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Aims: Initial studies of catheter-based renal arterial sympathetic denervation to lower blood pressure in resistant hypertensive patients renewed interest in the sympathetic nervous system's role in the pathogenesis of hypertension. However, the SYMPLICITY HTN-3 study failed to meet its prespecified blood pressure lowering efficacy endpoint. To date, only a limited number of studies have described the microanatomy of renal nerves, of which, only two involve humans.Methods and Results: Renal arteries were harvested from 15 cadavers from the Klinikum Osnabruck and Schuchtermann Klinik, Bad Rothenfelde. Each artery was divided longitudinally in equal thirds (proximal, middle, and distal), with each section then divided into equal superior, inferior, anterior, and posterior quadrants, which were then stained. Segments containing no renal nerves were given a score value = 0, 1-2 nerves with diameter <300 µm a score = 1; 3-4 nerves or nerve diameter 300-599 µm a score = 2, and >4 nerves or nerve diameter ≥600 µm a score = 3. A total of 22 renal arteries (9 right-sided, 13 left-sided) were suitable for examination. Overall, 691 sections of 5 mm thickness were prepared. Right renal arteries had significantly higher mean innervation grade (1.56 ± 0.85) compared to left renal arteries (1.09 ± 0.87) (P < 0.001). Medial (1.30 ± 0.59) and distal (1.39 ± 0.62) innervation was higher than the proximal (1.17 ± 0.55) segments (p < 0.001). When divided in quadrants, the anterior (1.52 ± 0.96) and superior (1.71 ± 0.89) segments were more innervated compared to posterior (0.96 ± 0.72) and inferior (0.90 ± 0.68) segments (P < 0.001).Conclusions: That the right renal artery has significantly higher innervation scores than the left. The anterior and superior quadrants of the renal arteries scored higher in innervation than the posterior and inferior quadrants did. The distal third of the renal arteries are more innervated than the more proximal segments. These findings warrant further evaluation of the spatial innervation patterns of the renal artery in order to understand how it may enhance catheter-based renal arterial denervation procedural strategy and outcomes.Condensed Abstract: The SYMPLICITY HTN-3 study dealt a blow to the idea of the catheter-based renal arterial sympathetic denervation. We investigated the location and patterns of periarterial renal nerves in cadaveric human renal arteries. To quantify the density of the renal nerves we created a novel innervation score. On average the right renal arteries were significantly more densely innervated than the left renal arteries, the anterior and superior segments were significantly more innervated compared to the posterior and inferior segments, absolute innervation scores in the proximal third of the left or right renal arteries were always lower when compared to distal segments. These findings may enhance catheter-based renal arterial denervation procedural strategy and outcomes. [ABSTRACT FROM AUTHOR]

Background Cannabis extracts have a wide therapeutic potential but in many countries they have not been approved for treatment in children so far. Objective We conducted an open, uncontrolled, retrospective study on the administration of dronabinol to determine the value, efficacy, and safety of cannabis-based medicines in the treatment of refractory spasticity in pediatric palliative care. Design and participants Sixteen children, adolescents and young adults having complex neurological conditions with spasticity (aged 1.3–26.6 years, median 12.7 years) were treated with dronabinol by our specialized pediatric palliative care team between 01.12.2010 and 30.04.2015 in a home-care setting. Therapeutic efficacy and side effects were closely monitored. Results Drops of the 2.5% oily tetrahydrocannabinol solution (dronabinol) were administered. A promising therapeutic effect was seen, mostly due to abolishment or marked improvement of severe, treatment resistant spasticity (n = 12). In two cases the effect could not be determined, two patients did not benefit. The median duration of treatment was 181 days (range 23–1429 days). Dosages to obtain a therapeutic effect varied from 0.08 to 1.0 mg/kg/d with a median of 0.33 mg/kg/d in patients with a documented therapeutic effect. When administered as an escalating dosage scheme, side effects were rare and only consisted in vomiting and restlessness (one patient each). No serious and enduring side effects occurred even in young children and/or over a longer period of time. Conclusions In the majority of pediatric palliative patients the treatment with dronabinol showed promising effects in treatment resistant spasticity. [ABSTRACT FROM AUTHOR]

Introduction Brain tumors have the highest disease-related mortality rate of all pediatric cancers. The goal of this study was to determine whether all children with incurable brain tumors cared for by a pediatric palliative care team in a home setting suffer from the same symptoms towards the end of their lives or whether there are differences between the tumor localizations with implications for palliative care. Patients and methods This study was conducted as a retrospective, single center chart review including all patients treated between January 1st 2000 and December 31st 2013. Results 70 children, adolescents and young adults were included in the analysis. Symptom burden was high with a mean number of symptoms of 7.2 per patient. 74% of the symptoms already existed one week before death. Within the last week of life, impaired consciousness (75.7%) most often occurred. Furthermore, symptoms considerably depended on tumor localization. Patients with supratentorial tumors presented more frequently with seizures ( p < 0.05), coma ( p < 0.01), nausea and emesis ( p < 0.01). Ataxia ( p < 0.001) occurred most frequently in infratentorial tumors and speech disturbances ( p < 0.05), cranial nerve paralysis ( p < 0.001), and tetraparesis ( p < 0.001) in brain stem tumors. 84.3% of the patients needed analgesics, only 64.4% WHO class III analgesics. Anticonvulsants were given more often in supratentorial tumors ( p < 0.01). Conclusions Caring for a dying child suffering from a brain tumor needs increased awareness of the neurological deterioration. The symptom pattern strongly depends on the tumor localization and significantly differs between supratentorial, infratentorial and brain stem tumors. [ABSTRACT FROM AUTHOR]

Pediatric advance care planning seeks to ensure end-of-life care conforming to the patients/their families' preferences. To expand our knowledge of advance care planning and "medical orders for life-sustaining treatment" (MOLST) in pediatric palliative home care, we determined the number of patients with MOLST, compared MOLST between the four "Together for Short Lives" (TfSL) groups and analyzed, whether there was a relationship between the content of the MOLST and the patients' places of death. The study was conducted as a single-center retrospective analysis of all patients of a large specialized pediatric palliative home care team (01/2013-09/2016). MOLST were available in 179/198 children (90.4%). Most parents decided fast on MOLST, 99 (55.3%) at initiation of pediatric palliative home care, 150 (83.4%) within the first 100 days. MOLST were only changed in 7.8%. Eighty/179 (44.7%) patients decided on a Do Not Attempt Cardio-Pulmonary Resuscitation (DNACPR) order, 58 (32.4%) on treatment limitations of some kind and 41 (22.9%) wished for the entire spectrum of life-sustaining measures (Full Code). Most TfSL group 1 families wanted DNACPR and most TfSL group 3/4 parents Full Code. The majority (84.9%) of all DNACPR patients died at home/hospice. Conversely, all Full Code patients died in hospital (80% in an intensive care setting). The circumstances of the childrens' deaths can therefore be predicted considering the content of the MOLST. Regular advance care planning discussions are thus a very important aspect of pediatric palliative home care., Competing Interests: CONFLICTS OF INTEREST The authors declare that there is no conflicts of interest.

Introduction: Hematologic malignancies (HM) represent the most common neoplasms in childhood. Despite improved overall survival rates, they are still a major contributor to cancer death in children., Aims: To determine the proportion of children with HM in pediatric palliative care (PPC) and to identify the clinical characteristics and symptoms in comparison to children with extracranial solid tumors (non HM patients)., Patients and Methods: This study was conducted as a single-center retrospective cohort study of patients in the care of a large specialized PPC team., Results: Fifteen HM and 50 non HM patients were included. Symptoms in which HM patients scored significantly higher than non HM patients were mucositis, difficulty moving, somnolence, fatigue, petechiae and paleness. Blood transfusions were more frequently administered to HM patients, but large external hemorrhage was not observed in any child. A large variety of drugs and appliances were needed by the patients, with morphine being the most frequently prescribed drug. During the study period, a much larger and over the years even increasing number of HM patients (not in the care of the PPC team) died in hospital with an (assumed) curative intent, with two thirds dying in the ICU., Conclusions: Children with HM were referred to outpatient PPC with almost the full clinical picture of advanced leukemia. Noteworthy, the number of children with HM dying at home is decreasing in our center, instead a substantial proportion received high-intensity medical hospital care including novel anticancer therapies. These patients thus seem to be at an increased risk of dying in hospital as the right time to transfer them to palliative care is oftentimes missed., Competing Interests: CONFLICTS OF INTEREST The authors have declared no conflicts of interest.

Introduction: Progressive and non-juvenile avascular osteonecrosis (AVN) is a rare condition in children. During the last decade, some data indicate that regional deep hyperthermia therapy (RHT) combined with either chemo- and / or radiotherapy in malignancies is associated with AVN in young patients. In this study, we present our data on AVN following RHT in children with intra-pelvic malignancies., Material and Methods: Localization, extent of AVN, and associated joint effusions were evaluated via MRI and X-ray findings in 37 patients treated with RHT and chemotherapy +/- additional radiotherapy for intra-pelvic malignancies in our study. AVN was classified in accordance to the Association Research Circulation Osseus (ARCO). In addition, the recurrence of sarcoma after RHT, the number of total joint replacements, and level of activity including sport activities were recorded in all patients. The mean follow-up was 6.2 years (SD: 4.1, range: 1-12 years)., Results: Eight out of 37 pediatric patients treated with RHT and chemotherapy +/- additional radiotherapy showed AVN of the femoral head within our follow-up period. Five out of the eight children developed bone marrow edema within 6 months after RHT procedure and three additional patients within the first year. All patients except one showed a rapid progression of AVN from ARCO stage 0 to the post-collapse-stages III and IV in our study. Seven out of eight AVN patients survived without evidence of further malignancy. Although advanced stages of AVN were observed in our patient group, they were able to still maintain a high quality of life. No patients in our group have undergone total hip replacement thus far., Conclusion: Based on our findings, we hypothesize a high risk of AVN in young children who receive RHT for pelvic sarcoma. However, further clinical investigation needs to be done to prove our hypothesis.

Chemokines orchestrate trafficking of immune effector cells during inflammation. Here we demonstrate that chemokines also serve to potentiate effector cell-mediated antineoplastic immune responses in vaccination strategies. As a critical mediator of inflammation, macrophage inflammatory protein 1alpha (CCL3/MIP-1alpha) attracts and stimulates both antigen-presenting and cytotoxic cells. In the A20 leukemia/lymphoma vaccine model, we explored the efficacy of MIP-1alpha in combination with interleukin-2 (IL-2) or granulocyte-macrophage colony-stimulating factor (GM-CSF). After subcutaneous injection of the MIP-1alpha + IL-2 or MIP-1alpha + GM-CSF combination vaccine, focal but pronounced infiltrates of CD4+ and CD8+ T cells were observed at the vaccination sites. In mice with preestablished leukemia/lymphoma, survival is significantly improved in animals treated with MIP-1alpha + GM-CSF- and MIP-1alpha + IL-2-secreting vaccines. Protection is superior in the MIP-1alpha + GM-CSF group, with the effects of MIP-1alpha and GM-CSF being synergistic. In contrast, suppression of lymphoblast proliferation by single-immunogen vaccines secreting MIP-1alpha, GM-CSF, or IL-2 alone does not translate to improved survival. The systemic protective effects afforded by the MIP-1alpha + IL-2 or MIP-1alpha + GM-CSF combination are mediated by different effector cell populations. In the MIP-1alpha + IL-2 group, antineoplastic defense is mediated by CD8+ T and NK cells, whereas in the MIP-1alpha + GM-CSF group CD4+ T cells are involved in addition to CD8+ cytotoxic T cells, underscoring that T cell help is critical for long-term protection. Thus combination of MIP-1alpha with different cytokines recruits different sets of effector cells into a potent antineoplastic immune response.