bluuebunny/crossref_metadata_2025 huggingface dataset:
Die ökonomische Herausforderung der zentralisierten Behandlung von Patienten mit periprothetischen Infektionen
Authors: Müller Michael , Trampuz Andrej , Winkler Tobias , Perka Carsten
Published: February 2018

Einleitung Die tiefe Infektion ist eine der schwersten Komplikationen der Endoprothetik. Die korrekte Diagnose und adäquate Therapie stellen eine enorme interdisziplinäre Herausforderung dar. Die notwendige Interdisziplinarität und Komplexität der Behandlung erfordert die Therapie in Zentren. Problematisch sind jedoch die hohen Kosten, die bisher noch kaum analysiert und diskutiert wurden. Das Ziel dieser Arbeit ist es daher, die Kosten innerhalb eines Behandlungsjahres in einer auf die Behandlung periprothetischer Infektionen spezialisierten Abteilung den Erlösen gegenüberzustellen.

Methodik Es erfolgte eine retrospektive Auswertung der im Jahr 2015 in unserem Centrum für Septische Chirurgie stationär behandelten Patienten anhand der Daten aus dem Krankenhausinformationssystem und des Klinikcontrollings. Die demografischen Daten, die Diagnosen, die Krankenhausverweildauer, die Anzahl der operativen Eingriffe und das Erregerspektrum wurden erfasst und die Kosten der Behandlung ermittelt. Diese wurden den DRG-Erlösen gegenübergestellt.

Ergebnisse Insgesamt wurden 281 Patienten im Jahr 2015 aufgrund einer Infektion des muskuloskeletalen Systems behandelt, davon 144 Fälle mit einer periprothetischen Infektion des Knie- oder Hüftgelenks (Verhältnis 1,5 : 1). Die durchschnittliche Verweildauer lag bei 16 Tagen, die mittleren Behandlungskosten pro Tag und Patient bei ca. 820 €. Die Gesamtkosten der 281 Behandlungen betrugen 3,3 Mill. € wovon lediglich 2,7 Mill. durch DRG-Erlöse gedeckt waren (Unterdeckung ca. − 20%). Dies entsprach einem Defizit von 633 000 €, bei einer mittleren Unterdeckung pro Behandlungsfall von 2300 €. Die Unterdeckung war bei Patienten mit einer infizierten Hüft-TEP im Mittel 5-mal (− 8585 €) so hoch wie das Defizit für einen Patienten mit infizierter Knieendoprothese (− 1638 €). Die wesentlichen Ursachen für die hohen Behandlungskosten waren die Liegedauer, Mehrfacheingriffe und die Besiedlung mit isolationspflichtigen Keimen.

Zusammenfassung Die zunehmende Zahl periprothetischer Infektionen erfordert die interdisziplinäre Behandlung in Zentren. Die nicht durch das DRG-System gedeckten Kosten verhindern jedoch eine solche hochspezialisierte Behandlung. Einhergehend damit ist ein Qualitätsverlust in der Behandlung. Hier besteht dringender gesellschaftlicher Diskussions- und Lösungsbedarf.
Vascular Anomalies (Part II): Interventional Therapy of Peripheral Vascular Malformations
Authors: Müller-Wille René , Wildgruber Moritz , Sadick Maliha , Wohlgemuth Walter
Published: February 2018

Background The International Society for the Study of Vascular Anomalies (ISSVA) categorizes vascular anomalies into vascular tumors and vascular malformations. Vascular malformations are further divided into slow-flow (venous, lymphatic, and capillary malformation) and fast-flow malformations (arteriovenous malformation and arteriovenous fistula). This interdisciplinary classification has therapeutic implications.

Methods The objective of this article is to provide concise information about the current terminology and treatment strategies of peripheral vascular malformations, based on the currently available literature, with a focus on interventional therapy of venous malformations (VM), lymphatic malformations (LM), arteriovenous malformations (AVM) and arteriovenous fistulae (AVF).

Results and Conclusion Accurate classification is crucial for appropriate therapy of peripheral vascular malformations. Modern imaging technologies and refined interventional treatment strategies are now central parts in the multidisciplinary management of these patients. Slow-flow and fast-flow vascular malformations can be treated successfully by percutaneous sclerotherapy and endovascular embolotherapy as first-line interventions.

Key points: 

Citation Format
Experimental study on secondary electron emission characteristics of Cu
Authors: Liu Shenghua , Liu Yudong , Wang Pengcheng , Liu Weibin , Pei Guoxi , Zeng Lei , Sun Xiaoyang
Published: February 2018

Secondary electron emission (SEE) of a surface is the origin of the multipacting effect which could seriously deteriorate beam quality and even perturb the normal operation of particle accelerators. Experimental measurements on secondary electron yield (SEY) for different materials and coatings have been developed in many accelerator laboratories. In fact, the SEY is just one parameter of secondary electron emission characteristics which include spatial and energy distribution of emitted electrons. A novel experimental apparatus was set up in China Spallation Neutron Source, and an innovative method was applied to obtain the whole characteristics of SEE. Taking Cu as the sample, secondary electron yield, its dependence on beam injection angle, and the spatial and energy distribution of secondary electrons were achieved with this measurement device. The method for spatial distribution measurement was first proposed and verified experimentally. This contribution also tries to give all the experimental results a reasonable theoretical analysis and explanation.
X-ray-induced acoustic computed tomography of concrete infrastructure
Authors: Tang Shanshan , Ramseyer Chris , Samant Pratik , Xiang Liangzhong
Published: February 2018

X-ray-induced Acoustic Computed Tomography (XACT) takes advantage of both X-ray absorption contrast and high ultrasonic resolution in a single imaging modality by making use of the thermoacoustic effect. In XACT, X-ray absorption by defects and other structures in concrete create thermally induced pressure jumps that launch ultrasonic waves, which are then received by acoustic detectors to form images. In this research, XACT imaging was used to non-destructively test and identify defects in concrete. For concrete structures, we conclude that XACT imaging allows multiscale imaging at depths ranging from centimeters to meters, with spatial resolutions from sub-millimeter to centimeters. XACT imaging also holds promise for single-side testing of concrete infrastructure and provides an optimal solution for nondestructive inspection of existing bridges, pavement, nuclear power plants, and other concrete infrastructure.
Classical coherent two-dimensional vibrational spectroscopy
Authors: Reppert Mike , Brumer Paul
Published: February 2018

Two-dimensional (2D) ultrafast spectroscopy is a powerful tool for studying the electronic and vibrational structures of complex systems. Unfortunately, the physical interpretation of these experiments is obscured by conceptual problems in classical response theory, i.e., the divergence of classical nonlinear response functions. We demonstrate that these difficulties are avoided by modeling classical 2D experiments nonperturbatively, illustrating that nonlinear spectroscopy and nonlinear response are not synonymous. Numerical simulations allow a direct comparison between classical and quantum 2D spectra for simple, weakly anharmonic systems relevant to vibrational spectroscopy. We find that nonperturbative classical theory—although differing in quantitative details—accurately captures the key qualitative features of the quantum 2D spectrum, including the separation of the signal into wavevector-selected pathways, formation of cross peaks between coupled vibrational modes, and coherent beating in the signal as a function of waiting time (so-called “quantum beats”). These results are discussed in terms of a simple analytical model which captures the key physical features of classical 2D spectroscopy and provides a link between classical and quantum descriptions. One interesting conclusion from this comparison is that the “coherence” observed in ultrafast spectroscopy may (at least in vibrational experiments) be understood as a purely classical phenomenon, without reference to quantum mechanics.
Neon ion beam induced pattern formation on amorphous carbon surfaces
Authors: Bobes Omar , Hofsäss Hans , Zhang Kun
Published: February 2018

We investigate the ripple pattern formation on amorphous carbon surfaces at room temperature during low energy Ne ion irradiation as a function of the ion incidence angle. Monte Carlo simulations of the curvature coefficients applied to the Bradley-Harper and Cater-Vishnyakov models, including the recent extensions by Harrison-Bradley and Hofsäss predict that pattern formation on amorphous carbon thin films should be possible for low energy Ne ions from 250 eV up to 1500 eV. Moreover, simulations are able to explain the absence of pattern formation in certain cases. Our experimental results are compared with prediction using current linear theoretical models and applying the crater function formalism, as well as Monte Carlo simulations to calculate curvature coefficients using the SDTrimSP program. Calculations indicate that no patterns should be generated up to 45° incidence angle if the dynamic behavior of the thickness of the ion irradiated layer introduced by Hofsäss is taken into account, while pattern formation most pronounced from 50° for ion energy between 250 eV and 1500 eV, which are in good agreement with our experimental data.
Adding a bio-response modifier and zinc oxide to piglet weaner diets influences immunological responses to weaning
Authors: De Ujjwal Kumar , Mukherjee Reena , Prakash Chandan , Patel Bhimnere Hanumanthagouda Manjunatha , Nandi Sukdeb , Dimri Umesh , Verma Ashok Kumar , Verma Med Ram
Published: February 2018

The effect of zinc oxide (ZnO) and a Mycobacterium smegmatis-derived bio-response modifier (BRM) supplementation on blood neutrophil functions, high-mobility group box 1 (HMGB1) protein and pro-inflammatory cytokine responses was studied in early weanling piglets. In total, 45 piglets were placed in the following five groups: basal diet only (I), supplemented with ZnO (II), supplemented with BRM (III), supplemented with ZnO plus BRM (IV) in basal diet and basal diet without weaning from dam (V). The phagocytic activity, superoxide anion and myeloperoxidase production in blood neutrophils and the concentrations of HMGB1, TNF-α, IFN-γ and IL-1β in blood plasma were measured before and after weaning. The neutrophil functions were impaired and the concentrations of HMGB1, inflammatory cytokines, were elevated in piglets during the post-weaning period. The neutrophil functions were not improved until Day 7 of weaning (P > 0.05) and pronounced elevation (P < 0.05) in the concentration of pro-inflammatory cytokines and HMGB1 was observed until Days 14 and 21 respectively, in Groups II and III. The addition of BRM plus ZnO in basal diet improved superoxide anion and myeloperoxidase production on Day 2 (P < 0.05) and decreased the TNF-α and IFN-γ concentrations on Day 7 (P < 0.05), with no significant change in the level of IL-1β and HMGB1 in Group IV. Finally, it is concluded that addition of ZnO plus BRM in the diet induced the neutrophil functions and reduced the inflammatory cytokine response much earlier to stimulate innate immunity than did ZnO or BRM alone.
Does carbon storage confer waterlogging tolerance? Evidence from four evergreen species of a temperate rainforest
Authors: Delgado M. , Zúñiga-Feest A. , Piper F. I.
Published: February 2018

Deep shade and waterlogging are two common stressors affecting seedling performance in the understorey of evergreen rainforests. It has been hypothesised that high levels of carbon storage confer shade- and waterlogging tolerances by preventing carbon limitation under such stresses. Whether the tolerance to both stresses is positively or negatively related remains unclear. To explore the role of carbon storage in the relationships of waterlogging and shade tolerance, we investigated the responses to waterlogging and the levels of carbon storage in two species pairs with contrasting shade tolerance: Embothrium coccineum J.R.Forst.&G.Forst. and Gevuina avellana Mol. (Proteaceae) and Nothofagus dombeyi (Mirb.) Oerst. and Nothofagus nitida (Phil.) Krasser (Nothofagaceae). We subjected seedlings to waterlogging or control conditions for 30 days and evaluated survival, relative growth rate (RGR), biomass distribution, leaf chlorophyll fluorescence (Fv/Fm), and concentrations of total soluble sugars, starch and non-structural carbohydrates in different plant tissues. Waterlogging reduced survival, Fv/Fm and RGR in all species; however, the magnitude of reduction of Fv/Fm and RGR was significantly higher in the shade-intolerant species than in their shade-tolerant counterparts. In general, shade-intolerant species had significantly higher non-structural carbohydrate concentrations in waterlogging than in control conditions. By contrast, shade-tolerant species had similar non-structural carbohydrate concentrations under both conditions. Our results indicate that relatively shade-tolerant species performed better under waterlogging. A reduction in non-structural carbohydrates under waterlogging was not observed in any of studied species; rather, shade-intolerant species exhibited non-structural carbohydrate accumulation suggesting that carbon storage does not confer waterlogging tolerance in these species.
Recruitment pattern of Scleractinian coral spats on neighbouring artificial substrates at Kurusadai Reef Complex, Gulf of Mannar, India
Authors: Marimuthu N. , Ramachandran Purvaja , Sathish M. , Dinesh N. , Ramesh R.
Published: February 2018

This study was conducted to assess the recruitment rate of coral spats and other invertebrates near to the coral reef ecosystem of Gulf of Mannar. The reef region examined was at Kurusadai Reef Complex (Gulf of Mannar) for this assessment. There were two sets of invertebrate settlement tripods deployed and exposed at a depth of 2m. Seventy two settlement tiles measuring 20x20 cm in two different angles were fixed in these tripods in the benthic reef ecosystem. In order to assess the impact of Sea surface temperature on the invertebrate settlement, Onset Hobo Pendant® Temperature logger was also attached with the tripods. The sediment traps in duplicate were also erected in the study site to assess the sedimentation rate of the reef ecosystem. About 80% of recruited coral spats were observed on the tiles which were exposed at 60° angle. Principal component analysis also supported that the most influencing species were coral spats followed by barnacles and bivalves in the 60° angle exposed settlement tiles. It was also observed that the most influencing place of coral spats’ recruitment was on the inner tiles. The mean sedimentation rate observed was 14.6 ± 4.8 mg.cm−2.d−1. The lower density of coral spats observed on 90° and 60° angle exposed outer tiles might be due to the observed sedimentation rate and it is believed that coral spats preferred the shaded environment initially for further perpetuation in the environment. Moreover, Bray-Curtis cluster analysis supported that the coral spats found on the inner tiles having 80% similarity in this assessment. The coral spats found in this assessment were species from Pocilloporidae and Poritidae.
Intragenerational Social Mobility and Changes in Blood Pressure: Longitudinal Analysis From the ELSA-Brasil Study
Authors: Guimarães Joanna M N , Griep Rosane H , Clarke Philippa J , Fonseca Maria J M , Barreto Sandhi M , Giatti Luana , Lotufo Paulo A , Mill Jose G , Pacheco Antonio G , Chor Dora
Published: February 2018

BACKGROUND

During the past 4 decades, the highest worldwide blood pressure (BP) levels have shifted from high-income countries to low- and middle-income countries. We investigated the association of intragenerational social mobility with changes in BP and also with the incidence of hypertension over a 4-year follow-up.

METHODS

Data for 6,529 baseline participants from ELSA-Brasil born between 1938 and 1975 were used. Based on a social mobility matrix, occupational social mobility was defined as the change in occupational social class between participants’ first occupation and current occupation (stable high; upward; downward; stable low). Incident hypertension was defined as systolic blood pressure (SBP) ≥ 140 mm Hg or diastolic blood pressure (DBP) ≥ 90 mm Hg or use of antihypertensive medication. Hypertensive participants at baseline were excluded. Mixed effects regression models were used.

RESULTS

Compared to the stable high group, the downwardly mobile group showed a higher increase over time in both SBP (β = 1.49, 95% CI 0.60; 2.37) and DBP (β = 0.96, 95% CI 0.32; 1.59) after adjustments for background characteristics and also proximal risk factors such as health-related behaviors and body mass index as time-dependent covariates, and diabetes. In contrast, upward mobility had no influence on BP changes (β = 0.67, 95% CI −0.07; 1.41 for SBP, and β = 0.47, 95% CI −0.05; 1.00 for DBP). Social mobility was not associated with the incidence of hypertension.

CONCLUSIONS

We showed socioeconomic inequalities in BP progression over the life course. The longitudinal changes in BP varied by social mobility groups in the context of low- and middle-income countries, where high BP has become most prevalent.
Memory for Serial Order in Alzheimer’s Disease and Vascular Dementia: A Competitive Queuing Analysis
Authors: Rhodes Emma , Lamar Melissa , Libon David J , Giovannetti Tania
Published: February 2018

Objective

Competitive Queuing (CQ) models of memory for serial order comprise two layers: parallel planning where target items are activated and competitive choice where serial order is specified. The application of CQ models regarding healthy and pathological aging has received little attention.

Method

Participants included patients with Alzheimer’s disease (AD; n = 26), vascular dementia (VaD; n = 29), and healthy controls (HC; n = 35). Memory for serial order in the visual domain was assessed using the Object Span Task, where participants briefly viewed then drew a sequence of four figures. Percent correct and total errors (omissions, intrusions, repetitions, transpositions) were computed for each serial position.

Results

Significant primacy effects were detected in each group. AD and VaD participants were less accurate and showed more omission and between-trial repetition errors than HC (HC < AD = VaD, p < .05). VaD participants produced more transposition and intrusion errors than the AD and HC groups (HC < AD < VaD, p < .05). A group × position interaction was significant for omissions (p < .05), with AD and VaD participants producing more omissions in later serial positions (SP1 < SP2 < SP3 < SP4, all p values < .05).

Conclusions

Analysis of accuracy and errors by serial position identified unique patterns of performance across groups that suggest involvement of distinct layers of response activation and selection. Serial order difficulties in AD may be due to weakened activation of task items affecting later serial positions, whereas poor performance in VaD may be due to weakened activation plus interference from extraneous stimuli at all serial positions.
Apolipoprotein E DNA methylation and late-life disease
Authors: Karlsson Ida K , Ploner Alexander , Wang Yunzhang , Gatz Margaret , Pedersen Nancy L , Hägg Sara
Published: February 2018

Background

This study aims to investigate if DNA methylation of the apolipoprotein E (APOE) locus affects the risks of dementia, Alzheimeŕs disease (AD) or cardiovascular disease (CVD).

Methods

DNA methylation across theAPOE gene has previously been categorized into three distinct regions: a hypermethylated region in the promoter, a hypomethylated region in the first two introns and exons and a hypermethylated region in the 3′exon that also harbours theAPOE ε2 and ε4 alleles. DNA methylation levels in leukocytes were measured using the Illumina 450K array in 447 Swedish twins (mean age 78.1 years). We used logistic regression to investigate whether methylation levels in those regions affect the odds of disease.

Results

We found that methylation levels in the promoter region were associated with dementia and AD after adjusting for sex, age at blood draw, education, smoking and relatedness among twins [odds ratio (OR) 1.32 per standard deviation increase in methylation levels, 95% confidence interval (CI) 1.08–1.62 for dementia; OR 1.38, 95% CI 1.07–1.78 for AD). We did not detect any difference in methylation levels between CVD cases and controls. Results were similar when comparing within discordant twin pairs, and did not differ as a function ofAPOE genotype.

Conclusions

We found that higher DNA methylation levels in the promoter region ofAPOE increase the odds of dementia and AD, but not CVD. The effect was independent ofAPOE genotype, indicating that allelic variation and methylation variation inAPOE may act independently to increase the risk of dementia.
Spinal Cord Stimulation for the Treatment of Chronic Pain Reduces Opioid Use and Results in Superior Clinical Outcomes When Used Without Opioids
Authors: Gee Lucy , Smith Heather C , Ghulam-Jelani Zohal , Khan Hirah , Prusik Julia , Feustel Paul J , McCallum Sarah E , Pilitsis Julie G
Published: February 2018

BACKGROUND

Chronic pain causes a significant burden to the US health care system, is difficult to treat, and remains a significant contributor to increased opioid use in the United States. Spinal cord stimulation (SCS) has been FDA approved for the treatment of chronic pain.

OBJECTIVE

To evaluate the hypothesis that SCS reduces opioid use, and alone maintains clinical outcome measures of pain and psychosocial determinants of health.

METHODS

In this prospective cohort study, we evaluated 86 patients undergoing SCS surgery for the treatment of chronic pain between September 2012 and August 2015. Preoperatively and postoperatively, patients completed the Numerical Rating Scale (NRS), McGill Pain Questionnaire (MPQ), Pain Catastrophizing Scale (PCS), Oswestry Disability Index (ODI), and Beck's Depression Inventory (BDI). VAS scores were retrospectively analyzed.

RESULTS

Fifty-three patients used opioids before SCS implantation. The 33 nonusers had lower mean VAS, NRS, and ODI scores than both opioid groups at 1 yr and improved significantly at 1 yr on the VAS (P < .001), NRS (P < .001), MPQ (P = .002), PCS (P < .001), BDI (P = .04), and ODI (P = .002). After surgery, 41.5% remained opioids and 58.5% reduced/eliminated use. Discontinued (n = 29) or reduced (n = 2) use resulted in VAS, NRS, total MPQ, and ODI score reduction (P < .001, P = .002, P = .002, and P = .009 respectively). At 1 yr, survey scores in opioid users were unchanged. There was no difference between groups in revision or failure rates.

CONCLUSION

Sixty-four percent of patients who were using opioids prior to SCS reduced (n = 2) or eliminated opioid use (n = 29) at 1 yr postoperatively. Patients who eliminated opioid use or never used opioids had superior clinical outcomes to those who continued use.
Autour des plus grands facteurs premiers d’entiers consÉcutifs voisins d’un entier criblé
Authors: Wang (Nancy) Zhiwei
Published: February 2018

Denote by P+(n) (resp. P−(n)) the largest (resp. the smallest) prime factor of the integer n. In this paper, we prove that there exists a positive proportion of integers n having no small prime factor such that P+(n)<P+(n+2). Especially, we prove that the pattern P+(P3)x1/3−δ,0<δ≤112, where P3 denote an integer having at most three prime factors taken with multiplicity. We also prove that the pattern P+(p−1)<P+(p+1) holds for a positive proportion of primes under the Elliott-Halberstam conjecture.
Navigating the Complexities of Undergraduate Medical Curriculum Change: Change Leaders’ Perspectives
Authors: Velthuis Floor , Varpio Lara , Helmich Esther , Dekker Hanke , Jaarsma A. Debbie C.
Published: February 2018

Purpose

Changing an undergraduate medical curriculum is a recurring, high-stakes undertaking at medical schools. This study aimed to explore how people leading major curriculum changes conceived of the process of enacting change and the strategies they relied on to succeed in their efforts.

Method

The first author individually interviewed nine leaders who were leading or had led the most recent undergraduate curriculum change in one of the eight medical schools in the Netherlands. Interviews were between December 2015 and April 2016, using a semistructured interview format. Data analysis occurred concurrently with data collection, with themes being constructed inductively from the data.

Results

Leaders conceived of curriculum change as a dynamic, complex process. They described three major challenges they had to deal with while navigating this process: the large number of stakeholders championing a multitude of perspectives, dealing with resistance, and steering the change process. Additionally, strategies for addressing these challenges were described. The authors identified an underlying principle informing the work of these leaders: being and remaining aware of emerging situations, and carefully constructing strategies for ensuring that the intended outcomes were reached and contributed to the progress of the change process.

Discussion

This empirical, descriptive study enriches the understanding of how institutional leaders navigate the complexities of major medical curriculum changes. The insights serve as a foundation for training and coaching future change leaders. To broaden the understanding of curriculum change processes, future studies could investigate the processes through alternative stakeholder perspectives.
Is Speed a Desirable Difficulty for Learning Procedures? An Initial Exploration of the Effects of Chronometric Pressure
Authors: Gas Becca L. , Buckarma EeeLN H. , Cook David A. , Farley David R. , Pusic Martin V.
Published: February 2018

Purpose

To determine whether “chronometric pressure” (i.e., a verbal prompt to increase speed) could predictably alter medical learners’ speed–accuracy trade-off during a simulated surgical task, thus modifying the challenge.

Method

The authors performed a single-task, interrupted time-series study, enrolling surgery residents and medical students from two institutions in September and October 2015. Participants completed 10 repetitions of a simulated blood vessel ligation (placement of two ligatures 1 cm apart). Between repetitions 5 and 6, participants were verbally encouraged to complete the next repetition 20% faster than the previous one. Outcomes included time and accuracy (ligature tightness, placement distance). Data were analyzed using random-coefficients spline models.

Results

The authors analyzed data from 78 participants (25 medical students, 16 first-year residents, 37 senior [second-year or higher] residents). Overall, time decreased from the 1st (mean [standard deviation] 39.8 seconds [18.4]) to the 10th (29.6 [12.5]) repetition. The spline model showed a decrease in time between repetitions 5 and 6 of 8.6 seconds (95% confidence interval: −11.1, −6.1). The faster time corresponded with declines in ligature tightness (unadjusted difference −19%; decrease in odds 0.86 [0.76, 0.98]) and placement accuracy (unadjusted difference −5%; decrease in odds 0.86 [0.75, 0.99]). Significant differences in the speed–accuracy trade-off were seen by training level, with senior residents demonstrating the greatest decline in accuracy as speed increased.

Conclusions

Chronometric pressure influenced the speed–accuracy trade-off and modified the challenge level in a simulated surgical task. It may help unmask correctable deficiencies or false plateaus in learners’ skill development.
Ulipristal Acetate for Treatment of Symptomatic Uterine Leiomyomas
Authors: Simon James A. , Catherino William , Segars James H. , Blakesley Rick E. , Chan Anna , Sniukiene Vilma , Al-Hendy Ayman
Published: February 2018

OBJECTIVE:

To assess efficacy and tolerability of ulipristal acetate, a selective progesterone receptor modulator, for treatment of symptomatic uterine leiomyomas.

METHODS:

This phase 3, double-blind, placebo-controlled study enrolled premenopausal women (aged 18–50 years) with abnormal uterine bleeding, one or more discrete leiomyomas, and uterine size 20 weeks of gestation or less. Patients were randomized 1:1:1 to 5 mg ulipristal, 10 mg ulipristal, or placebo once daily for 12 weeks followed by 12-week drug-free follow-up. Coprimary endpoints were rate of and time to amenorrhea, defined as no bleeding for the last 35 consecutive days of treatment. Secondary endpoints included rates of amenorrhea from day 11 and change from baseline to endpoint in the Revised Activities subscale of the Uterine Fibroid Symptom and Quality of Life questionnaire, which includes questions pertaining to physical and social activities. Safety assessments included adverse event monitoring and endometrial biopsies. A sample size of 150 was planned to compare separately each dose of ulipristal with placebo.

RESULTS:

From March 2014 to March 2016, 157 patients were randomized. Demographics were similar across treatment groups. Amenorrhea was achieved by 25 of 53 (47.2% [97.5% CI 31.6–63.2]) and 28 of 48 (58.3% [97.5% CI 41.2–74.1]) patients treated with 5 mg and 10 mg ulipristal, respectively, compared with 1 of 56 (1.8% [97.5% CI 0.0–10.9]) placebo-treated patients (both P<.001). Time to amenorrhea was shorter for both ulipristal doses compared with placebo (P<.001), and both doses of ulipristal resulted in improved quality of life compared with placebo (P<.001). Common adverse events (5% or greater in either ulipristal group during treatment) were hypertension, elevated blood creatinine phosphokinase, and hot flushes. Serious adverse events occurred in four patients, but none was considered related to treatment. Endometrial biopsies were benign.

CONCLUSION:

Ulipristal at 5 mg and 10 mg were well tolerated and superior to placebo in rate of and time to amenorrhea in women with symptomatic uterine leiomyomas.

CLINICAL TRIAL REGISTRATION:

Clinicaltrials.gov number, NCT02147197.
Exercise-Induced Abdominal Wall Muscle Injury Resulting in Rhabdomyolysis and Mimicking an Acute Abdomen
Authors: Echague Charlene G. , Csokmay John M.
Published: February 2018

BACKGROUND:

Rhabdomyolysis is characterized by muscle necrosis and release of intracellular constituents, causing muscle pain, weakness, and myoglobinuria. This can be attributed to muscle injury after strenuous exercise. If the abdominal wall is involved, clinical presentation may resemble an acute abdomen.

CASE:

A 27-year-old woman, gravida 4 para 2, presented with swelling and pain of the mons pubis and abdominal pain after intense powerlifting 2 days prior. A computed tomography scan was performed, revealing abdominal wall inflammation. Although myoglobinuria was absent, there was high suspicion for rhabdomyolysis, which was confirmed by an elevated creatine kinase level. The patient improved after receiving intravenous fluids and abstaining from physical activity.

CONCLUSION:

Abdominal wall muscle injury resulting in rhabdomyolysis can imitate an acute abdomen in a healthy woman presenting with abdominal pain and swelling.
Factors Affecting the Severity of Neurological Disorders in Thoracic Idiopathic Spinal Cord Herniation
Authors: Nakashima Hiroaki , Kanemura Tokumi , Yagi Hideki , Kato Fumihiko , Sato Koji , Kamiya Mitsuhiro , Yoshihara Hisatake , Ito Kenyu , Matsuyama Yukihiro , Ishiguro Naoki , Imagama Shiro
Published: February 2018

Study Design.

Retrospective multicenter case-controlled study.

Objective.

The objective of this study was to quantitatively examine imaging findings of idiopathic spinal cord herniation (ISCH) and determine the relationship between the image findings and the severity of pre- and postoperative neurological symptoms.

Summary of Background Data.

Many radiographic types of ISCH have been identified with regard to the location of the hernial opening or amount of herniated spinal cord. However, few previous studies have investigated the relationship between radiographic findings and the severity of neurological symptoms.

Methods.

Of 30,469 patients who underwent spinal surgery at 7 hospitals, 18 patients who underwent surgery for ISCH were identified. Their preoperative neurological severity, disease duration, magnetic resonance imaging findings, computed tomography myelography findings, surgical findings, and postoperative improvements were retrospectively examined. The spinal cord kink angle and minimum cord occupancy rate within the dural tube were measured. In addition, herniation was classified according to the location of the hiatus as either central (type C) or lateral (type L) type.

Results.

A negative correlation was found between the spinal cord kink angle and the minimum cord occupancy rate. Patient age was significantly higher in the severe paralysis group than in the mild paralysis group. In addition, the number of patients with type C herniation and the kink angle were significantly higher in the severe paralysis group. The number of patients with type L herniation was higher in the significant recovery group than in the mild recovery group; however, the difference was not significant.

Conclusion.

Patients with a large spinal cord kink angle had a smaller spinal cord occupancy rate within the dural tube, and this resulted in severe preoperative conditions. Type C ISCH cases had a severe preoperative neurological deficit and poor postoperative neurological recovery, and the spinal cord in such cases might be damaged irreversibly.

Level of Evidence: 4
Prediction Accuracy of Common Prognostic Scoring Systems for Metastatic Spine Disease
Authors: Choi David , Ricciardi Federico , Arts Mark , Buchowski Jacob M. , Bunger Cody , Chung Chun Kee , Coppes Maarten , Depreitere Bart , Fehlings Michael , Kawahara Norio , Leung Yee , Martin-Benlloch Antonio , Massicotte Eric , Mazel Christian , Meyer Bernhard , Oner Cumhur , Peul Wilco , Quraishi Nasir , Tokuhashi Yasuaki , Tomita Katsuro , Ulbricht Christian , Verlaan Jorrit-Jan , Wang Mike , Crockard Alan
Published: February 2018

Study Design.

A prospective multicenter cohort study.

Objective.

To assess the clinical accuracy of six commonly cited prognostic scoring systems for patients with spinal metastases.

Summary of Background Data.

There are presently several available methods for the estimation of prognosis in metastatic spinal disease, but none are universally accepted by surgeons for clinical use. These scoring systems have not been rigorously tested and validated in large datasets to see if they are reliable enough to inform day-to-day patient management decisions. We tested these scoring systems in a large cohort of patients. A total of 1469 patients were recruited into a secure internet database, and prospectively collected data were analyzed to assess the accuracy of published prognostic scoring systems.

Methods.

We assessed six prognostic scoring systems, described by the first authors Tomita, Tokuhashi, Bauer, van der Linden, Rades, and Bollen. Kaplan–Meier survival estimates were created for different patient subgroups as described in the original publications. Harrell's C-statistic was calculated for the survival estimates, to assess the concordance between estimated and actual survival.

Results.

All the prognostic scoring systems tested were able to categorize patients into separate prognostic groups with different overall survivals. However none of the scores were able to achieve “good concordance” as assessed by Harrell's C-statistic. The score of Bollen and colleagues was found to be the most accurate, with a Harrell's C-statistic of 0.66.

Conclusion.

No prognostic scoring system was found to have a good predictive value. The scores of Bollen and Tomita were the most effective with Harrell's C-statistic of 0.66 and 0.65, respectively. Prognostic scoring systems are calculated using data from previous years, and are subject to inaccuracies as treatments advance in the interim. We suggest that other methods of assessing prognosis should be explored, such as prognostic risk calculation.

Level of Evidence: 3
Early Systemic Alterations in Severe Spinal Cord Injury
Authors: Rodríguez-Romero Violeta , Guízar-Sahagún Gabriel , Castañeda-Hernández Gilberto , Reyes José L. , Cruz-Antonio Leticia
Published: February 2018

Study Design.

An experimental model of spinal cord injury (SCI) intended to characterize changes in renal function.

Objective.

The aim of this study was to evaluate the possible influence of SCI level on renal function during spinal shock.

Summary of Background Data.

SCI triggers multiple systemic and metabolic alterations. Among them, renal dysfunction stands out. Although several variables have been related to its extent, the impact of the cord injury level on renal function has not been clearly stated, particularly during the spinal shock.

Methods.

Anesthetized adult Sprague-Dawley rats were subjected to severe spinal cord contusion at low (T8) and high (T1) thoracic levels using the weight-drop method. Glomerular filtration rate (GFR) and tubular secretion (TS) were estimated 24 hours after injury, using a validated method based on the determination of plasma concentrations of iopamidol and p-aminohippuric acid by high-performance liquid chromatography.

Results.

GFR, fell to 33% (95% CI [24%, 43%]) and 10% (8%, 13%) of the sham-injured controls, whereas TS, decreased to 59% (95% CI [47%, 71%]), and 25% (18%, 32%) of the sham-injured controls, in T8 and T1 injury levels, respectively. Comparisons between cords injured and control rats, as well as between low and high-injured levels, were statistically significant (P < 0.01).

Conclusion.

Renal dysfunction occurs early after severe SCI. The damage is greater in high compared to low injuries. These findings could have important implications in the acute management of patients with high thoracic and cervical injuries, especially in pharmacotherapy using drugs eliminated by the kidney.

Level of Evidence. N/A
Determining the Upper and Lower Limits of Cerebral Autoregulation With Cerebral Oximetry Autoregulation Curves: A Case Series
Authors: Rivera-Lara Lucia , Zorrilla-Vaca Andres , Healy Ryan J. , Ziai Wendy , Hogue Charles , Geocadin Romergryko , Radzik Batya , Palmisano Caitlin , Mirski Marek A.
Published: February 2018

Objective:

Critical care guidelines recommend a single target value for mean arterial blood pressure in critically ill patients. However, growing evidence regarding cerebral autoregulation challenges this concept and supports individualizing mean arterial blood pressure targets to prevent brain and kidney hypo- or hyperperfusion. Regional cerebral oxygen saturation derived from near-infrared spectroscopy is an acceptable surrogate for cerebral blood flow and has been validated to measure cerebral autoregulation. This study suggests a novel mechanism to construct autoregulation curves based on near-infrared spectroscopy–measured cerebral oximetry.

Design:

Case-series study.

Setting:

Neurocritical care unit in a tertiary medical center.

Patients:

Patients with acute neurologic injury and Glasgow coma scale score less than or equal to 8.

Measurements and Main Results:

Autoregulation curves were plotted using the fractional-polynomial model in Stata after multimodal continuous monitoring of regional cerebral oxygen saturation and mean arterial blood pressure. Individualized autoregulation curves of seven patients exhibited varying upper and lower limits of autoregulation and provided useful clinical information on the autoregulation trend (curves moving to the right or left during the acute coma period). The median lower and upper limits of autoregulation were 86.5 mm Hg (interquartile range, 74–93.5) and 93.5 mm Hg (interquartile range, 83–99), respectively.

Conclusions:

This case-series study showed feasibility of delineating real trends of the cerebral autoregulation plateau and direct visualization of the cerebral autoregulation curve after at least 24 hours of recording without manipulation of mean arterial blood pressure by external stimuli. The integration of multimodal monitoring at the bedside with cerebral oximetry provides a noninvasive method to delineate daily individual cerebral autoregulation curves.
Implications of the New National Guidelines for Hypertension
Authors: Aronow Wilbert S. , Frishman William H.
Published: February 2018

Automated validated devices should be used for measuring blood pressure (BP). A systolic BP between 120 and 129 mm Hg with a diastolic BP < 80 mm Hg should be treated by lifestyle measures. Lifestyle measures plus BP lowering drugs should be used for secondary prevention of recurrent cardiovascular disease (CVD) events in persons with clinical CVD (coronary heart disease, congestive heart failure, and stroke) and an average systolic BP of ≥130 mm Hg or an average diastolic BP ≥ 80 mm Hg. Lifestyle measures plus BP lowering drugs should be used for primary prevention of CVD in persons with an estimated 10-year risk of atherosclerotic CVD ≥ 10% and an average systolic BP ≥130 mm Hg or an average diastolic BP ≥ 80 mm Hg. Lifestyle measures plus BP lowering drugs should be used for primary prevention of CVD in persons with an estimated 10-year risk of atherosclerotic CVD of <10% and an average systolic BP ≥ 140 mm Hg or an average diastolic BP ≥ 90 mm Hg. Initiate antihypertensive drug therapy with 2 first-line drugs from different classes either as separate agents or in a fixed-dose combination in persons with a BP ≥ 140/90 mm Hg or with a BP > 20/10 mm Hg above their BP target. White coat hypertension must be excluded before initiating treatment with antihypertensive drugs in persons with hypertension at low risk for atherosclerotic CVD. Antihypertensive drug treatment for different disorders is discussed.
Hepatoblastoma in a Child With Early-onset Cirrhosis
Authors: Bennett Julie , Kirby-Allen Melanie , Ng Vicky , Waye John S. , Chung Catherine T. , Shaikh Furqan
Published: February 2018

Hepatoblastoma is the most common hepatic malignancy of childhood with known genetic predispositions and perinatal risk factors, with rare case reports occurring in the setting of cirrhosis. This case describes a young patient with cirrhosis attributed to early-onset hereditary hemochromatosis who was diagnosed with hepatoblastoma with uncommon histologic findings, evidence of chemotherapy resistance who ultimately succumbed to her disease. It is important to consider diagnoses beyond hepatocellular carcinoma in this scenario and consider early biopsy. With atypical histology, the tumor may respond poorly to conventional treatment and aggressive surgery or intensive therapy should be contemplated.
Characteristics of Infants With Congenital Diaphragmatic Hernia Who Need Follow-Up of Pulmonary Hypertension
Authors: Kraemer Ulrike S. , Leeuwen Lisette , Krasemann Thomas B. , Wijnen René M. H. , Tibboel Dick , IJsselstijn Hanneke
Published: February 2018

Objectives:

Pulmonary hypertension is one of the main causes of mortality and morbidity in patients with congenital diaphragmatic hernia. Currently, it is unknown whether pulmonary hypertension persists or recurs during the first year of life.

Design:

Prospective longitudinal follow-up study.

Setting:

Tertiary university hospital.

Patients:

Fifty-two congenital diaphragmatic hernia patients admitted between 2010 and 2014.

Interventions:

None.

Measurements and Main Results:

Pulmonary hypertension was measured using echocardiography and electrocardiography at 6 and 12 months old. Characteristics of patients with persistent pulmonary hypertension were compared with those of patients without persistent pulmonary hypertension. At follow-up, pulmonary hypertension persisted in four patients: at 6 months old, in three patients (patients A–C), and at 12 months old, in two patients (patients C and D). Patients with persistent pulmonary hypertension had a longer duration of mechanical ventilation (median 77 d [interquartile range, 49–181 d] vs median 8 d [interquartile range, 5–15 d]; p = 0.002) and hospital stay (median 331 d [interquartile range, 198–407 d) vs median 33 d (interquartile range, 16–59 d]; p = 0.003) than patients without persistent pulmonary hypertension. The proportion of patients with persistent pulmonary hypertension (n = 4) treated with inhaled nitric oxide (100% vs 31%; p = 0.01), sildenafil (100% vs 15%; p = 0.001), and bosentan (100% vs 6%; p < 0.001) during initial hospital stay was higher than that of patients without persistent pulmonary hypertension (n = 48). At 6 months, all patients with persistent pulmonary hypertension were tube-fed and treated with supplemental oxygen and sildenafil.

Conclusions:

Less than 10% of congenital diaphragmatic hernia patients had persistent pulmonary hypertension at ages 6 and/or 12 months. Follow-up for pulmonary hypertension should be reserved for congenital diaphragmatic hernia patients with echocardiographic signs of persistent pulmonary hypertension at hospital discharge and/or those treated with medication for pulmonary hypertension at hospital discharge.
In Vitro Adsorption of Analgosedative Drugs in New Extracorporeal Membrane Oxygenation Circuits
Authors: Raffaeli Genny , Allegaert Karel , Koch Birgit , Cavallaro Giacomo , Mosca Fabio , Tibboel Dick , Wildschut Enno D.
Published: February 2018

Objective:

Evaluate drug disposition of sedatives and analgesics in the Xenios/Novalung extracorporeal membrane oxygenation circuits.

Design:

In vitro experimental study.

Setting:

Erasmus MC - Sophia Children’s Hospital, Rotterdam, The Netherlands.

Subjects:

Nine closed-loop extracorporeal membrane oxygenation circuits, made up of the iLA Activve console with four different iLA Activve kits: two X-lung kits, two iLA-Activve iLA kits, two MiniLung kits, and three MiniLung petite kits.

Interventions:

The circuits were primed with fresh whole blood and maintained under physiologic conditions (pH/temperature) throughout 24 hours. Paracetamol, morphine, midazolam, fentanyl, and sufentanil were injected as standard age-related doses into nine closed-loop extracorporeal membrane oxygenation circuits.

Measurements and Main Results:

Pre-membrane (P2) blood samples were obtained prior to drug injection and after injection at 2, 10, 30, 180, 360 minutes, and at 24 hours. A control sample at 2 minutes was collected for spontaneous drug degradation testing at 24 hours. Two hundred sixteen samples were analyzed. After correction for the spontaneous drug degradation, the mean drug loss at 24 hours was paracetamol 49%, morphine 51%, midazolam 40%, fentanyl 84%, sufentanil 83%. Spontaneous degradation was paracetamol 6%, morphine 0%, midazolam 11%, fentanyl 4%, and sufentanil 0%. The decline of drug concentration over time was more pronounced for the more lipophilic drugs.

Conclusions:

Loss of highly lipophilic drugs in the extracorporeal membrane oxygenation circuits at 24 hours was remarkable. Drug loss is comparable with other hollow fiber extracorporeal membrane oxygenation systems but less than in silicone-based membranes especially in the first hours after injection.