bluuebunny/crossref_metadata_2025 huggingface dataset:
MRI for Local Staging of Colon Cancer: Can MRI Become the Optimal Staging Modality for Patients With Colon Cancer?
Authors: Nerad Elias , Lambregts Doenja M. J. , Kersten Erik L. J. , Maas Monique , Bakers Frans C. H. , van den Bosch Harrie C. M. , Grabsch Heike I. , Beets-Tan Regina G. H. , Lahaye Max J.
Published: March 2017

BACKGROUND:

Colon cancer is currently staged with CT. However, MRI is superior in the detection of colorectal liver metastasis, and MRI is standard in local staging of rectal cancer. Optimal (local) staging of colon cancer could become crucial in selecting patients for neoadjuvant treatment in the near future (Fluoropyrimidine Oxaliplatin and Targeted Receptor Preoperative Therapy trial).

OBJECTIVE:

The purpose of this study was to evaluate the diagnostic performance of MRI for local staging of colon cancer.

DESIGN:

This was a retrospective study.

SETTINGS:

The study was conducted at the Maastricht University Medical Centre.

PATIENTS:

In total, 55 patients with biopsy-proven colon carcinoma were included.

MAIN OUTCOME MEASURES:

All of the patients underwent an MRI (1.5-tesla; T2 and diffusion-weighted imaging) of the abdomen and were retrospectively analyzed by 2 blinded, independent readers. Histopathology after resection was the reference standard. Both readers evaluated tumor characteristics, including invasion through bowel wall (T3/T4 tumors), invasion beyond bowel wall of ≥5 mm and/or invasion of surrounding organs (T3cd/T4), serosal involvement, extramural vascular invasion, and malignant lymph nodes (N+). Interobserver agreement was compared using κ statistics.

RESULTS:

MRI had a high sensitivity (72%–91%) and specificity (84%–89%) in detecting T3/T4 tumors (35/55) and a low sensitivity (43%–67%) and high specificity (75%–88%) in detecting T3cd/T4 tumors (15/55). For detecting serosal involvement and extramural vascular invasion, MRI had a high sensitivity and moderate specificity, as well as a moderate sensitivity and specificity in the detection of nodal involvement. Interobserver agreements were predominantly good; the more experienced reader achieved better results in the majority of these categories.

LIMITATIONS:

The study was limited by its retrospective nature and moderate number of inclusions.

CONCLUSIONS:

MRI has a good sensitivity for tumor invasion through the bowel wall, extramural vascular invasion, and serosal involvement. In addition, together with its superior liver imaging, MRI might become the optimal staging modality for colon cancer. However, more research is needed to confirm this. See Video Abstract at http://links.lww.com/DCR/A309.
Should we forget about embryos till day 5?
Authors: Bronet Fernando , Agudo David
Published: March 2017

Purpose of review

To find the way of having more and better blastocyst is essential. How to culture embryos up to blastocyst stage remains critical.

Recent findings

Several studies show how a blastocyst score can predict the implantation potential. If that score is enough to choose the best blastocyst, as culture conditions would not be affected in these days, we would not need to check early cleavage embryos, even it could be better for the embryo development.

The item that should be discussed is if it is better to evaluate or not embryos at early cleavage stages. If we do not check embryos on days 2 and 3, we should change our way to work and how to culture those embryos. First step would be to perform all embryo transfers on day 5 or 6. If we let embryos grow to blastocyst without any morphology evaluation, we should adapt several steps in our laboratory, for example we should move to a single-step culture medium or we should not do assisted hatching on day 3 embryos.
Efficacy of a biobehavioral intervention for hot flashes: a randomized controlled pilot study
Authors: Barton Debra L. , Schroeder Kelliann C. Fee , Banerjee Tanima , Wolf Sherry , Keith Timothy Z. , Elkins Gary
Published: March 2017

Objective:

The need for effective nonhormonal treatments for hot flash management without unwanted side effects continues. The primary aim of this pilot study was to evaluate the effect of combining a nonhormonal pharmacologic agent with a behavioral treatment for hot flash reduction.

Methods:

Seventy-one postmenopausal women were randomized to one of four groups: venlafaxine 75 mg + hypnosis (VH) versus venlafaxine 75 mg + sham hypnosis (VSH) versus a placebo pill + hypnosis (PH) versus placebo pill + sham hypnosis (PSH). Women recorded hot flash severity and frequency in a daily diary, in real time. The intrapatient difference in hot flash score (frequency × severity) at 8 weeks was analyzed using a General Estimating Equation model, using VSH as the referent arm, controlling for baseline hot flashes.

Results:

The active arms including PH or VH were not statistically significantly different than VSH (P = 0.34, P = 0.05, respectively). Women in each active arm reported hot flash reductions of about 50%, with the PSH group reporting a 25% reduction. Women receiving the PSH reported statistically significantly smaller reductions in hot flash score than women in the referent VSH arm (P = 0.001). There were no significant negative side effects during the course of the study.

Conclusions:

Hypnosis alone reduced hot flashes equal to venlafaxine alone, but the combination of hypnosis and venlafaxine did not reduce hot flashes more than either treatment alone. More research is needed to clarify whether combining hypnosis with a different antidepressant would provide synergistic benefits.
Predictors of Pharmacotherapy Response in Generalized Anxiety Disorder: A Systematic Review
Authors: Ferreira-Garcia Rafael , Mochcovitch Marina , Costa do Cabo Mariana , Nardi Antonio Egídio , Christophe Freire Rafael
Published: March 2017

Background

Pharmacotherapy for generalized anxiety disorder (GAD) may be effective in reducing symptoms in the majority of patients. The study of moderators and predictors of treatment response may help clinicians both to select appropriate interventions to maximize the probability of response and to inform the general prognosis.

Methods

A systematic literature search of electronic databases, selected authors, and reference lists was used to identify articles that reported trials of drug monotherapy in GAD. Data on predictors and moderators were extracted. Quality of evidence was determined by the presence of a priori hypotheses, number of variables investigated, adequate quality of the measurement, and use of interaction-effects testing.

Results

From the 98 articles meeting inclusion criteria, 24 reported a total of 22 factors associated with treatment response. The reported results were heterogeneous, ranging over sociodemographic, clinical, comorbidity, genetic, and functional-imaging studies. Major depressive symptoms were found to moderate treatment outcome in favor of antidepressants versus benzodiazepines. Neuroticism, previous treatment, genetic polymorphisms (including serotonin receptor gene 2A), and functional activation of the anterior cingulate cortex and amygdala were identified as potential predictors of treatment response.

Conclusions

Correlates of poor emotion regulation predicted poor treatment response, but subclinical depression was the only variable capable of informing treatment selection in this review. Future research should focus on further exploring the value of depression as a moderator and on a narrower list of potential genetic, brain-imaging, and temperament predictors of response to pharmacotherapy in GAD.
PROPHYLACTIC PERIPHERAL LASER AND FLUORESCEIN ANGIOGRAPHY AFTER BEVACIZUMAB FOR RETINOPATHY OF PREMATURITY
Authors: Garcia Gonzalez Jose M. , Snyder Laura , Blair Michael , Rohr Ashley , Shapiro Michael , Greenwald Mark
Published: March 2017

Purpose:

To report reactivation rate after bevacizumab treatment for retinopathy of prematurity (ROP) in eyes with classic ROP (CROP) versus aggressive posterior ROP (APROP) and to report peripheral fluorescein angiography findings in these eyes.

Methods:

Retrospective chart review was conducted on consecutive infants treated with bevacizumab for ROP, followed by fluorescein angiography and prophylactic laser to persistent avascular retina.

Results:

Sixty-four eyes of 33 patients were included. Mean gestational age was 25 weeks with mean birth weight of 674 g. Mean follow-up was 125 weeks post-menstrual age (PMA). Reactivation requiring treatment after initial bevacizumab was more common in eyes with APROP (8/16) than with CROP (2/48; P < 0.0001). At mean 73 weeks PMA, eyes with APROP had more avascular retina (mean 4.4 disk diameters vs. 2.6 disk diameters; P = 0.0004) and higher percentage of leakage (11/11 eyes vs. 22/38 eyes; P = 0.01) on fluorescein angiography than in eyes with CROP. Unfavorable outcome occurred in 1 of 16 eyes with APROP and in no eyes with CROP. No eye that underwent prophylactic laser after bevacizumab had a poor structural outcome.

Conclusion:

In our study, bevacizumab-treated eyes with APROP have a higher likelihood of recurrence and larger area of persistent nonperfusion than in eyes with CROP. Treatment of ROP with bevacizumab followed by prophylactic laser has a low rate of unfavorable structural outcome.
BLIND-SIDED BY COSMETIC VEIN SCLEROTHERAPY: A CASE OF OPHTHALMIC ARTERIAL OCCLUSION
Authors: Arunakirinathan Meena , Walker Robbie J. E. , Hassan Noor , Ameen Sally , Younis Saad
Published: March 2017

Purpose:

Cosmetic vein sclerotherapy is increasingly used to treat varicose veins because of its effectiveness and adherence with British Pharmacopoeia specifications. We present the first documented case of ophthalmic artery occlusion resulting in panocular ischemia secondary to intravascular injection of sodium tetradecyl sulfate sclerosant in a young healthy women seeking treatment for prominent facial veins in her forehead.

Methods:

The patient presented with unilateral sudden loss of vision. Funduscopy demonstrated a pale retina, cherry-red spot, and sclerosant visualized directly at the macula. She underwent emergency treatment for central retinal artery occlusion followed by fundal photographs, fluorescein angiography, and optical coherence tomography.

Results:

Despite intervention, the vision remained no perception to light. Magnetic resonance imaging, echocardiography, and Doppler ultrasound were unremarkable. The patient later developed neovascular sequelae requiring laser pan-retinal photocoagulation.

Conclusion:

Widely regarded as safe, and approved by the U.S. Food and Drug Administration, the only published ocular side effects of foam sclerotherapy are transient visual disturbances or temporary scotomas. This case demonstrates irreversible loss of vision as a previously unreported complication. While undoubtedly rare, we believe physicians and surgeons using sclerosant in the orbital adnexa, face, nose, and sinuses should be aware of this sight-threatening complication of injection and counsel potential patients accordingly.
MRGPRX2, atopic dermatitis, and red man syndrome
Authors: Azimi Ehsan , Reddy Vemuri B. , Lerner* Ethan A.
Published: March 2017

Vancoymycin causes red man syndrome, an itchy erythematous eruption involving the face, neck, and upper torso. Atopic dermatitis also manifests itch and erythema, and staphylococcus δ-toxin contributes to this process. The antibiotic and toxin each provoke mast cell degranulation but the mechanism had not been understood. We have determined that these compounds evoke degranulation via interaction with the same receptor, MRGPRX2, on mast cells. A receptor antagonist inhibits this process. Antagonists of this receptor may have therapeutic potential.
Diagnostic accuracy of laser-evoked potentials in diabetic neuropathy
Authors: Di Stefano Giulia , La Cesa Silvia , Leone Caterina , Pepe Alessia , Galosi Eleonora , Fiorelli Marco , Valeriani Massimiliano , Lacerenza Marco , Pergolini Mario , Biasiotta Antonella , Cruccu Giorgio , Truini Andrea
Published: March 2017

Although the most widely agreed neurophysiological tool for investigating small fiber damage is laser-evoked potential (LEP) recording, no study has documented its diagnostic accuracy. In this clinical, neurophysiological, and skin biopsy study, we collected age-corrected LEP normative ranges, verified the association of LEPs with pinprick sensory disturbances in the typical diabetic mixed fiber polyneuropathy, and assessed the sensitivity and specificity of LEPs in diabetic small fiber neuropathy. From 288 LEP recordings from the face, hand, and foot in 73 healthy subjects, we collected age-corrected normative ranges for LEPs. We then selected 100 patients with mixed-fiber diabetic neuropathy and 25 patients with possible small-fiber diabetic neuropathy. In the 100 patients with mixed fiber neuropathy, we verified how LEP abnormalities were associated with clinically evident pinprick sensory disturbances. In the 25 patients with possible pure small fiber neuropathy, using the skin biopsy for assessing the intraepidermal nerve fiber density as a reference standard, we calculated LEP sensitivity and specificity. In healthy participants, age strongly influenced normative ranges for all LEP variables. By applying age-corrected normative ranges for LEPs, we found that LEPs were strongly associated with pinprick sensory disturbances. In relation to the skin biopsy findings, LEPs yielded 78% sensitivity and 81% specificity in the diagnosis of diabetic small fiber neuropathy. Our study, providing age-corrected normative ranges for the main LEP data and their diagnostic accuracy, helps to make LEPs more reliable as a clinical diagnostic tool, and proposes this technique as a less invasive alternative to skin biopsy for diagnosing diabetic small fiber neuropathy.
Prevalence and incidence of chronic pain with or without neuropathic characteristics in patients with cancer
Authors: Bouhassira Didier , Luporsi Elisabeth , Krakowski Ivan
Published: March 2017

This prospective national multicenter study was carried out to estimate the prevalence and incidence of chronic pain with or without neuropathic characteristics in patients with cancer in France. All consecutive outpatients (n = 1885) seen over 2 weeks for cancer treatment in 12 oncology units were invited to participate in the study, and 1805 were included. Patients underwent a clinical examination during visit 1, and a questionnaire was completed to detect chronic pain (defined as daily pain for at least 3 months), and to characterize its intensity, location, and neuropathic characteristics (ie, DN4 score ≥4). The impact of pain on quality of life was assessed with the Brief Pain Inventory. Patients without pain at visit 1 were included in the incidence study and were seen at 3 and 6 months after visit 1. The overall prevalence of chronic pain was 28.2% (95% CI: 26.3-30.5), ranging from 22.5% to 35.4%, depending on the location of the primary tumor. Neuropathic characteristics were present in 20.9% of these patients, with a prevalence of 2.9% to 9.7%, depending on primary tumor location. Pain intensity and interference were higher in patients with neuropathic characteristics. In total, 1285 patients were included in the incidence study, 873 of whom were seen at least once, 3, or 6 months after the first visit. The incidence of chronic pain during the 6-month follow-up period ranged from 13% to 28%, depending on primary tumor location, and neuropathic characteristics were found in 19.9% of patients with chronic pain.
Natural History and Treatment Outcomes of Severe Autoimmune Hepatitis
Authors: Sonthalia Nikhil , Rathi Pravin M. , Jain Samit S. , Surude Ravindra G. , Mohite Ashok R. , Pawar Sunil V. , Contractor Qais
Published: March 2017

Goals:

The aim of this study was to analyze the natural history and treatment outcomes of autoimmune hepatitis (AIH) variants presenting with severe-AIH.

Background:

Severe acute presentation is an uncommon manifestation of AIH, and it remains poorly characterized.

Materials and Methods:

We included 101 patients with AIH from January 2011 to December 2015. Patients were classified as seropositive-AIH and seronegative-AIH. Patients with acute liver failure, acute-on-chronic liver failure, and severe acute hepatitis were defined as severe-AIH patients. Patient characteristics and treatment outcomes with follow-up until 12 months were analyzed between the different groups.

Results:

Out of 101 cases, 24 (23.76%) had severe AIH. Of them 9 (37.5%) had severe acute hepatitis, 3 (12.5%) had acute liver failure, and 12 (50%) had acute-on-chronic liver failure. Seronegative-AIH patients presented with severe-AIH significantly more frequently compared with seropositive-AIH patients (50% vs. 20.27%, P=0.022). Severe-AIH had 50% complete responders, 25% partial responders, and 25% treatment failures. Jaundice (88.88% vs. 68.7%, P=0.048), encephalopathy (55.55% vs. 6.66%, P=0.014), and higher international normalized ratio values (2.17±0.60 vs. 1.82±0.14, P=0.038) were factors associated with nonresponse rather than the presence or absence of autoantibodies in severe-AIH. The hazard ratio for predicting remission in the non-severe AIH group as compared with the severe-AIH group was 1.502, which was statistically not significant (95% CI, 0.799-2.827; P=0.205).

Conclusion:

Approximately 24% of patients with AIH have severe-AIH. Conventional autoantibodies are often absent in severe-AIH; however, it does not alter the outcome. Immunosuppressants should be given expediently in patients with severe-AIH.
Cutaneous manifestations of systemic viral diseases in neonates: an update
Authors: Castillo Stephanie A. , Pham Anh Khoa , Dinulos James G.
Published: March 2017

Purpose of review

Dermatologic findings may be the first signs of a neonatal viral infection. This review provides an update of the diagnostic features and therapies for selected viral illnesses [herpes simplex virus (HSV), varicella zoster virus, enterovirus, and Zika virus] that present with cutaneous manifestations in the neonate.

Recent findings

HSV DNA polymerase chain reaction of plasma and cerebrospinal fluid, routinely used in the diagnosis of neonatal HSV, may have expanded utility in assessing prognosis and acyclovir therapeutic efficacy. Maternal antiviral suppressive therapy may alter the clinical appearance of congenital HSV, resulting in delayed diagnosis and treatment. VariZIG, a varicella zoster immune globulin, is a US Food and Drug Administration approved form of prophylaxis for varicella. The Centers for Disease Control and Prevention has expanded the period of VariZIG eligibility for preterm infants, a group particularly susceptible to severe varicella infection. For severe neonatal enterovirus sepsis, the results of a randomized, double-blind, placebo-controlled trial of pleconaril, a viral capsid inhibitor, suggest that this compound is an effective therapy. Human Parechovirus type 3, a strain within a newly formed viral genus, has a similar, and potentially underestimated, clinical presentation to enterovirus sepsis. However, a distinctive erythematous palmoplantar rash may be specific to human Parechovirus type 3 infection. Perinatal Zika virus infection in the neonate may present with a nonspecific macular and papular rash. As this rash is not specific, obtaining a maternal travel history and, if appropriate, requesting additional diagnostic testing are critical for early diagnosis.

Neonatal rashes may be harmless and transient, whereas others may reflect the presence of a severe systemic illness. Recognizing key cutaneous features of viral-associated rashes may aid in the prompt and accurate diagnosis and treatment of neonatal viral illnesses.
Nephrogenic diabetes insipidus
Authors: Bockenhauer D. , Bichet Daniel G.
Published: March 2017

Purpose of review

In nephrogenic diabetes insipidus (NDI), the kidney is unable to concentrate urine despite elevated concentrations of the antidiuretic hormone arginine-vasopressin. In congenital NDI, polyuria and polydipsia are present from birth and should be immediately recognized to avoid severe episodes of dehydration. Unfortunately, NDI is still often recognized late after a ‘diagnostic odyssey’ involving false leads and dangerous treatments.

Once diagnosed, appropriate treatment can be started. Moreover, laboratory studies have identified promising new compounds, which may help achieve urinary concentration independent of vasopressin.

Recent findings

MAGED2 mutations caused X-linked polyhydramnios with prematurity and a severe but transient form of antenatal Bartter's syndrome.

We distinguish two types of hereditary NDI: a ‘pure’ type with loss of water only and a complex type with loss of water and ions. Mutations in the AVPR2 or AQP2 genes, encoding the vasopressin V2 receptor and the water channel Aquaporin2, respectively, lead to a ‘pure’ NDI with loss of water but normal conservation of ions. Mutations in genes that encode membrane proteins involved in sodium chloride reabsorption in the thick ascending limb of Henle's loop lead to Bartter syndrome, a complex polyuric-polydipsic disorder often presenting with polyhydramnios. A new variant of this was recently identified: seven families were described with transient antenatal Bartter's syndrome, polyhydramnios and MAGED2 mutations.

Multiple compounds have been identified experimentally that may stimulate urinary concentration independently of the vasopressin V2 receptor. These compounds may provide new treatments for patients with X-linked NDI.

A plea for early consideration of the diagnosis of NDI, confirmation by phenotypic and/or genetic testing and appropriate adjustment of treatment in affected patients.
Improved Starch Digestion of Sucrase‐deficient Shrews Treated With Oral Glucoamylase Enzyme Supplements
Authors: Nichols Buford L. , Avery Stephen E. , Quezada‐Calvillo Roberto , Kilani Shadi B. , Lin Amy Hui‐Mei , Burrin Douglas G. , Hodges Benjamin E. , Chacko Shaji K. , Opekun Antone R. , Hindawy Marwa El , Hamaker Bruce R. , Oda Sen‐Ichi
Published: March 2017

Background and Objective:

Although named because of its sucrose hydrolytic activity, this mucosal enzyme plays a leading role in starch digestion because of its maltase and glucoamylase activities. Sucrase‐deficient mutant shrews, Suncus murinus, were used as a model to investigate starch digestion in patients with congenital sucrase‐isomaltase deficiency. Starch digestion is much more complex than sucrose digestion. Six enzyme activities, 2 α‐amylases (Amy), and 4 mucosal α‐glucosidases (maltases), including maltase‐glucoamylase (Mgam) and sucrase‐isomaltase (Si) subunit activities, are needed to digest starch to absorbable free glucose. Amy breaks down insoluble starch to soluble dextrins; mucosal Mgam and Si can either directly digest starch to glucose or convert the post‐α‐amylolytic dextrins to glucose. Starch digestion is reduced because of sucrase deficiency and oral glucoamylase enzyme supplement can correct the starch maldigestion. The aim of the present study was to measure glucogenesis in suc/suc shrews after feeding of starch and improvement of glucogenesis by oral glucoamylase supplements.

Methods:

Sucrase mutant (suc/suc) and heterozygous (+/suc) shrews were fed with 13C‐enriched starch diets. Glucogenesis derived from starch was measured as blood 13C‐glucose enrichment and oral recombinant C‐terminal Mgam glucoamylase (M20) was supplemented to improve starch digestion.

Results:

After feedings, suc/suc and +/suc shrews had different starch digestions as shown by blood glucose enrichment and the suc/suc had lower total glucose concentrations. Oral supplements of glucoamylase increased suc/suc total blood glucose and quantitative starch digestion to glucose.

Conclusions:

Sucrase deficiency, in this model of congenital sucrase‐isomaltase deficiency, reduces blood glucose response to starch feeding. Supplementing the diet with oral recombinant glucoamylase significantly improved starch digestion in the sucrase‐deficient shrew.
Outcomes in Pediatric Autoimmune Hepatitis and Significance of Azathioprine Metabolites
Authors: Sheiko Melissa A. , Sundaram Shikha S. , Capocelli Kelley E. , Pan Zhaoxing , McCoy Annette M. , Mack Cara L.
Published: March 2017

Objectives:

Autoimmune hepatitis (AIH) is a common pediatric liver disease and long‐term remission is usually maintained with azathioprine (AZA). There is no consensus on the target range for AZA active metabolite 6‐thioguanine (6‐TGN) levels in pediatric AIH. The aim of the present study was to characterize the outcomes of pediatric patients with AIH and determine correlations between AZA dosing or 6‐TGN metabolite levels and biochemical remission.

Methods:

A retrospective chart review was performed and data on presentation, laboratories including AZA metabolite levels, medication use, and outcomes were collected.

Results:

Between 2002 and 2013, 66 children with AIH were identified (mean age at diagnosis 9.6 ± 5.1 years) with a mean follow‐up period of 2.9 ± 3.2 years. Common presenting symptoms included jaundice, fatigue, and abdominal pain. The majority of subjects received steroids for induction and AZA for maintenance of remission. Seventy‐nine percent achieved biochemical remission (mean time to remission 6.2 ± 9.2 months), 14% were in the induction phase of therapy, 6% required liver transplantation, and 18% were weaned off immunosuppression and remained in remission. 6‐TGN levels ranging from 50 to 250 pmol/8 × 108 red blood cell count were associated with biochemical remission (alanine aminotransferase levels of ⩽50 U/L).

Conclusions:

The vast majority of children with AIH maintain a sustained remission with AZA monotherapy. Biochemical remission was maintained with 6‐TGN levels much lower than that recommended for inflammatory bowel disease. These findings suggest that patients should be maintained at the lowest AZA dose possible that is associated with biochemical remission.
The Diagnostic Value of Hepatic Arterial Velocity in Venoocclusive Disease After Pediatric Hematopoietic Stem Cell Transplantation
Authors: Kaya Nusabe , Erbey Fatih , Atay Didem , Akçay Arzu , Bozkurt Ceyhun , Ozturk Gulyuz
Published: March 2017

The aim of this study was to determine usefulness of measurements of maximal systolic velocity of the hepatic artery with Doppler ultrasonography in the diagnosis of venoocclusive disease (VOD) after hematopoietic stem cell transplantation. We prospectively obtained 5 sonograms per patient: pretransplantation, day +1, +7, +14, and +28 on 36 nonconsecutive children who underwent hematopoietic stem cell transplantation. We examined the hepatic artery, the portal, hepatic and splenic veins, the thickness of the gallbladder wall, the presence of ascites, and the liver and spleen size. The diagnosis of VOD was based on clinical and laboratory data. Patients were divided into 2 groups: those with VOD (n=18) and those without VOD (n=18). The variance of 2 groups was analyzed.Vmaxof the hepatic artery had a strong correlation with clinical VOD diagnosis (P<0.001). There was no statistically significant difference in the other Doppler parameters. The results of our study showed that the measurement ofVmaxof the hepatic artery can provide important support in the diagnosis of VOD and can be useful in the follow-up of treatment response.
Osteosarcoma Metastases With Direct Cardiac Invasion: A Case Report and Review of the Pediatric Literature
Authors: Hartemayer Robert , Kuo Christopher , Kent Paul
Published: March 2017

Metastatic osteosarcoma with direct cardiac involvement is an exceptionally rare finding, with only 63 total reported cases in the English literature over the past 123 years. Although the precise incidence is unknown, we estimate that direct cardiac involvement currently occurs in <2% of metastatic osteosarcoma cases. We also find that before the adoption of adjuvant chemotherapy as a standard of care therapy for osteosarcoma, metastatic osteosarcoma to the heart was much more common than it is today, as cardiac involvement occurred in ∼20% of cases of metastatic osteosarcoma before the 1980s. This suggests that adjuvant chemotherapy has not only improved the overall prognosis of osteosarcoma, but also altered the metastatic pattern of disease. In this paper we present the case of an 11-year-old boy with metastatic osteosarcoma to the cardiac interventricular septum, as well as review 20 other previously reported pediatric cases of metastatic osteosarcoma to the heart. We also analyzed the cardiac surgical outcomes for 11 pediatric patients with metastatic osteosarcoma to the heart. The median disease-free survival time was 12 months, demonstrating that metastatic osteosarcoma to the heart is currently a rare occurrence with a poor prognosis.
A Rare Cause of Neonatal Hemolytic Anemia: Glutathione Synthetase Deficiency
Authors: Soylu Ustkoyuncu Pembe , Mutlu Fatma Türkan , Kiraz Aslihan , Tag Balkis Zuhal , Yel Sibel
Published: March 2017

Background:

Isolated hemolysis or hemolytic anemia and 5-oxoprolinuria are 2 distinct medical conditions in the clinical spectrum associated with glutathione synthetase deficiency.

Clinical Observation:

A 1-day-old female baby presented with anemia and respiratory distress. Her hemoglobin level was 9.5 g/dL and the total serum bilirubin level was 5.6 mg/dL. Metabolic acidosis was detected in her blood gas analysis. Metabolic acidosis recurred despite treatment and further investigation was required. Her 5-oxoproline level was 3815 mmol/mol creatinine in urine organic acid analysis, and a homozygous mutation [p.R125H (c.374G>A)] was found in the glutathione synthetase gene.

Conclusions:

GSD has been observed in very few patients and is rarely considered in the differential diagnosis of hemolytic anemia in newborns.
Should We Pay Attention to the Delay Before Admission to a Pediatric Intensive Care Unit for Children With Cancer? Impact on 1-Month Mortality. A Report From the French Children’s Oncology Study Group, GOCE
Authors: Fausser Jeanne-L. , Tavenard Aude , Rialland Fanny , Le Moine Philippe , Minckes Odile , Jourdain Anne , Tirel Olivier , Pellier Isabelle , Gandemer Virginie
Published: March 2017

Acute complications requiring admission to pediatric intensive care unit (PICU) are frequent for children with cancer. Our objective was to determine early prognostic factors of mortality in a cohort of children with cancer hospitalized in PICU for acute complications and particularly to assess whether the delay before admission to a PICU is an early predictor of mortality. We conduct a retrospective multicenter analysis. All patients transferred in PICU for acute complications between January 2002 and December 2012 were included. One-month mortality of the 224 patients analyzed was 24.5%. Delay before PICU admission was a significant prognostic factor of 1-month mortality with nonsurvivors experiencing a longer median delay than survivors (24 vs. 12 h, respectively, P<0.05). Time from diagnosis to PICU admission (P<0.001), hematopoietic stem cell transplant (P<0.05), the duration of neutropenia (P<0.01), infection type (P<0.001), number of organ dysfunctions (P<0.001), and reaching any grade 4 toxicity before PICU admission (P<0.001) also affected mortality rate at 1-month post-PICU discharge. In the multivariate analysis, only reaching any grade 4 toxicity before PICU admission influenced 1-month mortality (odds ratio, 2.30; 95% confidence interval, 1.07-4.96; P<0.05). These results suggest that PICU admission before severe impairment leads to a better outcome for children with cancer.
Sirolimus as an Effective Agent in the Treatment of Immune Thrombocytopenia (ITP) and Evans Syndrome (ES): A Single Institution’s Experience
Authors: Jasinski Sylwia , Weinblatt Mark E. , Glasser Chana L.
Published: March 2017

Background:

Autoimmune cytopenias are characterized by immune-mediated destruction of hematopoietic cell lines with immune thrombocytopenia (ITP) affecting platelets and Evans syndrome (ES) affecting platelets and red blood cells. For patients with persistent disease, limited options for effective and well-tolerated therapies exist.

Objectives:

Our aim is to describe our institution’s experience with sirolimus as therapy for pediatric patients with persistent ITP and ES.

Design/Method:

A retrospective analysis was performed in patients with persistent ITP and ES treated with sirolimus. Responses were categorized as complete response (CR), partial response, modest response, or no response.

Results:

Of the 17 patients treated, 12 had ITP and 5 had ES. Seventy-three percent of ITP patients achieved a CR, 78% of them by 3 months. Only 2 patients did not achieve a durable response. Eighty percent of ES patients had a response, with 50% of them achieving CR and the other 50% an asymptomatic partial response. One patient with ES achieved modest response, but discontinued therapy due to an adverse effect. Of the patients that achieved CR, 90% remain off all therapy for a median of 2 years.

Conclusions:

Our data suggest that sirolimus is a safe and effective steroid-sparing agent in the treatment of persistent ITP and ES.
Gynecologic Malignancies in Pregnancy: Balancing Fetal Risks With Oncologic Safety
Authors: Cordeiro Christina N. , Gemignani Mary L.
Published: March 2017

Importance

Cancer occurs in 0.05% to 0.1% of all pregnancies. Despite literature reporting good oncologic and fetal outcomes in women treated for cancer during pregnancy, as many as 44% of gynecologists would offer termination, and 37% would not administer chemotherapy or radiotherapy in pregnancy.

Objectives

The aims of this study were to summarize current recommendations for the treatment of cervical and ovarian cancers in pregnancy and to review updates on existing knowledge regarding the safety of surgical and chemotherapeutic treatments in pregnancy, including both oncologic and fetal outcomes.

Evidence Acquisition

A detailed literature review was performed on PubMed.

Results

The treatment of gynecologic malignancies during pregnancy mirrors that outside pregnancy, with a balance between maternal versus fetal health. Fertility-sparing surgery can be offered to stage IA2 and low-risk IB1 cervical, stage I epithelial ovarian, germ cell ovarian, or sex-cord stromal ovarian tumors. Delayed treatment can be offered for stage IB1 cervical cancer. Neoadjuvant and/or adjuvant chemotherapy can be given for advanced gynecologic cancers with good disease-free survival without significant adverse neonatal outcomes.

Conclusions

A multidisciplinary approach and improved education of providers regarding the surgical and chemotherapeutic treatments in pregnancy are needed in order to fully inform patients regarding treatment options. Further research in women who are pregnant is needed to determine the safety of diagnostic and therapeutic procedures used in the nonpregnant woman.

Relevance

This article reviews and supports treatment of gynecologic cancer during pregnancy, calls for additional study and long-term follow-up, and justifies improved education of patients and providers regarding treatment options.

Target Audience

Obstetricians and gynecologists, family physicians.

Learning Objectives

After completing this activity, the learner should be better able to (1) review general principles in the management and treatment of gynecologic cancers in pregnancy, (2) review the diagnosis and treatment of cervical cancer in pregnancy, and (3) review the diagnosis and treatment of ovarian cancer in pregnancy.
Is Mirabegron Equally as Effective When Used as First- or Second-Line Therapy in Women With Overactive Bladder?
Authors: Serati Maurizio , Roberti Maggiore Umberto Leone , Sorice Paola , Cantaluppi Simona , Agrò Enrico Finazzi , Ghezzi Fabio
Published: March 2017

(Abstracted from Int Urogynecol J 2016; DOI 10.1007/s00192-016-3219-x)

Oral antimuscarinic agents have been the criterion standard of pharmacotherapy for the treatment of overactive bladder (OAB) symptoms for several decades. Mirabegron, a selective β3-adrenergic receptor agonist, represents a new class of drugs for OAB with proven efficacy, good safety, and tolerability.
Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention
Authors: Fowler Mary G. , Qin Min , Fiscus Susan A. , Currier Judith S. , Flynn Patricia M. , Chipato Tsungai , McIntyre James , Gnanashanmugam Devasena , Siberry George K. , Coletti Anne S. , Taha Taha E. , Klingman Karin L. , Martinson Francis E. , Owor Maxensia , Violari Avy , Moodley Dhayendre , Theron Gerhard B. , Bhosale Ramesh , Bobat Raziya , Chi Benjamin H. , Strehlau Renate , Mlay Pendo , Loftis Amy J. , Browning Renee , Fenton Terence , Purdue Lynette , Basar Michael , Shapiro David E. , Mofenson Lynne M.
Published: March 2017

(Abstracted from N Engl J Med 2016;375:1726–1737)

Antiretroviral regimens used for the prevention of mother-to-child transmission of the human immunodeficiency virus (HIV) have evolved over the years. Combination antiretroviral therapy (ART) is currently used for prevention of mother-to-child transmission of HIV but has shown more adverse effects compared with regimens containing fewer antiretroviral agents.
Optic Neuropathy Associated with Primary Sjögren’s Syndrome: A Case Series
Authors: Bak Eunoo , Yang Hee Kyung , Hwang Jeong-Min
Published: March 2017

Purpose

To determine the diverse clinical features of optic neuropathy associated with primary Sjögren’s syndrome in Korean patients.

Methods

Five women with acute and/or chronic optic neuropathy who were diagnosed as primary Sjögren’s syndrome were retrospectively evaluated. Primary Sjögren’s syndrome was diagnosed by signs and symptoms of keratoconjunctivitis sicca, positive serum anti-Ro/SSA and/or anti-La/SSB antibodies, and/or minor salivary gland biopsy. All patients underwent a complete ophthalmologic examination.

Results

Among the five patients diagnosed as optic neuropathy related to primary Sjögren’s syndrome, four patients had bilateral optic neuropathy and one patient was unilateral. The clinical course was chronic in three patients and one of them showed acute exacerbation and was finally diagnosed with neuromyelitis optica spectrum disorder. The other two patients presented as acute optic neuritis and one was diagnosed with neuromyelitis optica spectrum disorder. Sicca symptoms were present in four patients, but only two patients reported these symptoms before the onset of optic neuropathy. Patients showed minimal response to systemic corticosteroids or steroid dependence, requiring plasmapheresis in the acute phase and immunosuppressive agents for maintenance therapy.

Conclusions

Optic neuropathy associated with primary Sjögren’s syndrome may show variable clinical courses, including acute optic neuritis, insidious progression of chronic optic atrophy, or in the context of neuromyelitis optica spectrum disorders. Optic neuropathy may be the initial manifestation of primary Sjögren’s syndrome without apparent sicca symptoms, which makes the diagnosis often difficult. The presence of specific antibodies including anti-Ro/SSA, anti-La/SSB, and anti-aquaporin-4 antibodies are supportive for the diagnosis and treatment in atypical cases of optic neuropathy.
A survey of modelling methods for high-fidelity wind farm simulations using large eddy simulation
Authors: Breton S.-P. , Sumner J. , Sørensen J. N. , Hansen K. S. , Sarmast S. , Ivanell S.
Published: March 2017

Large eddy simulations (LES) of wind farms have the capability to provide valuable and detailed information about the dynamics of wind turbine wakes. For this reason, their use within the wind energy research community is on the rise, spurring the development of new models and methods. This review surveys the most common schemes available to model the rotor, atmospheric conditions and terrain effects within current state-of-the-art LES codes, of which an overview is provided. A summary of the experimental research data available for validation of LES codes within the context of single and multiple wake situations is also supplied. Some typical results for wind turbine and wind farm flows are presented to illustrate best practices for carrying out high-fidelity LES of wind farms under various atmospheric and terrain conditions.

This article is part of the themed issue ‘Wind energy in complex terrains’.
Linearized simulation of flow over wind farms and complex terrains
Authors: Segalini Antonio
Published: March 2017

The flow over complex terrains and wind farms is estimated here by numerically solving the linearized Navier–Stokes equations. The equations are linearized around the unperturbed incoming wind profile, here assumed logarithmic. The Boussinesq approximation is used to model the Reynolds stress with a prescribed turbulent eddy viscosity profile. Without requiring the boundary-layer approximation, two new linear equations are obtained for the vertical velocity and the wall-normal vorticity, with a reduction in the computational cost by a factor of 8 when compared with a primitive-variables formulation. The presence of terrain elevation is introduced as a vertical coordinate shift, while forestry or wind turbines are included as body forces, without any assumption about the wake structure for the turbines. The model is first validated against some available experiments and simulations, and then a simulation of a wind farm over a Gaussian hill is performed. The speed-up effect of the hill is clearly beneficial in terms of the available momentum upstream of the crest, while downstream of it the opposite can be said as the turbines face a decreased wind speed. Also, the presence of the hill introduces an additional spanwise velocity component that may also affect the turbines’ operations. The linear superposition of the flow over the hill and the flow over the farm alone provided a first estimation of the wind speed along the farm, with discrepancies of the same order of magnitude for the spanwise velocity. Finally, the possibility of using a parabolic set of equations to obtain the turbulent kinetic energy after the linearized model is investigated with promising results.

This article is part of the themed issue ‘Wind energy in complex terrains’.
An optimal control framework for dynamic induction control of wind farms and their interaction with the atmospheric boundary layer
Authors: Munters W. , Meyers J.
Published: March 2017

Complex turbine wake interactions play an important role in overall energy extraction in large wind farms. Current control strategies optimize individual turbine power, and lead to significant energy losses in wind farms compared with lone-standing wind turbines. In recent work, an optimal coordinated control framework was introduced (Goit & Meyers 2015
J. Fluid Mech.
768
, 5–50 (
doi:10.1017/jfm.2015.70
)). Here, we further elaborate on this framework, quantify the influence of optimization parameters and introduce new simulation results for which gains in power production of up to 21% are observed.

This article is part of the themed issue ‘Wind energy in complex terrains’.
Complex terrain experiments in the New European Wind Atlas
Authors: Mann J. , Angelou N. , Arnqvist J. , Callies D. , Cantero E. , Arroyo R. Chávez , Courtney M. , Cuxart J. , Dellwik E. , Gottschall J. , Ivanell S. , Kühn P. , Lea G. , Matos J. C. , Palma J. M. L. M. , Pauscher L. , Peña A. , Rodrigo J. Sanz , Söderberg S. , Vasiljevic N. , Rodrigues C. Veiga
Published: March 2017

The New European Wind Atlas project will create a freely accessible wind atlas covering Europe and Turkey, develop the model chain to create the atlas and perform a series of experiments on flow in many different kinds of complex terrain to validate the models. This paper describes the experiments of which some are nearly completed while others are in the planning stage. All experiments focus on the flow properties that are relevant for wind turbines, so the main focus is the mean flow and the turbulence at heights between 40 and 300 m. Also extreme winds, wind shear and veer, and diurnal and seasonal variations of the wind are of interest. Common to all the experiments is the use of Doppler lidar systems to supplement and in some cases replace completely meteorological towers. Many of the lidars will be equipped with scan heads that will allow for arbitrary scan patterns by several synchronized systems. Two pilot experiments, one in Portugal and one in Germany, show the value of using multiple synchronized, scanning lidar, both in terms of the accuracy of the measurements and the atmospheric physical processes that can be studied. The experimental data will be used for validation of atmospheric flow models and will by the end of the project be freely available.

This article is part of the themed issue ‘Wind energy in complex terrains’.
Non-steady wind turbine response to daytime atmospheric turbulence
Authors: Nandi Tarak N. , Herrig Andreas , Brasseur James G.
Published: March 2017

Relevant to drivetrain bearing fatigue failures, we analyse non-steady wind turbine responses from interactions between energy-dominant daytime atmospheric turbulence eddies and the rotating blades of a GE 1.5 MW wind turbine using a unique dataset from a GE field experiment and computer simulation. Time-resolved local velocity data were collected at the leading and trailing edges of an instrumented blade together with generator power, revolutions per minute, pitch and yaw. Wind velocity and temperature were measured upwind on a meteorological tower. The stability state and other atmospheric conditions during the field experiment were replicated with a large-eddy simulation in which was embedded a GE 1.5 MW wind turbine rotor modelled with an advanced actuator line method. Both datasets identify three important response time scales: advective passage of energy-dominant eddies (≈25–50 s), blade rotation (once per revolution (1P), ≈3 s) and sub-1P scale (<1 s) response to internal eddy structure. Large-amplitude short-time ramp-like and oscillatory load fluctuations result in response to temporal changes in velocity vector inclination in the aerofoil plane, modulated by eddy passage at longer time scales. Generator power responds strongly to large-eddy wind modulations. We show that internal dynamics of the blade boundary layer near the trailing edge is temporally modulated by the non-steady external flow that was measured at the leading edge, as well as blade-generated turbulence motions.

This article is part of the themed issue ‘Wind energy in complex terrains’.
Sound propagation from a ridge wind turbine across a valley
Authors: Van Renterghem Timothy
Published: March 2017

Sound propagation outdoors can be strongly affected by ground topography. The existence of hills and valleys between a source and receiver can lead to the shielding or focusing of sound waves. Such effects can result in significant variations in received sound levels. In addition, wind speed and air temperature gradients in the atmospheric boundary layer also play an important role. All of the foregoing factors can become especially important for the case of wind turbines located on a ridge overlooking a valley. Ridges are often selected for wind turbines in order to increase their energy capture potential through the wind speed-up effects often experienced in such locations. In this paper, a hybrid calculation method is presented to model such a case, relying on an analytical solution for sound diffraction around an impedance cylinder and the conformal mapping (CM) Green's function parabolic equation (GFPE) technique. The various aspects of the model have been successfully validated against alternative prediction methods. Example calculations with this hybrid analytical–CM–GFPE model show the complex sound pressure level distribution across the valley and the effect of valley ground type. The proposed method has the potential to include the effect of refraction through the inclusion of complex wind and temperature fields, although this aspect has been highly simplified in the current simulations.

This article is part of the themed issue ‘Wind energy in complex terrains’.