Behaviour of non-donor specific antibodies during rapid re-synthesis of donor specific HLA antibodies after antibody incompatible renal transplantation

Background: HLA directed antibodies play an important role in acute and chronic allograft rejection. During viral infection of a patient with HLA antibodies, the HLA antibody levels may rise even though there is no new immunization with antigen. However it is not known whether the converse occurs, and whether changes on non-donor specific antibodies are associated with any outcomes following HLA antibody incompatible renal transplantation. Methods: 55 patients, 31 women and 24 men, who underwent HLAi renal transplant in our center from September 2005 to September 2010 were included in the studies. We analysed the data using two different approaches, based on; i) DSA levels and ii) rejection episode post transplant. HLA antibody levels were measured during the early post transplant period and corresponding CMV, VZV and Anti-HBs IgG antibody levels and blood group IgG, IgM and IgA antibodies were quantified. Results: Despite a significant DSA antibody rise no significant non-donor specific HLA antibody, viral or blood group antibody rise was found. In rejection episode analyses, multiple logistic regression modelling showed that change in the DSA was significantly associated with rejection (p = 0.002), even when adjusted for other antibody levels. No other antibody levels were predictive of rejection. Increase in DSA from pre treatment to a post transplant peak of 1000 was equivalent to an increased chance of rejection with an odds ratio of 1.47 (1.08, 2.00). Conclusion: In spite of increases or decreases in the DSA levels, there were no changes in the viral or the blood group antibodies in these patients. Thus the DSA rise is specific in contrast to the viral, blood group or third party antibodies post transplantation. Increases in the DSA post transplant in comparison to pre-treatment are strongly associated with occurrence of rejection

ABCD² risk score does not predict the presence of cerebral microemboli in patients with hyper-acute symptomatic critical carotid artery stenosis

ABCD² risk score and cerebral microemboli detected by transcranial Doppler (TCD) have been separately shown to the predict risk of recurrent acute stroke. We studied whether ABCD² risk score predicts cerebral microemboli in patients with hyper-acute symptomatic carotid artery stenosis. We studied 206 patients presenting within 2 weeks of transient ischaemic attack or minor stroke and found to have critical carotid artery stenosis (≥50%). 86 patients (age 70±1 (SEM: years), 58 men, 83 Caucasian) had evidence of microemboli; 72 (84%) of these underwent carotid endarterectomy (CEA). 120 patients (age 72±1 years, 91 men, 113 Caucasian) did not have microemboli detected; 102 (85%) of these underwent CEA. Data were analysed using X2 and Mann-Whitney U tests and receiver operating characteristic (ROC) curves. 140/206 (68%: 95% CI 61.63 to 74.37) patients with hyper-acute symptomatic critical carotid stenosis had an ABCD2 risk score ≥4. There was no significant difference in the NICE red flag criterion for early assessment (ABCD² risk score ≥4) for patients with cerebral microemboli versus those without microemboli (59/86 vs 81/120 patients: OR 1.05 ABCD² risk score ≥4 (95% CI 0.58 to 1.90, p=0.867)). The ABCD² risk score was <4 in 27 of 86 (31%: 95% CI 21 to 41) embolising patients and in 39 of 120 (31%: 95% CI 23 to 39) without cerebral microemboli. After adjusting for pre-neurological event antiplatelet treatment (APT), area under the curve (AUC) of ROC for ABCD2 risk score showed no prediction of cerebral microemboli (no pre-event APT, n=57: AUC 0.45 (95% CI 0.29 to 0.60, p=0.531); pre-event APT, n=147: AUC 0.51 (95% CI 0.42 to 0.60, p=0.804)). The ABCD² score did not predict the presence of cerebral microemboli or carotid disease in over one-quarter of patients with symptomatic critical carotid artery stenosis. On the basis of NICE guidelines (refer early if ABCD² ≥4), assessment of high stroke risk based on ABCD² scoring may lead to inappropriate delay in urgent treatment in many patients

Multimodal analysis of the effects of dexamethasone on high-altitude cerebral oedema : protocol for a pilot study

Background Acute mountain sickness (AMS) is a cluster of symptoms that commonly occur in those ascending to high altitudes. Symptoms can include headaches, nausea, insomnia and fatigue. Exposure to high altitude can also lead to high-altitude cerebral oedema (HACE), which is a potential cause of death whilst mountaineering. Generally, AMS precedes the development of HACE. Historical studies have demonstrated the effectiveness of regular dexamethasone administration in reducing the symptoms of AMS. However, the mechanism by which dexamethasone works to reduce symptoms AMS remains poorly understood. Further studies, simulating altitude using hypoxic tents, have characterised the effect of prolonged exposure to normobaric hypoxia on cerebral oedema and blood flow using MRI. This randomised trial assesses the effect of dexamethasone on hypoxia-induced cerebral oedema in healthy adult volunteers. Methods/design D4H is a double-blind placebo-controlled randomised trial assessing the effect of dexamethasone on hypoxia-induced cerebral oedema. In total, 20 volunteers were randomised in pairs to receive either 8.25 mg dexamethasone or normal saline placebo intravenously after 8 h of hypoxia with an FiO2 of 12%. Serial MRI images of the brain and spinal cord were obtained at hours 0, 7, 11, 22 and 26 of the study along with serum and urinary markers to correlate with the severity of cerebral oedema and the effect of the intervention. Discussion MRI has been used to identify changes in cerebral vasculature in the development of AMS and HACE. Dexamethasone is effective at reducing the symptoms of AMS; however, the mechanism of this effect is unknown. If this study demonstrates a clear objective benefit of dexamethasone in this setting, future studies may be able to demonstrate that dexamethasone is an effective therapy for oedema associated with brain and spinal cord ischaemia beyond AMS

Magnetic resonance investigation into the mechanisms involved in the development of high-altitude cerebral edema

Rapid ascent to high altitude commonly results in acute mountain sickness, and on occasion potentially fatal high-altitude cerebral edema. The exact pathophysiological mechanisms behind these syndromes remain to be determined. We report a study in which 12 subjects were exposed to a FiO2 = 0.12 for 22 h and underwent serial magnetic resonance imaging sequences to enable measurement of middle cerebral artery velocity, flow and diameter, and brain parenchymal, cerebrospinal fluid and cerebral venous volumes. Ten subjects completed 22 h and most developed symptoms of acute mountain sickness (mean Lake Louise Score 5.4; p < 0.001 vs. baseline). Cerebral oxygen delivery was maintained by an increase in middle cerebral artery velocity and diameter (first 6 h). There appeared to be venocompression at the level of the small, deep cerebral veins (116 cm3 at 2 h to 97 cm3 at 22 h; p < 0.05). Brain white matter volume increased over the 22-h period (574 ml to 587 ml; p < 0.001) and correlated with cumulative Lake Louise scores at 22 h (p < 0.05). We conclude that cerebral oxygen delivery was maintained by increased arterial inflow and this preceded the development of cerebral edema. Venous outflow restriction appeared to play a contributory role in the formation of cerebral edema, a novel feature that has not been observed previously

Hey! Ho! Let’s Go [Back to Islam]! : Exploring the Interplay of Punk and Piety in Java, Indonesia

Dans les années 1990, la musique punk fit son entrée dans la société indonésienne. Coïncidant avec une vaste lutte politique contre le régime du Nouvel Ordre du président Suharto, le punk fut rapidement adopté comme plate-forme de ralliement pour exprimer une insatisfaction collective envers ce gouvernement répressif. En 2018, le punk continue de séduire par son attitude rebelle, son style non conformiste et son esprit indépendant. Pourtant, à Java, l’île centrale de l’Indonésie, le punk détient récemment d’une nouvelle fonction: le prosélytisme. Au sein de ce nouveau mouvement, on trouve des groupes religieux conservateurs qui adoptent la philosophie et les emblèmes du punk à des fins de prosélytisme, d'anciens punks qui deviennent des autorités religieuses, et un marché prospérant où des symboles punk et islamiques se voient transformés en marchandise. L'interaction curieuse entre les domaines du punk et de l'islam soulève de nombreuses questions sur ce que signifie d’être punk et d’être musulman à la suite du renouveau islamique. En m'appuyant sur les résultats d'un séjour ethnographique de trois mois à Java, je m’interroge sur la façon dont les punks javanais articulent l'individualisme du punk avec la normativité de l'islam. Ce phénomène nous invite à réexaminer les limites que nous utilisons pour circonscrire les mondes rhétoriques du punk et de l’islam. De plus, il suscite une réflexion sur les paramètres et les paradoxes du prosélytisme punk. C’est un cas parmi plusieurs qui témoigne de l’agencement dynamique entre la religion, l'économie de marché et la culture populaire au 21e siècle.During the 1990s, punk music made its entry into Indonesian society. Coinciding with a nationwide political struggle against President Suharto’s New Order regime, punk was quickly adopted as a rallying point for expressing discontent towards the current repressive government. In 2018, two decades after the fall of Suharto, punk continues to entice with its unapologetic attitude, nonconformist style, and independent ethos. Yet in Java, Indonesia’s central island, punk has gained a new and rather unexpected function: proselytism. The Muslim Punk trend reveals that conservative religious groups are adopting punk ethos and imagery for proselytism, that a growing number of punks are becoming religious authorities, and that a thriving market is rendering both punk and Islamic symbols into commodities. The curious interplay between the realms of punk and Islam raises numerous questions about what it means to be punk and be Muslim, not only in the age of consumer culture and globalization, but also in the wake of the Islamic Revival. Drawing on the results of a three-month ethnographic sojourn in Java, I question how Javanese punks articulate the individualism of punk with the normativity of Islam. In sum, the Muslim Punk phenomenon invites us to reassess the discursive boundaries we commonly use to circumscribe the rhetorical worlds of ‘punk’ and ‘Islam’, and opens up a new debate about the parameters and paradoxes of punk proselytism. My thesis analyses and confirms the dynamic interrelation between religion, market economy, and popular culture in the 21st century

Reduced Cardiovascular Reserve in Chronic Kidney Failure: A Matched Cohort Study

Background: Patients with chronic kidney failure (CKF) experience impaired functional cardiovascular reserve with reduced oxygen consumption at peak exercise (Vo2peak). No studies have examined whether this is related to impaired cardiovascular compliance as a consequence of loss of adaptive structural alterations, resulting from chronic uremia or hypertension. Study Design: Prospective matched-cohort study. Setting & Participants: We assessed CKF in parallel with patients with essential hypertension but without cardiovascular disease. Patients with CKF were either scheduled for kidney transplantation or transplant waitlisted. 80 patients with CKF and 80 with essential hypertension matched in age, sex, and body mass index were evaluated. 61 patients with CKF (76.3%) were dialysis dependent. Predictor: CKF versus essential hypertension without cardiovascular disease. Measurements & Outcomes: Vo2peak was measured during maximal exercise testing. 2-dimensional echocardiography and arterial applanation tonometry were performed prior to exercise testing. To evaluate for the difference in Vo2peak between study groups, statistically significant predictors of Vo2peak in multiple regression models were additionally assessed by fitting models comprising the interaction term of patient group with the predictor variable of interest. Results: Vo2peak was significantly lower in patients with CKF than those with essential hypertension (18.8 vs 24.5 mL/min·kg; P < 0.001). Independent predictors of Vo2peak for CKF included left ventricular (LV) filling pressure (E/mean e′; unstandardized regression coefficient: change in Vo2peak [in mL/min·kg] per 1-unit change of variable = −5.1) and pulse wave velocity (−4.0); in essential hypertension, these were LV mass index (0.2), LV end-diastolic volume index (0.4), peak heart rate (0.2), and pulse wave velocity (−8.8). The interaction effect of Vo2peak between patient groups with LV mass index (P < 0.001), LV end-diastolic volume index (P < 0.001), and peak heart rate (P < 0.01) were significantly stronger in the hypertension group, whereby higher values led to greater Vo2peak. Limitations: Skeletal muscle strength was not assessed. Conclusion: This study suggests that maladaptive LV changes, as well as blunted chronotropic response, are important mechanistic factors resulting in reduced cardiovascular reserve in patients with CKF, beyond predominantly vascular changes associated with hypertension

Reduced functional measure of cardiovascular reserve predicts admission to critical care unit following kidney transplantation

Background: There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO2AT) could identify these patients. Methods: Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial applanation tonometry were performed. Results: There were 70 participants (age 41.7614.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO2AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27–0.68; p,0.001) and in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12–0.59; p = 0.001). The area under the receiveroperating- characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission. Conclusions: To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO2AT has the potential to predict perioperative morbidity in kidney transplant recipients

Changes in metabolic energy measures for daily living activities and exercise in men and women following arduous activity in Antarctica

This study reports pre- to post-expedition (pre|post) changes in energy expenditure and substrate utilisation during daily living activities (DLAs including rest, sleep, modest exercise, sedentary work and leisure) and maximum aerobic power (V̇O2max) for participants in the Inspire-22 expedition (6 men, 3 women) who undertook a 47 day unassisted Antarctic traverse from the Ronne Ice Shelf to the South Pole. DLA measurements were carried out during a 36 hour study in a whole-body calorimeter whilst measurements of maximum oxygen uptake (V̇O2max), capillary glucose and lactate during incremental stepping exercise to volitional exhaustion were carried out under normobaric normoxic and hypoxic (14% O2) conditions in an environmental chamber. Non-exercise measures were normalised to non-fat tissue weight; exercise measures, including those in the DLAs, to body weight. Statistical analysis used the Aligned Rank Transform (ART) non-parametric ANOVA technique with covariants pre|post expedition, sex and hypoxia|normoxia as appropriate. There were no systematic differences between pre- and post-expedition energy expenditure but significant differences between men and women for the majority of the DLAs (p&lt;0.05). There was increased carbohydrate utilisation post-expedition for sleep and the two lower intensity exercise levels (p&lt;0.05) but not during rest or the highest intensity exercise (p&gt;0.05); a sex-independent subset of 4 showing much higher utilisation. Women had a lower protein utilisation than men during the DLA exercise activities (p&lt;0.05). V̇O2max was lower in hypoxia than normoxia (p&lt;0.001) and reduced glucose and lactate between pre- and post-expedition measures. There was also a significant interaction between sex and pre|post measurements for V̇O2max and lactate suggesting that adaptation to the environment and high workloads was different between men and women; a suggestion supported by the difference in fat-free tissue measured pre- and post-expedition, but neither sex showed major differences between the pre- and post-expedition measurements.</p