Routine laboratory measures of heparin anticoagulation for children on extracorporeal membrane oxygenation: Systematic review and meta-analysis.

OBJECTIVE: Specific protocols for anticoagulation for children on ECMO vary across institutions, with most using a continuous infusion of unfractionated heparin. The goal of this study is to aid clinician's decision on the best measure of heparin anticoagulation test; which would be the one that correlates well with heparin activity and helps in predicting hemorrhagic and thrombotic complications. DATA SOURCES: A comprehensive search of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, and Scopus was conducted from each database's inception to 07/13/2018. STUDY SELECTION: Studies evaluating children (<18 years) treated with ECMO and evaluating ACT, aPTT, TEG and Anti-Xa in any language were included. DATA EXTRACTION: Two reviewers selected and appraised studies independently, and abstracted data. RESULTS: We included 19 studies (759 patients, mean age 19.8 months). Meta-analysis showed strong correlation between heparin dosing and anti-Xa. Additionally, there was not a strong correlation between laboratory tests and complications (hemorrhagic and thrombosis), or mortality. CONCLUSION: Based on current evidence, Anti-Xa is the only laboratory test that shows strong correlation with heparin infusion dose and seems like the most suitable test for monitoring of anticoagulation with heparin in children on ECMO.

Secretory diarrhea and hypokalemia associated with colonic pseudo-obstruction: A case study and systematic analysis of the literature.

BACKGROUND: Colonic pseudo-obstruction (CPO) is characterized by colonic distention in the absence of mechanical obstruction or toxic megacolon. Concomitant secretory diarrhea (SD) with hypokalemia (SD-CPO) due to gastrointestinal (GI) loss requires further characterization. AIM: To perform a systematic review of SD-CPO, report a case study, and compare SD-CPO with classical CPO (C-CPO). METHODS: We performed a search of MEDLINE, EMBASE, Cochrane, and Scopus for reports based on a priori criteria for CPO, SD and GI loss of potassium. An additional case at Mayo Clinic was included. RESULTS: Nine publications met inclusion criteria, with a total of 14 cases. Six studies had high, three moderate, and our case high methodological quality. Median age was 74 years (66-97), with 2:1 male/female ratio. Kidney disease was present in 6/14 patients. Diarrhea was described as profuse, watery, or viscous in 10 patients. Median serum, stool, and urine potassium concentrations (mmol/L) were 2.4 (range: 1.9-3.1), 137 (100-180), and 17 (8-40), respectively. Maximal diameter of colon and cecum (median) were 10.2 cm and 10.5 cm, respectively. Conservative therapy alone was effective in five out of 14 patients. Median potassium supplementation was 124 mEq/d (40-300). Colonic decompression was effective in three out of six patients; one had a total colectomy; three out of 14 had died. The main differences between SD-CPO and C-CPO were lower responses to treatments: conservative measures (35.7% vs 73.6%, P=.01), neostigmine (17% vs 89.2%, P<.001), and colonic decompression (50% vs 82.4%, P=.02). CONCLUSION: SD-CPO is a rare phenotype associated with increased fecal potassium and is more difficult to treat than C-CPO.

The pharmacotherapy of cirrhosis: concerns and proposed investigations and solutions.

WHAT IS KNOWN AND OBJECTIVE: The presence of cirrhosis has a multifaceted impact on hepatic drug metabolism. An area of concern and uncertainty in the care of patients with cirrhosis is the safe use of both prescription and over-the-counter medications. COMMENT: Retrospective studies indicate a high incidence of adverse drug reactions (ADRs) among patients with cirrhosis related to use of certain medication classes including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and non-steroidal anti-inflammatory drugs. Conversely, use of appropriate medications, such as statins, may be decreased in this population due to fear of precipitating hepatotoxicity. WHAT IS NEW AND CONCLUSION: Pharmacotherapy in cirrhosis is an area of uncertainty and heterogeneity in clinical practice. Prescribing and dosing guidelines are needed to decrease the risk of serious ADRs in this high-risk patient population.

Bone turnover markers in Paget's disease of the bone: A Systematic review and meta-analysis.

UNLABELLED: The aim of this systematic review and meta-analysis is to study the utility of the commonly used bone turnover markers in evaluating disease activity in patients with Paget's disease of bone before and after treatment with bisphosphonates. We found good correlation between the bone turnover marker concentrations and disease activity assessed by bone scintigraphy. INTRODUCTION: Paget's disease of bone is a common skeletal disorder of the elderly. Bone turnover marker concentrations are used for diagnosis and follow-up. We aimed to compare the available bone turnover markers and determine their utility in assessing disease activity when compared to quantitative bone scintigraphy. METHODS: We conducted a systematic review and meta-analysis searching MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus. We evaluated total alkaline phosphatase (total ALP), bone-specific alkaline phosphatase (bone ALP), procollagen type 1 amino-terminal propeptide (P1NP), serum, and urine C-terminal telopeptide (uCTx and sCTx, respectively), and urine N-terminal telopeptide (uNTx). The main outcome of interest was the correlation of disease activity with concentrations of bone turnover markers in Paget's disease patients before and after treatment with bisphosphonates. Correlation coefficients were pooled across studies using the random effects model. RESULTS: We included 17 observational studies and one trial reporting on 953 patients. Prior to treatment, all studied bone turnover markers had moderate to strong correlation with scintigraphic indices (correlation coefficients ranging from 0.58 to 0.80) with no statistically significant difference between the bone turnover markers overall (p = 0.08). P1NP, uNTx, and bone ALP tend to have higher correlation with scintigraphy. After starting treatment with bisphosphonate, there was moderate to strong correlation with disease activity with all markers except bone ALP (correlation coefficients ranging from 0.43 to 0.70). CONCLUSION: The findings of this meta-analysis suggest the Paget's disease activity is best monitored by following P1NP levels. However, total ALP, bone ALP, and uNTx are good alternatives as markers of disease activity in untreated patients. Total ALP and uNTx can be useful in following patients with Paget's disease after treatment if P1NP is not available. Clinicians, however, should take availability, cost, and the presence of liver disease into consideration when deciding which bone turnover marker is most appropriate when evaluating patients with Paget's disease.

Intensive rearing of male calves during the first three weeks of life has long-term effects on number of islets of Langerhans and insulin stained area in the pancreas.

Permanent effects of early postnatal nutrition on the development and function of tissues and organs have been previously demonstrated primarily in humans and rodents. The objective of this study in calves was to analyze the impact of rearing conditions during the first 3 wk of life on morphology of insulin-producing pancreatic ß-cells. Forty-two male Holstein calves were raised during the first 3 wk of life either intensively (intensively reared [INT]; ad libitum milk feeding and individual hutches; = 21) or according to an established restrictive rearing protocol (4 L milk/d) during wk 1 in hutches and 720 g/d milk replacer (MR) from d 8 to 21 in group pens (restrictively reared [CON]; = 21). Thereafter, all calves were housed and fed under comparable conditions. Birth weight and weekly BW up to wk 10 were recorded. Plasma glucose, insulin, IGF-1, and GH levels were assessed in wk 1, 2, 3, and 10 of life. Slaughtering took place after 8 mo and pancreatic tissue from the medium body (corpus pancreatic) was removed. The number of islets of Langerhans and the insulin stained area were examined histologically. Total milk intake of INT calves was nearly double the intake in CON calves in the first 3 wk of life ( < 0.01). Daily starter intake during wk 4 to 10 of life did not differ between groups ( = 0.24). During the first 3 wk, the ADG were up to 9 times higher in INT calves compared to CON calves ( < 0.01), yet BW at time of slaughter did not differ ( = 0.18). Intensive rearing led to increased plasma glucose, insulin, and IGF-1 concentrations after 3 wk of life compared with rearing to the established standard protocol (all < 0.05), whereas GH was lower in INT calves during the second week of life. At time of slaughter, the mean number of islets of Langerhans was higher in INT calves compared to CON calves (9.1 ± 0.3 vs. 7.8 ± 0.3; < 0.01). Also, the total insulin stained area per photograph was higher in INT calves compared to CON calves (107,180 ± 4,987 vs. 84,249 ± 4,962 µm; < 0.01). Number of islets of Langerhans was negatively associated with birth weight but positively correlated with insulin and in trend with IGF-1 plasma levels during the second week of life. Insulin stained area tended to be linked with IGF-1 concentration during the third week of life. In conclusion, differences in the morphology of pancreatic islets of Langerhans indicate that calves can be programmed metabolically by an altered postnatal rearing intensity.

Neutralization of (NK-cell-derived) B-cell activating factor by Belimumab restores sensitivity of chronic lymphoid leukemia cells to direct and Rituximab-induced NK lysis.

Natural killer (NK) cells are cytotoxic lymphocytes that substantially contribute to the therapeutic benefit of antitumor antibodies like Rituximab, a crucial component in the treatment of B-cell malignancies. In chronic lymphocytic leukemia (CLL), the ability of NK cells to lyse the malignant cells and to mediate antibody-dependent cellular cytotoxicity upon Fc receptor stimulation is compromised, but the underlying mechanisms are largely unclear. We report here that NK-cells activation-dependently produce the tumor necrosis factor family member 'B-cell activating factor' (BAFF) in soluble form with no detectable surface expression, also in response to Fc receptor triggering by therapeutic CD20-antibodies. BAFF in turn enhanced the metabolic activity of primary CLL cells and impaired direct and Rituximab-induced lysis of CLL cells without affecting NK reactivity per se. The neutralizing BAFF antibody Belimumab, which is approved for treatment of systemic lupus erythematosus, prevented the effects of BAFF on the metabolism of CLL cells and restored their susceptibility to direct and Rituximab-induced NK-cell killing in allogeneic and autologous experimental systems. Our findings unravel the involvement of BAFF in the resistance of CLL cells to NK-cell antitumor immunity and Rituximab treatment and point to a benefit of combinatory approaches employing BAFF-neutralizing drugs in B-cell malignancies.

Routine screening for psychosocial distress following hematopoietic stem cell transplantation.

The diagnosis and treatment of cancer is often associated with high levels of psychosocial distress, yet exploration of these issues is rarely included in routine oncologic care. We conducted a pilot study to evaluate the feasibility of screening for psychosocial distress after autologous and allogeneic stem cell transplantation. A total of 80 adults were enrolled in Boston, MA, USA. Subjects completed self-administered assessments prior to hospital admission, at their first clinic visit after hospital discharge, and at 100 days post transplant. Assessments included validated instruments assessing psychosocial distress and quality of life (QOL). Elevated levels of anxiety and/or depression were detected in 55% of those providing pre-transplant assessments and were associated with compromised QOL. Post transplant screening was successfully performed in 69% of subjects and identified that 44% had symptoms of depression, anxiety or post traumatic stress disorder. Pre-transplant distress was associated with detection of distress after transplantation (81 vs 13%, P< 0.0001). In summary, we detected high levels of distress in transplant patients using self-administered tools. Pre-transplant distress appears to be highly predictive of distress post transplant and is a feasible marker to target screening and intervention programs.

Vectorially oriented monolayers of detergent-solubilized Ca(2+) -ATPase from sarcoplasmic reticulum.

A method for tethering proteins to solid surfaces has been utilized to form vectorially oriented monolayers of the detergent-solubilized integral membrane protein Ca(2+) -ATPase from the sarcoplasmic reticulum (SR). Bifunctional, organic self-assembled monolayers (SAMs) possessing "headgroup" binding specificity for the substrate and "endgroup" binding specificity for the enzyme were utilized to tether the enzyme to the substrate. Specifically, an amine-terminated 11-siloxyundecaneamine SAM was found to bind the Ca(2+)-ATPase primarily electrostatically. The Ca(2+)-ATPase was labeled with the fluorescent probe 5-(2-[(iodoacetyl)amino]ethyl)aminonaphthalene-1-sulfonic acid before monolayer formation. Consequently, fluorescence measurements performed on amine-terminated SAM/enzyme monolayers formed on quartz substrates served to establish the nature of protein binding. Formation of the monolayers on inorganic multilayer substrates fabricated by molecular beam epitaxy made it possible to use x-ray interferometry to determine the profile structure for the system, which was proved correct by x-ray holography. The profile structures established the vectorial orientation of the Ca(2+)-ATPase within these monolayers, to a spatial resolution of approximately 12 A. Such vectorially oriented monolayers of detergent-solubilized Ca(2+)-ATPase from SR make possible a wide variety of correlative structure/function studies, which would serve to elucidate the mechanism of Ca(2+) transport by this enzyme.

Methadone-substitution and driving ability.

A general statement about the driving ability of HIV-positive as well as HIV-negative addicts undergoing methadone-substitution treatment cannot be made with certainty. Even isolated observations are not significant; only an individually performed assessment, free of prejudice and conscientiously done is decisive. The formal assertion that addiction equals driving-inability, which is largely practised at present, is inadmissible and therefore harmful to the therapeutic efforts for rehabilitation.

Upper-extremity rehabilitation: conditioning and orthotics for the athlete and performing artist.

Rehabilitation of athletes or musicians with hand injuries begins immediately after injury. Accurate diagnosis of the injury and tissues involved is followed by specific acute and rehabilitative therapies to correct the injury and determine any biomechanical changes that may have occurred. Medication and physical methods aid in decreasing inflammation and pain. Mobility is progressively restored, with the aid of appropriate heating modalities, as soon as signs and symptoms allow. Proprioception and neuromuscular coordination are then retrained. This is followed by balanced muscle strength training. Finally, sport-specific endurance and biomechanical skills are developed. Emotional aspects of the injury may be dealt with by investigating the physical and emotional stresses of the performance, and discussing them with the patient. Some patients may also be helped by psychologic counseling. Orthotics may be used to decrease swelling, decrease pain, and inhibit unwanted motion. Some variations allow for progressive range of motion and strength building. Attention to these details maximizes the chances of successful return to performance in the athlete or performing artist with a hand injury.

[Principles and general practice of a goal-oriented training plan for diabetic patients participating in sports]. / Grundlagen und Praxis einer zielorientierten Trainingsplanung für den sporttreibenden Diabetiker.

Due to a well known experience physical work in patients with diabetes mellitus II is a very important part of the therapy beside diet and medicament treatment. To guarantee a high training efficiency an individual training regimen has to be worked out for the patient. To influence the impaired glucose metabolism the endurance exercise should be carried out at an intensity near the anaerobic threshold. Therefore it is necessary to have a stepwise incremental exercise test including lactate determination after each work load of the patient. Basing on exercise test this paper is designed to give an example of a training regimen in various sport activities (bicycle, running, ski cross country running, swimming) which enables the physician to handle his diabetic patient with an stepwise increasing training program to an optimal training intensity.

Resting echocardiographic parameters after cessation of regular endurance training.

Resting echocardiograms were examined in nonathletic healthy young men (controls, n = 16), in highly trained endurance athletes (n = 20), and in endurance athletes who stopped regular training (n = 40). The relative muscular wall thickness (Rel. MWTd), left ventricular internal diameters both in diastole and in systole (LVIDd, LVIDs), thus also the end-diastolic and end-systolic volumes (LVEDV, LVESV), and the stroke volume index (SVI) were greater in the endurance athletes still in training than in the nonathletes. The ejection fraction (EF), heart rate (HR), cardiac index (CI), and mean circumferential shortening velocity (Vcf) were significantly lower in the athletes. During the 60 days of detraining no change was seen in the Rel. MWTd, LVEDV, LVESV, and HR. The SVI became even greater; EF and Vcf rose up to the control level while CI exceeded it. The cardiovascular regulation is therefore assumed to undergo a peculiar shift during detraining in that a persisting cardiac enlargement and bradycardia is associated with a temporarily unstable autonomous control. This imbalance often leads to a hyperkinesis-like syndrome when an athlete stops endurance training abruptly.

Endurance capacity of trained older aged athletes.

Seven older cyclists (mean age 66.9 years) still engaged in severe endurance training (mean = 8114.3 km year-1) were examined medically, echocardiographically and they underwent a maximal stress test on a bicycle. Mean maximal values were VO2,max = 44.7 ml, Wmax = 261.4 and heart rate = 157.4 beats min-1. The heart volume/max O2-pulse ratio (mean = 46.1) and the TEDD/max O2-pulse ratio (mean = 3.37) were lower compared with age related untrained persons and demonstrate therefore the strong correlation between heart size and function in healthy older aged athletes. Parameters at the anaerobic threshold (lactate concentration 4 mmol l-1) and at the individual anaerobic threshold (lactate concentration 4.08 mmol l-1) showed no significant difference: for heart rate, mean = 133.7; and for W, mean 182.7. The relative oxygen consumption at the anaerobic threshold (mean = 77%/VO2,max) reflect a high endurance capacity of trained old persons, which enables those athletes to outstanding training and competition performance. Derived from that the results show in general the importance of regular endurance training, maintaining an improvement of the cardiovascular system during aging process.