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Kidneys from donation after circulatory death (DCD) donors are utilized variably worldwide, in part due to high rates of delayed graft function (DGF) and putative associations with adverse longer-term outcomes. We aimed to determine whether the presence of DGF and its duration were associated with poor longer-term outcomes after kidney transplantation from DCD donors. Using the UK transplant registry, we identified 4714 kidney-only transplants from controlled DCD donors to adult recipients between 2006 and 2016; 2832 recipients (60·1%) had immediate graft function and 1882 (39·9%) had DGF. Of the 1847 recipients with DGF duration recorded, 926 (50·1%) had DGF 7 days, 576 (31·2%) had DGF 7-14 days, and 345 (18·7%) had DGF14 days. After risk adjustment, the presence of DGF was not associated with inferior long-term graft or patient survivals. However, DGF duration of14 days was associated with an increased risk of death-censored graft failure (hazard ratio 1·7, p = ·001) and recipient death (hazard ratio 1·8, p ·001) compared to grafts with immediate function. This study suggests that shorter periods of DGF have no adverse influence on graft or patient survival after DCD donor kidney transplantation and that DGF14 days is a novel early biomarker for significantly worse longer-term outcomes.

Vaccine-induced immune thrombosis and thrombocytopenia (VITT) syndrome is a new entity, characterised by severe thrombocytopenia and multiple sites of thrombosis1 . The presumed mechanism is driven by anti-platelet factor 4 (PF4) antibodies causing platelet activation1 . Donors with VITT syndrome have a particular relevance for liver transplantation (LT), due to the associated risk of passenger lymphocyte syndrome, and a predisposition for porto-mesenteric or hepatic vein thrombosis2 .

Vaccine-induced thrombosis and thrombocytopenia (VITT) may follow immunisation with the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2. Autoantibodies to platelet factor 4 (PF4) may mediate VITT through antibody-dependent platelet activation, though the underlying etiology is uncertain. Anti-PF4 antibodies are also seen in heparin-induced thrombocytopenia, though most cases of VITT do not have prior heparin exposure. More than 20 million people in the United Kingdom (UK) have received the ChAdOx1 nCoV-19 vaccine.

Background and objectives The Effect of a Reduction in GFR after Nephrectomy on Arterial Stiffness and Central Hemodynamics (EARNEST) study was a multicenter, prospective, controlled study designed to investigate the associations of an isolated reduction in kidney function on BP and arterial hemodynamics. Design, setting, participants, & measurements Prospective living kidney donors and healthy controls who fulfilled criteria for donation were recruited from centers with expertise in vascular research. Participants underwent office and ambulatory BP measurement, assessment of arterial stiffness, and biochemical tests at baseline and 12 months. Results A total of 469 participants were recruited, and 306 (168 donors and 138 controls) were followed up at 12 months. In the donor group, mean eGFR was 27 ml/min per 1.73 m2 lower than baseline at 12 months. Compared with baseline, at 12 months the mean within-group difference in ambulatory day systolic BP in donors was 0.1 mm Hg (95% confidence interval, −1.7 to 1.9) and 0.6 mm Hg (95% confidence interval, −0.7 to 2.0) in controls. The between-group difference was −0.5 mm Hg (95% confidence interval, −2.8 to 1.7; P=0.62). The mean within-group difference in pulse wave velocity in donors was 0.3 m/s (95% confidence interval, 0.1 to 0.4) and 0.2 m/s (95% confidence interval, −0.0 to 0.4) in controls. The between-group difference was 0.1 m/s (95% confidence interval, −0.2 to 0.3; P=0.49). Conclusions Changes in ambulatory peripheral BP and pulse wave velocity in kidney donors at 12 months after nephrectomy were small and not different from controls. Clinical Trial registry name and registration number NCT01769924 (https://clinicaltrials.gov/ct2/show/NCT01769924).

BACKGROUND: There is little evidence regarding the use of organs from deceased donors with infective endocarditis. We performed a retrospective analysis of the utilization, safety, and long-term survival of transplants from donors with infective endocarditis in the United Kingdom. METHODS: We studied deceased donor transplants over an 18-y period (2001-2018) using data from the UK Transplant Registry. We estimated the risk of infection transmission, defined as a microbiological isolate in the recipient matching the causative organism in the donor in the first 30 days posttransplant. We examined all-cause allograft failure up to 5 years in kidney and liver recipients, comparing transplants from donors with endocarditis with randomly selected matched control transplants. RESULTS: We studied 88 transplants from 42 donors with infective endocarditis. We found no cases of infection transmission. There was no difference in allograft failure between transplants from donors with infective endocarditis and matched control transplants, among either kidney (hazard ratio, 1.48; 95% CI, 0.66-3.34) or liver (hazard ratio, 1.14; 95% CI, 0.54-2.41) recipients. Compared with matched controls, donors with infective endocarditis donated fewer organs (2.3 versus 3.2 organs per donor; P < 0.001) and were less likely to become kidney donors (odds ratio, 0.29; 95% CI, 0.16-0.55). CONCLUSIONS: We found acceptable safety and long-term allograft survival in transplants from selected donors with infective endocarditis in the United Kingdom. This may have implications for donor selection and organ utilization.

AIMS: To determine whether initiation of treatment with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers (ACEI/ARBs) is associated with a subsequent reduction in haemoglobin in the general population. METHODS: We undertook a national cohort study over a thirteen-year period (2004 to 2016), using routine primary healthcare data from the United Kingdom Clinical Practice Research Datalink. We compared ACEI/ARB initiation with calcium channel blocker (CCB) initiation, to minimise confounding by indication. We included all first ACEI/ARB or CCB prescriptions in adults with at least one haemoglobin result in the 12 months before and six months after drug initiation. Our primary outcome was a ≥1g/dL haemoglobin reduction in the six months after drug initiation. RESULTS: We examined 146,610 drug initiation events in 136,655 patients. Haemoglobin fell by ≥1g/dL after drug initiation in 19.5% (16,936/86,652) of ACEI/ARB initiators and 15.9% (9,521/59,958) of CCB initiators. The adjusted odds ratio of a ≥1g/dL haemoglobin reduction in ACEI/ARB initiators vs. CCB initiators was 1.15 (95%CI 1.12-1.19). CONCLUSIONS: ACEI/ARBs are associated with a modest increase in the risk of a haemoglobin reduction. For every 100 patients in our study that initiated a CCB, 16 experienced a ≥1g/dL haemoglobin decline. If the effect is causal, three additional patients would have experienced this outcome if they had received an ACEI/ARB. This may have implications for drug choice and monitoring for many patients in primary care. Further research could identify patients at higher risk of this outcome, who may benefit from closer monitoring.

BACKGROUND AND OBJECTIVES: Kidneys from elderly deceased donors are often discarded after procurement if the expected outcomes from single kidney transplantation are considered unacceptable. An alternative is to consider them for dual kidney transplantation. We aimed to examine the utilization of kidneys from donors aged ≥60 years in the United Kingdom and compare clinical outcomes of dual versus single kidney transplant recipients.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data from the United Kingdom Transplant Registry from 2005 to 2017 were analyzed. We examined utilization rates of kidneys retrieved from deceased donors aged ≥60 years, and 5-year patient and death-censored graft survival of recipients of dual and single kidney transplants. Secondary outcomes included eGFR. Multivariable analyses and propensity score analysis were used to correct for differences between the groups.RESULTS: During the study period, 7841 kidneys were procured from deceased donors aged ≥60 years, of which 1338 (17%) were discarded; 356 dual and 5032 single kidneys were transplanted. Donors of dual transplants were older (median, 73 versus 66 years; PCONCLUSIONS: Recipients of kidneys from donors aged ≥60 years have similar 5-year graft survival and better graft function at 12 months with dual compared with single deceased donor kidney transplants.

Kidney dialysis patients with sarcopenia have increased mortality. Screening for low muscle mass may allow interventions at an earlier stage to help improve outcomes. We wished to determine the prevalence of low muscle mass in a cohort of peritoneal dialysis (PD) patients. We measured lean body mass index (LBMI) in 490 PD patients by bioimpedance, grading patients using two different classifications of sarcopenia. LBMI was 9.7±1.9 kg/m2, mean age was 55.3±16.4 years, 53.1% were male, 33.7% were diabetic and 51% were Caucasoid. 98.5% of patients were classified as having sarcopenia based on LBMI cutoffs from NHANES data, whereas 28.8% had moderate and 6.3% severe sarcopenia using a grading correlated with functional disability. Lower muscle mass was associated with increasing co-morbidity (β=0.34, P=0.02) and age (β=0.01, P=0.006), and negatively with body mass index (β=−0.23, P

Background: Muscle weakness is a risk factor for mortality in haemodialysis (HD) patients; we wished to determine whether measuring the composition of the arm with bioimpedance was associated with arm muscle strength. Methods: We measured pinch strength (PS) and hand grip strength (HGS) in 250 adult HD patients with corresponding post-dialysis multifrequency bioelectrical assessments with segmental body analysis. Results: Mean age 64.0 ± 15.6, 66% male and 45.6% diabetic. The maximum HGS in the dominant or non-fistula arm was 18.9 ± 9.2 kg and PS 4.09 ± 1.96 kg respectively, with a correlation of r = 0.80, p < 0.001. HGS was associated with body cell mass (β 0.37, p < 0.001) and PS with appendicular muscle mass (β 0.06, p < 0.001). Both HGS and PS were independently associated with the ratio of extracellular water (ECW) to total body water (TBW); β -139.5, p = 0.024, β -44.8, p < 0.001 in the arm. The presence of an arterio-venous fistula increased the ECW/TBW ratio in the arm from 0.383 ± 0.009 to 0.390 ± 0.012, p < 0.05. Conclusion: Muscle strength measured by HGS and PS was associated with both markers of whole body and segmental body composition within the arm, particularly ECW/TBW. Bioimpedance measurements and assessment of muscle strength should be measured in the non-fistula arm.

BACKGROUND: A 44-year-old male presented to a general neurology clinic with a 6-month history of progressive right-sided spastic hemiparesis without sensory symptoms or signs. The thigh muscle in the affected leg showed signs of wasting. The patient had a remote family history of celiac disease. INVESTIGATIONS: Neurological examination, neurophysiological studies, brain MRI scan, routine blood tests, duodenal biopsy, cerebrospinal fluid analysis including polymerase chain reaction test for JC virus DNA, serological testing for HIV and for the presence of serum antibodies to endomysium, gliadin and tissue transglutaminase. DIAGNOSIS: Celiac disease with neurological involvement, mimicking amyotrophic lateral sclerosis. MANAGEMENT: Strict gluten-free diet.

Rapidly progressive glomerulonephritis (RPGN) results from severe crescentic damage to glomeruli and leads to irreversible kidney failure if not diagnosed and managed in a timely fashion. Traditional treatment has relied on glucocorticoids and cyclophosphamide, with additional plasmapheresis for certain conditions. Here we describe updates in the management of RPGN, according to the underlying renal pathology. However, there remains a paucity of trials that have enrolled patients with more advanced renal disease, dialysis dependence or with RPGN, and we are therefore still reliant on extrapolation of data from studies of patients with a less severe form of disease. In addition, reporting bias results in publication of cases or cohorts showing benefit for newer agents in advanced disease or RPGN, but it remains unclear how many unsuccessful outcomes in these circumstances take place. Since clinical trials specifically in RPGN are unlikely, use of biologic registries or combination of sufficient sized cohort series may provide indications of benefit outside of a clinical trial setting and should be encouraged, in order to provide some evidence for the efficacy of therapeutic regimens in RPGN and advanced renal disease.

Objectives: to briefly outline the development and validation of the Parkinson's Disease Questionnaire (PDQ-39) and then to provide evidence for the use of the measure as either a profile of health status scores or a single index figure. Design: the PDQ-39 was administered in two surveys: a postal survey of patients registered with local branches of the Parkinson's Disease Society of Great Britain (n = 405) and a survey of patients attending neurology clinics for treatment for Parkinson's disease (n = 146). Data from the eight dimensions of the PDQ-39 were factor-analysed. This produced a single factor on the data from both surveys. Outcome measures: the eight dimensions of the PDQ-39 and the new single index score—the Parkinson's disease summary index (PDSI), together with clinical assessments (the Columbia rating scale and the Hoehn and Yahr staging score). Results: in the postal survey 227 patients returned questionnaires (58.2%). All 146 patients approached in the clinic sample agreed to take part. Higher-order principal-components factor analysis was undertaken on the eight dimensions of the PDQ-39 and produced one factor on both datasets. Consequently it was decided that the scores of the eight domains could be summed to produce a single index figure. The psychometric properties of this index were explored using reliability tests and tests of construct validity. The newly derived single index was found to be both internally reliable and valid. Discussion: data from the PDQ-39 can be presented either in profile form or as a single index figure. The profile should be of value in studies aimed at determining the impact of treatment regimes upon particular aspects of functioning and well-being in patients with Parkinson's disease, while the PDSI will provide a summary score of the impact of the illness on functioning and well-being and will be of use in the evaluation of the overall effect of different treatments. Furthermore, the PDSI reduces the number of statistical comparisons and hence the role of chance when exploring data from the PDQ-39.

Objective To assess the validity and responsiveness of a questionnaire to assess health-related quality of life in Parkinson's disease (PD)--the 39-item Parkinson's Disease Questionnaire (PDQ-39)--and to report problems experienced by patients by means of the questionnaire. Methods Patients completed the PDQ-39 and the SF-36 at baseline and 4 months later. At the same assessments, neurologists rated patients with Hoehn and Yahr and Columbia Scales. Results Evidence for validity of the new questionnaire was observed by agreement of scores with clinical scales at both assessments. Evidence for responsiveness of scales assessing physical function, particularly mobility and activities of daily living, was observed from significant paired t tests for differences between scores at baseline and follow-up, and correlations with patients' retrospective judgments and changes in the SF-36 summary scores. However, there were no significant associations with changes in neurologists' clinical scores. Patients most frequently reported problems of physical function in the PDQ-39. Scores for several dimensions of the PDQ-39 were significantly more favorable than those reported by nonclinic samples of patients with PD. Conclusions The PDQ-39 has validity for use among patients attending neurological clinics for treatment of PD. There is also some evidence of responsiveness. The questionnaire identifies problems that are important to patients and that appear to be more commonly experienced by nonclinic attenders.

The purpose of this paper was to document the impact of Parkinson's disease (PD) upon patients using both a generic health status measure (the Short-form 36 health survey questionnaire, SF-36) and a disease-specific measure (the 39-item Parkinson's Disease Questionnaire, PDQ-39). Comparing the results of the SF-36 in this population with a similar aged group selected randomly from two general practices it was evident that the disease has considerable impact on general levels of functioning and well-being. Furthermore, other areas not contained on the SF-36 were found to be relevant to PD patients. It is suggested that the disease-specific measure will be of value, ideally alongside a generic measure, in studies aimed at determining the impact of a treatment regimen upon PD patients, or to monitor the long-term progress of cohorts of patients with PD. The paper highlights the need for careful consideration of measures for evaluation.

Parkinson's disease is a common degenerative neurological condition. A number of general health status measures exist but these may not address areas salient to specific diseases. We report here the development and validation of a short 39 item health status questionnaire for use in Parkinson's disease. Questionnaire items, generated from in-depth interviews with people with Parkinson's disease, were developed into a 65 item questionnaire. Data from a postal survey using the 65 item questionnaire were statistically analysed to produce a shorter questionnaire with 39 items and eight scales addressing different dimensions of Parkinson's disease. A second postal survey was conducted in order to assess the reliability and validity of the new 39 item questionnaire. The final questionnaire, referred to here as the 39 item Parkinson's Disease Questionnaire (PDQ-39), proved to have satisfactory internal and test-retest reliability, and construct validity in relation to other measures, reported by respondents with Parkinson's disease.

The difficulties inherent in measuring the prevalence of subfertility are discussed. Four subtypes of subfertility are defined, enabling comparisons to be made between the widely different approaches previously reported. A detailed assessment was made of the prevalence of subfertility in two different samples of British women aged 25 to 44 years, using interviews, postal questionnaires, and medical record searches. Data were collected on 872 women from a general practice and 702 hospital patients. The combined data showed that 24% of all women attempting to conceive experience an episode of subfertility at some stage in their reproductive life. Thirteen percent experience this in attempting to conceive their first child, and 17% when attempting to conceive a subsequent child. Three percent of women are involuntarily childless and 6% of parous women are not able to have as many children as they would wish.

Background: Progressive neurological dysfunction is a key aspect of human aging. Because of underlying differences in the aging of mice and humans, useful mouse models have been difficult to obtain and study. We have used gene-expression analysis and polymorphism screening to study molecular senescence of the retina and hippocampus in two rare inbred mouse models of accelerated neurological senescence (SAMP8 and SAMP10) that closely mimic human neurological aging, and in a related normal strain (SAMR1) and an unrelated normal strain (C57BL/6J). Results: The majority of age-related gene expression changes were strain-specific, with only a few common pathways found for normal and accelerated neurological aging. Polymorphism screening led to the identification of mutations that could have a direct impact on important disease processes, including a mutation in a fibroblast growth factor gene, Fgf1, and a mutation in and ectopic expression of the gene for the chemokine CCL19, which is involved in the inflammatory response. Conclusion: We show that combining the study of inbred mouse strains with interesting traits and gene-expression profiling can lead to the discovery of genes important for complex phenotypes. Furthermore, full-genome polymorphism detection, sequencing and gene-expression profiling of inbred mouse strains with interesting phenotypic differences may provide unique insights into the molecular genetics of late-manifesting complex diseases.

l. Die Ausbildung des Geruchsorgans der Vampirfledermause stellt diese zu den makrosmatischen Saugetieren. Es finden sich neben Naso- und Maxilloturbinale vier Endoturbinalia und drei Ectoturbinalia. 2. In einer 5fach Wahlanlage wurden zwei Vampirfledermause darauf dressiert, mit Buttersaure getrankte Filterpapierplattchen aufzuspuren. Die Erkennungsschwelle lag zwischen 3,9 · 10−3 Vol.-% und 7.81 · 10−3 Vol.-% Buttersaure. Ein Vergleich mit Menschen in ahnlicher Versuchssituation zeigte, das die Vampire ein besseres Geruchsvermogen besitzen. Die Menschen konnten die Buttersaure in der dargebotenen Quantitat nur bis 3,12 · 10−2 Vol.-% wahrnehmen. Aus diesen Befunden last sich schliesen, das die Vampirfledermause auch in der Natur ihre Beutetiere geruchlich auffinden konnen.

On admission to hospital during the acute phase of a stroke presumed due to ischaemic infarction in one cerebral hemisphere 93 patients were examined to determine the factors associated with a poor prognosis for immediate survival. The patients particularly at risk were those who were overtly unconscious and those with any combination of impaired consciousness, dense hemiplegia, and failure of conjugate ocular gaze towards the side of the limb weakness. Necropsy evidence suggested that these signs usually indicate infarction of the whole of one middle cerebral artery territory which is often secondary to internal carotid artery occlusion and commonly produces fatal cerebral oedema.

IN public health investigations it is essential that animal hosts and reservoirs be correctly identified. Specialists, particularly mammalogists, are usually willing to identify specimens collected in return for retaining all or a portion of the mammals submitted, especially if the specimens, such as bats, come from a zoologically interesting area, are rare in collections, or might present some challenging taxonomic problem. Since there is an increasing interest in the public health importance of bats (such as their involvement with rabies), countries which have not yet made surveys of their bat populations for the incidence of rabies are being encouraged to do so (Expert Committee on Rabies—Fourth Report, W.H.O. Tech. Rep. Ser. No. 201, 1960). For the purposes of accurate identification, the head is the most important part of the body to the mammalogist, while its contents are of paramount importance to the epidemiologist. The conventional laboratory techniques used for brain tissue removal in rabies diagnosis (W.H.O. Monogr. Ser. No. 23, 1954, and U.S. Public Health Service Pub. No. 568, 1957) frequently mutilate the skin and skull and not only make identification difficult but ruin the specimen for museum purposes.