Spindle-slow wave coupling and problem-solving skills: Impact of age.

We examined how aging affects the role of sleep in the consolidation of newly learned cognitive strategies. Forty healthy young adults (20-35 years) and 30 healthy older adults (60-85 years) were included. Participants were trained on the Tower of Hanoi (ToH) task, then, half of each age group were assigned to either the 90-minute nap condition, or stayed awake, before retesting. The temporal co-occurrence between slow-waves (SW) and sleep spindles (SP) during NREM sleep was examined as a function of age in relation to memory consolidation of problem-solving skills. We found that despite intact learning, older adults derived a reduced benefit of sleep for problem-solving skills relative to younger adults. As expected, the percentage of coupled spindles was lower in older compared to younger individuals from control to testing sessions. Furthermore, coupled spindles in young adults were more strongly coupled to the SW upstate compared to older individuals. Coupled spindles in older individuals were lower in amplitude (mean area under curve; µV) compared to the young group. Lastly, there was a significant relationship between offline gains in accuracy on the ToH and percent change of spindles coupled to the upstate of the slow wave in older, but not younger adults. Multiple regression revealed that age accounted for differences in offline gains in accuracy, as did spindle coupling during the upstate. These results suggest that with aging, spindle-slow wave coupling decreases. However, the degree of the preservation of coupling with age correlates with the extent of problem-solving skill consolidation during sleep.

Global transcriptomic analysis in avocado nursery trees reveals differential gene expression during asymptomatic infection by avocado sunblotch viroid (ASBVd).

Avocado sunblotch viroid (ASBVd) is the type species of the family Avsunviroidae and the causal agent of avocado sunblotch disease. The disease is characterised by the presence of chlorotic lesions on avocado fruit, leaves and/or stems. Infected trees may remain without chlorosis for extended periods of time, though distorted growth and reduced yield has been observed in these cases. The molecular effects of ASBVd on avocado, and members of the Avsunviroidae on their respective hosts in general, remain poorly understood. Host global transcriptomic studies within the family Pospiviroidae have identified several host pathways that are affected during these plant-pathogen interactions. In this study, we used RNA sequencing to investigate host gene expression in asymptomatic avocado nursery trees infected with ASBVd. Transcriptome data showed that 631 genes were differentially expressed, 63 % of which were upregulated during infection. Plant defence responses, phytohormone networks, gene expression pathways, secondary metabolism, cellular transport as well as protein modification and degradation were all significantly affected by ASBVd infection. This work represents the first global gene expression study of ASBVd-infected avocado, and the transcriptional reprogramming observed during this asymptomatic infection improves our understanding of the molecular interactions underlying broader avsunviroid-host interactions.

How can patient registries facilitate guideline-based healthcare? A retrospective analysis of the CEDATA-GPGE registry for pediatric inflammatory bowel disease.

BACKGROUND: Early diagnosis is mandatory for the medical care of children and adolescents with pediatric-onset inflammatory bowel disease (PIBD). International guidelines ('Porto criteria') of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition recommend medical diagnostic procedures in PIBD. Since 2004, German and Austrian pediatric gastroenterologists document diagnostic and treatment data in the patient registry CEDATA-GPGE on a voluntary basis. The aim of this retrospective study was to analyze whether the registry CEDATA-GPGE reflects the Porto criteria and to what extent diagnostic measures of PIBD according to the Porto criteria are documented. METHODS: Data of CEDATA-GPGE were analyzed for the period January 2014 to December 2018. Variables representing the Porto criteria for initial diagnostic were identified and categorized. The average of the number of measures documented in each category was calculated for the diagnoses CD, UC, and IBD-U. Differences between the diagnoses were tested by Chi-square test. Data on possible differences between data documented in the registry and diagnostic procedures that were actually performed were obtained via a sample survey. RESULTS: There were 547 patients included in the analysis. The median age of patients with incident CD (n = 289) was 13.6 years (IQR: 11.2-15.2), of patients with UC (n = 212) 13.1 years (IQR: 10.4-14.8) and of patients with IBD-U (n = 46) 12.2 years (IQR: 8.6-14.7). The variables identified in the registry fully reflect the recommendations by the Porto criteria. Only the disease activity indices PUCAI and PCDAI were not directly provided by participants but calculated from obtained data. The category 'Case history' were documented for the largest part (78.0%), the category 'Imaging of the small bowel' were documented least frequently (39.1%). In patients with CD, the categories 'Imaging of the small bowel' (χ2 = 20.7, Cramer-V = 0.2, p < 0.001) and 'Puberty stage' (χ2 = 9.8, Cramer-V = 0.1, p < 0.05) were documented more often than in patients with UC and IBD-U. CONCLUSION: The registry fully reproduces the guideline's recommendations for the initial diagnosis of PIBD. The proportion of documented diagnostic examinations varied within the diagnostic categories and between the diagnoses. Despite technological innovations, time and personnel capacities at participating centers and study center are necessary to ensure reliable data entry and to enable researchers to derive important insights into guideline-based care.

How Sleep Research in Extreme Environments Can Inform the Military: Advocating for a Transactional Model of Sleep Adaptation.

PURPOSE OF REVIEW: We review the literature on sleep in extreme environments. Accordingly, we present a model that identifies the need for mitigating interventions to preserve sleep quality for military deployments. RECENT FINDINGS: Situational factors that affect sleep in extreme environments include cold temperatures, isolated and confined areas, fluctuating seasonality, photoperiodicity, and extreme latitudes and altitudes. Results vary across studies, but general effects include decreased total sleep time, poor sleep efficiency, and non-specific phase delays or phase advances in sleep onset and sleep architecture. Considering habitability measures (e.g., light or temperature control) and individual differences such as variable stress responses or sleep need can mitigate these effects to improve mood, cognition, and operational performance. Although the situational demands during military missions inevitably reduce total sleep time and sleep efficiency, mitigating factors can attenuate sleep-related impairments, hence allowing for optimal mission success and personnel safety.

Does left atrial epicardial conduction time reflect atrial fibrosis and the risk of atrial fibrillation recurrence after thoracoscopic ablation? Post hoc analysis of the AFACT trial.

OBJECTIVES: To determine the association between left atrial epicardial conduction time (LAECT), fibrosis and atrial fibrillation (AF) recurrence after thoracoscopic surgical ablation of persistent AF. SETTING: Single tertiary care centre in the Netherlands. PARTICIPANTS: Patients with persistent AF from the randomised Atrial Fibrillation Ablation and Autonomic Modulation via Thoracoscopic Surgery (AFACT)-trial were included. Patients eligible for thoracoscopic AF ablation were included, full inclusion and exclusion criteria were previously published. All patients underwent thoracoscopic ablation, encompassing pulmonary vein isolation with an additional roof and trigone lesion. In patients with conduction block across the roof and trigone lesion, LAECT was measured. LAECT was defined as the time to local activation at one side of the roofline on pacing from the opposite side. Collagen fibre density was quantified from left atrial appendage histology. OUTCOME MEASURES: Primary outcome: AF recurrence during 2 years of follow-up. RESULTS: 121 patients were included, of whom 35(29%) were women, age was 60.4±7.8 and 51% (62) had at least one AF recurrence during 2 years of follow-up. LAECT was longer in patients with versus without AF recurrence (182±43 ms vs 147±29 ms, p<0.001). LAECT was longer in older patients, in patients with a higher body mass index (BMI) and in patients using class IC antiarrhythmic drugs. LAECT was shorter in patients with higher collagen fibre density. A previously failed catheter ablation, LAECT and BMI were independently associated with AF recurrence. CONCLUSION: LAECT is correlated with collagen fibre density and BMI and is independently associated with AF recurrence in patients with persistent AF. In these patients, LAECT appears to reflect substrate characteristics beyond clinical AF type and left atrial volume. TRIAL REGISTRATION NUMBER: NCT01091389.

Sleep Enhances Consolidation of Memory Traces for Complex Problem-Solving Skills.

Sleep consolidates memory for procedural motor skills, reflected by sleep-dependent changes in the hippocampal-striatal-cortical network. Other forms of procedural skills require the acquisition of a novel strategy to solve a problem, which recruit overlapping brain regions and specialized areas including the caudate and prefrontal cortex. Sleep preferentially benefits strategy and problem-solving skills over the accompanying motor execution movements. However, it is unclear how acquiring new strategies benefit from sleep. Here, participants performed a task requiring the execution of a sequence of movements to learn a novel cognitive strategy. Participants performed this task while undergoing fMRI before and after an interval of either a full night sleep, a daytime nap, or wakefulness. Participants also performed a motor control task, which precluded the opportunity to learn the strategy. In this way, we subtracted motor execution-related brain activations from activations specific to the strategy. The sleep and nap groups experienced greater behavioral performance improvements compared to the wake group on the strategy-based task. Following sleep, we observed enhanced activation of the caudate in addition to other regions in the hippocampal-striatal-cortical network, compared to wakefulness. This study demonstrates that sleep is a privileged time to enhance newly acquired cognitive strategies needed to solve problems.

Care and referral patterns in a large, dedicated nurse-led atrial fibrillation outpatient clinic.

INTRODUCTION: Atrial fibrillation (AF) is the most common arrhythmia and imposes a high burden on the healthcare system. A nurse-led AF outpatient clinic may alleviate the burden on the cardiology outpatient clinic by triaging patients who need care by a cardiologist or general practitioner (GP). However, care and referral patterns after initial assessment in a nurse-led AF outpatient clinic are unknown. We examined the proportion of AF patients assessed in a nurse-led clinic without outpatient follow-up by a cardiologist. METHODS: All patients with AF referred to our tertiary medical centre underwent cardiac work-up in the nurse-led AF outpatient clinic and were prospectively followed. Data on patient characteristics, rhythm monitoring and echocardiography were collected and described. Odds ratio (OR) for continuing care in the nurse-led AF outpatient clinic was calculated. RESULTS: From 2014 to 2018, 478 consecutive individual patients were referred to the nurse-led AF outpatient clinic. After the initial cardiac work-up, 139 patients (29.1%) remained under nurse-led care and 121 (25.3%) were referred to a cardiologist and 218 (45.6%) to a GP. Patients who remained under nurse-led care were significantly younger, were more symptomatic, more often had paroxysmal AF and had less comorbidities than the other two groups. After multivariable testing, CHA2DS2-VASc score ≥ 2 was associated with discontinued nurse-led care (OR 0.57, 95% confidence interval 0.34-0.95). CONCLUSION: After initial cardiac assessment in the nurse-led outpatient clinic, about half of the newly referred AF patients were referred back to their GP. This strategy may reduce the burden of AF patients on secondary or tertiary cardiology outpatient clinics.

Save the children by treating their mothers (PriVileG-M-study) - study protocol: a sequentially randomized controlled trial of individualized psychotherapy and telemedicine to reduce mental stress in pregnant women and young mothers and to improve Child's health.

BACKGROUND: As early as pregnancy, maternal mental stress impinges on the child's development and health. Thus, this may cause enhanced risk for premature birth, lowered fetal growth, and lower fetal birth weight as well as enhanced levels of the stress hormone cortisol and lowered levels of the bonding hormone oxytocin. Maternal stress further reduces maternal sensitivity for the child's needs which impairs the mother-child-interaction and bonding. Therefore, prevention and intervention studies on mental stress are necessary, beginning prenatally and applying rigorous research methodology, such as randomized controlled trials, to ensure high validity. METHODS: A randomized controlled trial is used to assess the impact of psychotherapy and telemedicine on maternal mental stress and the child's mental and physical health. Mentally stressed pregnant women are randomized to an intervention (IG) and a not intervened control group. The IG receives an individualized psychotherapy starting prenatal and lasting for 10 months. Afterwards, a second randomization is used to investigate whether the use of telemedicine can stabilize the therapeutic effects. Using ecological momentary assessments and video recordings, the transfer into daily life, maternal sensitivity and mother-child-bonding are assessed. Psycho-biologically, the synchronicity of cortisol and oxytocin levels between mother and child are assessed as well as the peptidome of the colostrum and breast milk, which are assumed to be essential for the adaptation to the extra-uterine environment. All assessments are compared to an additional control group of healthy women. Finally, the results of the study will lead to the development of a qualification measure for health professionals to detect mental stress, to treat it with low-level interventions and to refer those women with high stress levels to mental health professionals. DISCUSSION: The study aims to prevent the transgenerational transfer of psychiatric and somatic disorders from the mother to her child. The effects of the psychotherapy will be stabilized through telemedicine and long-term impacts on the child's and mothers' mental health are enhanced. The combination of psychotherapy, telemedicine and methodologies of ecological momentary assessment, video recording and bio banking are new in content-related and methodological manner. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00017065. Registered 02 May 2019. World Health Organization, Universal Trial Number: U1111-1230-9826. Registered 01 April 2019.

Mild water stress-induced priming enhance tolerance to Rosellinia necatrix in susceptible avocado rootstocks.

BACKGROUND: White root rot (WRR) disease caused by Rosellinia necatrix is one of the most important threats affecting avocado orchards in temperate regions. The eradication of WRR is a difficult task and environmentally friendly control methods are needed to lessen its impact. Priming plants with a stressor (biotic or abiotic) can be a strategy to enhance plant defense/tolerance against future stress episodes but, despite the known underlying common mechanisms, few studies use abiotic-priming for improving tolerance to forthcoming biotic-stress and vice versa ('cross-factor priming'). To assess whether cross-factor priming can be a potential method for enhancing avocado tolerance to WRR disease, 'Dusa' avocado rootstocks, susceptible to R. necatrix, were subjected to two levels of water stress (mild-WS and severe-WS) and, after drought-recovery, inoculated with R. necatrix. Physiological response and expression of plant defense related genes after drought-priming as well as the disease progression were evaluated. RESULTS: Water-stressed avocado plants showed lower water potential and stomatal limitations of photosynthesis compared to control plants. In addition, NPQ and qN values increased, indicating the activation of energy dissipating mechanisms closely related to the relief of oxidative stress. This response was proportional to the severity of the water stress and was accompanied by the deregulation of pathogen defense-related genes in the roots. After re-watering, leaf photosynthesis and plant water status recovered rapidly in both treatments, but roots of mild-WS primed plants showed a higher number of overexpressed genes related with plant defense than severe-WS primed plants. Disease progression after inoculating primed plants with R. necatrix was significantly delayed in mild-WS primed plants. CONCLUSIONS: These findings demonstrate that mild-WS can induce a primed state in the WRR susceptible avocado rootstock 'Dusa' and reveal that 'cross-factor priming' with water stress (abiotic stressor) is effective for increasing avocado tolerance against R. necatrix (biotic stressor), underpinning that plant responses against biotic and abiotic stress rely on common mechanisms. Potential applications of these results may involve an enhancement of WRR tolerance of current avocado groves and optimization of water use via low frequency deficit irrigation strategies.

Sleep preferentially enhances memory for a cognitive strategy but not the implicit motor skills used to acquire it.

Sleep is known to be beneficial to the strengthening of two distinct forms of procedural memory: memory for novel, cognitively simple series of motor movements, and memory for novel, cognitively complex strategies required to solve problems. However, these two types of memory are intertwined, since learning a new cognitive procedural strategy occurs through practice, and thereby also requires the execution of a series of simple motor movements. As a result, it is unclear whether the benefit of sleep results from the enhancement of the cognitive strategy, or the motor skills required to execute the solution. To disentangle the role of sleep in these aspects of procedural memory, we employed two tasks: (1) the Tower of Hanoi (ToH), and, (2) a modified version of the ToH, akin to an implicit Motor Sequence Learning (MSL) task. The MSL task involved the identical series of motor movements as the ToH, but without access to the information necessary to execute the task according to the underlying cognitive procedural strategy. Participants (n = 28) were trained on the 3-disk ToH, then retested on 5-disk versions of both ToH and MSL tasks. Half (n = 15) were trained and immediately tested at 8 PM and retested at 8 AM after a night of sleep. They were retested again at 8 PM after a day of wake (PM-AM-PM condition). The other half (n = 13) were trained and immediately tested at 8 AM, retested at 8 PM after a day of wake, and retested again at 8 AM after a night of sleep (AM-PM-AM condition). ToH performance only improved following a period of sleep. There was no benefit of sleep to implicit MSL. Our results show that sleep, but not wake, allowed individuals to extrapolate what was learned on a simpler 3-disk version of the task to the larger 5-disk problem, which included new elements to which they had not yet been exposed. Here, we isolate the specific role sleep plays for cognitive procedural memory: sleep benefits the cognitive strategy, rather than strengthening implicitly acquired motor sequences required to learn and execute the underlying strategy itself.

The best of both worlds: a hybrid approach for optimal pre- and intraoperative identification of sentinel lymph nodes.

PURPOSE: Hybrid image-guided surgery technologies such as combined radio- and fluorescence-guidance are increasingly gaining interest, but their added value still needs to be proven. In order to evaluate if and how fluorescence-guidance can help realize improvements beyond the current state-of-the-art in sentinel node (SN) biopsy procedures, use of the hybrid tracer indocyanine green (ICG)-99mTc-nancolloid was evaluated in a large cohort of patients. PATIENTS AND METHODS: A prospective trial was conducted (n = 501 procedures) in a heterogeneous cohort of 495 patients with different malignancies (skin malignancies, oral cavity cancer, penile cancer, prostate cancer and vulva cancer). After injection of ICG-99mTc-nanocolloid, SNs were preoperatively identified based on lymphoscintigraphy and SPECT/CT. Intraoperatively, SNs were pursued via gamma tracing, visual identification (blue dye) and/or near-infrared fluorescence imaging during either open surgical procedures (head and neck, penile, vulvar cancer and melanoma) or robot assisted laparoscopic surgery (prostate cancer). As the patients acted as their own control, use of hybrid guidance could be compared to conventional radioguidance and the use of blue dye (n = 300). This was based on reported surgical complications, overall survival, LN recurrence free survival, and false negative rates (FNR). RESULTS: A total of 1,327 SN-related hotspots were identified on 501 preoperative SPECT/CT scans. Intraoperatively, a total number of 1,643 SNs were identified based on the combination of gamma-tracing (>98%) and fluorescence-guidance (>95%). In patients wherein blue dye was used (n = 300) fluorescence-based SN detection was superior over visual blue dye-based detection (22-78%). No adverse effects related to the use of the hybrid tracer or the fluorescence-guidance procedure were found and outcome values were not negatively influenced. CONCLUSION: With ICG-99mTc-nanocolloid, the SN biopsy procedure has become more accurate and independent of the use of blue dye. With that, the procedure has evolved to be universal for different malignancies and anatomical locations.

Can we spice up our Christmas dinner? : Busting the myth of the 'Chinese restaurant syndrome'.

BACKGROUND: Monosodium glutamate (MSG), also referred to as Vetsin or E621, is a flavour enhancer frequently used in Asian cuisine and abundantly present in the famous Chinese dish Peking duck. MSG is notorious for triggering the onset of the so-called 'Chinese restaurant syndrome' (CRS), a complex of unpleasant symptoms, which might include flushing, sweating and the onset of atrial fibrillation (AF). This study aims to determine the effects of MSG on the occurrence of AF. METHODS: We conducted a placebo self-controlled single-arm study in the Academic Medical Centre in Amsterdam. We included paroxysmal AF patients who reported a consistent onset of AF upon MSG intake. During three admissions, participants were subsequently administered: placebo, 1.5 g and 3 g MSG. If AF was recorded after the dose of 1.5 g MSG, patients were given another placebo instead of 3 g MSG. The primary outcome was the onset of AF registered by 24-hour Holter monitoring. The secondary outcomes were any other arrhythmia and the onset of CRS defined as two or more symptoms of CRS after MSG intake. RESULTS: Six men participated in the study. Both 1.5 g and 3 g MSG were unrelated to CRS, arrhythmias or AF occurrence. CONCLUSION: Peking duck can be put on the Christmas menu without risking guests to be admitted to the emergency department with new episodes of AF.

Aldosterone Pathway Blockade to Prevent Atrial Fibrillation: A Systematic Review and Meta-Analysis.

BACKGROUND: Despite advances in therapeutic interventions AF remains a progressive and symptomatic disease. Therefore, novel therapeutic interventions targeting the underlying arrhythmogenic substrate for AF is needed. Atrial fibrosis is an important component of the arrhythmogenic substrate of AF and may be initiated by aldosterone binding to the mineralocorticoid receptor. We hypothesized that aldosterone pathway blockade with mineralocorticoid receptor antagonists (MRA) reduces atrial fibrosis, and thus AF. METHODS: We searched OVID MEDLINE, OVID EMBASE and the Cochrane Central Register of Controlled Trials from inception to June 10th, 2016 for randomized controlled trials (RCT) and observational studies addressing MRA and providing information on AF occurrence. Two independent reviewers selected and appraised the data. We performed random-effects meta-analyses. Summary odds ratios (OR) with 95% confidence intervals (CI) were calculated. RESULTS: We included 14 studies, 5 RCT and 9 observational cohorts, with a cumulative number of 5332 patients (male: 74.9%, age: 65.3years); 2397 (45.0%) received an MRA (spironolactone or eplerenone). During follow-up, 204 (8.5%) patients treated with MRAs, developed AF, compared to 547 (18.6%) patients, without MRA treatment. Meta-analyses showed a significant overall reduction of AF risk in MRA treated patients (OR: 0.48 CI: 0.38-0.60 p<0.001), including a reduction of new-onset AF (OR: 0.52 CI: 0.37-0.74 p<0.001) and recurrent AF (OR: 0.37 CI: 0.24-0.57 p<0.001), but not post-operative AF (POAF) (OR: 0.60 CI: 0.33-1.09 p=0.09). CONCLUSIONS: MRAs significantly reduce new-onset AF and recurrent AF, but not POAF. MRA treatment can be considered an additive therapeutic strategy in AF.

Fluorinated steroids do not improve outcome of isolated atrioventricular block.

INTRODUCTION: Congenital atrioventricular block (CAVB) is a rare disorder with a significant morbidity and mortality. Consensus regarding the prescription and efficacy of prenatal corticosteroids is lacking. This nationwide study was initiated to evaluate the effects of prenatal treatment with corticosteroids on the outcome of CAVB in The Netherlands. METHODS: All fetuses identified with isolated congenital AVB-II° or AVB-III° in any of the eight academic fetal heart centers of The Netherlands between 2003 and 2013 were included and reviewed. RESULTS: Fifty-six fetuses were included. Fourteen (25%) fetuses were treated with dexamethasone. We found no differences between the steroid-treated and untreated cases regarding in utero progression of the AVB (63% vs 67% respectively), survival to birth (86% vs 84%), pacemaker implantations (74% vs 58%) or long-term dilated cardiomyopathy (13% vs 17%). Steroid treated fetuses demonstrated more in utero growth restriction (38% vs 11%). CONCLUSION: No benefit from prenatal corticosteroid treatment was demonstrated for fetuses with isolated CAVB in this study. However, we found negative side effects. Our data provide no evidence to support the routine administration of corticosteroids for the treatment of fetal CAVB.

Transcriptome responses of an ungrafted Phytophthora root rot tolerant avocado (Persea americana) rootstock to flooding and Phytophthora cinnamomi.

BACKGROUND: Avocado (Persea americana Mill.) is a commercially important fruit crop worldwide. A major limitation to production is the oomycete Phytophthora cinnamomi, which causes root rot leading to branch-dieback and tree death. The decline of orchards infected with P. cinnamomi occurs much faster when exposed to flooding, even if flooding is only transient. Flooding is a multifactorial stress compromised of several individual stresses, making breeding and selection for tolerant varieties challenging. With more plantations occurring in marginal areas, with imperfect irrigation and drainage, understanding the response of avocado to these stresses will be important for the industry. RESULTS: Maintenance of energy production was found to be central in the response to flooding, as seen by up-regulation of transcripts related to glycolysis and induction of transcripts related to ethanolic fermentation. Energy-intensive processes were generally down-regulated, as evidenced by repression of transcripts related to processes such as secondary cell-wall biosynthesis as well as defence-related transcripts. Aquaporins were found to be down-regulated in avocado roots exposed to flooding, indicating reduced water-uptake under these conditions. CONCLUSIONS: The transcriptomic response of avocado to flooding and P. cinnamomi was investigated utilizing microarray analysis. Differences in the transcriptome caused by the presence of the pathogen were minor compared to transcriptomic perturbations caused by flooding. The transcriptomic response of avocado to flooding reveals a response to flooding that is conserved in several species. This data could provide key information that could be used to improve selection of stress tolerant rootstocks in the avocado industry.

[Legal Analysis of the Implementation Rules of Delegation of Home Visits by Family Doctors to Non-Physician Health Professionals: Is the Implementation in Accordance with the Intention of the Law?] / Juristische Analyse der Umsetzungsregelungen der Delegation vertragsärztlicher Hausbesuche an nicht-ärztliche Gesundheitsberufe ­ ist die Umsetzung in Einklang mit dem Willen des Gesetzgebers?

Objective: Triggered by the AGnES model project of the University Medicine Greifswald, the Code of Social Law V was changed by the German Lower and Upper House of Parliament (Bundestag and Bundesrat) in 2008 so that the delegation of GP's activities to non-physician colleagues was allowed under highly restricted preconditions. Delegated home visits should become an integral part of the standard care in Germany. In this study, the implementation of § 87 para 2b clause 5 SGB V, established in Annex 8 of the Federal Collective Agreement, was checked for its legality in terms of qualification. Methods: The problem was checked with the legal methods of interpretation in pursuance of the norm and the methods of systematic, historic and teleologic interpretation. Results: Even though the Parliament clearly required orientation to the AGnES model project (in order to assure safety and effective care of delegated home visits), self-management in the implementation of the law remained far behind these guidelines. The main outcome of the legal analysis was that the implementation arrangements of the Code of Social Law V are predominantly illegal. Conclusions: The parties of the Federal Collective Agreement have to change the arrangements to meet the requirements of the Parliament and to avoid risks of liability for delegating GPs.

Hybrid radioguided occult lesion localization (hybrid ROLL) of (18)F-FDG-avid lesions using the hybrid tracer indocyanine green-(99m)Tc-nanocolloid.

PURPOSE: To assess if combined fluorescence- and radio-guided occult lesion localization (hybrid ROLL) is feasible in patients scheduled for surgical resection of non-palpable (18)F-FDG-avid lesions on PET/CT. METHODS: Four patients with (18)F-FDG-avid lesions on follow-up PET/CT that were not palpable during physical examination but were suspected to harbor metastasis were enrolled. Guided by ultrasound, the hybrid tracer indocyanine green (ICG)-(99m)Tc-nanocolloid was injected centrally in the target lesion. SPECT/CT imaging was used to confirm tracer deposition. Intraoperatively, lesions were localized using a hand-held gamma ray detection probe, a portable gamma camera, and a fluorescence camera. After excision, the gamma camera was used to check the wound bed for residual activity. RESULTS: A total of six (18)F-FDG-avid lymph nodes were identified and scheduled for hybrid ROLL. Comparison of the PET/CT images with the acquired SPECT/CT after hybrid tracer injection confirmed accurate tracer deposition. No side effects were observed. Combined radio- and fluorescence-guidance enabled localization and excision of the target lesion in all patients. Five of the six excised lesions proved tumor-positive at histopathology. CONCLUSION: The hybrid ROLL approach appears to be feasible and can facilitate the intraoperative localization and excision of non-palpable lesions suspected to harbor tumor metastases. In addition to the initial radioguided detection, the fluorescence component of the hybrid tracer enables high-resolution intraoperative visualization of the target lesion. The procedure needs further evaluation in a larger cohort and wider range of malignancies to substantiate these preliminary findings.