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

Association between Preoperative Vitamin D Status and Short-Term Physical Performance after Total Hip Arthroplasty : A Prospective Study

Background: Insufficient serum vitamin D concentrations (50-75 nmol/L) are prevalent in 40-65% of patients who require total hip arthroplasty (THA). This could impair physical recovery after surgery. This study investigated the association between preoperative vitamin D status and physical performance after THA. Additionally, postoperative changes in vitamin D concentrations were measured. Methods: We included 87 patients scheduled for elective THA and aged ≥65 years. Three groups were recruited: patients classified as vitamin D deficient ( 75 nmol/L, n = 32). Serum 25-hydroxyvitamin D3 (25[OH]D3) concentration and physical performance were measured perioperatively. Linear mixed models were used to examine differences between groups. Results: Change in physical performance over time was not affected by preoperative vitamin D status. In contrast, for physical activity, both vitamin D (p = 0.021) and time (p 3 concentration 6 weeks postoperatively was correlated with improved hip function (Pearson's r = -0.471, p = 0.018). Overall, serum 25(OH)D3 declined with 32% one day after surgery (p < 0.001), to nearly return to baseline values 6 weeks later in all groups. Conclusion: Vitamin D status did not appear to affect physical recovery after THA. The drop in vitamin D after surgery deserves further investigation, but could possibly be explained by hemodilution.</p

Personal meaning in relation to daily functioning of a patient in physical therapy practice: narratives of a patient, a family member, and physical therapist

<p><b>Purpose:</b> To get insight into personal meaning of a person involved in a physical therapy intervention.</p> <p><b>Methods:</b> Mrs. A, a 76-year-old woman is referred to a physical therapist (PT) for assessment of functioning and training before total hip arthroplasty (THA). The patient, her daughter, and PT were asked to write a story about their daily life. Stories were analyzed according to the narrative scheme based on a method to find meaning in daily life, which consists of four phases: 1. Motivation; 2. Competences; 3. Performance; and 4. Evaluation.</p> <p><b>Results:</b> Mrs. A was mainly motivated by her will to do enjoyable social activities and stay independent. Although she tried her best to undertake activities (performance) that made her proud (evaluation), her pain and physical limitations were anti-competences that motivated her to attend healthcare. Although the PT seemed to be aware of personal participation goals, her main motivation was to improve and evaluate functions and activities. The daughter was motivated by good relationships and did not see herself as informal caregiver.</p> <p><b>Conclusions:</b> The narrative method was a valuable tool to clarify motivations, competences, and values in the process of creating personal meaning related to functioning. This knowledge could help caregivers in applying patient-centered goal-setting and treatment on a participation level.</p> <p>Implications for rehabilitation</p><p>Personal meaning of people’s functioning within their daily context can be clarified from daily life stories.</p><p>This case report demonstrates that motivations and goals may differ between patient and therapist; the PT seems to focus on improving and evaluating functions and activities, while the patient seems to focus her motivations and personal meaning on participation.</p><p>This approach may help in patient-centered goal-setting at the level of activities and participation.</p><p></p> <p>Personal meaning of people’s functioning within their daily context can be clarified from daily life stories.</p> <p>This case report demonstrates that motivations and goals may differ between patient and therapist; the PT seems to focus on improving and evaluating functions and activities, while the patient seems to focus her motivations and personal meaning on participation.</p> <p>This approach may help in patient-centered goal-setting at the level of activities and participation.</p

Preoperative prediction of inpatient recovery of function after total hip arthroplasty using performance-based tests: a prospective cohort study

Item does not contain fulltextPURPOSE: The aim of this study was to evaluate the value of conventional factors, the Risk Assessment and Predictor Tool (RAPT) and performance-based functional tests as predictors of delayed recovery after total hip arthroplasty (THA). METHOD: A prospective cohort study in a regional hospital in the Netherlands with 315 patients was attending for THA in 2012. The dependent variable recovery of function was assessed with the Modified Iowa Levels of Assistance scale. Delayed recovery was defined as taking more than 3 days to walk independently. Independent variables were age, sex, BMI, Charnley score, RAPT score and scores for four performance-based tests [2-minute walk test, timed up and go test (TUG), 10-meter walking test (10 mW) and hand grip strength]. RESULTS: Regression analysis with all variables identified older age (>70 years), Charnley score C, slow walking speed (10 mW >10.0 s) and poor functional mobility (TUG >10.5 s) as the best predictors of delayed recovery of function. This model (AUC 0.85, 95% CI 0.79-0.91) performed better than a model with conventional factors and RAPT scores, and significantly better (p = 0.04) than a model with only conventional factors (AUC 0.81, 95% CI 0.74-0.87). CONCLUSIONS: The combination of performance-based tests and conventional factors predicted inpatient functional recovery after THA. Implications for Rehabilitation Two simple functional performance-based tests have a significant added value to a more conventional screening with age and comorbidities to predict recovery of functioning immediately after total hip surgery. Patients over 70 years old, with comorbidities, with a TUG score >10.5 s and a walking speed >1.0 m/s are at risk for delayed recovery of functioning. Those high risk patients need an accurate discharge plan and could benefit from targeted pre- and postoperative therapeutic exercise programs