Hypocalcemia induced by tyrosine kinase inhibitors:targeted treatment with 'untargeted' side effects

Experimentele farmacotherapi

Genome Haploidisation with Chromosome 7 Retention in Oncocytic Follicular Thyroid Carcinoma

Contains fulltext : 108012.pdf (publisher's version ) (Open Access)BACKGROUND: Recurrent non-medullary thyroid carcinoma (NMTC) is a rare disease. We initially characterized 27 recurrent NMTC: 13 papillary thyroid cancers (PTC), 10 oncocytic follicular carcinomas (FTC-OV), and 4 non-oncocytic follicular carcinomas (FTC). A validation cohort composed of benign and malignant (both recurrent and non-recurrent) thyroid tumours was subsequently analysed (n = 20). METHODS: Data from genome-wide SNP arrays and flow cytometry were combined to determine the chromosomal dosage (allelic state) in these tumours, including mutation analysis of components of PIK3CA/AKT and MAPK pathways. RESULTS: All FTC-OVs showed a very distinct pattern of genomic alterations. Ten out of 10 FTC-OV cases showed near-haploidisation with or without subsequent genome endoreduplication. Near-haploidisation was seen in 5/10 as extensive chromosome-wide monosomy (allelic state [A]) with near-haploid DNA indices and retention of especially chromosome 7 (seen as a heterozygous allelic state [AB]). In the remaining 5/10 chromosomal allelic states AA with near diploid DNA indices were seen with allelic state AABB of chromosome 7, suggesting endoreduplication after preceding haploidisation. The latter was supported by the presence of both near-haploid and endoreduplicated tumour fractions in some of the cases. Results were confirmed using FISH analysis. Relatively to FTC-OV limited numbers of genomic alterations were identified in other types of recurrent NMTC studied, except for chromosome 22q which showed alterations in 6 of 13 PTCs. Only two HRAS, but no mutations of EGFR or BRAF were found in FTC-OV. The validation cohort showed two additional tumours with the distinct pattern of genomic alterations (both with oncocytic features and recurrent). CONCLUSIONS: We demonstrate that recurrent FTC-OV is frequently characterised by genome-wide DNA haploidisation, heterozygous retention of chromosome 7, and endoreduplication of a near-haploid genome. Whether normal gene dosage on especially chromosome 7 (containing EGFR, BRAF, cMET) is crucial for FTC-OV tumour survival is an important topic for future research. MICROARRAYS: Data are made available at GEO (GSE31828)

Therapeutic Validity and Effectiveness of Preoperative Exercise on Functional Recovery after Joint Replacement: A Systematic Review and Meta-Analysis

Background: Our aim was to develop a rating scale to assess the therapeutic validity of therapeutic exercise programmes. By use of this rating scale we investigated the therapeutic validity of therapeutic exercise in patients awaiting primary total joint replacement (TJR). Finally, we studied the association between therapeutic validity of preoperative therapeutic exercise and its effectiveness in terms of postoperative functional recovery. Methods: (Quasi) randomised clinical trials on preoperative therapeutic exercise in adults awaiting TJR on postoperative recovery of functioning within three months after surgery were identified through database and reference screening. Two reviewers extracted data and assessed the risk of bias and therapeutic validity. Therapeutic validity of the interventions was assessed with a nine-itemed, expert-based rating scale (scores range from 0 to 9; score ≥6 reflecting therapeutic validity), developed in a four-round Delphi study. Effects were pooled using a random-effects model and meta-regression was used to study the influence of therapeutic validity. Results: Of the 7,492 articles retrieved, 12 studies (737 patients) were included. None of the included studies demonstrated therapeutic validity and two demonstrated low risk of bias. Therapeutic exercise was not associated with 1) observed functional recovery during the hospital stay (Standardised Mean Difference [SMD]: −1.19; 95%-confidence interval [CI], −2.46 to 0.08); 2) observed recovery within three months of surgery (SMD: −0.15; 95%-CI, −0.42 to 0.12); and 3) self-reported recovery within three months of surgery (SMD −0.07; 95%-CI, −0.35 to 0.21) compared with control participants. Meta-regression showed no statistically significant relationship between therapeutic validity and pooled-effects. Conclusion: Preoperative therapeutic exercise for TJR did not demonstrate beneficial effects on postoperative functional recovery. However, poor therapeutic validity of the therapeutic exercise programmes may have hampered potentially beneficial effects, since none of the studies met the predetermined quality criteria. Future review studies on therapeutic exercise should address therapeutic validity. (aut.ref.

Optimization of physical functioning of patients before and after total hip arthroplasty

Vulnerable elderly people with poor physical fitness and comorbidity are at risk of delayed recovery from daily activities (transfers, walking, stair climbing) following a hip replacement and therefore spending longer in the hospital. Very few training programmes are geared towards this group of elderly people. Measuring physical fitness and muscle function before surgery can help to predict the patient's risk of delayed recovery and can also help determine the preventative measures to be implemented to prevent prolonged hospital stays and admission to a rehabilitation centre. This dissertation found that it's possible to offer vulnerable elderly people an intensive therapeutic training programme at home before surgery. Elderly people are more likely to participate in this programme if it is offered at home instead of in the hospital. The programme, which is tailored to the personal capabilities and needs of the patient, helps to prevent a further decline in physical fitness. Listening to patients and their families can shed light on the motivation, participation goals and relationships within the therapy process

Personal meaning: van narratieve analyse tot geestelijke zorg

The religious origins of medical care tell us that care is always also a manner of coping with the uncontrollable sides of life. Present day medical care, however, finds it difficult to deal with this manner of coping, because it is a very personal and individualized matter. On the other hand, the personal manner of coping – religiously, spiritually or other – is considered an important aspect of care practice. The (spiritual) councelor may have a special role in this process and develop special skills in order to assist it. This article investigates coping with the uncontrollable sides of life as a personal involvement in which meaning is generated. By a narrative analysis of the stories of three different persons involved in this process – the patient, her daughter and the physical therapist – we can follow how they are generating meaning together. Relying on powers of motivation, collecting or hoping for competences, the patient tries to realize a valuable situation, transforming an uncontrollable into a meaningful life event. The daughter and physical therapist, each one following their own program are helping the patient. The narrative approach of personal meaning may help the councelor to follow the manner in which a person copes with his or her situation, and to tune the programs of different persons involved in this situation to one another.</jats:p

Personal meaning: van narratieve analyse tot geestelijke zorg

The religious origins of medical care tell us that care is always also a manner of coping with the uncontrollable sides of life. Present day medical care, however, finds it difficult to deal with this manner of coping, because it is a very personal and individualized matter. On the other hand, the personal manner of coping – religiously, spiritually or other – is considered an important aspect of care practice. The (spiritual) councelor may have a special role in this process and develop special skills in order to assist it. This article investigates coping with the uncontrollable sides of life as a personal involvement in which meaning is generated. By a narrative analysis of the stories of three different persons involved in this process – the patient, her daughter and the physical therapist – we can follow how they are generating meaning together. Relying on powers of motivation, collecting or hoping for competences, the patient tries to realize a valuable situation, transforming an uncontrollable into a meaningful life event. The daughter and physical therapist, each one following their own program are helping the patient. The narrative approach of personal meaning may help the councelor to follow the manner in which a person copes with his or her situation, and to tune the programs of different persons involved in this situation to one another

Predicting Short Stay Total Hip Arthroplasty by use the Timed Up and Go-test

Abstract BackgroundEstablishing patient criteria is one of the most important steps before implementing short stay total hip arthroplasty (THA). Most existing risk models are mainly based on medical condition, but as physical functioning is associated with outcome after THA, we assume a measure of physical functioning might be of added value to predict short-stay THA.MethodsWe used retrospective data of 1559 patients who had anterior THA. Logistic regression analyses were done to study the predictive value of preoperative physical functioning by use of the Timed Up and Go test (TUG), in a basic model with age, and the American Society of Anesthesiologists (ASA)-score for short stay THA (&lt;36 hours). The receiver operating characteristic (ROC) curve was use to define a cut off point for TUG associated with LOS.Results TUG was significantly associated with LOS (OR 0.84, 95%CI 0.82-0.87) in univariate regression analysis. In multivariate regression, a model with the TUG had a better performance with an AUC of 0.77 (95%CI 0.74-0.79) and R2 of 0.27 then the basic model (AUC 0.75, 95% CI 0.73-0.77, R2 0.24). Patients with a preoperative TUG less than 10 seconds had an OR of 3.64 (95%CI 2.86-4.62) of being discharged within 36 hours.ConclusionsPerformance based physical functioning, measured by the TUG, is associated with short stay THA. This knowledge will help in the decision-making process for the planning, expectations and needs in outpatient THA protocols with the advantage that the TUG is a simple and fast instrument to be carried out.</jats:p

Predicting short stay total hip arthroplasty by use of the timed up and go-test

Abstract Background One of the most important steps before implementing short stay total hip arthroplasty (THA) is establishing patient criteria. Most existing criteria are mainly based on medical condition, but as physical functioning is associated with outcome after THA, we aim to evaluate the added value of a measure of physical functioning to predict short-stay THA. Methods We used retrospective data of 1559 patients who underwent an anterior THA procedure. Logistic regression analyses were performed to study the predictive value of preoperative variables among which preoperative physical functioning by use of the Timed Up and Go test (TUG) for short stay THA (&lt; 36 h). The receiver operating characteristic (ROC) curve and Youden Index were used to define a cutoff point for TUG associated with short stay THA. Results TUG was significantly associated with LOS (OR 0.84, 95%CI 0.82–0.87) as analyzed by univariate regression analysis. In multivariate regression, a model with the TUG had a better performance with an AUC of 0.77 (95%CI 0.74–0.79) and a R2 of 0.27 compared to the basic model (AUC 0.75, 95%CI 0.73–0.77, R2 0.24). Patients with a preoperative TUG less than 9.7 s had an OR of 4.01 (95%CI 3.19–5.05) of being discharged within 36 h. Conclusions Performance based physical functioning, measured by the TUG, is associated with short stay THA. This knowledge will help in the decision-making process for the planning and expectations in short stay THA protocols with the advantage that the TUG is a simple and fast instrument to be carried out. </jats:sec