was then developed from the multivariate conditional logistic regression model to predict the risk of refractory disease occurrence. The optimal cut-off value for predicting the occurrence of RAIR-TC was assessed by receiver operating characteristic (ROC) curves and Youden's statistic. RESULTS: We analyzed 159 RAIR-TC cases for a total of 759 controls and found 7 independent risk factors for predicting RAIR-TC occurrence: age at diagnosis ≥ 55, vascular invasion, synchronous cervical, pulmonary and bone metastases at initial work-up, cervical and pulmonary recurrence during follow-up. The predictive score of RAIR-disease showed a high discrimination power with a cut-off value of 8.9 out of 10 providing 86% sensitivity and 92% specificity with an area under the curve (AUC) of 0.95. CONCLUSION: Predicting the occurrence of RAIR-disease in DTC patients may allow clinicians to focus on systemic redifferentiating strategies and/or local treatments for metastatic lesions rather than pursuing with ineffective RAI-therapies.

Impact of age on survival in radioiodine refractory differentiated thyroid cancer patients.

OBJECTIVE: The objectives of our study were to analyze the influence of age on the survival of patients with RAIR-DTC and to determine their prognostic factors according to age. METHODS: This single-center, retrospective study enrolled 155 patients diagnosed with RAIR-DTC. The primary end point was overall survival (OS) according to different cutoff (45, 55, 65, 75 years). Secondary endpoints were progression free survival (PFS) and prognostic factors in patients under and over 65 years. RESULTS: Median OS after RAIR diagnosis was 8.2 years (95% IC: 5.3-9.6). There was no difference according to age with a 65 (P = 0.47) and 55 years old cutoff (P = 0.28). Median OS improved significantly before 45 years old (P = 0.0043). After 75 years old, median OS significantly decreased (P = 0.0008). Median PFS was 2.1 years (95% CI: 0.8-3) in patients < 65 years old, and 1 year in patients ≥ 65 years old (95% CI: 0.8-1.55) with no statistical difference (P = 0.22). There was no impact of age on PFS with any cutoff. In both groups, progressive disease despite 131I treatment reduced OS. In patients < 65 years old, an interval of less than 3 years between the initial diagnosis and the diagnosis of RAIR metastatic disease was predictive of poor survival. In patients > 65 years old, the presence of a mediastinum metastasis was a significant factor for mortality (HR: 4.55, 95% CI: 2.27-9.09). CONCLUSION: In RAIR-DTC patients, a cut-off age of 65 years old was not a significant predictive factor of survival. Forty-five and 75-years-old cutoff were predictive for OS but not PFS.

Clinical pharmacology of anti-angiogenic drugs in oncology.

Abnormal vasculature proliferation is one of the so-called hallmarks of cancer. Angiogenesis inhibitor therapies are one of the major breakthroughs in cancer treatment in the last two decades. Two types of anti-angiogenics have been approved: monoclonal antibodies and derivatives, which are injected and target the extracellular part of a receptor, and protein kinase inhibitors, which are orally taken small molecules targeting the intra-cellular Adenosine Triphosphate -pocket of different kinases. They have become an important part of some tumors' treatment, both in monotherapy or in combination. In this review, we discuss the key pharmacological concepts and the major pitfalls of anti-angiogenic prescriptions. We also review the pharmacokinetic and pharmacodynamics profile of all approved anti-angiogenic protein kinase inhibitors and the potential role of surrogate markers and of therapeutic drug monitoring.

Understanding student early departure from a Master of Public Health programme in South Africa

Background. Student departure from university without completing a qualification is a major concern in higher education. Higher Education South Africa reported that in undergraduate studies, 35% of students depart after the first year and only 15% of students who enrol complete their degree within the minimum permissible time. At postgraduate level, the departure from Masters programmes in South Africa (SA) ranged from 30% to 67% in 2010. Early departure refers to students who leave an academic programme within the first semester of commencing their studies. At one SA university, there were a total of 109 first-time Master of Public Health (MPH) student registrations in 2013 and 2014. By the end of the first semester in the respective years, a total of 27 students actively deregistered from the programme and 11 students did not sit the first-semester examinations, representing an aggregate 35% rate of early departure. The factors associated with early departure at the University of KwaZulu-Natal are not well understood.Objective. To understand factors associated with early departure in the MPH programme at the University of KwaZulu-Natal.Method. A mixed-methods design was implemented. Students who departed within the first semester of commencing the MPH programme in 2013/2014 were followed up. Data were collected using self-administered questionnaires and in-depth interviews.Results. Failure to balance work and academic obligations with poor time management, stress and academic demands related to the programme, and insufficient academic progress were found to be associated with student early departure from the MPH programme.Conclusion. Student early departure from the MPH programme was influenced by multifaceted factors. Senior students can mentor new students as early as possible in their programme. The orientation block should include development activities such as time management, stress management and effective study skills to assist mature students to cope with the demands of part-time postgraduate studies

Benefit of adjuvant trastuzumab-based chemotherapy in T1ab node-negative HER2-overexpressing breast carcinomas: a multicenter retrospective series.

BACKGROUND: Randomized clinical trials showed the benefit of adjuvant trastuzumab-based chemotherapy (ATBC) for node-positive and/or >1 cm HER2+ breast carcinomas. No efficacy data have been published on ATBC in large series of pT1abN0 HER2+ tumors. PATIENTS AND METHODS: This retrospective study evaluated 276 cases of pT1abN0 HER2+ breast tumors in eight French cancer centers. Factors associated with prognosis and ATBC prescription were analyzed. RESULTS: A total of 129 cases (47%) were treated with ATBC (ATBC+), 19 with chemotherapy alone, 5 with trastuzumab alone, and 123 (45%) with neither trastuzumab nor chemotherapy (ATBC-). ATBC use was associated with the date of diagnosis (before or after June 2005) and with poor prognostic features. At a median follow-up of 44 months, there were 13 recurrences in the ATBC- group and 2 in the ATBC+ group. ATBC was associated with a significant survival benefit (99% 40-month disease-free survival for ATBC+ versus 93% for ATBC- cases; P = 0.018). Lack of hormone receptors (HRs) and the presence of lymphovascular invasion (LVI) were significantly associated with a poor prognosis and a greater benefit of ATBC. CONCLUSIONS: ATBC was associated with a significantly reduced risk of recurrence in pT1abN0 HER2+ tumors, and was more beneficial in HR- and/or LVI+ tumors.

[Pain and bone metastases]. / Douleur et métastases osseuses.

Average 20% of the cancer patients will have bone metastasis most of time painful and with variable clinical expressions. Due to animal models, the bone metastasis pain is better known and it explains the different treatments mechanisms. After a suitable evaluation of the pain, several therapeutic approaches can be suggested. In addition to the classical analgesics, several medications are known to be efficient in few indications like neuropathic pain. Besides a local surgery, an external radiotherapy or an interventional radiology treatment can often be useful along with a medical treatment. When there is a bone progression, the anti-cancer treatment by chemotherapy, hormonotherapy or targeted therapies must always be reviewed, because if efficient it could have an analgesic action.

Seismogenic lavas and explosive eruption forecasting.

Volcanic dome-building episodes commonly exhibit acceleration in both effusive discharge rate and seismicity before explosive eruptions. This should enable the application of material failure forecasting methods to eruption forecasting. To date, such methods have been based exclusively on the seismicity of the country rock. It is clear, however, that the rheology and deformation rate of the lava ultimately dictate eruption style. The highly crystalline lavas involved in these eruptions are pseudoplastic fluids that exhibit a strong component of shear thinning as their deformation accelerates across the ductile to brittle transition. Thus, understanding the nature of the ductile-brittle transition in dome lavas may well hold the key to an accurate description of dome growth and stability. Here we present the results of rheological experiments with continuous microseismic monitoring, which reveal that dome lavas are seismogenic and that the character of the seismicity changes markedly across the ductile-brittle transition until complete brittle failure occurs at high strain rates. We conclude that magma seismicity, combined with failure forecasting methods, could potentially be applied successfully to dome-building eruptions for volcanic forecasting.

Case reports of on-site investigations of auger-related farm injuries.

Previous reports have indicated that injuries involving augers (screw conveyors) are a serious problem in agriculture, but to date on-site engineering inspections linking injuries to mechanical and procedural aspects have not been available. This article details four events involving injuries as the result of being entangled in auger flighting. In each report, the circumstances surrounding the injury event are outlined, and the machinery involved is evaluated in terms of its compliance with current safety standards. In three of the four instances, the machinery did not conform to current guarding standards or to safety sign standards. In these three cases, injuries were preventable with improved guarding according to ASAE Standards. In the other case, the machine complied with ASAE Standards, but the injury could have been prevented with improved guarding of the auger flighting.

Ultrasound screening for abdominal aortic aneurysms in patients with atherosclerotic peripheral vascular disease.

The rapidly rising incidence of abdominal aortic aneurysm (AAA) and the grave prognosis in cases of rupture call for early detection and operative intervention. However, there is as yet no consensus on which groups in the population should be selected for screening. Some Authors have suggested the screening of populations at risk by virtue of their age, sex and/or the presence of arterial hypertension, and report the incidence of AAA in these populations as 5.3%, 3.4% and 0.25%, respectively. In this study we screened a group of patients with atherosclerotic peripheral vascular disease. Within this group the incidence of aneurysms was found to be 5.9%, which is at least twice the estimated incidence in the general population. Three of the six patients discovered, successfully underwent surgery. We conclude that screening of this specific population group is considerably more cost-effective than universal screening.

Suppressor T cells in mycosis fungoides and so-called premycotic eruptions.

The proportions of suppressor T cells (TG) and helper T cells (TM) were determined in 5 patients with Mycosis fungoides (MF), 4 patients with parapsoriasis en plaques/poikiloderma atrophicans vasculare and 3 patients with generalized chronic dermatitis. All the MF patients showed increased proportions of suppressor T cells, whereas the others did not differ from age- and sex-matched healthy controls.