Depression is a common neuropsychiatric symptom in Parkinson's disease (PD). In previous research, PD-related depression was associated with striatal dopaminergic deficits, presumably due to ...degeneration of brainstem dopaminergic projections. Segregated areas of the striatum are crucially involved in various parallelly arranged cortical-striatal-thalamocortical circuits and serve functions in, among others, motor control or emotion. This suggests regional specificity of dopaminergic deficits in the striatum in motor and depressive symptoms in PD.
In this cross-sectional retrospective study, we correlated severity scores of depressive and motor symptoms in 100 non-demented PD patients (median Hoehn & Yahr stage: 2) with dopamine loss in specific regions of the striatum as measured by (123)IFP-CIT SPECT tracer binding to the dopamine transporter (DaT).
Depressive symptoms were related to lower DaT binding in the right caudate nucleus, while motor symptoms were associated with decreased DaT binding in the right putamen. This double dissociation was most pronounced in early-stage PD patients.
These results suggest that depressive symptoms in PD are associated with dopamine loss in the caudate nucleus, possibly related to degeneration of dopaminergic projections from the ventral tegmental area, while motor symptoms are associated with low dopamine signalling to the putamen and loss of nigrostriatal projections. This is consistent with the neuroanatomy of partially segregated cortical-striatal-thalamocortical circuits and supports the role of dysfunctional associative and motivational circuits in PD-related depression.
The long-term impact of acromegaly on subjective well-being after treatment of GH excess is unclear. Therefore, we evaluated quality of life by validated questionnaires in a cross-sectional study of ...118 successfully treated acromegalic patients. The initial treatment was transsphenoidal surgery in most patients (92%), if necessary followed by radiotherapy or octreotide. All patients were in remission at the time of assessment (GH, <1.9 μg/liter; normal IGF-I for age). General perceived well-being was reduced compared with controls for all subscales (P < 0.001) as measured by the Nottingham Health Profile and the Short Form-36. Acromegalic patients also had lower scores on fatigue (Multidimensional Fatigue Index) and anxiety and depression (Hospital Anxiety and Depression Scale). Radiotherapy was associated with decreased quality of life in all subscales except for the Hospital Anxiety and Depression Scale, and worsened quality of life significantly, according to the fatigue scores. Somatostatin analog treatment was not associated with improved quality of life. Independent predictors of quality of life were age (physical subscales and Nottingham Health Profile), disease duration (social isolation and personal relations), and radiotherapy (physical and fatigue subscales). In conclusion, patients cured after treatment for acromegaly have a persistently decreased quality of life despite long-term biochemical cure of GH excess. Radiotherapy especially is associated with a reduced quality of life.
The System Usability Scale (SUS) is used to measure usability of internet-based Cognitive Behavioural Therapy (iCBT). However, whether the SUS is a valid instrument to measure usability in this ...context is unclear. The aim of this study is to assess the factor structure of the SUS, measuring usability of iCBT for depression in a sample of professionals. In addition, the psychometric properties (reliability, convergent validity) of the SUS were tested.
A sample of 242 professionals using iCBT for depression from 6 European countries completed the SUS. Confirmatory Factor Analysis (CFA) was conducted to test whether a one-factor, two-factor, tone-model or bi-direct model would fit the data best. Reliability was assessed using complementary statistical indices (e.g. omega). To assess convergent validity, the SUS total score was correlated with an adapted Client Satisfaction Questionnaire (CSQ-3).
CFA supported the one-factor, two-factor and tone-model, but the bi-factor model fitted the data best (Comparative Fit Index = 0.992, Tucker Lewis Index = 0.985, Root Mean Square Error of Approximation = 0.055, Standardized Root Mean Square Residual = 0.042 (respectively χ
(9) = 69.82, p < 0.001; χ
(8)
33.04, p < 0.001). Reliability of the SUS was good (ω = 0.91). The total SUS score correlated moderately with the CSQ-3 (CSQ1 r
= .49, p < 0.001; CSQ2 r
= .46, p < 0.001; CSQ3 r
= .38, p < 0.001), indicating convergent validity.
Although the SUS seems to have a multidimensional structure, the best model showed that the total sumscore of the SUS appears to be a valid and interpretable measure to assess the usability of internet-based interventions when used by professionals in mental healthcare.
Summary
Introduction The treatment of craniopharyngiomas is associated with long‐term morbidity.
Aim of the study To assess the long‐term functional outcome and mortality rates after treatment for ...craniopharyngiomas, we audited our data with special focus on cardiovascular, neurological and psychosocial morbidity.
Patients and methods Between 1965 and 2002, 54 consecutive patients underwent surgery for craniopharyngiomas at the Leiden University Medical Centre (LUMC). Fifteen patients (25%) received additional postoperative radiation therapy. The median follow‐up period was 10 years (range 1–37 years).
Results Long‐term cure rate was 82% and long‐term recurrence rate 18%. Visual fields/visual acuity stabilized or improved in 74% of cases. The long‐term prevalence rate of hypopituitarism was 89%. In addition, long‐term cardiovascular, neurological and psychosocial morbidity rates were high: 22% (risk factors 57%), 49% and 47%, respectively. Female sex was an independent predictor of increased cardiovascular, neurological and psychosocial morbidity (odds ratio 3·78, P = 0·031). Ten patients (18%) died during an 828 person‐year follow‐up. The actuarial patient survival rates 5, 10 and 20 years after the initial operation were 95, 85 and 85%, respectively. The standardized mortality ratio (SMR) was 2·88 95% confidence interval (CI) 1·35–4·99.
Conclusion Craniopharyngioma is associated with excessive long‐term multisystem morbidity and mortality, especially in female patients, despite a high cure rate. These observations indicate that dedicated long‐term follow‐up of these patients is required. The purpose of the follow‐up should be: first, to look for recurrences and to ensure appropriate endocrine replacement, especially oestrogen replacement in premenopausal females; and second, to achieve intensive control of glucose, lipids, blood pressure and weight, as in any other patient with increased risk for cardiovascular disease.
Purpose
Non-medullary thyroid cancer (NMTC) treatment is based on the ability of thyroid follicular cells to accumulate radioactive iodide (RAI). However, in a subset of NMTC patients tumor ...dedifferentiation occurs, leading to RAI resistance. Digoxin has been demonstrated to restore iodide uptake capacity
in vitro
in poorly differentiated and anaplastic NMTC cells, termed redifferentiation. The aim of the present study was to investigate the
in vivo
effects of digoxin in TPO-Cre/LSL-Braf
V600E
mice and digoxin-treated NMTC patients.
Methods
Mice with thyroid cancer were subjected to 3D ultrasound for monitoring tumor growth and
124
I PET/CT for measurement of intratumoral iodide uptake. Post-mortem analyses on tumor tissues comprised gene expression profiling and measurement of intratumoral autophagy activity. Through PALGA (Dutch Pathology Registry), archived tumor material was obtained from 11 non-anaplastic NMTC patients who were using digoxin. Clinical characteristics and tumor material of these patients were compared to 11 matched control NMTC patients never treated with digoxin.
Results
We found that in mice, tumor growth was inhibited and
124
I accumulation was sustainably increased after short-course digoxin treatment. Post-mortem analyses revealed that digoxin treatment increased autophagy activity and enhanced expression of thyroid-specific genes in mouse tumors compared to vehicle-treated mice. Digoxin-treated NMTC patients exhibited significantly higher autophagy activity and a higher differentiation status as compared to matched control NMTC patients, and were associated with favourable clinical outcome.
Conclusions
These
in vivo
data support the hypothesis that digoxin may represent a repositioned adjunctive treatment modality that suppresses tumor growth and improves RAI sensitivity in patients with RAI-refractory NMTC.
Blood pressure (BP) reduction after renal sympathetic denervation (RDN) is highly variable. Renal nerve stimulation (RNS) can localize sympathetic nerves. The RNS trial aimed to investigate the ...medium-term BP-lowering effects of the use of RNS during RDN, and explore if RNS can check the completeness of the denervation.
Forty-four treatment-resistant hypertensive patients were included in the prospective, single-center RNS trial. The primary study endpoint was change in 24-h BP at 6- to 12-month follow-up after RDN. The secondary study endpoints were the acute procedural RNS-induced BP response before and after RDN; number of antihypertensive drugs at follow-up; and the correlation between the RNS-induced BP increase before versus after RDN (delta Δ RNS-induced BP).
Before RDN, the RNS-induced systolic BP rise was 43(±21) mmHg, and decreased to 9(±12) mmHg after RDN (p < 0.001). Mean 24-h systolic/diastolic BP decreased from 147(±12)/82(±11) mmHg at baseline to 135(±11)/76(±10) mmHg (p < 0.001/<0.001) at follow-up (10 6-12 months), with 1 antihypertensive drug less compared to baseline. The Δ RNS-induced BP and the 24-h BP decrease at follow-up were correlated for systolic (R = 0.44, p = 0.004) and diastolic (R = 0.48, p = 0.003) BP. Patients with ≤0 mmHg residual RNS-induced BP response after RDN had a significant lower mean 24-h systolic BP at follow-up compared to the patients with >0 mmHg residual RNS-induced BP response (126 ± 4 mmHg versus 135 ± 10 mmHg, p = 0.04). 83% of the patients with ≤0 mmHg residual RNS-induced BP response had normal 24-h BP at follow-up, compared to 33% in the patients with >0 mmHg residual RNS-induced BP response (p = 0.023).
The use of RNS during RDN leads to clinically significant and sustained lowering of 24-h BP with fewer antihypertensive drugs at follow-up. RNS-induced BP changes were correlated with 24-h BP changes at follow-up. Moreover, patients with complete denervation had significant lower BP compared to the patients with incomplete denervation.
Summary Background The evidence justifying the use of acellular dermal matrices (ADMs) in implant-based breast reconstruction (IBBR) is limited. We did a prospective randomised trial to compare the ...safety of IBBR with an ADM immediately after mastectomy with that of two-stage IBBR. Methods We did an open-label, randomised, controlled trial in eight hospitals in the Netherlands. Eligible women were older than 18 years with breast carcinoma or a gene mutation linked with breast cancer who intended to undergo skin-sparing mastectomy and immediate IBBR. Randomisation was done electronically, stratified per centre and in blocks of ten to achieve roughly balanced groups. Women were assigned to undergo one-stage IBBR with ADM (Strattice, LifeCell, Branchburg, NJ, USA) or two-stage IBBR. The primary endpoint was quality of life and safety was assessed by the occurrence of adverse outcomes. Analyses were done per protocol with logistic regression and generalised estimating equations. This study is registered at Nederlands Trial Register, number NTR5446. Findings 142 women were enrolled between April 14, 2013, and May 29, 2015, of whom 59 (91 breasts) in the one-stage IBBR with ADM group and 62 (92 breasts) in the two-stage IBBR group were included in analyses. One-stage IBBR with ADM was associated with significantly higher risk per breast of surgical complications (crude odds ratio 3·81, 95% CI 2·67–5·43, p<0·001), reoperation (3·38, 2·10–5·45, p<0·001), and removal of implant, ADM, or both (8·80, 8·24–9·40, p<0·001) than two-stage IBBR. Severe (grade 3) adverse events occurred in 26 (29%) of 91 breasts in the one-stage IBBR with ADM group and in five (5%) of 92 in the two-stage IBBR group. The frequency of mild to moderate adverse events was similar in the two groups. Interpretation Immediate one-stage IBBR with ADM was associated with adverse events and should be considered very carefully. Understanding of selection of patients, risk factors, and surgical and postsurgical procedures needs to be improved. Funding Pink Ribbon, Nuts-Ohra, and LifeCell.
This study evaluated myocardial function in relation to high-energy phosphate (HEP) metabolism in asymptomatic patients with uncomplicated type 2 diabetes mellitus using magnetic resonance (MR) ...techniques.
Myocardial dysfunction may occur in patients with type 2 diabetes mellitus in the absence of coronary artery disease or left ventricular (LV) hypertrophy. The mechanisms underlying this diabetic cardiomyopathy are largely unknown, but may involve altered myocardial energy metabolism.
We assessed myocardial systolic and diastolic function and HEP metabolism in 12 asymptomatic normotensive male patients with recently diagnosed, well-controlled type 2 diabetes and 12 controls, using MR imaging and phosphorus-31-nuclear MR spectroscopy (31P-MRS) on a 1.5 T clinical scanner; 31P-MR spectra were quantified, and myocardial HEP metabolism was expressed as phosphocreatine to adenosine-triphosphate (PCr/ATP) ratio.
No differences were found in LV mass and systolic function between patients and controls. However, early (E) acceleration peak, deceleration peak, peak filling rate, and transmitral early-to-late diastolic peak flow (E/A) ratio, all indexes of diastolic function, were significantly decreased in patients compared with controls (p < 0.02). In addition, myocardial PCr/ATP in patients was significantly lower than in controls (1.47 vs. 1.88, p < 0.01). Inverse associations were found between myocardial PCr/ATP and E acceleration peak, E deceleration peak, and E peak filling rate (all, p < 0.05).
These results indicate that altered myocardial energy metabolism may contribute to LV diastolic functional changes in patients with recently diagnosed, well-controlled and uncomplicated type 2 diabetes.
Background
Aggressive forms of thyroid carcinoma (TC) show an abundant infiltration of immune cells, and this correlates with prognosis. However, little is known about circulating immune cell levels ...in advanced TC.
Objective
Investigate T‐cell and myeloid‐derived suppressor cell (MDSC) levels in peripheral blood of patients with advanced TC and correlate them with survival.
Methods
T cells and MDSCs were quantified by flow cytometry in peripheral blood from nine patients with advanced TC and nine healthy volunteers.
Results
No significant differences in MDSC or regulatory T‐cell levels were detected between patients with TC and healthy controls. CD3, CD4, and CD8 T‐cell levels were significantly lower in patients with TC. CD3 and CD4 T‐cell levels further decreased in patients with survival of less than 1 month.
Conclusion
These data suggest that T‐cell lymphopenia in patients with TC indicates an aggressive tumor behavior and might influence therapeutic choices in the future. Restoring T‐cell levels may become a potential therapeutic option within the multitarget approaches.
This article assesses the presence of immune cell populations in the peripheral blood of patients with advanced or metastatic thyroid carcinoma, focusing on correlation to patient prognosis.
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