Consensus-Based Best Practice Guidelines for the Management of Spinal Deformity and Associated Tumors in Pediatric Neurofibromatosis Type 1: Screening and Surveillance, Surgical Intervention, and Medical Therapy.

BACKGROUND: Spinal conditions, such as scoliosis and spinal tumors, are prevalent in neurofibromatosis type 1 (NF1). Despite the recognized importance of their early detection and treatment, there remain knowledge gaps in how to approach these manifestations. The purpose of this study was to utilize the experience of a multidisciplinary committee of experts to establish consensus-based best practice guidelines (BPGs) for spinal screening and surveillance, surgical intervention, and medical therapy in pediatric patients with NF1. METHODS: Using the results of a prior systematic review, 10 key questions that required further assessment were first identified. A committee of 20 experts across medical specialties was then chosen based on their clinical experience with spinal deformity and tumors in NF1. These were 9 orthopaedic surgeons, 4 neuro-oncologists/oncologists, 3 neurosurgeons, 2 neurologists, 1 pulmonologist, and 1 clinical geneticist. An initial online survey on current practices and opinions was conducted, followed by 2 additional surveys via a formal consensus-based modified Delphi method. The final survey involved voting on agreement or disagreement with 35 recommendations. Items reaching consensus (≥70% agreement or disagreement) were included in the final BPGs. RESULTS: Consensus was reached for 30 total recommendations on the management of spinal deformity and tumors in NF1. These were 11 recommendations on screening and surveillance, 16 on surgical intervention, and 3 on medical therapy. Five recommendations did not achieve consensus and were excluded from the BPGs. CONCLUSION: We present a set of consensus-based BPGs comprised of 30 recommendations for spinal screening and surveillance, surgical intervention, and medical therapy in pediatric NF1.

Critical appraisal of international guidelines for the management of fecal incontinence in adults: is it possible to define what to do in different clinical scenarios?

Fecal incontinence (FI) is a complex often multifactorial functional disorder which is associated with a significant impact on patients' quality of life. There is a broad spectrum of symptoms, and degrees of severity and diverse patient backgrounds. Several treatment algorithms from different professional societies and experts are available in the literature. However, no consensus has been reached on several aspects of FI management. We performed a critical review of the most recently published guidelines on FI, emphasising the lack of consensus, highlighting specific topics mentioned in each of the guidelines that are not covered in the others and defining the treatment proposed in different clinical scenarios.

Sacral neuromodulation in patients with congenital faecal incontinence. Special issues and review of the literature.

BACKGROUND: The aim of the present study was to evaluate the effectiveness of sacral neuromodulation (SNM) as a treatment for congenital faecal incontinence (FI). METHODS: A retrospective study was conducted on patients with congenital FI who had SNM surgery at our institution between October 2005 and June 2013. An initial percutaneous nerve evaluation was performed, and patients with an improvement of more than 50% in their symptoms had permanently implants for SNM treatment. RESULTS: There were 4 patients who received a permanent implant. Mean duration of follow-up was 67.5 months (range 45-135 months). At last follow-up, 2 patients maintained significant improvement with SNM, 1 was explanted after 4 years of treatment due to infection but remained asymptomatic and SNM failed in the remaining patient who went on to graciloplasty. CONCLUSIONS: SNM may be of value for treating FI in patients with anorectal malformations.

Superficial femoral artery endothelial responses to a short-term altered shear rate intervention in healthy men.

In animal and in-vitro models, increased oscillatory shear stress characterized by increased retrograde shear-rate (SR) is associated with acutely decreased endothelial cell function. While previous research suggests a possible detrimental role of elevated retrograde SR on endothelial-function in the brachial artery in humans, little research has been conducted examining arteries in the leg. Examinations of altered shear pattern in the superficial femoral artery (SFA) are important, as this vessel is both prone to atherosclerosis and leg exercise is a common form of activity in humans. Seven healthy men participated; bilateral endothelial-function was assessed via flow-mediated-dilation (FMD) before and after 30-minute unilateral inflations of a thigh blood pressure cuff to either 75 mmHg or 100 mmHg on two separate visits. Inflation of the cuff induced increases in maximum anterograde (p<0.05), maximum retrograde (p<0.01), and oscillatory shear index (OSI) (p<0.001) in the cuffed leg at both inflation pressures. At 100 mmHg the increases in SR were larger in the retrograde than the anterograde direction evidenced by a decrease in mean SR (p<0.01). There was an acute decrease in relative FMD in the cuffed leg alone following inflation to both pressures. These results indicate that in the SFA, altered SR profiles incorporating increased retrograde and OSI influence the attenuation in FMD after a 30-minute unilateral thigh-cuff inflation intervention. Novel information highlighting the importance of OSI calculations and assessments of flow profiles add to current body of knowledge regarding the influence of changes in SR patterns on FMD. Findings from the current study may provide additional insight when designing strategies to combat impaired vascular function in the lower extremity where blood vessels are more prone to atherosclerosis in comparison to the upper extremity.

Project ALERT with outside leaders: what leader characteristics are important for success?

A previously published effectiveness study of Project ALERT delivered in schools by outside providers from Cooperative Extension found no positive effects for the adult or teen-assisted delivery of the curriculum despite high-quality implementation. Those findings and the likelihood that more outside providers will deliver evidence-based drug prevention programs in the future, led to this investigation of possible influences of leaders' personal characteristics on ALERT's program effects. Influence of leader characteristics on students' drug use and mediating variables for use were assessed by modeling program effects on within-student change as a function of leader characteristics. Students in classrooms with adult leaders who were more conscientious, sociable, or individuated were more likely to experience beneficial program effects. Students in teen-assisted classrooms with teen leaders who were more sociable or, to a lesser extent, highly individuated, showed more positive effects. Implications for research and practice are discussed.

PET/CT imaging: detection of choroidal melanoma.

AIM: To determine the size of untreated choroidal melanomas resolved by whole body positron emission tomography fused with computed tomography (PET/CT). METHODS: 50 consecutive patients with untreated choroidal melanomas underwent whole body PET/CT. A functionally fused helical CT scan and 18-fluoro-2-deoxyglucose (FDG) PET scans were employed. The tumours were identified (both quantitatively and qualitatively) and compared with clinical measurements derived from ophthalmoscopic, angiographic, and ultrasonographic imaging. Standardised uptake values (SUV) of more than 2.5 were considered positive. RESULTS: Among the 50 patients with choroidal melanoma, PET/CT scan SUVs of more than 2.5 were noted in 14 (28%) tumours. No AJCC T1 class tumours, 33.3% of T2 melanomas, and 75% of T3 melanomas were physiologically identifiable on PET/CT. With respect to COMS group classifications, no small choroidal tumours, 33% of medium, and 75% of large melanomas were physiologically identifiable. The sole ring melanoma was identifiable on PET/CT imaging. The smallest tumour physiologically identifiable by PET/CT had basal dimensions of 3x5.9 and an apical height of 2.9 mm. CONCLUSION: Though PET/CT was found to be capable of physiologically identifying certain medium (T2) and most large sized (T3) choroidal melanomas, physiological imaging was not completely dependent upon tumour size. Functionally fused PET/CT localised the tumours within the eye and assessed their physiological activity.

Whole body PET/CT for initial staging of choroidal melanoma.

AIM: To investigate the value of whole body positron emission tomography/computed tomography (PET/CT) in screening for metastatic choroidal melanoma in patients initially diagnosed with choroidal melanoma. METHODS: 52 patients with choroidal melanoma underwent whole body PET/CT as part of their metastatic investigation. PET/CT scans were used as a screening tool at the time of their initial diagnosis. A physical examination, liver function tests, and a baseline chest x ray were also obtained. PET/CT images (utilising intravenous18-fluoro-2-deoxyglucose (FDG)) were studied for the presence of metastatic melanoma. The standards for reference were further imaging and/or subsequent biopsies. RESULTS: Two of 52 (3.8%) patients were found to have metastatic melanoma before treatment. The most common sites for metastases were the liver (100%), bone (50%), and lymph nodes (50%). Brain involvement was also present in one patient. One patient (50%) had involvement of multiple sites. Haematological liver enzyme assays were normal in both patients. PET/CT showed false positive results in three patients (5.7%) when further evaluated by histopathology and/or additional imaging. In seven patients (13.4%) PET/CT imaging detected benign lesions in the bone, lung, lymph nodes, colon, and rectum. CONCLUSION: PET/CT imaging can be used as a screening tool for the detection and localisation of metastatic choroidal melanoma. Liver enzyme assays did not identify liver metastases, while PET/CT revealed both hepatic and extrahepatic metastatic melanoma. PET/CT imaging may improve upon the conventional methods of screening for detection of metastatic disease in patients initially diagnosed with choroidal melanoma.

Results of an independent evaluation of Project ALERT delivered in schools by Cooperative Extension.

Reported are results of an independent effectiveness study of the Project ALERT drug prevention program implemented in eight Pennsylvania middle schools by outside program leaders employed by Cooperative Extension. In this randomized, 2-cohort longitudinal evaluation, 1,649 seventh-grade students completed a pretest and four waves of posttests over the 2-year program and 1-year follow-up. Project ALERT's effectiveness was tested through a 3-level hierarchical linear model. Analyses failed to yield any positive effects for substance use or mediators for use in the adult or teen-assisted delivery of the curriculum. An extensive set of additional analyses detected no differential program effects by student risk level, gender, school, or level of implementation quality. Potential explanations for outcomes relative to Project ALERT's original effectiveness trial are discussed, as well as implications for future research, including the need to conduct independent effectiveness studies of previously validated programs in a variety of contexts.

Modern external beam radiation therapy for refractory dissecting cellulitis of the scalp.

BACKGROUND: Dissecting cellulitis of the scalp can be an extremely painful and disfiguring dermatological condition. The associated pain can be severe enough in some cases to require opioid analgesics, and this pain in conjunction with the disfigurement can induce significant emotional distress. Conservative treatments often fail to provide relief. Radiation therapy has been successfully used in the past but with outdated equipment and techniques. OBJECTIVES: To evaluate the efficacy and toxicity of modern external beam radiation therapy techniques for the treatment of dissecting cellulitis of the scalp. METHODS: Four patients with intractable dissecting cellulitis of the scalp were treated with electrons or a combination of electrons and photons to the entire scalp. Daily fraction sizes were 2.5 or 3 Gy and initially prescribed to 15-21 Gy. Patients were re-evaluated 3-4 weeks after completion of therapy. Any residual hair growth was treated with additional radiation treatments to ensure full epilation, up to a maximum dose of 35 Gy. RESULTS: Rapid resolution of pain was seen in all patients with pain. Regression of nodules and decreased discharge was seen in all patients following treatment and cosmesis was subjectively improved. No long-term toxicity has been observed. CONCLUSIONS: Using modern techniques and equipment, radiation therapy appears to be a reasonable option for patients with severe/refractory dissecting cellulitis of the scalp. Acute effects are mild and well tolerated. Aside from alopecia, which was present to some extent in all patients before treatment, no long-term complications have been observed.

Cerebrovascular abnormalities in a population of children with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is associated with vasculopathy, which may result in a variety of cerebrovascular complications. The purpose of this study was to evaluate the spectrum of cerebrovascular disease in a pediatric population with NF1. Of 316 patients with NF1 who underwent brain MRI, 8 (2.5%) children were reported to have an abnormality of the cerebrovascular system, including narrowed or ectatic vessels, vascular stenoses, aneurysm, and moyamoya.

Neurocognitive dysfunction in children with neurofibromatosis type 1.

The cognitive dysfunction associated with neurofibromatosis type 1 (NF1) is an intriguing aspect of this phenotypically heterogeneous genetic neurocutaneous disorder. A broad range of both nonverbal and verbal learning disabilities are evident in approximately 30% to 65% of children with NF1. Deficits in IQ, executive function, attention, and motor skills have also been documented. Current challenges lie in discovering the underlying multifactorial etiologies of the cognitive abnormalities found in NF1. Likely answers lie in neuroanatomic correlates as seen on neuroimaging as well as in molecular and genetic advances into the role of neurofibromin, the protein product of the NF1 gene. The development of NF1 animal models with learning and memory difficulties similar to those seen in humans demonstrates promising preliminary evidence that medical treatment of cognitive abnormalities may one day be possible.

Aicardi syndrome: spectrum of disease and long-term prognosis in 77 females.

Aicardi syndrome is an X-linked-dominant condition characterized by infantile spasms, agenesis of the corpus callosum, and chorioretinal lacunae. We reviewed the Aicardi Syndrome Foundation's compilation of family-based, self-reported questionnaires for the year 2000. Information was obtained from 77 females with Aicardi syndrome regarding developmental milestones, seizure frequency, seizure classification, antiepileptic drug use, and medical problems. Patient ages ranged from 1 to 25 years (mean = 7.2 years). All patients were significantly developmentally delayed with milestones ranging from 2 to 36 months. Of the patients, 91% attained milestones no higher than 12 months. Seizures were reported in 92% of patients and occurred daily in 67%. Infantile spasms were the most common seizure type observed in 17%, although a variety of other seizure types were also reported. Multiple antiepileptic drugs were used in these patients with 73% of patients taking two or more antiepileptic drugs. Five patients had a vagal nerve stimulator implanted, and one patient underwent a hemispherectomy. The most common medical problems cited included scoliosis, constipation, gastroesophageal reflux, aspiration pneumonia, and otitis media, but overall health was perceived to be good. Our review demonstrates the spectrum of developmental disabilities, epilepsy severity, and prognosis in a large group of Aicardi patients.

L-arginine inhibits balloon catheter-induced intimal hyperplasia.

Intimal hyperplasia that results from therapeutic revascularization is an important etiologic factor in the failure of these procedures (i.e., restenosis). Drugs which donate nitric oxide have been shown to inhibit the proliferation of vascular smooth muscle cells in vitro. We tested the hypothesis that administration of L-arginine (0.5 g/kg/day), the precursor of nitric oxide, would inhibit development of intimal hyperplasia following balloon catheter-induced injury. L-arginine administration from 2 days prior to and 2 weeks following catheter-induced injury to the rabbit thoracic aorta attenuated the development of intimal hyperplasia by 39% as compared with untreated controls. This effect was due to decreased intimal area. The effect of L-arginine was inhibited by co-administration of an inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester (0.5 g/kg/day). These data demonstrate that L-arginine attenuates intimal hyperplasia and suggest that the mechanism for this effect is the conversion of L-arginine to nitric oxide.

Spermicide permeation through biocompatible polymers.

Although spermicides are safe and effective contraceptive/prophylactic agents, they are inconvenient to use. Formulations that provide a controlled release of spermicide may improve user acceptance, and therefore effectiveness. Using a two-chamber diffusion cell, we measured the rates of permeation of nonoxynol-9 (N9), benzalkonium chloride (BC), and chlorhexidine (CH) through films of ethylene-vinyl acetate copolymer (EVAc) and silicone elastomer (SILASTIC). In addition, we encapsulated N9, BC, and CH into solid polymer matrices and measured the rate of spermicide release following immersion in water. We also developed equations for predicting the release rate of spermicide from a vaginal ring containing encapsulated spermicide, and tested these equations using hollow SILASTIC rings containing pure N9 or BC. N9 diffuses through a thin film of SILASTIC several orders of magnitude slower than through water. The rates of permeation of N9 through EVAc, BC through SILASTIC, and CH through SILASTIC were too low to detect over a one-week experiment. Polymer matrices of EVAc or SILASTIC released N9 at a controlled rate for several days. Based on these measurements, we predict that a vaginal ring containing an inner core of EVAc/N9 surrounded by a thin, permeable layer of SILASTIC will provide a controlled, constant release of N9 for over 30 days. Because of its low permeability in SILASTIC, BC is probably not a good spermicide for a long-acting vaginal ring. Because of its low solubility in water, CH is also not a good candidate for controlled release into the vaginal mucus.