TROPHY registry - status report.

INTRODUCTION: The TROPHY registry has been established to conduct an international multicenter prospective data collection on the surgical management of neonatal intraventricular hemorrhage (IVH)-related hydrocephalus to possibly contribute to future guidelines. The registry allows comparing the techniques established to treat hydrocephalus, such as external ventricular drainage (EVD), ventricular access device (VAD), ventricular subgaleal shunt (VSGS), and neuroendoscopic lavage (NEL). This first status report of the registry presents the results of the standard of care survey of participating centers assessed upon online registration. METHODS: On the standard of treatment forms, each center indicated the institutional protocol of interventions performed for neonatal post-hemorrhagic hydrocephalus (nPHH) for a time period of 2 years (Y1 and Y2) before starting the active participation in the registry. In addition, the amount of patients enrolled so far and allocated to a treatment approach are reported. RESULTS: According to the standard of treatment forms completed by 56 registered centers, fewer EVDs (Y1 55% Y2 46%) were used while more centers have implemented NEL (Y1 39%; Y2 52%) to treat nPHH. VAD (Y1 66%; Y2 66%) and VSGS (Y1 42%; Y2 41%) were used at a consistent rate during the 2 years. The majority of the centers used at least two different techniques to treat nPHH (43%), while 27% used only one technique, 21% used three, and 7% used even four different techniques. Patient data of 110 infants treated surgically between 9/2018 and 2/2021 (13% EVD, 15% VAD, 30% VSGS, and 43% NEL) were contributed by 29 centers. CONCLUSIONS: Our results emphasize the varying strategies used for the treatment of nPHH. The international TROPHY registry has entered into a phase of growing patient recruitment. Further evaluation will be performed and published according to the registry protocol.

Determination of endocannabinoids and endocannabinoid-like substances in human K3EDTA plasma - LC-MS/MS method validation and pre-analytical characteristics.

The determination of endocannabinoids and endocannabinoid-like substances in biological human samples is a vibrant field of research with great significance due to postulated relevance of these substances in diseases such as Alzheimer's disease, multiple sclerosis, cancer and cardiovascular diseases. For a possible use as biomarker in early prediction or diagnosis of a disease as well as examination of a successful treatment, the valid determination of the analytes in common accessible human samples, such as plasma or serum, is of great importance. A method for the determination of arachidonoyl ethanolamide, oleoyl ethanolamide, palmitoyl ethanolamide, 1-arachidonoyl glycerol and 2-arachidonoyl glycerol in human K3EDTA plasma using liquid-liquid-extraction in combination with liquid chromatography-tandem-mass spectrometry has been developed and validated for the quantification of the aforementioned analytes. Particular emphasis was placed on the chromatographic separation of the isomers 1-arachidonoyl glycerol and 2-arachidonoyl glycerol, arachidonoyl ethanolamide and O-arachidonoyl ethanolamine (virodhamine) as well as oleoyl ethanolamide and vaccenic acid ethanolamide. During the validation process, increasing concentrations of 1-arachidonoyl glycerol and 2-arachidonoyl glycerol while storing plasma samples were observed. In-depth investigation of pre-analytical sample handling revealed rising concentrations for both analytes in plasma and for arachidonoyl ethanolamide, oleoyl ethanolamide and palmitoyl ethanolamide in whole blood, dependent on the period and temperature of storage. Prevention of the increase in concentration was not possible, raising the question whether human K3EDTA plasma is suitable for the determination of endocannabinoids and endocannabinoid-like substances. Especially the common practice to calculate the concentration of 2-arachidonoyl glycerol as sum of 1-arachidonoyl glycerol and 2-arachidonoyl glycerol is highly questionable because the concentrations of both analytes increase unequally while storing the plasma samples in the fridge.

A validated LC-MS/MS method for the determination of homocysteic acid in biological samples.

The role of homocysteic acid (HCA) in severe diseases like Alzheimer's disease is under discussion and some recent studies correlate elevated HCA concentrations with the diagnosis of Alzheimer's. However, non-selective and insufficiently sensitive methods have been used to quantitate HCA and results of different studies show large differences in the determined HCA concentration in samples from patients and controls, and therefore non-comparable results. An accurate and precise quantitation method for the determination of HCA in human serum, urine and CSF has been developed by using a combination of protein precipitation and solid phase extraction for sample preparation followed by an LC-MS/MS analysis using a combination of a HILIC separation and tandem mass spectrometry. The developed method has been fully validated in accordance with the guidelines provided by the US Food and Drug administration FDA and the European Medicines Agency EMA. Furthermore, the method has demonstrated its ability to determine the endogenous HCA concentration in serum and urine samples from healthy volunteers.

Management of Intracranial Incidental Findings on Brain MRI.

The wider use of MRI for imaging of the head in both research and clinical practice has led to an increasing number of intracranial incidental findings. Most of these findings have no immediate medical consequences. Nevertheless, knowledge of common intracranial incidental findings and their clinical relevance is necessary to adequately discuss the findings with the patient. Based on the author´s experiences from a large population-based study, the most common incidental MR findings in the brain will be presented, discussing their clinical relevance and giving recommendations for management according to the current literature and guidelines. Key points: • Intracranial incidental findings are common.• The majority of these findings have no immediate medical consequences.• Knowledge of common incidental findings is necessary for appropriate management. Citation Format: • Langner S, Buelow R, Fleck S et al. Management of Intracranial Incidental Findings on Brain MRI. Fortschr Röntgenstr 2016; 188: 1123 - 1133.

Decreased risk of graft failure with maternal liver transplantation in patients with biliary atresia.

The presence of maternal cells in offspring may promote tolerance to noninherited maternal antigens (NIMAs). Children with biliary atresia (BA) have increased maternal cells in their livers, which may impact tolerance. We hypothesized that patients with BA would have improved outcomes when receiving a maternal liver. We reviewed all pediatric liver transplants recorded in the SRTR database from 1996 to 2010 and compared BA and non-BA recipients of maternal livers with recipients of paternal livers for the incidences of graft failure and retransplantation. Rejection episodes after parental liver transplantation were examined for patients transplanted at our institution. BA patients receiving a maternal graft had lower rates of graft failure compared to those receiving a paternal graft (3.7% vs. 10.5%, p = 0.02) and, consequently, fewer episodes of retransplantation (2.7% vs. 7.5%, p = 0.04). These differences were not seen among non-BA patients or among BA patients who received female deceased donor grafts. In patients transplanted at our institution, paternal liver transplantation was associated with an increased incidence of refractory rejection compared to maternal liver transplantation only in BA. Our data support the concept that maternal cells in BA recipients promote tolerance to NIMAs and may be important in counseling BA patients who require liver transplantation.

Percutaneous balloon kyphoplasty with the patient under intravenous analgesia and sedation: a feasibility study.

BACKGROUND AND PURPOSE: Kyphoplasty is a minimally invasive procedure for the treatment of malignant or osteoporotic vertebral compression fractures, normally performed with the patient under general anesthesia. This may cause a therapeutic dilemma because these patients often have a very high risk for general anesthesia due to concomitant diseases. The aim of this study was to evaluate the safety and feasibility of percutaneous kyphoplasty by using IV anesthesia and sedation with midazolam and piritramide. MATERIALS AND METHODS: From June 2007 to June 2009, we prospectively included 133 patients (77 women, 56 men; mean age, 69.18 ± 11.45 years) who were referred for BKP. Kyphoplasty was always performed under fluoroscopic guidance with a biplane angiographic system by using a transpedicular or extrapedicular approach. The individual anesthesia risk was assessed by using the ASA criteria. All procedures were performed with the patient under IV anesthesia and sedation with fractionated administration of midazolam and piritramide. Pain was assessed before and after treatment by using a VAS. RESULTS: Ninety-nine patients (74.4%) had a significantly increased risk for general anesthesia (ASA score, ≥ 3). A total of 162 kyphoplasty procedures were performed. The mean amounts of midazolam and piritramide used were 11.3 ± 4.38 mg and 11.8 ± 3.98 mg, respectively. No complications related to IV anesthesia and sedation occurred. Periprocedural pain management was rated as sufficient, and all patients would undergo the procedure again. CONCLUSIONS: Percutaneous BKP with the patient under IV anesthesia and sedation with midazolam and piritramide is a safe and feasible method for treating vertebral compression fractures in patients with an increased risk for general anesthesia.

Effects of a supervised exercise program on the physical fitness and immunological function of HIV-infected patients.

AIM: Exercise effects in subjects with HIV/AIDS are not entirely understood. The study aimed to investigate the effects of a supervised exercise program on the physical fitness and immunological function of HIV-infected subjects. METHODS: Twenty-seven highly active antiretroviral therapy treated HIV-infected patients (age: 45±2 years; CD4-T: 21.3±2.2%) were assigned to a control (CG, n=8) or experimental (EG, n=19) group. The EG participated in a 12-week exercise program, consisting of aerobic training, strength, and flexibility exercises (3 times/wk; aerobic-30min: PWC 150; strength-50min: 3 sets of 12 reps of 5 exercises at 60-80% 12 RM; flexibility-10min: 2 sets of 30 s at maximal range of motion of 8 exercises). RESULTS: Prior to training there was no significant difference in any variable between the EG and the CG. Flexibility (23%, P<0.05), 12 repetition maximum in the leg press and seated bilateral row exercises (54% and 65% respectively, P<0.05) increased, while the heart rate at a given cycle ergometer workload declined (19% for slope and 12% for intercept, P<0.05) in the EG, but not in the CG. No significant differences were found for the relative and absolute CD4 T-cell counts between groups prior to or after training, but there was a slight enhancement trend in the EG (16%, P=0.19). CONCLUSION: Overall training can improve the muscle and aerobic fitness of HIV-infected patients with no negative effect on their immunological function.

Effects of resistance training on cytokines.

It is speculated that exercise training decreases resting levels of tumor necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP); reduces body mass and leptin (LP); and increases adiponectin (AD) and insulin sensitivity. This systematic review analyzed the effectiveness of resistance training (RT) longitudinal clinical studies on AD, LP, CRP and TNF-alpha. Seventeen studies were included and the majority of randomized controlled trials support that RT produces increases in AD, and decreases in both LP and CRP. Greater responses in AD and LP were evident in overweight and obese individuals; while RT appeared to be effective in reducing CRP in obese individuals, and older adults. Additionally, women may be more responsive to RT effects on AD, LP and CRP. Training duration and intensity may affect the response of AD and CRP with greater responses shown with 16 weeks or more of training and/or with intensities greater than 80% of one repetition maximum. No response to RT of TNF-alpha levels was apparent. Although based on a limited number of studies, some of which are uncontrolled non-randomized in design, our review suggests some positive effects of RT programs on cytokine levels, but specifics of the responses in different populations need further elucidation.

Whole-body CT trauma imaging with adapted and optimized CT angiography of the craniocervical vessels: do we need an extra screening examination?

BACKGROUND AND PURPOSE: Blunt carotid and vertebral artery injury (BCVI) is rare but potentially devastating. The objective of our study was to prospectively evaluate the usefulness of a dedicated and optimized CT angiography (CTA) protocol of the craniocervical vessels as part of a whole-body CT work-up of patients with multiple trauma in a population of patients with blunt trauma. MATERIAL AND METHODS: From February 2006 to July 2007, a total of 368 consecutive patients with trauma were evaluated. All examinations were performed on a 16-row multisection CT (MSCT) scanner. CTA was performed from the level of the T2 vertebra to the roof of the lateral ventricles with 40 mL of iodinated contrast agent. Images were reconstructed with use of the angiography and bone window settings to evaluate vessels and bones. RESULTS: Of all eligible patients imaged, 100 had injuries to the head and neck including 35 skull base fractures (9.5%), 24 maxillofacial (6.5%), and 11 cervical spine fractures (3%). CTA was diagnostic in all patients. BCVI was diagnosed in 6 cases (6 lesions of the internal carotid artery, 3 lesions of the vertebral artery); among them were 2 who did not meet the screening criteria. No patient with negative results on CTA subsequently had development of neurologic deficits suspicious for BCVI. CONCLUSION: This study confirms that optimized craniocervical CTA can be easily integrated into a whole-body CT protocol for patients with multiple trauma. No additional screening technique is necessary to identify clinically relevant vascular injuries. Earlier recognition enables earlier treatment and may decrease mortality and morbidity rates of these rare but potentially devastating injuries.

The value of intraoperative three dimensional fluoroscopy in anterior decompressive surgery of the cervical spine.

PURPOSE: Intraoperative use of the mobile Siremobil Iso-C3D C-arm (Siemens AG, Medical Solutions, Erlangen) considerably improves the information available during cervical spine surgery. We report our experiences with the Iso-C3D fluoroscopic unit during anterior decompressive surgery of the cervical spine. METHODS: We used the mobile Siremobil Iso-C3D C-arm during decompressive cervical spine surgery. The study included 25 patients (22 males, 3 females) with degenerative cervical stenosis. Mean age was 55.9 years (42-73 years). Eighteen patients were surgically treated for one-level, six for two-level and one for three-level disease. Intraoperative 3D imaging was performed to evaluate the extent of bony decompression and to assist correct positioning of the cages when the surgeon believed that sufficient decompression had been achieved. RESULTS: Visualization of the extent of bone removal was good in all patients. In 3 patients, insufficient bony decompression with persisting dorsal osteophytic spurs was noticed on sagittal and axial images. In these patients, surgery had to be continued. Successful decompression was proved thereafter by a second scan. The quality of the images of the cervical spine was sufficient, although slightly inferior to that of a CT scan. CONCLUSION: The Siremobil Iso-C3D provides intraoperative 3D images of bony structures of the cervical spine. Although the imagine quality is inferior to that of a CT, in our series surgical revisions could be avoided in 12.5% of the patients on the basis of these intraoperative images of incomplete bony decompression. This means a reduction of additional costs which would arise with surgical revision.

Plasma volume during weight lifting.

The magnitude and pattern of the hematocrit (Hct), hemoglobin (Hb), and plasma volume (PV) responses during and upon recovery from two resistance training protocols based on either a ten-repetition maximum (10 RM) or five-repetition maximum (5 RM) resistance was examined. Twelve college-aged male resistance exercise trainers were equally divided between the protocols and performed at least four workouts prior to testing to determine the 10 RM or 5 RM for each exercise set. Each protocol included three sets of nine exercises. The 10-RM session used one-minute rest periods between sets, and two minutes between exercises. The 5-RM session employed three-minute rest periods between sets and exercises. A catheter inserted in the forearm allowed for venous blood sampling after twenty minutes supine rest, the last set of each exercise, and at fifteen and thirty minutes of recovery. Control conditions were included for posture (P) and limb motion (U). Loaded exercise (L) was significantly different from U and P controls for Hct, Hb, and PV responses. For 10 RM and 5 RM respectively, the mean change from rest was 6.2 (+/- 0.9) and 3.5 (+/- 0.4) % for Hct, 2.2 (+/- 0.2) and 1.2 (+/- 0.1) gm . dl (-1) for Hb, and - 22.6 (+/- 2.3) and - 13.0 (+/- 1.2) % for PV. The main effect for protocol was significant for Hct (p = 0.0006) and Hb (p = 0.0033), with 10-RM changes being greater than 5 RM. The greatest increase in Hct and Hb occurred after the first set for both protocols. An increase in Hct and Hb during the protocol was observed for the 10 RM, but not the 5 RM. During recovery, Hct and Hb were elevated above rest for 10 RM, but not 5 RM. PV decreases mirrored Hct and Hb in pattern of change and significance. The data demonstrate that magnitude and pattern of Hct, Hb, and PV was dependent on the type of resistance training protocol.

Effects of detraining on the functional capacity of previously trained breast cancer survivors.

The purpose of this study was to assess the effects of a relatively short (8-weeks) period of detraining on cardiorespiratory capacity, dynamic strength endurance, task specific functional muscle capacity and quality of life (QOL) of breast cancer survivors who had previously undergone a combined supervised (aerobic and resistance) training program. Eleven women survivors of stage I - II ductal breast carcinoma (47 +/- 7 yrs) entered the study and performed a battery of tests (including anthropometric evaluation, a graded cycle ergometer test, tests of strength endurance [leg and bench press] and the sit-stand test) and completed a specific QOL questionnaire (EORTC-C30) at three time points: i) before, ii) after an exercise program (including aerobic and resistance exercises) of 8-weeks duration, and iii) after a subsequent 8-weeks period of training cessation. Training-induced improvements in strength endurance, muscle functional capacity (sit-stand test) and QOL were not significantly changed after detraining (p > 0.05 for post-training vs. detraining comparisons). The lack of significant loss in muscle strength endurance occurred despite significant losses in estimated total muscle mass after detraining (27.3 +/- 2.4 kg) compared with post-training (28.5 +/- 2.9 kg). In contrast, cardiorespiratory capacity was significantly decreased during detraining (V.O (2peak) of 29.0 +/- 4.6 vs. 22.7 +/- 3.9 ml . kg ( -1) . min (-1) at post-training vs. detraining, p < 0.01). In conclusion, cancer survivors who have participated in a combined training program can retain some of the training gains (particularly improved QOL and muscle strength endurance/functional performance) after a relatively short duration detraining period.

Exercise capacity in a 78 year old patient with McArdle's disease: it is never too late to start exercising.

The case is reported of a 78 year old man with McArdle's disease and a history of treated coronary heart disease. Despite the pre-exercise administration of sucrose allowing the patient to exercise with normal physiological responses, and without typical McArdle's symptoms or biochemical evidence of muscle damage, his exercise capacity was very low (V(O2)peak = 10.7 ml/min/kg), probably attributable to his lifetime of sedentary living. The data suggest that, with pre-exercise sucrose administration, such patients may be candidates for systematic reconditioning, which may improve functional capacity and quality of life.

Combined aerobic and resistance training in breast cancer survivors: A randomized, controlled pilot trial.

The purpose of this pilot study was to examine the effects of a combined cardiorespiratory and resistance exercise training program of short duration on the cardiorespiratory fitness, strength endurance, task specific functional muscle capacity, body composition and quality of life (QOL) in women breast cancer survivors. Sixteen subjects were randomly assigned to either a training (n = 8; age: 50 +/- 5 yrs) or control non-exercising group (n = 8; age: 51 +/- 10 yrs). The training group followed an 8-week exercise program consisting of 3 weekly sessions of 90-min duration, supervised by an experienced investigator and divided into resistance exercises and aerobic training. Before and after the intervention period, all of the subjects performed a cardiorespiratory test to measure peak oxygen uptake (VO2peak), a dynamic strength endurance test (maximum number of repetitions for chest and leg press exercise at 30 - 35 % and 100 - 110 % of body mass, respectively) and a sit-stand test. Quality of life was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 (EORTC-C30) questionnaire. In response to training, QOL, VO2peak (mean 3.9 ml/kg/min; 95 % CI, 0.93, 6.90) performance in leg press (17.9 kg; 95 % CI, 12.8, 22.4) and sit-stand test (- 0.67 s; 95 % CI, - 0.52, - 1.2) improved (p < or = 0.05). We observed no significant changes in the control group. Combined cardiorespiratory and resistance training, even of very brief duration, improves the QOL and the overall physical fitness of women breast cancer survivors.

The chemotherapy of rodent malaria. LX. The importance of formulation in evaluating the blood schizontocidal activity of some endoperoxide antimalarials.

The activities of artemisinin (QHS) and a number of its semi-synthetic analogues, as well as Fenozan B07 (B07), a synthetic 1,2,4-trioxane, and arteflene (ATF), a synthetic surrogate of yingzhaosu, were compared in mice infected with drug-sensitive Plasmodium berghei or chloroquine-resistant P. yoelii ssp. NS. The studies were stimulated by the observation that B07, in certain aqueous preparations, appears to be equipotent by the subcutaneous (sc) or oral (po) routes in the rodent model but not in a simian model. In the rodent model, B07 was found to undergo rapid alteration (with a half-life of <24h) in an aqueous stock solution prepared using dimethyl sulphoxide (DMSO) to pre-dissolve the drug. Therefore, for all later experiments with aqueous preparations, the test material was newly formulated each day. In a carboxymethylcellulose formulation used as a 'standard suspending vehicle' (SSV), B07 and dihydroartemisinin (DIHYD) were found to be, respectively, one sixth and one 10th as active po as when the drugs were pre-dissolved in DMSO and then diluted with water. ATF in DMSO given po was less than one 20th as active as when used sc in the rodent model, and this drug in SSV was almost inactive po. The relatively low oral activity of these three compounds (especially DIHYD and ATF) may be attributable to extensive first-pass metabolism in the mouse. Oral beta-artemether (AM) and beta-arteether (AE) were highly active when used in SSV. ATF has been found to have low activity in simian models and clinical trials because of its poor absolute bio-availability. In in-vivo studies of the blood schizontocidal action of anti-malarials, in rodent malaria models, the data collected on the structure-activity relationships (SAR) of the drugs must be viewed critically when selecting specific compounds from a chemical series for further development. A study of the influence of drug formulation on the activity of other, novel antimalarials is crucial to the evaluation of the drugs, and merits high priority.

A method to study lumbar spine response to axial compression during magnetic resonance imaging: technical note.

STUDY DESIGN: A magnetic resonance imaging (MRI)-compatible device was developed to apply calibrated compression loads to the lumbar spine during imaging. Experiments were performed to establish a protocol to measure lumbar load-response and estimate muscle-force contribution to spinal load. OBJECTIVE: To develop experimental methodology for direct study of lumbar spine response to compression load. SUMMARY OF BACKGROUND DATA: Most lumbar MRI scans require subjects to lie relaxed and supine, but spinal stenosis has been demonstrated to increase during moderate compressive loading. Several devices have been used to load the spine during MRI, but they could not maintain and/or change calibrated loads during MRI experiments. Furthermore, artifact from viscoelastic creep during imaging was not considered. METHODS: An MRI-compatible spine compression unit with pneumatic load elements was developed to produce calibrated compression loads. Young healthy men were loaded with 140% body weight for up to 10 minutes to establish an appropriate test protocol. Muscle force contribution to spinal load was estimated from electromyography experiments. RESULTS: The spine compression unit produced specified loads +/- 29 N (standard deviation). Spine viscoelastic creep reached steady state by 6.5 minutes, leaving 3.5 minutes for image acquisition. The subjects could support 1.0 body weight for the requisite 10 minutes. Muscle compressive force estimates were only 135 N during application of 1.4 x body weight external compression load; thus, internal muscle forces during supine spine compression could be neglected. CONCLUSIONS: The lumbar load/image protocol fits within the time constraints of creep deformation and subject endurance. These methods allow acute lumbar mechanical response measurements during loading.

Physiological and performance responses to tournament wrestling.

PURPOSE: The purpose of this study was to investigate the physiological and performance responses to a simulated freestyle wrestling tournament after typical weight loss techniques used by amateur wrestlers. METHODS: Twelve Division I collegiate wrestlers (mean +/- SD;19.33 +/- 1.16 yr) lost 6% of total body weight during the week before a simulated, 2-d freestyle wrestling tournament. A battery of tests was performed at baseline and before and immediately after each individual match of the tournament. The test battery included assessment for body composition, reaction/movement time, lower and upper body power and isokinetic strength, and a venous blood sample. RESULTS: Lower body power and upper body isometric strength were significantly reduced as the tournament progressed (P < or = 0.05). Significant elevations in testosterone, cortisol, and lactate were observed after each match (P < or = 0.05). However, there was a significant reduction (P < or = 0.05) in resting testosterone values in the later matches. Norepinephrine increased significantly (P < or = 0.05) after each match, whereas epinephrine increased significantly (P < or = 0.05) after each match except the last match of each day. Plasma osmolality was consistently higher than normal values at all times including baseline, with significant increases observed after each match (P < or = 0.05). CONCLUSIONS: Tournament wrestling augments the physiological and performance decrements of weight loss and its impact is progressive over 2 d of competition. The combined effects of these stresses may ultimately be reflected in a wrestler's ability to maintain physical performance throughout a tournament.