bluuebunny/crossref_metadata_2025_split huggingface dataset:
High‐dose methylprednisolone and endothelial glycocalyx in paediatric heart surgery
Authors: Pesonen E. , Keski‐Nisula J. , Andersson S. , Palo R. , Salminen J. , Suominen P. K. 
Published: September 2016

BackgroundCorticosteroids are used in paediatric heart surgery to attenuate systemic inflammatory response. Glycocalyx regulates vascular permeability, shear stress and cell adhesion on the endothelium. Syndecan‐1 serves as a biomarker of glycocalyx degradation. Hydrocortisone decreased endothelial glycocalyx degradation in an experimental model. Our hypothesis was that high‐dose methylprednisolone decreases glycocalyx degradation as measured by plasma sydecan‐1 concentration in children undergoing cardiac surgery.MethodsTwo double‐blinded, randomized, placebo‐controlled trials were conducted. In the first trial (‘neonatal trial’), 40 neonates undergoing open heart surgery received either 30 mg/kg intravenous methylprednisolone (n = 20) or placebo (n = 20). In the second trial (‘VSD trial’), 45 infants and very young children, undergoing ventricular or atrioventricular septal defect correction received one of the following: 30 mg/kg of methylprednisolone intravenously after anaesthesia induction (n = 15), 30 mg/kg methylprednisolone in the cardiopulmonary bypass prime solution (n = 15) or placebo (n = 15). Plasma syndecan‐1 concentrations were measured. Results were expressed both as absolute concentrations and in relative concentrations as multiples of the baseline values of syndecan‐1.ResultsThere were no statistically significant differences between the neonate trial groups for absolute syndecan‐1 concentrations. However, operative administration of methylprednisolone to neonates significantly reduced the relative increases of syndecan‐1 at weaning from cardiopulmonary bypass (P = 0.008) and at 6 h post‐operatively (P = 0.018). There were no statistically significant differences in absolute or relative increases of syndecan‐1 between the VSD trial study groups.ConclusionHigh‐dose methylprednisolone reduces shedding of glycocalyx in neonates after complex cardiac surgery but not in older infants after repair of VSD/AVSD with shorter ischaemia times.
Liability and Informed Consent in the Context of Shared Decision Making
Authors: Lindor Rachel A. , Kunneman Marleen , Hanzel Matt , Schuur Jeremiah D. , Montori Victor M. , Sadosty Annie T. 
Published: September 2016

AbstractThe idea of shared decision making (SDM) is gaining traction within emergency medicine, although concerns about potential legal consequences of its use may be slowing its adoption. We describe the similarities and differences between informed consent (IC) requirements and SDM, highlighting their different purposes, scope, and implementation. We also illustrate several areas in which SDM may affect clinicians’ liability risks and suggest that while SDM is likely to reduce net liability risks, it may increase providers’ liability risks in certain situations or with select patients. Overall, engaging in SDM should be understood as clearly distinct from the process of obtaining IC and could reduce clinicians’ risk of liability when applied carefully and thoughtfully.
Unaffected twins discordant for affective disorders show changes in anterior callosal white matter microstructure
Authors: Macoveanu J. , Vinberg M. , Madsen K. , Kessing L. V. , Siebner H. R. , Baaré W. 
Published: September 2016

ObjectiveThe neurobiological mechanisms mediating an increased risk to develop affective disorders remain poorly understood. In a group of individuals with a family history of major depressive (MDD) or bipolar disorder (BD), we investigated the microstructural properties of white matter fiber tracts, that is, cingulum bundle, uncinate fasciculus, anterior limb of the internal capsule, and corpus callosum, that facilitate the communication between brain regions implicated in affective disorders.MethodEighty‐nine healthy mono‐ or dizygotic twins with a co‐twin diagnosed with MDD or BD (high‐risk) and 57 healthy twins with a co‐twin with no familial history of affective disorders (low‐risk) were included in a diffusion tensor imaging study.ResultThe high‐risk group showed decreased fractional anisotropy (FA), a measure of water diffusion directionality, and increased radial diffusivity in the anterior region of corpus callosum compared to the low‐risk group. This abnormality was not associated with zygosity or type of depressive disorder of co‐twin.ConclusionThe observed decreased anterior callosal fiber FA in the high‐risk group may be indicative of a compromised interhemispheric communication between left and right frontal regions critically involved in mood regulation. Reduced anterior callosal FA may act as a vulnerability marker for affective disorders in individuals at familial risk.
NUDT15 polymorphisms are better than thiopurine S‐methyltransferase as predictor of risk for thiopurine‐induced leukopenia in Chinese patients with Crohn's disease
Authors: Zhu X. , Wang X.‐D. , Chao K. , Zhi M. , Zheng H. , Ruan H.‐L. , Xin S. , Ding N. , Hu P.‐J. , Huang M. , Gao X. 
Published: September 2016

SummaryBackgroundThiopurine‐induced leukopenia is the most common dangerous adverse event in Asians. NUDT15 R139C was recently proposed to be a promising biomarker for leukopenia with thiopurine therapy in Asians, but this has not been replicated in the Chinese population.AimTo investigate the influence of NUDT15 R139C, thiopurine S‐methyltransferase (TPMT), 6‐TGN and 6‐MMPR on thiopurine‐induced leukopenia in Chinese patients with Crohn's disease.MethodsClinical and epidemiological characteristics were reviewed from medical records. NUDT15 R139C and TPMT were genotyped. 6‐TGN/6‐MMPR concentrations were measured with high‐performance liquid chromatography (HPLC).ResultsA total of 253 patients were included, 65 (25.7%) of whom experienced leukopenia. The median follow‐up with thiopurine treatment was 38.0 weeks (range, 1–192 weeks). NUDT15 R139C was strongly associated with the incidence of leukopenia (70.2% mutation vs. 12.8% wild type; P=8.61×10−19; odds ratio, 10.80; 95% CI, 5.89–19.83). However, TPMT genotype was not found to be correlated with the incidence of leukopenia (P = 0.44). In subgroup of NUDT15 wild type, there was significant difference of 6TGN concentration between patients with and without leukopenia (413.0 (174.2–831.4) vs. 279.7 (77.3–666.9) pmol/8 × 108 RBC, P = 0.0055). In contrast, no association was found in patients with NUDT15 R139C variant alleles (P = 0.26). 6‐MMPR was not correlated with leukopenia (P = 0.84).ConclusionsIn Chinese patients, it is strongly recommended to detect NUDT15 genotype rather than TPMT before initiating thiopurine drugs. 6TGN concentration should be routinely monitored in CD patients with NUDT15 wild type. As for CT genotype, starting at low dose and careful monitoring for leukopenia and 6TGN levels is recommended.
Hydroxycarbamide treatment and brain MRI/MRA findings in children with sickle cell anaemia
Authors: Nottage Kerri A. , Ware Russell E. , Aygun Banu , Smeltzer Matthew , Kang Guolian , Moen Joseph , Wang Winfred C. , Hankins Jane S. , Helton Kathleen J. 
Published: September 2016

SummarySilent cerebral infarction (SCI) is the most common neurological abnormality among children with sickle cell anaemia (SCA). The effect of hydroxycarbamide (also termed hydroxyurea) on the development and progression of SCI is unclear. We evaluated brain magnetic resonance imaging/angiography (MRI/MRA) in children with SCA receiving long‐term hydroxycarbamide therapy. Fifty participants (median 9·4 years, range 1·1–17·3) enrolled in the Hydroxyurea Study of Long‐Term Effects (HUSTLE; NCT00305175) underwent brain MRI/MRA and laboratory evaluations before hydroxycarbamide initiation and after 3 and 6 years of treatment to maximum tolerated dose. SCI and vascular stenosis were evaluated. At baseline, 3 and 6 years, SCI were present in 19/50 (38%), 20/49 (41%), and 7/17 (41%), respectively. At 3 years, one child developed a SCI lesion, and another progressed (single lesion to multiple). Lower haemoglobin (Hb) (80 g/l vs. 86 g/l, P = 0·049), fetal Hb (5·0% vs. 10·4%, P < 0·001) and oxygen saturation (97% vs. 98%, P = 0·027) before hydroxycarbamide initiation were associated with SCI. No patients had vascular stenosis identified on MRA, transient ischaemic attack or stroke. Our data indicate that children receiving hydroxycarbamide over a 3‐ to 6‐year period have a low rate of new or worsening cerebrovascular disease. Further studies are needed to confirm that hydroxycarbamide can prevent the onset and progression of SCI.
New developments in anti‐sickling agents: can drugs directly prevent the polymerization of sickle haemoglobin in vivo?
Authors: Oder Esther , Safo Martin K. , Abdulmalik Osheiza , Kato Gregory J. 
Published: September 2016

SummaryThe hallmark of sickle cell disease is the polymerization of sickle haemoglobin due to a point mutation in the β‐globin gene (HBB). Under low oxygen saturation, sickle haemoglobin assumes the tense (T‐state) deoxygenated conformation that can form polymers, leading to rigid erythrocytes with impaired blood vessel transit, compounded or initiated by adhesion of erythrocytes to endothelium, neutrophils and platelets. This process results in vessel occlusion and ischaemia, with consequent acute pain, chronic organ damage, morbidity and mortality. Pharmacological agents that stabilize the higher oxygen affinity relaxed state (R‐state) and/or destabilize the lower oxygen affinity T‐state of haemoglobin have the potential to delay the sickling of circulating red cells by slowing polymerization kinetics. Relevant classes of agents include aromatic aldehydes, thiol derivatives, isothiocyanates and acyl salicylates derivatives. The aromatic aldehyde, 5‐hydroxymethylfurfural (5‐HMF) increases oxygen affinity of sickle haemoglobin and reduces hypoxia‐induced sickling in vitro and protects sickle cell mice from effects of hypoxia. It has completed pre‐clinical testing and has entered clinical trials as treatment for sickle cell disease. A related molecule, GBT440, has shown R‐state stabilization and increased oxygen affinity in preclinical testing. Allosteric modifiers of haemoglobin as direct anti‐sickling agents target the fundamental pathophysiological mechanism of sickle cell disease.
Acute stress alters individual risk taking in a time‐dependent manner and leads to anti‐social risk
Authors: Bendahan S. , Goette L. , Thoresen J. , Loued‐Khenissi L. , Hollis F. , Sandi C. 
Published: September 2016

AbstractDecision‐making processes can be modulated by stress, and the time elapsed from stress induction seems to be a crucial factor in determining the direction of the effects. Although current approaches consider the first post‐stress hour a uniform period, the dynamic pattern of activation of the physiological stress systems (i.e., the sympathetic nervous system and hypothalamic‐pituitary‐adrenal axis) suggests that its neurobehavioural impact might be heterogeneous. Here, we evaluate economic risk preferences on the gain domain (i.e., risk aversion) at three time points following exposure to psychosocial stress (immediately after, and 20 and 45 min from onset). Using lottery games, we examine decisions at both the individual and social levels. We find that risk aversion shows a time‐dependent change across the first post‐stress hour, evolving from less risk aversion shortly after stress to more risk averse behaviour at the last testing time. When risk implied an antisocial outcome to a third party, stressed individuals showed less regard for this person in their decisions. Participants’ cortisol levels explained their behaviour in the risk, but not the antisocial, game. Our findings reveal differential stress effects in self‐ and other‐regarding decision‐making and highlight the multidimensional nature of the immediate aftermath of stress for cognition.
Normalization of Dialysis Dose for Daily Dialysis
Authors: Gotch Frank A. 
Published: September 2016

The equilibrated Kt/V (eKtV) is widely used in hemodialysis (HD) as a measure of the intensity (magnitude) of an individual dialysis treatment. Adequate eKt/V for thrice‐weekly hemodialysis (twHD) has been extensively studied, and a value in the range 1.0 – 1.1 per treatment (3.0 – 3.3 weekly) is generally considered to represent adequate therapy for this specific frequency of dialysis. However, for other schedules, summing eKt/V's and time‐averaging the clearance is not appropriate. This was first demonstrated several years ago by the observation that a weekly eKt/V of 2.0 in continuous ambulatory peritoneal dialysis (CAPD) is therapeutically equal to a weekly eKt/V of 3.0 in twHD. That paradox has been resolved by the standard Kt/V (stdKt/V), which accounts for the first order nature of solute removal by dialysis, and which correctly predicts a normalized weekly stdKt/V of 2.0 for both CAPD and twHD.The equivalent renal clearance (EKR) has also been advanced as a method to normalize dose for varying treatment schedules. However, mathematical consideration shows that EKR is an exact time‐averaged clearance. Analysis of data reported for daily dialysis by Piccoli et al. in the present issue of Hemodialysis International shows that the EKRct/V calculated for daily dialysis is identical to the sum of eKt/V's for the individual dialyses. We therefore conclude that EKR is not a suitable parameter for normalizing the dialysis dose, because it fails to reflect the effect of dialysis frequency in HD therapy.
Daily Dialysis and Flexible Schedules: How to Assess Kt/V and EKRc?
Authors: Piccoli Giorgina B. , Calderini Mario , Bechis Francesca , Pacitti Alfonso , Iacuzzo Candida , Mezza Elisabetta , Quaglia Marco , Burdese Manuel , Gai Massimo , Anania Patrizia , Jeantet Alberto , Segoloni Giuseppe Paolo 
Published: September 2016

Despite the growing interest in daily hemodialysis (DHD), logistic and economic factors limit its dissemination. Not the least of these factors is the lack of uniform criteria for measuring efficiency.From November 1998 to November 2000, 19 patients were on DHD in our unit. The dialysis prescription was bicarbonate buffer; 6 sessions per week; 2 – 3 hours; blood flow 250 – 350 mL/min; individual K, HCO3, and Na levels; membrane 1.6 – 2 m2 (polysulfone, polycarbonate). The prescription represented the minimum dialysis requirement; patients were free to add up to 30 minutes per session, further increase or any decreases needed confirmation by the caregivers.The aim of the study was to assess Kt/Vurea variability in this clinical setting, and to identify the minimum number of dialysis sessions required to obtain a reliable estimate of weekly Kt/Vurea [relative error (RE) < 10%].We studied 169 dialysis sessions in 13 clinically stable patients on DHD for ≥ 3 months, with ≥ 3 Kt/Vurea measurements within 2 weeks (median: 10; range: 3 – 32 sessions), tested in the same laboratory. To assess variability, we employed the simplest formula (the Lowrie Kt/Vurea), the widely used Daugirdas II formula, and the derived single‐pool equivalent renal clearance (EKRc), according to Casino.The variability of Kt/Vurea per session was high (Lowrie: RE = 2.5% – 22.1%; Daugirdas II and EKRc: RE = 3.6% – 24%). Averaging several dialysis sessions leads to a more reliable estimate of weekly efficiency (6 sessions: RE = 0; 3 sessions, Lowrie formula: Kt/Vurea RE = 1.1% – 9.7%; Daugirdas II and EKRc: RE = 1.6% – 10.6%). In patients with wide time variations, variability may be lower if weekly efficiency is determined on the basis of “average hourly Kt/Vurea,” which is calculated by dividing Kt/Vurea by the number of hours in the studied sessions, and then multiplying by the hours of dialysis performed in the whole week (Lowrie formula, Kt/Vurea: RE = 4.8% – 16.6% for 1 session, 2.1% – 7.3% for 3 sessions). Once again, the RE decreases sharply when data from 3 sessions are considered. Therefore, for flexible DHD, we suggest averaging the data from ≥ 3 sessions for weekly Kt/Vurea assessment.
Lipid Metabolism and Cardiovascular Morbidity and Mortality in Hemodialysis Patients: Role of Factors Modulating Cytosolic Calcium
Authors: Gadallah Merit F. , El-Shahawy Mohamed , Andrews George , Torres–Rivera Carlos , Hanna Dina , Blatt Marc , Ibrahim Magued , Morkos Atef , Abbassian Mohammad , Cooper Mark 
Published: September 2016

Animal studies indicate that insulin resistance and glucose intolerance leading to dyslipidemia in uremic rats are associated with increased cytosolic calcium ([Ca++ i]). The resistance and intolerance are reversed with verapamil, but recur after its discontinuation. This finding suggests that hyperparathyroid‐induced [Ca ++ i] increase is responsible for the metabolic derangement.We retrospectively examined, over a 12‐year period, the effects of factors that lower [Ca ++i] on total serum cholesterol and triglycerides in 332 hemodialysis (HD) patients. Because the study was retrospective, detailed lipid profiles were not available. We therefore relied on morbidity and mortality outcomes related to atherosclerotic vascular disease. Patients with diabetes mellitus were excluded, because their dyslipidemia and vascular disease are mediated via a different mechanism.Four groups emerged: group I [high parathormone (PTH) in the absence of calcium channel blockers (CCBs), n = 107], representing the highest [Ca++ i]; group II (high PTH in the presence of CCBs, n = 76) and group III (lower PTH in the absence of CCBs, n = 66), representing intermediate [Ca ++ i]; and group IV (lower PTH in the presence of CCBs, n = 83) representing the lowest [Ca ++i]. The theoretically lower [Ca ++ i] was achieved via CCB therapy or lower PTH, or both.The mean serum cholesterol in group I was 322 ± 24 mg/dL and the level of triglycerides was 398 ± 34 mg/dL. Group II had mean serum cholesterol of 196 ± 16 mg/dL and triglycerides of 157 ± 17 mg/dL. Group III had a mean serum cholesterol of 202 ± 19 mg/dL and triglycerides of 160 ± 15 mg/dL. Group IV had a mean serum cholesterol of 183 ± 9 mg/dL and triglycerides of 94 ± 6 mg/dL. The differences in cholesterol and triglyceride levels among four groups were significant (p < 0.001) by one‐way analysis of variance (ANOVA). The incidence of cardiovascular morbidity and mortality events was 61% in group I, 24% in group II, 28% in group III, and 18% in group IV (χ 2 = 47.7, p < 0.001).We conclude that, in non diabetic HD patients, hyperparathyroidism, especially in the absence of CCBs, is associated with severe dyslipidemia and increased risk of cardiovascular morbidity and mortality. Dyslipidemia may be related to a hyperparathyroid‐induced increase in cytosolic calcium [Ca++i]. Lowering [Ca++i] by decreasing PTH or by blocking calcium entry into cells (via CCBs), or both, is associated with less dyslipidemia and improved long‐term cardiovascular morbidity and mortality. Prospective randomized studies, with actual measurement of [Ca ++i], are needed to verify the results of this study.
Phosphorus Clearance Using Two Hemodialyzers Placed in Parallel
Authors: Rosner Mitchell H. , Helmandollar Allen , Evans Ryan , Abdel-Rahman Emaad 
Published: September 2016

Control of hyperphosphatemia is a major goal in patients with end‐stage renal disease. However, removal of retained inorganic phosphorus during hemodialysis remains a major problem. We compared clearances and total phosphate removal in large patients treated with two F‐80 dialyzers (Fresenius Medical Care of North America, Lexington, MA, U.S.A.) placed in parallel, and small patients dialyzed with a single F‐80 dialyzer (SD). Clearances were obtained using total dialysate collections. Eight dialysate collections (5 patients) using double parallel dialyzers (DD group) were compared with 5 dialysate collections (4 patients) using single dialyzers (SD group). Blood and dialysate flow rates and time of dialysis treatment were identical between the groups.The DD group's Kt/V urea was 1.46 ± 0.13; SD group's Kt/V urea was 1.35 ± 0.09 (p = 0.2). Absolute phosphorus removal was 1594 ± 300 mg for the DD group, compared to 1108 ± 285 mg in the SD group (p = 0.03). Urea clearance in the DD group was 285 ± 25 mL/minute and 251 ± 27 mL/ min in the SD group (p = 0.082). Phosphorus clearance was 178 ± 32 mL/min in the DD group and 149 ± 38 mL/min in the SD group (p = 0.039). There was no correlation between phosphorus clearance and dialyzer reuse. The bulk of phosphorus removal was achieved during the first 2 hours of hemodialysis. This finding is consistent with the hypothesis that there are at least two pools of body phosphorus.Using hemodialyzers placed in parallel led to higher phosphate clearance and total phosphorus removal. This higher phosphate removal may be related in part to increasing the concentration gradient for transfer out of a second compartment.
A digital advocate? Reactions of rural people who experience homelessness to the idea of recording clinical encounters
Authors: Grande Stuart W. , Castaldo Mary Ganger , Carpenter‐Song Elizabeth , Griesemer Ida , Elwyn Glyn 
Published: September 2016

AbstractBackgroundAre the benefits of recording clinical encounters shared across different groups, or do they vary based on social position? Studies show that educated patients record their clinical visits to enhance their experience, but very little is known about recording benefits among “hard‐to‐reach” populations.ObjectiveTo examine the reactions of homeless people to the idea of using a smartphone to record their own clinical encounter, either covertly or with permission from their physician.MethodWe conducted semi‐structured interviews with individuals at a temporary housing shelter in Northern New England. A thematic analysis identified themes that were iteratively refined into representative groups.ResultsEighteen (18) interviews were conducted, 12 with women and six with men. Initial reactions to clinical recordings were positive (11 of 18). A majority (17 of 18) were willing to use recordings in future visits. A thematic analysis characterized data in two ways: (i) by providing reliable evidence for review, they functioned as an advocacy measure for patients; (ii) by promoting transparency and levelling social distance, this technology modified clinical relationships.DiscussionRecordings permitted the sharing of data with others, providing tangible proof of behaviour and refuting misconceptions. Asking permission to record appeared to modify relationships and level perceived social distance with clinicians.ConclusionsWe found that while many rural, disadvantaged individuals felt marginalized by the wide social distance between themselves and their clinicians, recording technology may serve as an advocate by holding both patients and doctors accountable and by permitting the burden of clinical proof to be shared.