The role of salvage extended lymph node dissection in patients with rising PSA and PET/CT scan detected nodal recurrence of prostate cancer.

BACKGROUND: Non-prostatic bed recurrence of prostate cancer (PCa) is usually treated with androgen deprivation therapy (ADT). We analyzed the impact of salvage extended lymph node dissection (sLND) on cancer control in patients with rising PSA and lymph node (LN) metastases. METHODS: Between 2009 and 2016 we performed sLND in 87 patients with biochemical recurrence (BCR) and positive LNs on 18FEC and 68Ga-PSMA positron emission tomography/X-ray computer tomography (PET/CT) after primary treatment (PT) of PCa. Intra- and postoperative complications according to Clavien-Dindo were assessed and the rates of biochemical response (BR), BCR-free and clinical recurrence (CR)-free survival, as well as time to initiation of systemic treatment were evaluated. RESULTS: Mean age of patients and mean PSA at sLND was 66.7 years (46-80 years) and 2.63 ng ml-1 (1.27-3.75 ng ml-1), respectively. With 87.4% radical prostatectomy (RP) was the most common PT. In all, 57.9% of patients additionally underwent adjuvant/salvage radiation therapy (RT) and 18.4% received ADT before sLND. Complete BR (cBR) was diagnosed in 27.5% of patients and incomplete BR in 40.6%. In total, 62.2% of patients remained without ADT at follow-up. With a median follow-up of 21 months (1-75 months), the cancer-specific mortality rate was 3.7%. The 3-year BCR-free, systemic therapy-free and CR-free survival rates for patients with cBR were 69.3%, 77.0% and 75%, respectively. CONCLUSIONS: sLND can be performed without significant complications and achieves an immediate BR, thus allowing a significant postponement of systemic therapy in selected patients with BCR and nodal recurrence of PCa. Therefore, sLND following 68Ga-PSMA PET/CT should be considered as part of a multimodal diagnostic and treatment concept for selective patients.

Understanding the origin of band gap formation in graphene on metals: graphene on Cu/Ir(111).

Understanding the nature of the interaction at the graphene/metal interfaces is the basis for graphene-based electron- and spin-transport devices. Here we investigate the hybridization between graphene- and metal-derived electronic states by studying the changes induced through intercalation of a pseudomorphic monolayer of Cu in between graphene and Ir(111), using scanning tunnelling microscopy and photoelectron spectroscopy in combination with density functional theory calculations. We observe the modifications in the band structure by the intercalation process and its concomitant changes in the charge distribution at the interface. Through a state-selective analysis of band hybridization, we are able to determine their contributions to the valence band of graphene giving rise to the gap opening. Our methodology reveals the mechanisms that are responsible for the modification of the electronic structure of graphene at the Dirac point, and permits to predict the electronic structure of other graphene-metal interfaces.

Attention deficit hyperactivity disorder (ADHD) and executive functioning in affected and unaffected adolescents and their parents: challenging the endophenotype construct.

BACKGROUND: The results of twin and sibling studies suggest that executive functioning is a prime candidate endophenotype in attention deficit hyperactivity disorder (ADHD). However, studies have not assessed the co-segregation of executive function (EF) deficits from parents to offspring directly, and it is unclear whether executive functioning is an ADHD endophenotype in adolescents, given the substantial changes in prefrontal lobe functioning, EF and ADHD symptoms during adolescence. METHOD: We recruited 259 ADHD and 98 control families with an offspring average age of 17.3 years. All participants were assessed for ADHD and EF [inhibition, verbal (VWM) and visuospatial working memory (VsWM)]. Data were analysed using generalized estimating equations (GEEs). RESULTS: Parental ADHD was associated with offspring ADHD and parental EF was associated with offspring EF but there were no cross-associations (parental ADHD was not associated with offspring EF or vice versa). Similar results were found when siblings were compared. EF deficits were only found in affected adolescents and not in their unaffected siblings or (un)affected parents. CONCLUSIONS: The core EFs proposed to be aetiologically related to ADHD, that is working memory and inhibition, seem to be aetiologically independent of ADHD in adolescence. EF deficits documented in childhood in unaffected siblings were no longer present in adolescence, suggesting that children 'grow out' of early EF deficits. This is the first study to document ADHD and EF in a large family sample with adolescent offspring. The results suggest that, after childhood, the majority of influences on ADHD are independent from those on EF. This has potential implications for current aetiological models of causality in ADHD.

[Muscle invasive bladder cancer after radical cystectomy. Prognostic factors of adjuvant chemotherapy]. / Muskelinvasives Harnblasenkarzinom nach radikaler Zystektomie. Prognosefaktoren der adjuvanten Chemotherapie.

BACKGROUND: The indications to administer adjuvant systemic chemotherapy to patients with urothelial carcinoma of the bladder who underwent radical cystectomy is discussed controversially and all international guidelines are very restrictive with regard to its recommendation for routine daily practice due to the low scientific evidence concerning its therapeutic benefit. Currently, adjuvant systemic chemotherapy should be preferably administered within clinical trials. In the daily routine adjuvant treatment might be given in patients with lymph node positive disease. Clinical, pathohistological and molecular biomarkers which might be associated with a positive or negative treatment response have been evaluated sparsely in the past. RESULTS: The presence of hemangiosis/lymphangiosis carcinomatosa and/or extranodal expansion in patients with lymph node metastases appears to be associated with a poor outcome. The markers ERCC-1, XAF and anti-apoptotic proteins of the Bcl-2 family seem to represent the most promising biomarkers associated with response to adjuvant cisplatin-based chemotherapy.

Metastatic castration-resistant prostate cancer: integrating new learnings to optimise treatment outcomes.

The approval or clinical evaluation of several new agents - cabazitaxel, abiraterone acetate, enzalutamide, sipuleucel-T, and radium-223 - has changed the management of patients with metastatic castration-resistant prostate cancer (mCRPC) prior to or after docetaxel-based chemotherapy significantly. All of these agents have resulted in a significant survival benefit as compared to their control group. However, treatment responses might differ depending on the associated comorbidities and the extent and the biological aggressiveness of the disease. Furthermore, treatment associated side effects differ between the various drugs. As new drugs become approved, new treatment strategies and markers to best select which patients will best respond to which drug are needed. It is the aim of the current article to: (1) summarize the data of established treatment options in mCRPC; (2) highlight new developments of medical treatment; (3) provide clinically useful algorithms for the daily routine and to (4) point out future developments of medical treatment.

Electronic structure and imaging contrast of graphene moiré on metals.

Realization of graphene moiré superstructures on the surface of 4d and 5d transition metals offers templates with periodically modulated electron density, which is responsible for a number of fascinating effects, including the formation of quantum dots and the site selective adsorption of organic molecules or metal clusters on graphene. Here, applying the combination of scanning probe microscopy/spectroscopy and the density functional theory calculations, we gain a profound insight into the electronic and topographic contributions to the imaging contrast of the epitaxial graphene/Ir(111) system. We show directly that in STM imaging the electronic contribution is prevailing compared to the topographic one. In the force microscopy and spectroscopy experiments we observe a variation of the interaction strength between the tip and high-symmetry places within the graphene moiré supercell, which determine the adsorption sites for molecules or metal clusters on graphene/Ir(111).

Psychometric properties of an informant personality questionnaire (the HAP) in a sample of older adults in the Netherlands and Belgium.

In geriatric psychiatry, informant reports are often important due to cognitive problems and related impaired insight and judgment. Informant questionnaires to identify personality traits among older adults are sparse. The Dutch informant personality questionnaire (the HAP) is especially developed to address this need. The objective of this study is the psychometric evaluation of the HAP among older adults in the Netherlands and Belgium. We investigated the internal consistency, gender differences, the test-retest and inter-rater reliability, the factorial structure, and the concurrent validity. Informants completed the HAP ratings of nursing home residents (n = 385) and elderly psychiatric patients (n = 204). The internal consistency of the scales is good. Medium gender differences on three scales were found in the population Psychiatry. The inter-rater and test-retest reliability are good to excellent. There are significant similarities between a number of HAP scales and dimensions of the Big Five. The congruence between the factor structures in both samples is very high. We labeled the three factors externalizing/antagonistic, internalizing/neurotic, and compulsive. The HAP meets the need for validated and reliable informant instruments for personality assessment among older adults in geriatric psychiatry. The content scales of the questionnaire address traits of the premorbid personality. Therefore, the HAP might be useful for personality assessment and selecting treatment options in mental healthcare and can be applied in scientific research in the area of personality aspects in late life.

Are peak oxygen uptake and power output at maximal lactate steady state obtained from a 3-min all-out cycle test?

The aim of the study was to examine whether 1) the power output attained in the last 30 s of a 3-min all-out test (P (end)) correlates with the power output at maximal lactate steady state (P (MLSS)) and whether 2) peak oxygen uptake (VO (2peak)) can be obtained from a 3-min all-out test in well-trained cyclists. 18 cyclists (23±3 years; 186.1±6.9 cm; 79.1±8.2 kg; VO (2peak): 63.2±5.2 mL · kg (-1) · min (-1)) performed a ramp test, a 3-min all-out test and several submaximal constant 30 min-workload tests at +15, 0, -15, -30, -45, -60,-75, -90 W of P (end) to obtain P (MLSS). P (MLSS) was significantly lower compared to P (END) ( P<0.001; mean difference: 54±18 W) with a high correlation (r=0.93; R (2)=0.87; P<0.001) but great intra-individual variability (15-90 W). There were no mean differences between the ramp-VO (2peak) and 3-min all-out cycling VO (2peak) ( P=0.29; mean difference: 133±514 mL · min (-1)) showing significant correlation (r=0.60; R (2)=0.37; P=0.006) but great intra-individual variability (1 057-1 312 mL · min (-1)). We therefore suggest that in well-trained cyclists a 3-min all-out test is 1) not sufficient to obtain P (MLSS) and 2) should not be applied to assess VO (2peak).

[Premorbid personality and aggressive behavior: a study with residents of psychogeriatric nursing homes]. / Boos, bedreigd of impulsief? Een onderzoek naar premorbide persoonlijkheid en agressie bij psychogeriatrische verpleeghuisbewoners.

From experimental research it appears that personality plays a role in causes and onset of aggressive behavior in adults. However, studies about the influence of premorbid personality on aggressive behavior of older persons with dementia show contradictory results. In this study we gathered data on personality and behavior of 166 residents of psychogeriatric nursing homes. Nursing staff filled out the Cohen-Mansfield Agitation Inventory (Dutch version, CMAI-D). Proxy family members completed the Hetero Anamnestic Personality questionnaire (HAP). Results showed that on the CMAI-D aggression could be distinguished from other forms of agitation. Four subscales of the HAP showed significant positive correlations with aggression as measured with the CMAI-D. These subscales were: Antagonism, Whimsical and impulsive behavior, Rigid behavior, and Being vulnerable in social interactions. Although the influence of personality decreased with increasing cognitive impairment, it was still present in stage 6 of the Reisberg Global Deterioration Scale. In depth analysis items of the HAP revealed a first profile of the aggression prone personality.

[Oral galantamine versus rivastigmine transdermal patch: a descriptive study at a memory clinic in The Netherlands]. / Galantamine of rivastigmine pleister. Een beschrijvend onderzoek op een geheugenpolikliniek in Nederland.

OBJECTIVES: Since January 2008 in The Netherlands, two cholinesterase inhibitors, oral galantamine and rivastigmine transdermal patch, are registered as a one-day symptomatic treatment for Alzheimer's disease. As no head to head study was performed yet, the objective of this study was to describe the daily practice of oral galantamine and rivastigmine transdermal patch in a real life population of a memory clinic of a suburban teaching hospital in The Netherlands. METHODS: A randomized open label study in 84 ambulant Alzheimer's patients with at least 6 months follow-up and treated either with oral galantamine (group G) or rivastigmine transdermal patch (group R). Data collection included patients' demographic and disease variables. Adverse events were collected and, in case of interruption of the primary treatment, the alternative treatment was registered. RESULTS: Serious adverse events did not occur. In group G respectively group R adverse events occurred in 20 patients (50%) and 18 patients (41%). No difference occurred in the frequency of nausea or vomiting. In group R more patients noted dermatological adverse events. In group G respectively group R medication was stopped in 12 patients (30%) and 14 patients (32%). However, compared to group G after stopping the treatment in group R more patients received a new anti-dementia medication (respectively 11 patients (79%) and 4 patients (33%)) (chi2(1) = 5.418, p = .026). CONCLUSION: Despite different forms, the use of oral galantamine and rivastigmine transdermal patch showed neither difference in the frequency of adverse events neither in the frequency of stopping primary treatment. However, compared to oral galantamine use, rivastigmine transdermal patch resulted in more dermatological adverse events and after stopping rivastigmine transdermal patch, new anti-dementia medication or form was more often started. More research is urgently needed.

[Applicability and validity of the Dutch version of the Montreal Cognitive Assessment (moCA-d) in diagnosing MCI]. / Bruikbaarheid en validiteit van de Nederlandse versie van de Montreal Cognitive Assessment (MoCA-D) bij het diagnosticeren van Mild Cognitive Impairment.

OBJECTIVE: The MoCA is a new screening test to detect Mild Cognitive Impairment (MCI). Purpose of this study is validating the Dutch version (MoCA-D). METHOD: We administered the MoCA-D to healthy control subjects and to elderly with MCI or dementia from a memory disorder outpatient clinic and a geriatric (outpatient) clinic (n = 30, 32, 37 respectively, age > or = 60). Neuropsychological testing was part of the standard procedure for patients to diagnose MCI. Sensitivity, specificity and predictive values (positive: PPV and negative: NPV) of the MoCA-D were assessed. RESULTS: A significant effect of group was found on MoCA-D total score (F (2.95) =67.9; p < 0.01). With a cutoff score of < or = 25, sensitivity and specificity to detect MCI in relation to healthy controls were 72% and 73%, respectively. PPV and NPV were 84% and 56%, respectively. With a cut-off score of < or = 20, sensitivity to detect dementia in relation to MCI was 100% for severe dementia and 75% for mild dementia. Specificity for dementia was 81%, PPV 94% and NPV 55%. CONCLUSION: The MoCA-D distinguishes between healthy elderly, MCI patients and dementia patients. However, in this study, insufficient sensitivity and poor specificity were found. For the present, applying a broader and flexible screening procedure in order to detect MCI seems a more useful method than the interpretation of one test result in particular.