86 research outputs found
Low-dose liquorice ingestion resulting in severe hypokalaemic paraparesis, rhabdomyolysis and nephrogenic diabetes insipidus
No full textCHEK2 mutations and papillary thyroid cancer : correlation or coincidence?
No full textWe report the case of a breast cancer survivor, diagnosed with an underlying CHEK2 c.1100delC heterozygosity, who developed a papillary thyroid cancer 5 years later. A CHEK2 c.1100delC (likely) pathogenic variant is associated with an increased risk of breast, prostate and colorectal cancer and therefore risk-specific screening will be offered. Current national and international screening guidelines do not recommend routine screening for thyroid cancer. Hence, we reviewed the literature to explore the possible association between a CHEK2 mutation and thyroid cancer. A weak association was found between the various CHEK2 mutations and papillary thyroid cancer. The evidence for an association with CHEK2 c.1100delC in particular is the least robust. In conclusion, there is insufficient evidence to warrant systematic thyroid screening in CHEK2 carriers
The effects of avoidant instructions on golf putting proficiency and kinematics
No full textObjectives.
Although the effects of avoidant or negative instructions on skilled performance in sport has received little research attention, de la Pena, Murray, and Janelle (2008) reported recently that novice golfers who were instructed not to leave a putt short of a circle, overcompensated by leaving their putts significantly longer than at baseline, and vice versa. It is unclear, however, whether athletes' propensity to engage in over-compensatory behaviour is affected by their level of expertise.
Design.
To address this unresolved issue, the present study investigated the influence of avoidant instructions on golfers' putting stroke proficiency (i.e., as measured by an index of putting performance and the direction in which putts are missed) and on their putting stroke performance (as measured by motion analysis).
Methods.
14 high-skilled and 14 low-skilled golfers were required to putt from a distance of 2.5 m on a sloped surface which caused the ball to move left-to-right as it approached the hole. All participants performed in a condition in which they were given no instructions and in a condition in which they were instructed not to miss a putt in a specific direction (i.e., left or right of the hole).
Results.
High-skilled golfers' overall putting proficiency was unaffected by avoidant instructions. In contrast, low-skilled golfers' performance was significantly degraded due to disruption of certain kinematic features of their putting stroke (e.g., putter path and forward-swing times).Author has checked copyrightAM
Genetic testing in prostate cancer in clinical practice
No full textMutations in DNA damage repair (DDR) genes are relatively common in prostate cancer (PC), and may guide therapy selection. Approximately half of somatic DDR mutations are also present in the germline and lead to a heritable cancer predisposition syndrome (CPS), which informs on future risk, prostate cancer prognosis, and therapeutic options. In germline carriers, genetic counselling is essential to help psychosocial coping and to provide pre-symptomatic testing in relatives, who upon carrier identification can opt for intensified surveillance or – in some cases – prophylactic surgery
Comparison of Allogeneic Stem Cell Transplantation and Non-Transplant Approaches in Elderly Patients with Advanced Myelodysplastic Syndrome: Optimal Statistical Approaches and a Critical Appraisal of Clinical Results Using Non-Randomized Data
No full textAllogeneic stem cell transplantation (ASCT) from related or unrelated donors may cure patients with myelodysplastic syndromes (MDS), a heterogeneous group of clonal stem cell disorders. We analysed 384 elderly patients (55-69 years) with advanced MDS who received either ASCT (n=247) and were reported to The European Group for Blood and Marrow Transplantation (EBMT) or a non -transplant approach (n=137) reported to the Dusseldorf registry. Besides an attempt to answer the question of "comparison", the purpose of this work is to explain the difficulties in comparing a non-transplant with a transplant cohort, when death before transplant is likely but unknown and the selection of patients for transplant is based on assumptions. It shows which methods are almost always biased and that even the most sophisticated approaches crucially rely on clinical assumptions. Using the most appropriate model for our data, we derive an overall univariate non-significant survival disadvantage for the transplant cohort (HR: 1.29, p=0.11). We show that such an "average" hazard ratio is however misleading due to non-proportionality of the hazards reflecting early treatment related mortality, the occurring of which is logically correlated with the interval between diagnosis and transplant creating a disproportional drop in the (reconstructed) survival curve of the transplanted patients. Also in multivariate analysis (correcting for age > 60 (HR: 1.4, p=0.02) and abnormal cytogenetics (HR: 1.46, p=0.01)), transplantation seems to be worse (HR: 1.39, p=0.05) but only in the (incorrect but commonly applied) model without time varying covariates. The long term (time depending) hazard ratio is shown to be virtually 1 and overall survival is virtually identical in both groups. Nonetheless no conclusion can be reached from a clinical point of view without assumptions which are by their very nature untestable unless all patients would be followed from diagnosis
Treatment of anemia in patients with solid tumors receiving chemotherapy in palliative setting : usual practice versus guidelines
No full textBackground: Anemia is frequent in patients with cancer and is often multifactorial. Treatment depends on etiology and can consist of transfusions, intravenous iron (IV Fe), and/or erythropoiesis-stimulating agents (ESA). Several studies have shown that cancer-related anemia is undertreated. The aim of this study is to compare usual practice in a university hospital with the international guidelines.
Methods: Using the hospital and pharmacy informatics all adults (18years), who received a treatment for anemia (transfusion, IV Fe, ESA) from February to August 2016 during palliative chemotherapy, were identified. Episodes of care were defined as the start of palliative chemotherapy up until 4weeks after end of chemotherapy. After informed consent, relevant data in the episode of care were collected. Usual practice was compared to international guidelines adapted to Belgium reimbursement criteria.
Results: A total of 72 episodes of care were included. At initiation of chemotherapy, anemia was present in 59.7% of cases. Iron status was measured in 54.2% of all cases. Iron deficiency was found in 34.7% of patients. Only 52% of the iron deficient patents received IV Fe. Fifteen cases were considered eligible for ESA, six (40%) of these patients received an ESA. The most frequent treatments for anemia were transfusions (91.7%), followed by IV Fe (18.1%). Only 8.3% received an ESA.
Conclusion: Assessment for iron, Vitamin B12, and FA deficits are underused. We detected a high rate of transfusions. In contrast there is still a low use of IV Fe and ESA's. There has been no major improvement in the implementation of the international guidelines in the last decade. We estimate that in at least 16.7-26.4% of our patients less to no transfusions would have been required, if guidelines were strictly followed
Cancer prognosis and treatment results in patients with PTEN Hamartoma Tumour Syndrome (PHTS)-a European cohort study
No full textPrognosis; Treatment results; Hamartoma tumour syndromePronòstic; Resultats del tractament; Síndrome de tumor hamartomaPronóstico; Resultados del tratamiento; Síndrome de tumor hamartomaBackground: PTEN hamartoma tumour syndrome (PHTS) patients have a high hereditary risk of cancer, especially breast (BC), endometrial (EC), and thyroid cancer (TC). However, the prognosis of PHTS-related cancers is unknown.
Methods: This European cohort study included adult PHTS patients with data from medical files, registries, and/or questionnaires. Overall survival (OS) was assessed using Kaplan-Meier analyses and were compared with sporadic cancer and the general population using standardized mortality (SMR) and relative survival rates (RSR). Survival bias was addressed using left-truncation.
Results: Overall, 147 BC patients were included. The 10y-OS was 77% (95%CI = 66-90), decreasing with increasing stage from 90% (95%CI = 73-100) for stage 0 to 0% (95%CI = 0-0) for stage IV. BC relative survival was comparable to sporadic BC in the first two years (2y-RSR = 1.1; 95%CI = 1.1-1.1) and increasing thereafter (5y-RSR = 1.7; 95%CI = 1.6-1.7). For TC (N = 56) and EC (N = 35), 10y-OS was 87% (95%CI = 74-100) and 64% (95%CI = 38-100), respectively. Overall and cancer-specific mortality in female PHTS patients exceeded general population rates (SMR = 3.7; 95%CI = 2.6-5.0 and SMR = 2.7; 95%CI = 1.6-4.4).
Conclusions: The prognosis of PHTS-related cancers was comparable to the general population. The higher overall mortality in PHTS patients is presumably related to their higher cancer incidence. These findings, and the high survival observed in early-stage cancer, emphasise the importance of recognising PHTS early to facilitate cancer surveillance.This work has been funded, in part, by the PTEN Research Foundation, a charity governed by English law (charity number 117358) to L.A.J.H. and J.R.V. under grant number RUM 17-002; and Horizon Europe to K.C.J.V. under grant number 101095483
Somatic mosaics in hereditary tumor predisposition syndromes
No full textHistorically, it is estimated that 5-10% of cancer patients carry a causative genetic variant for a tumor predisposition syndrome. These conditions have high clinical relevance as they are actionable regarding risk-specific surveillance, predictive genetic testing, reproductive options, and - in some cases - risk reducing surgery or targeted therapy. Every individual is born with on average 0.5-1 exonic mosaic variants prevalent in single or multiple tissues. Depending on the tissues affected, mosaic conditions can abrogate the clinical phenotype of a tumor predisposition syndrome and can even go unrecognized, because it can be impossible or difficult to detect them with routine genetic testing in blood/leucocytes. On the other hand, it is estimated that at least 4% of presumed de novo variants are the result of low-level mosaicism (variant allele frequency <10%) in a parent, while around 7% are true mosaic variants with a higher variant allele frequency, which can sometimes be confused for heterozygous variants. Clonal hematopoiesis however can simulate a mosaic tumor predisposition in genetic diagnostics and has to be taken into account, especially for TP53 variants. Depending on the technique, variant allele frequencies of 2-3% can be detected for single nucleotide variants by next generation sequencing, copy number variants with variant allele frequencies of 5-30% can be detected by array-based technologies or MLPA. Mosaic tumor predisposition syndromes are more common than previously thought and may often remain undiagnosed. The clinical suspicion and diagnostic procedure for several cases with mosaic tumor predisposition syndromes are presented
Not just a 'usual' Li-Fraumeni syndrome
No full textThe Li-Fraumeni syndrome (LFS) is characterised clinically by the appearance of tumours in multiple organs, generally at an early age. This hereditary condition is caused by germinal mutations in the TP53 gene, which codifies for the tumour suppressor gene p53.
We present here the case of a patient aged 40 with the diagnosis of LFS who presented with premenopausal breast cancer. She had a positive family history of cancer. As a consequence, she was referred to genetic counselling. Genetic analysis revealed a TP53 germline mutation, which is diagnostic for LFS. However, further genetic analysis of different tissues showed a genetic mosaicism in our patient.
Patients with LFS have a high risk for a broad spectrum of tumours. The diagnosis and management of Li-Fraumeni syndrome should be performed by a multidisciplinary team, and genetic counselling should be offered to patients and their relatives. Targeted next-generation sequencing represents an efficient approach for the identification of mutations in families with a heterogeneous phenotype. Theoretically, since mosaics do not have mutations in all of their cells, the cells that do not have mutant p53 are less likely to undergo malignant transformation or have the same risk of everyone else
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