Early and eighteen month clinical outcomes of first UK case of percutaneous deep vein arterialisation (pDVA) to treat "no option" chronic limb-threatening ischemia using the LimFlow system.

BACKGROUND: Chronic limb-threatening ischaemia (CLTI) in cases where there are no further standard treatment options for limb salvage represents the most advanced stage of peripheral arterial disease. For these "no-option" CLTI patients, an experimental treatment of foot vein arterialisation (FVA) was first described in 1912, however, it was never widely adopted as outcomes varied significantly most likely due to the complexity of the surgical intervention and lack of standardisation. In recent years there have been significant developments in performing FVA fully percutaneously and standardising the procedure with the introduction of specific indications for patient selection, a dedicated set of devices and structured follow up. This case represents the first UK use of the dedicated LimFlow System as a standardised procedure to perform percutaneous deep vein arterialisation (pDVA) in a "no option" CLTI patient according to the latest treatment recommendations in the literature, with outcomes out to 18 months post-procedure. CASE PRESENTATION: We present the case of a 78 year old male diabetic patient with a history of contralateral below knee amputation who presented with ischaemic rest pain and dry gangrene involving his left heel and first and second toes. Following review by the lower limb multi-disciplinary team at our institution, the patient was deemed to have no surgical or endovascular treatment options, apart from major amputation, as there was no suitable target for either angioplasty or bypass. He was therefore referred as a candidate for percutaneous deep vein arterialisation (pDVA) with the LimFlow System (LimFlow SA, France). After screening of the patient according to the indications for use, the pDVA procedure was successfully performed resulting in complete resolution of ischaemic rest pain immediately following the procedure, and adequate revascularisation of the foot. Following the index procedure, the subject went on to have minor amputation of the first, second and third toes 2 months post initial procedure with further secondary angioplasty procedures to optimise the flow throughout the arterialised circuit up to 4 months after the initial procedure. He underwent elective completion transmetatarsal amputation at 13 months post index procedure. The surgical wounds post minor amputation and the heel wound showed continued healing, especially after secondary optimisation of the pDVA outflow, with tissue epithelialisation by 6 months and complete healing by 18 months after the index procedure. CONCLUSIONS: This case report demonstrates the clinical outcomes of a technically-successful standardised pDVA procedure with the LimFlow system including both limb salvage and wound healing at 18 months. It also highlights the importance of close clinical and radiological surveillance post-index procedure and the requirement for re-interventions to optimise wound healing.

Transcranial focused ultrasound, pulsed at 40 Hz, activates microglia acutely and reduces Aß load chronically, as demonstrated in vivo.

OBJECTIVE: Iaccarino et al. (2016) [1] exposed 1 h of light flickering at 40 Hz to awake 5XFAD Alzheimer's Disease (AD) mouse models, generating action potentials at 40 Hz, activating ∼54% of microglia to colocalize with Aß plaque, acutely, and clearing âˆ¼ 50% of Aß plaque after seven days, but only in the visual cortex. HYPOTHESIS: Transcranially delivered, focused ultrasound (tFUS) can replicate the results of Iaccarino et al. (2016) [1] but throughout its area of application. METHODS: We exposed sedated 5XFAD mice to tFUS (2.0 MHz carrier frequency, 40 Hz pulse repetition frequency, 400 µs-long pulses, spatial peak pulse average value of 190 W/cm2). Acute studies targeted tFUS into one hemisphere of brain centered on its hippocampus for 1 h. Chronic studies targeted comparable brain in each hemisphere for 1 h/day for five days. RESULTS: Acute application of tFUS activated more microglia that colocalized with Aß plaque relative to sham ultrasound (36.0 ± 4.6% versus 14.2 ± 2.6% [mean ± standard error], z = 2.45, p < 0.014) and relative to the contralateral hemisphere of treated brain (36.0 ± 4.6% versus 14.3 ± 4.0%, z = 2.61, p < 0.009). Chronic application over five days reduced their Aß plaque burden by nearly half relative to paired sham animals (47.4 ± 5.8%, z = - 2.79, p < 0.005). CONCLUSION: Our results compare to those of Iaccarino et al. (2016) [1] but throughout the area of ultrasound-exposed brain. Our results also compare to those achieved by medications that target Aß, but over a substantially shorter period of time. The proximity of our ultrasound protocol to those shown safe for non-human primates and humans may motivate its rapid translation to human studies.

A sea change in our view of overturning in the subpolar North Atlantic.

To provide an observational basis for the Intergovernmental Panel on Climate Change projections of a slowing Atlantic meridional overturning circulation (MOC) in the 21st century, the Overturning in the Subpolar North Atlantic Program (OSNAP) observing system was launched in the summer of 2014. The first 21-month record reveals a highly variable overturning circulation responsible for the majority of the heat and freshwater transport across the OSNAP line. In a departure from the prevailing view that changes in deep water formation in the Labrador Sea dominate MOC variability, these results suggest that the conversion of warm, salty, shallow Atlantic waters into colder, fresher, deep waters that move southward in the Irminger and Iceland basins is largely responsible for overturning and its variability in the subpolar basin.

Nasal Foreign Bodies: A Sweet Experiment.

INTRODUCTION: It is generally accepted that paediatric intranasal foreign bodies should be removed in the emergency setting. In the case of a difficult to access dissolvable foreign body in an uncooperative child, the question must be raised regarding whether or not a watch and wait strategy is more appropriate. We ask: How long does it take for popular sweets (candy) to dissolve in the human nose? METHODS: Five popular UK sweets were placed in the right nasal cavity of a 29-year-old male (the author) with no sino-nasal disease. Time taken to dissolve was recorded. RESULTS: All five sweets were completely dissolved in under one hour. DISCUSSION: A watch and wait strategy in favour of examination under anaesthetic may be a viable option in some cases. Limitations of the study include the age of the participant and size of the sweets. It is also important in practice that the clinician is able to elicit an accurate history regarding the exact nature of the foreign body. CONCLUSION: It remains prudent to perform an examination under anaesthetic of an uncooperative child with a solid or unknown nasal foreign body. However, if the clinician can be certain the foreign body is a small sugar or chocolate based sweet only, a watch and wait strategy may be a reasonable choice.

Determination of the photolysis rate coefficient of monochlorodimethyl sulfide (MClDMS) in the atmosphere and its implications for the enhancement of SO2 production from the DMS + Cl2 reaction.

In this work, the photolysis rate coefficient of CH3SCH2Cl (MClDMS) in the lower atmosphere has been determined and has been used in a marine boundary layer (MBL) box model to determine the enhancement of SO2 production arising from the reaction DMS + Cl2. Absorption cross sections measured in the 28000-34000 cm(-1) region have been used to determine photolysis rate coefficients of MClDMS in the troposphere at 10 solar zenith angles (SZAs). These have been used to determine the lifetimes of MClDMS in the troposphere. At 0° SZA, a photolysis lifetime of 3-4 h has been obtained. The results show that the photolysis lifetime of MClDMS is significantly smaller than the lifetimes with respect to reaction with OH (≈ 4.6 days) and with Cl atoms (≈ 1.2 days). It has also been shown, using experimentally derived dissociation energies with supporting quantum-chemical calculations, that the dominant photodissocation route of MClDMS is dissociation of the C-S bond to give CH3S and CH2Cl. MBL box modeling calculations show that buildup of MClDMS at night from the Cl2 + DMS reaction leads to enhanced SO2 production during the day. The extra SO2 arises from photolysis of MClDMS to give CH3S and CH2Cl, followed by subsequent oxidation of CH3S.

Abnormal cerebral microstructure in premature neonates with congenital heart disease.

BACKGROUND AND PURPOSE: Abnormal cerebral microstructure has been documented in term neonates with congenital heart disease, portending risk for injury and poor neurodevelopmental outcome. Our hypothesis was that preterm neonates with congenital heart disease would demonstrate diffuse cerebral microstructural abnormalities when compared with critically ill neonates without congenital heart disease. A secondary aim was to identify any association between microstructural abnormalities, white matter injury (eg, punctate white matter lesions), and other clinical variables, including heart lesions. MATERIALS AND METHODS: With the use of tract-based spatial statistics, an unbiased, voxelwise method for analyzing diffusion tensor imaging data, we compared 21 preterm neonates with congenital heart disease with 2 cohorts of neonates without congenital heart disease: 28 term and 27 preterm neonates, identified from the same neonatal intensive care unit. RESULTS: Compared with term neonates without congenital heart disease, preterm neonates with congenital heart disease had microstructural abnormalities in widespread regions of the central white matter. However, 42% of the preterm neonates with congenital heart disease had punctate white matter lesions. When neonates with punctate white matter lesions were excluded, microstructural abnormalities remained only in the splenium. Preterm neonates with congenital heart disease had similar microstructure to preterm neonates without congenital heart disease. CONCLUSIONS: Diffuse microstructural abnormalities were observed in preterm neonates with congenital heart disease, strongly associated with punctate white matter lesions. Independently, regional vulnerability of the splenium, a structure associated with visual spatial function, was observed in all preterm neonates with congenital heart disease.

Severe retinal injuries from paintball projectiles.

BACKGROUND: To determine the outcomes and circumstances of retinal injuries caused by blunt trauma from paintball pellet projectiles. METHODS: Retrospective case series of all patients who presented with retinal injuries due to paintball-related trauma to 2 retina specialists in a clinical setting from 2004 to 2005. Patients were followed for a mean of 7.3 months, and retinal trauma was documented with retinal photographs and ocular coherence tomography as needed. Best corrected visual acuity (BCVA) was the main outcome measure. RESULTS: Three eyes of 3 patients suffered severe retinal injuries after blunt trauma from a paintball pellet. Together, the 3 eyes demonstrated extensive retinal findings, including commotio retinae, choroidal rupture, and macular hole. BCVA at last follow-up ranged from 20/80 to hand motions. INTERPRETATION: Our small case series indicates that retinal trauma from paintball injuries is not uncommon and results in severe long-term visual morbidity. The sale of paintball guns and pellets should be strictly prohibited for minors, and adults should be educated about the need for appropriate ocular protection and the potentially serious consequences of the use of these guns outside of commercial settings.

Safety profile of intravitreal triamcinolone acetonide.

BACKGROUND: There is currently a widespread use of intravitreal triamcinolone acetonide (IVTA) for age-related macular degeneration, diabetic macular edema, cystoid macular edema secondary to retinal vein occlusions, and uveitis. The aim of this investigation was to assess the rates of various complications associated with this treatment and to determine which factors are associated with the development of these complications. METHODS: A retrospective interventional case series of all patients from one retina specialist undergoing IVTA was conducted in a clinical setting from 2002 to 2005. All disease entities were included. Patients were followed for a mean of 9.5 months after receiving 4 mg (0.1 mL) of nonfiltered triamcinolone acetonide (TA). All complications associated with the injection procedure or with the TA were noted. RESULTS: Two hundred and twenty-three (223) eyes of 192 patients received a total of 336 IVTA injections between 2002 and 2005. The mean age was 73.3 years and mean follow-up was 9.5 months. A single injection was performed in 144 eyes (64.6%); 2 IVTAs in 55 eyes (24.7%); 3 IVTAs in 16 eyes (7.2%), and 3.6% of eyes had more than 3 injections at a minimal interval of 3 months. The only immediate complication was a single injection (0.3%) associated with a temporary occlusion of the central retinal artery, which opened immediately following anterior paracentesis. Late complications included endophthalmitis in 1 of 336 (0.3%) injections and a steroid response requiring glaucoma medication in 60 of 192 patients (31.3%). In patients with preexisting glaucoma, 58.8% required additional glaucoma medication. Glaucoma-filtering surgery was required in 2 of 192 patients (1.0%). CONCLUSIONS: In the study center, the IVTA is extremely safe in patients without a history of glaucoma. However, patients with preexisting glaucoma with progressive optic neuropathy must be treated with great caution.

Cost of multiple sclerosis by level of disability: a review of literature.

We performed a review of the economic literature to identify what is known about the relationship between Expanded Disability Status Scale (EDSS) categories and cost of multiple sclerosis (MS). We sought cohort studies of patients with multiple sclerosis that described the costs attributed to each EDSS score and utilized specific inclusion criteria for the selection of 10 studies. We found that both direct and indirect costs rise continuously with increasing EDSS category, and this rise is qualitatively exponential. The rise in indirect costs appears at lower EDSS scores. The cost of a relapse occurring in any given EDSS category exceeds that associated with that particular EDSS category. Few studies comprehensively assessed the entire spectrum of the costs, and much of the literature is based on EDSS categories in coarse groupings. In spite of several variations between studies, one important conclusion that we can draw is that rise in cost is positively correlated to scores on the EDSS categories, and therefore agents with a capacity to prevent or arrest the rate of MS progression may affect the overall cost of MS.

A lay person versus a trained endoscopist: can the preop endoscopy simulator detect a difference?

The purpose of this study was to establish construct validation of a flexible sigmoidoscopy simulator by comparing training-level grouped subjects. These included clerical staff (n = 10), residents (n = 19), and experts (n = 5). Each participant performed 3 scopes. The ANOVA group-based results for trainer-measured variables are shown in Table 1. These results demonstrate that the flexible sigmoidoscopy simulator distinguished the trained from the untrained and the resident from the expert. Although there was no statistically significant differences between the senior residents and the experts, the expert commonly outperformed the residents. Establishing the transferability of simulator training to real life is next. If the transfer of skill can be established, it may give rise to a new skills training approach.

Familial vocal fold paralysis.

Familial clustering of congenital bilateral abductor vocal fold paralysis has been reported very rarely. So far, only a handful of cases have been reported, mostly with the autosomal dominant of X-linked recessive mode of inheritance. We describe the cases of a brother and sister, who presented with neonatal stridor due to bilateral abductor vocal fold paralysis. First-degree parental consanguinity suggests an autosomal recessive mode of inheritance. Karyotype analysis revealed a paracentric balanced inversion of chromosome 13 in both cases, that was also present in the unaffected mother. An updated review of the literature on this interesting but rare condition is also presented.

Body image and weight consciousness among South Asian, Italian and general population women in Britain.

Italians in Britain have low rates of coronary heart disease while South Asians have high rates, which correspond to a tendency to central abdominal fat deposition and overweight. World variations in attitudes to body size are thought to be related to economic security. This cross-sectional study employed a range of measures including photographic silhouettes of known BMI to investigate the attitudes of 259 South Asian, Italian and general population women (aged 20-42 years) towards body size. Migrants are compared with British-born minority members. Our results indicate that although migrant South Asians were less happy with their weight than migrant Italians, fewer had tried to lose weight in the past or had experienced external pressures to change their bodies. More migrant South Asians than Italians or general population women equated one of the four largest shapes (BMI 28-38) with health and successful reproduction. All groups wanted to resemble one of the two thinnest shapes, equating them with longevity, likelihood of marriage and job success. British-born South Asians generally showed a considerable degree of convergence towards general population women's negative attitudes to large body size, but British-born Italians' attitudes were significantly more negative even than general population women. The study's conclusions were that South Asian health beliefs are an important focus of resistance to slimness. The tendency of migrant South Asians to equate large size with health contrasts with the opposing views of Italian and general population women. British-born South Asians' views are modifying from those of migrants, but significant differences remain when compared with general population women and British-born Italians. Present differences in economic security offer only a partial explanation; South Asian attitudes may be explained by economic insecurity in the past.

Large-volume, coolable spectroscopic cell for aerosol studies.

We have constructed a coolable spectroscopic cell for characterizing the physical and chemical properties of simulated atmospheric aerosol particles. The cell is designed for experiments in which the refractive indices, freezing temperatures, and the phase and chemical composition of a wide range of aerosol types are measured. The relatively large volume (0.075 m(3)) of the cell reduces wall-aerosol interactions and allows the aerosol residence time to exceed 2 h. The cell has been optically interfaced to Fourier-transform spectrometers to record broadband infrared, visible, and ultraviolet extinction spectra of aerosol particles and gas-phase components over a range of temperatures (180-300 K). The data generated with the cell have applications in remote sensing, radiative transfer models, heterogeneous atmospheric chemistry, and pollution studies.

Final report of the FOPE II Pediatric Subspecialists of the Future Workgroup.

The report of the Pediatric Subspecialists of the Future Workgroup of the Second Task Force on Pediatric Education reviews the critical changes of the past 2 decades that have affected the provision of pediatric subspecialty services, education of pediatric health care providers, and the acquisition and application of new knowledge. The report considers the future needs that will determine the ability of pediatric subspecialists to meet identified goals. Recommendations for change in the education, role, and financing of the pediatric subspecialist are reported together with those of other workgroups. Pediatrics 2000;106(suppl):1224-1244; pediatric subspecialist, pediatric subspecialist workforce, education pediatric subspecialist, research pediatric subspecialist.