Incidence, Nature and Natural History of Additional Histological Findings in Preimplantation and Implantation Kidney Transplant Biopsies.

The quality assurance provided by preimplantation biopsy quantification of chronic damage may allow greater use of kidneys from expanded criteria donors, and thereby expand the deceased donor pool. Preimplantation biopsy may, however, identify additional acute or chronic pathologies not considered in the scoring of chronic damage, and these may influence the decision to implant or discard the kidney. This single-centre retrospective cohort study of a contemporary UK donor population systematically characterised the nature of additional findings in 1,046 preimplantation and implantation biopsies over an eight-year period. A diverse range of findings were identified in 111/1,046 (11%) organs; most frequently diabetic glomerulopathy, focal segmental glomerulosclerosis, (micro)thrombi, neutrophil casts, and immunoglobulin/complement staining. Seventy (63%) of these were transplanted, with subsequent biopsy in 41 (58%) cases confirming that 80% of the initial acute changes had spontaneously resolved, while there was no progression of diabetic glomerulopathy, and the lesions of focal segmental glomerulosclerosis were not identified. Over 75% of assessable grafts with additional histological findings at the time of transplant showed adequate function at one-year following transplant. In conclusion, most histological abnormalities that may be identified in addition to chronic scarring in preimplantation kidney biopsies would not preclude transplantation nor predict poor graft function.

The use of cerebral computed tomographic angiography as an ancillary investigation to support a clinical diagnosis of death using neurological criteria: a consensus guideline.

This multidisciplinary consensus statement was produced following a recommendation by the Faculty of Intensive Care Medicine to develop a UK guideline for ancillary investigation, when one is required, to support the diagnosis of death using neurological criteria. A multidisciplinary panel reviewed the literature and UK practice in the diagnosis of death using neurological criteria and recommended cerebral CT angiography as the ancillary investigation of choice when death cannot be confirmed by clinical criteria alone. Cerebral CT angiography has been shown to have 100% specificity in supporting a diagnosis of death using neurological criteria and is an investigation available in all acute hospitals in the UK. A standardised technique for performing the investigation is described alongside a reporting template. The panel were unable to make recommendations for ancillary testing in children or patients receiving extracorporeal membrane oxygenation.

The aetiology of rickets-like lower limb deformities in Malawian children.

UNLABELLED: Debilitating rickets-like lower limb deformities are common in children throughout the world, particularly in Malawi, Africa where the causes are unknown. We have identified that Blount disease and calcium deficiency rickets are the likely causes of these deformities and propose calcium supplementation as a potential treatment of Malawian rickets. INTRODUCTION: Surgical correction of rickets-like lower limb deformities is the most common paediatric operation performed at Beit Cure Orthopaedic Hospital, Malawi. The aim of this study was to investigate the aetiology of these deformities. METHODS: Children with a tibio-femoral angle of deformity >20° were enrolled (n = 42, 3.0-15.0 years). Anthropometric and early life and well-being data were collected. Early morning serum and urine samples were collected on the morning of the operation for markers of calcium and phosphate homeostasis. Knee radiographs were obtained, and the children were diagnosed with either Blount (BD, n = 22) or evidence of rickets disease (RD, n = 20). As BD is a mechanical rather than metabolic disease, BD were assumed to be biochemically representative of the local population and thus used as a local reference for RD. RESULTS: There were no differences in anthropometry or early life experiences between BD and RD. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D, total alkaline phosphatase and urinary phosphate were significantly higher and serum phosphate, 25-hydroxyvitamin D (25OHD) and tubular maximal reabsorption of phosphate significantly lower in RD than BD. There was no difference in serum calcium, fibroblast growth factor 23 or markers of iron status between groups. All children had 25OHD > 25 nmol/L. CONCLUSIONS: Vitamin D deficiency is not implicated in the aetiology of RD or BD in Malawian children. The cause of RD in Malawi is likely to be dietary calcium deficiency leading to elevated PTH resulting in increased losses of phosphate from the bone and glomerular filtrate. The causes of BD remain unclear; there was no evidence in support of previously suggested risk factors such as being overweight or starting to walk early. Prior to surgical intervention, supplementation with calcium should be considered for children with RD.

Successful transplantation of kidneys from elderly circulatory death donors by using microscopic and macroscopic characteristics to guide single or dual implantation.

Most kidneys from potential elderly circulatory death (DCD) donors are declined. We report single center outcomes for kidneys transplanted from DCD donors over 70 years old, using preimplantation biopsy Remuzzi grading to inform implantation as single or dual transplants. Between 2009 and 2012, 43 single transplants and 12 dual transplants were performed from elderly DCD donors. Remuzzi scores were higher for dual than single implants (4.4 vs. 3.4, p < 0.001), indicating more severe baseline injury. Donor and recipient characteristics for both groups were otherwise similar. Early graft loss from renal vein thrombosis occurred in two singly implanted kidneys, and in one dual-implanted kidney; its pair continued to function satisfactorily. Death-censored graft survival at 3 years was comparable for the two groups (single 94%; dual 100%), as was 1 year eGFR. Delayed graft function occurred less frequently in the dual-implant group (25% vs. 65%, p = 0.010). Using this approach, we performed proportionally more kidney transplants from elderly DCD donors (23.4%) than the rest of the United Kingdom (7.3%, p < 0.001), with graft outcomes comparable to those achieved nationally for all deceased-donor kidney transplants. Preimplantation biopsy analysis is associated with acceptable transplant outcomes for elderly DCD kidneys and may increase transplant numbers from an underutilized donor pool.

Standardized deceased donor kidney donation rates in the UK reveal marked regional variation and highlight the potential for increasing kidney donation: a prospective cohort study†.

BACKGROUND: The UK has implemented a national strategy for organ donation that includes a centrally coordinated network of specialist nurses in organ donation embedded in all intensive care units and a national organ retrieval service for deceased organ donors. We aimed to determine whether despite the national approach to donation there is significant regional variation in deceased donor kidney donation rates. METHODS: The UK prospective audit of deaths in critical care was analysed for a cohort of patients who died in critical care between April 2010 and December 2011. Multivariate logistic regression was used to identify the factors associated with kidney donation. The logistic regression model was then used to produce risk-adjusted funnel plots describing the regional variation in donation rates. RESULTS: Of the 27 482 patients who died in a critical care setting, 1528 (5.5%) became kidney donors. Factors found to influence donation rates significantly were: type of critical care [e.g. neurointensive vs general intensive care: OR 1.53, 95% confidence interval (CI) 1.34-1.75, P<0.0001], patient ethnicity (e.g. 'Asian' vs 'white': OR 0.17, 95% CI 0.11-0.26, P<0.0001), age (e.g. age >69 vs age 18-39 yr: OR 0.2, 0.15-0.25, P<0.0001), and cause of death [e.g. 'other' (excluding 'stroke' and 'trauma') vs 'trauma': OR 0.04, 95% CI 0.03-0.05, P<0.0001]. Despite correction for these variables, kidney donation rates for the 20 UK kidney donor regions showed marked variation. The overall standardized donation rate ranged from 3.2 to 7.5%. Four regions had donation rates of >2 standard deviations (sd) from the mean (two below and two above). Regional variation was most marked for donation after circulatory death (DCD) kidney donors with 9 of the 20 regions demonstrating donation rates of >2 sd from the mean (5 below and 4 above). CONCLUSIONS: The marked regional variation in kidney donation rates observed in this cohort after adjustment for factors strongly associated with donation rates suggests that there is considerable scope for further increasing kidney donation rates in the UK, particularly DCD.

Expansion of the kidney donor pool by using cardiac death donors with prolonged time to cardiorespiratory arrest.

Donation after Cardiac Death (DCD) is an increasingly important source of kidney transplants, but because of concerns of ischemic injury during the agonal phase, many centers abandon donation if cardiorespiratory arrest has not occurred within 1 h of controlled withdrawal of life-supporting treatment (WLST). We report the impact on donor numbers and transplant function using instead a minimum 'cut-off' time of 4 h. The agonal phase of 173 potential DCD donors was characterized according to the presence or absence of: acidemia; lactic acidosis; prolonged (>30 min) hypotension, hypoxia or oliguria, and the impact of these characteristics on 3- and 12-month transplant outcome evaluated by multivariable regression analysis. Of the 117 referrals who became donors, 27 (23.1%) arrested more than 1 h after WLST. Longer agonal-phase times were associated with greater donor instability, but surprisingly neither agonal-phase instability nor its duration influenced transplant outcome. In contrast, 3- and 12-month eGFR in the 190 transplanted kidneys was influenced independently by donor age, and 3-month eGFR by cold ischemic time. DCD kidney numbers are increased by 30%, without compromising transplant outcome, by lengthening the minimum waiting time after WLST from 1 to 4 h.

Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease.

Several molecular subtypes of sporadic Creutzfeldt-Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications have demonstrated a potentially important role for magnetic resonance imaging in the pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease. Magnetic resonance imaging signal alterations correlate with distinct sporadic Creutzfeldt-Jakob disease molecular subtypes and thus might contribute to the earlier identification of the whole spectrum of sporadic Creutzfeldt-Jakob disease cases. This multi-centre international study aimed to provide a rationale for the amendment of the clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Patients with sporadic Creutzfeldt-Jakob disease and fluid attenuated inversion recovery or diffusion-weight imaging were recruited from 12 countries. Patients referred as 'suspected sporadic Creutzfeldt-Jakob disease' but with an alternative diagnosis after thorough follow up, were analysed as controls. All magnetic resonance imaging scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus and cerebellum. Magnetic resonance imaging scans were evaluated in 436 sporadic Creutzfeldt-Jakob disease patients and 141 controls. The pattern of high signal intensity with the best sensitivity and specificity in the differential diagnosis of sporadic Creutzfeldt-Jakob disease was identified. The optimum diagnostic accuracy in the differential diagnosis of rapid progressive dementia was obtained when either at least two cortical regions (temporal, parietal or occipital) or both caudate nucleus and putamen displayed a high signal in fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging. Based on our analyses, magnetic resonance imaging was positive in 83% of cases. In all definite cases, the amended criteria would cover the vast majority of suspected cases, being positive in 98%. Cerebral cortical signal increase and high signal in caudate nucleus and putamen on fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging are useful in the diagnosis of sporadic Creutzfeldt-Jakob disease. We propose an amendment to the clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease to include findings from magnetic resonance imaging scans.

MRI in the classical MM1 and the atypical MV2 subtypes of sporadic CJD: an inter-observer agreement study.

BACKGROUND AND PURPOSE: To establish radiological features in the atypical MV2 subtype of sCJD compared with the classical MM1 subtype, as well as region- and sequence-dependent inter-observer correlation. METHODS: MRI hyperintensity of basal ganglia (BG), cortex and thalamus was evaluated in 31 MM1 and 32 MV2 patients. Each MR scan was analyzed independently by two neuroradiologists blinded to PRNP genotype/prion protein type. RESULTS: Cumulative T2-sensitivity for BG hyperintensity was higher in the MV2 subtype (84% for both observers versus 61% in observer 1/42% in observer 2 in MM1 patients). Significant inter-observer agreement was found for BG and thalamus on T2, FLAIR, PD and DWI, but for cortex only on DWI. Thalamic changes were significantly more frequent in MV2 than in MM1 patients (cumulative sensitivity 86% vs. 12.5% on DWI). DISCUSSION: The high frequency of thalamic hyperintensity in the MV2 subtype allowed differentiation from MM1 patients. Good inter-observer agreement was found for BG and thalamus in all sequences. DWI showed the highest inter-observer correlation independent of the investigated brain region and was therefore not only highly sensitive but also relatively independent of investigator bias. Since inter-observer correlation for cortical hyperintensity in T2, FLAIR and PD is relatively low, the cortical changes should not be over-interpreted with these sequences.

Energy and structure of inertial range turbulence deduced from an evolution of fluid impulse.

We explore numerically a very simple idea that may provide a material explanation for inertial range turbulence. We base a Lagrangian model of viscous incompressible fluid flow on an evolving ensemble of vortex doublet sheets. Initially these are randomly oriented and randomly distributed within a disk in two-dimensional space. These sheets are then actively transported (in two dimensions) according to the Oseledets equation of motion for fluid impulse. The mutual interaction of these sheets, and their diffusion, establishes a velocity fluctuation field. In a specific sense this evolution is self-affine, and we exploit this property to calculate standard statistical measures for the fluctuation field. We determine from this simple model the second-order structure function and the energy spectrum of inertial range turbulence.

Chordoma masquerading as a nerve root tumour -- a clinical lesson.

Chordomas usually arise in bone and are most commonly found in the midline axial skeleton. An accurate pre-operative diagnosis of chordoma is crucial, as survival is optimal when radical en bloc resection is performed at primary surgery. We report a rare case of cervical chordoma masquerading radiologically as an extracranial nerve sheath tumour. A laterally situated chordoma (centred extra-osseously in the neural foramen) was diagnosed radiologically as a neurofibroma pre-operatively. We review the key radiological features for diagnosis of chordoma. We consider the importance of pre-operative diagnosis of chordoma in guiding management and in determining survival.

MRI lesion profiles in sporadic Creutzfeldt-Jakob disease.

BACKGROUND: With respect to sporadic Creutzfeldt-Jakob disease (sCJD), six molecular subtypes (MM1, MM2, MV1, MV2, VV1, and VV2) have been described, which vary with respect to age at disease onset, disease duration, early symptoms, and neuropathology. MRI signal alterations were reported to correlate with distinct Creutzfeldt-Jakob disease (CJD) subtypes. This multicenter, international study aimed to describe the brain MRI findings associated with each of the sCJD molecular subtypes. METHODS: Pathologically confirmed sCJD cases with codon 129 genotype (MM, MV, and VV), PrP(Sc) type, and fluid-attenuated inversion recovery (FLAIR) or diffusion-weighted imaging (DWI) were collected in seven countries. All MRI scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus, and cerebellum. RESULTS: MRI scans were evaluated in 211 CJD patients (98 MM1, 23 MM2, 19 MV1, 30 MV2, 9 VV1, and 32 VV2). Basal ganglia hyperintensities occurred most frequently in MV2, VV2, and MM1 subtypes (79, 77, and 70%). Wide cerebral cortical signal increase was most common in VV1, MM2, and MV1 subtypes (86, 77, and 77%). Thalamic hyperintensities occurred most often in VV2 (45%) and MV2 (43%). The most consistent finding across most subtypes was high signal in basal ganglia, with these abnormalities found in 63% (FLAIR) and 71% (DWI). CONCLUSION: Cortical signal increase and hyperintensities in the basal ganglia and thalamus are detected by MRI across all molecular sporadic Creutzfeldt-Jakob disease subtypes. Our findings argue that characteristic MRI lesion patterns may occur for each molecular subtype.

Myxopapillary ependymoma with intracranial metastases.

We report spontaneous seeding within the subarachnoid space from a myxopapillary ependymoma that progressed despite surgery and radiotherapy treatment.

Third ventricular chordoid glioma: clinicopathological study of two cases with evidence for a poor clinical outcome despite low grade histological features.

Chordoid glioma of the third ventricle is a rare glial tumour whose precise histogenesis remains uncertain. We describe two cases that presented recently to our department and review the background literature. The neoplasm tends to occur in women and its clinical presentation is variable, resulting from acute hydrocephalus or impingement upon local structures. However, the radiological appearance is distinct, with an ovoid shape, hyperdensity and uniform contrast enhancement on computerized tomography and magnetic resonance imaging. Intraoperative smear diagnosis is difficult because of the lack of specific features, although the presence of metachromatic extracellular mucin may be useful. The characteristic histological appearance is that of cords and clusters of cohesive, oval-to-polygonal epithelioid cells with abundant eosinophilic cytoplasm and a mucinous background. There is often a mixed chronic inflammatory infiltrate with lymphocytes and plasma cells with Russell bodies. The main differentials for histological diagnosis include chordoid meningiomas, pilocytic astrocytomas and ependymomas. An immunohistochemical panel including antibodies to glial fibrillary acidic protein, CD 34, epithelial membrane antigen, pan cytokeratin, S100 and vimentin can be used to distinguish between these possibilities. Ultrastructurally the tumour cells have basal lamina and microvilli, reminiscent of ependymomas. The clinical outcome in our cases was poor because of the location of the lesion and its close relation to the hypothalamus. Limited follow-up after surgery with or without radiotherapy suggests that as-full-as-possible resection favours a better outcome, although surgery in this area carries significant operative risks.

Numerical vorticity creation based on impulse conservation.

The problem of creating solenoidal vortex elements to satisfy no-slip boundary conditions in Lagrangian numerical vortex methods is solved through the use of impulse elements at walls and their subsequent conversion to vortex loops. The algorithm is not uniquely defined, due to the gauge freedom in the definition of impulse; the numerically optimal choice of gauge remains to be determined. Two different choices are discussed, and an application to flow past a sphere is sketched.