bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prenatal imaging findings in fetal Zika virus infection
Authors: Araujo Júnior Edward , Carvalho Francisco H.C. , Tonni Gabriele , Werner Heron 
Published: February 2017

Purpose of review
The aim of this review is to report the most recent observations concerning intrauterine Zika virus (ZIKV) infection and associated neuroimaging.

Recent findings
ZIKV outbreak in Brazil in 2015 was associated with an impressive registration of cases of congenital microcephaly in women with symptoms suggestive of ZIKV infection. Clinical and laboratory testing for ZIKV and hypothetic etiopathogenetic mechanisms are described. Diagnostic tests on blood, urine and amniotic fluid should be performed in all mothers with symptoms suggestive of intrauterine ZIKV infection. ZIKV causes multiple teratogenic malformations, mainly affecting the developing brain.

Summary
Neuroimaging investigation contributes to the prenatal detection of microcephaly and other brain abnormalities in cases of intrauterine ZIKV infection. Neuroimaging is based antenatally on two-dimensional and three-dimensional ultrasound and fetal MRI, whereas computed tomography scan is performed postnatally. Although neuropathology associated with intrauterine ZIKV infection is characterized by nonspecific findings of brain disorder, reduced cortical gyration and white-matter hypomyelination or dysmyelination and cerebellar hypoplasia have been consistently observed in the majority of fetuses and newborns. Prenatal or postnatal genetic workup should be carried out to exclude cases of primary microcephaly. Follow-up should rely upon MRI and computed tomography scan as well as neuropediatrician to better define developmental outcome in survivors.
Noninvasive prenatal diagnosis for single gene disorders
Authors: Allen Stephanie , Young Elizabeth , Bowns Benjamin 
Published: February 2017

Purpose of review
Noninvasive prenatal diagnosis for single gene disorders is coming to fruition in its clinical utility. The presence of cell-free DNA in maternal plasma has been recognized for many years, and a number of applications have developed from this. Noninvasive prenatal diagnosis for single gene disorders has lagged behind due to complexities of technology development, lack of investment and the need for validation samples for rare disorders.

Recent findings
Publications are emerging demonstrating a variety of technical approaches and feasibility of clinical application. Techniques for analysis of cell-free DNA including digital PCR, next-generation sequencing and relative haplotype dosage have been used most often for assay development. Analysis of circulating fetal cells in the maternal blood is still being investigated as a viable alternative and more recently transcervical trophoblast cells. Studies exploring ethical and social issues are generally positive but raise concerns around the routinization of prenatal testing.

Summary
Further work is necessary to make testing available to all patients with a pregnancy at risk of a single gene disorder, and it remains to be seen if the development of more powerful technologies such as isolation and analysis of single cells will shift the emphasis of noninvasive prenatal diagnosis. As testing becomes possible for a wider range of conditions, more ethical questions will become relevant.
CHOROIDAL THICKNESS IN PATIENTS WITH STARGARDT DISEASE
Authors: Vural Esra , Acar Ugur , Sevinc Mehmet K. , Erdurmus Mesut , Kucuk Bekir , Aykas Seckin , Sobaci Gungor 
Published: February 2017

Purpose:
To investigate the relationship between choroidal thicknesses (CT), central foveal thicknesses, multifocal electroretinography (mf-ERG) responses, and best-corrected visual acuity levels in patients with Stargardt disease (STGD).

Methods:
A total of 30 eyes of 30 patients with STGD, and 30 age- and sex-matched healthy controls were included in the study. All participants underwent detailed ophthalmic examination including best-corrected visual acuity and spectral domain optical coherence tomography measurements, and also patients with STGD were performed mf-ERG.

Results:
The mean subfoveal CT values were 271.95 ± 85.57 μm in patients with STGD and 355.73 ± 87.41 μm in the control group (P < 0.001). The mean central foveal thickness values were 223.56 ± 61.38 μm in patients with STGD and 272.46 ± 27.52 μm in the control group (P < 0.001). The mean central and paracentral mf-ERG responses (45.71 ± 26.60 and 16.47 ± 10.75 Nv/deg2 respectively) in patients with STGD were significantly lower from the normal ranges (66.6–130.8 Nv/deg2 and 30.9–77.7 Nv/deg2, respectively; P < 0.001 for both). There was a statistically significant correlation between subfoveal CT and best-corrected visual acuity levels (P = 0.012, r = −0.452), and between parafoveal CT and inner retinal thickness and paracentral mf-ERG responses (P = 0.043, r = +0.372 and P = 0.049, r = +0.363, respectively). Paracentral mf-ERG responses were also correlated with outer retinal thickness values (P = 0.005, r = +0.503).

Conclusion:
Patients with STGD have a thinner CT, which may be responsible for some of the clinical findings. The pathophysiological significance of these findings needs further study.
Association of Epithelial Atypia With Recurrence After Surgical Excision in Conjunctival Papilloma
Authors: Yazu Hiroyuki , Dogru Murat , Miyauchi Jun , Tanaka Yoichi , Yamaguchi Takefumi , Den Seika , Satake Yoshiyuki , Tsubota Kazuo , Shimazaki Jun 
Published: February 2017

Purpose:
To investigate the association between recurrence of conjunctival papillomas and presence of atypical epithelial changes in patients undergoing surgical excision for conjunctival papilloma.

Methods:
We retrospectively reviewed 1,195 ophthalmic pathology specimens from 2004 to 2014 at Ichikawa General Hospital. Pathologic specimens of 5 patients with a final diagnosis of “conjunctival papilloma” were stained with hematoxylin–eosin, Ki 67, p53, human papillomavirus (HPV) 16 and 18 antibodies.

Results:
Of 1,195 patients, 5 patients (4 men, 1 woman; age range: 27∼57 years, mean age: 38.4 years) had a diagnosis of conjunctival papilloma, which constituted to 0.42% of the pathologic diagnosis made for the ophthalmology specimens. All specimens displayed multiple fronds of thickened conjunctival epithelium that enclosed cores of vascularized connective tissues. Three patients with recurrence after surgical excision demonstrated moderate to severe epithelial atypia, who also showed higher staining with Ki67 and p53 compared with patients with no recurrence. HPV16 and 18 antibodies staining did not appear to relate to recurrences.

Conclusions:
Conjunctival papillomas with higher positive staining for Ki67 and p53 seem to have a higher risk of recurrence even after complete surgical excision and necessitate careful follow-up.
Postinterventional critical care management of aneurysmal subarachnoid hemorrhage
Authors: Datar Sudhir , Rabinstein Alejandro A. 
Published: February 2017

Purpose of review
Subarachnoid hemorrhage from a ruptured aneurysm (aSAH) is a complex disorder with the potential to have devastating effects on the brain as well as other organ systems. After more than 3 decades of research, the underlying pathophysiologic mechanisms remain incompletely understood and important questions remain regarding the evaluation and management of these patients. The purpose of this review is to analyze the recent literature and improve our understanding of certain key clinical aspects.

Recent findings
Growing body of evidence highlights the usefulness of CT perfusion scans in the diagnosis of vasospasm and delayed cerebral ischemia (DCI). Hypervolemia leads to worse cardiopulmonary outcomes and does not improve DCI. The traditional triple H therapy is falling out of favor with hemodynamic augmentation alone now considered the mainstay of medical management. Randomized controlled trials have shown that simvastatin and intravenous magnesium do not prevent DCI or improve functional outcomes after aneurysmal subarachnoid hemorrhage (aSAH). Emerging data using multimodality monitoring has further advanced our understanding of the pathophysiology of DCI in poor grade aSAH.

Summary
The brief review will focus on the postinterventional care of aSAH patients outlining the recent advances over the past few years.
Advancements in the critical care management of status epilepticus
Authors: Bauerschmidt Andrew , Martin Andrew , Claassen Jan 
Published: February 2017

Purpose of review
Status epilepticus has a high morbidity and mortality. There are little definitive data to guide management; however, new recent data continue to improve understanding of management options of status epilepticus. This review examines recent advancements regarding the critical care management of status epilepticus.

Recent findings
Recent studies support the initial treatment of status epilepticus with early and aggressive benzodiazepine dosing. There remains a lack of prospective randomized controlled trials comparing different treatment regimens. Recent data support further study of intravenous lacosamide as an urgent-control therapy, and ketamine and clobazam for refractory status epilepticus. Recent data support the use of continuous EEG to help guide treatment for all patients with refractory status epilepticus and to better understand epileptic activity that falls on the ictal–interictal continuum. Recent data also improve our understanding of the relationship between periodic epileptic activity and brain injury.

Summary
Many treatments are available for status epilepticus and there are much new data guiding the use of specific agents. However, there continues to be a lack of prospective data supporting specific regimens, particularly in cases of refractory status epilepticus.
Intracranial pressure management in patients with traumatic brain injury: an update
Authors: Stocchetti Nino , Zoerle Tommaso , Carbonara Marco 
Published: February 2017

Purpose of review
Intracranial pressure (ICP) monitoring and treatment is central in the management of traumatic brain injury. Despite 4 decades of clinical use, several aspects remain controversial, including the indications for ICP and treatment options.

Recent findings
Two major trials tested surgical decompression and mild hypothermia as treatments for high ICP. Both were rigorous, randomized, multicenter studies, with different designs. Decompression was tested for ICP refractory to conventional treatment, whereas hypothermia was offered as an alternative to conventional medical therapy. Decompression reduced mortality, but at the expense of more disability. The hypothermia trial was stopped because of a worse outcome in the treated arm. Indications for ICP monitoring have been reviewed and new international guidelines issued. New contributions published in 2016 have dealt with computerized analysis for predicting ICP crises; noninvasive or innovative methods for measuring ICP; reassessment of standard therapeutic interventions, such as hypertonic solutions and the level of intensity of ICP therapy.

Summary
Aggressive strategies for ICP control, like surgical decompression or hypothermia, carefully tested, have controversial effects on outcome. Several articles have made worthwhile contributions to important clinical issues, but with no real breakthroughs.
Central nervous system infections in immunocompromised patients
Authors: Sonneville Romain , Magalhaes Eric , Meyfroidt Geert 
Published: February 2017

Purpose of review
Although rare, central nervous system (CNS) infections are increasingly being recognized in immunocompromised patients. The goal of the present review is to provide a practical diagnostic approach for the intensivist, and to briefly discuss some of the most prevalent conditions.

Recent findings
Immunocompromised patients presenting with new neurological symptoms should always be suspected of a CNS infection. These infections carry a poor prognosis, especially if intracranial hypertension, severely altered mental status or seizures are present. Clinical examination and serum blood tests should be followed by brain imaging, and when no contra-indications are present, a lumbar puncture including cerebrospinal fluid PCR to identify causative organisms. Empirical therapy depends on the type of immunodeficiency. In HIV-infected patients, the most common CNS infection is cerebral toxoplasmosis, whereas in other immunocompromised patients, aspergillosis, cryptococcal meningitis and tuberculous meningitis are more prevalent. Multiple pathogens can be detected in up to 15% of patients. The diagnostic value of fast multiplex PCR has yet to be evaluated in this setting.

Summary
CNS infections represent a rare but severe complication in immunocompromised patients. A systematic approach including early diagnosis, appropriate antimicrobial treatment, early ICU admission and aggressive measures to reduce intracranial pressure may improve outcome.
Advanced monitoring in traumatic brain injury: microdialysis
Authors: Carpenter Keri L.H. , Young Adam M.H. , Hutchinson Peter J. 
Published: February 2017

Purpose of review
Here, we review the present state-of-the-art of microdialysis for monitoring patients with severe traumatic brain injury, highlighting the newest developments. Microdialysis has evolved in neurocritical care to become an established bedside monitoring modality that can reveal unique information on brain chemistry.

Recent findings
A major advance is recent consensus guidelines for microdialysis use and interpretation. Other advances include insight obtained from microdialysis into the complex, interlinked traumatic brain injury disorders of electrophysiological changes, white matter injury, inflammation and metabolism.

Summary
Microdialysis has matured into being a standard clinical monitoring modality that takes its place alongside intracranial pressure and brain tissue oxygen tension measurement in specialist neurocritical care centres, as well as being a research tool able to shed light on brain metabolism, inflammation, therapeutic approaches, blood–brain barrier transit and drug effects on downstream targets. Recent consensus on microdialysis monitoring is paving the way for improved neurocritical care protocols. Furthermore, there is scope for future improvements both in terms of the catheters and microdialysate analyser technology, which may further enhance its applicability.
The walking dead: macrophage inflammation and death in atherosclerosis
Authors: Kavurma Mary M. , Rayner Katey J. , Karunakaran Denuja 
Published: February 2017

Purpose of review
To highlight recent studies that describe novel inflammatory and signaling mechanisms that regulate macrophage death in atherosclerosis.

Recent findings
Macrophages contribute to all stages of atherosclerosis. The traditional dogma states that in homeostatic conditions, macrophages undergo apoptosis and are efficiently phagocytosed to be cleared by a process called efferocytosis. In advanced atherosclerosis, however, defective efferocytosis results in secondary necrosis of these uncleared apoptotic cells, which ultimately contributes to the formation of the characteristic necrotic core and the vulnerable plaque. Here, we outline the different types of lesional macrophage death: apoptosis, autophagic and the newly defined necroptosis (i.e. a type of programmed necrosis). Recent discoveries demonstrate that macrophage necroptosis directly contributes to necrotic core formation and plaque instability. Further, promoting the resolution of inflammation using preresolving mediators has been shown to enhance efferocytosis and decrease plaque vulnerability. Finally, the canonical ‘don’t eat me’ signal CD47 has recently been described as playing an important role in atherosclerotic lesion progression by impairing efficient efferocytosis. Although we have made significant strides in improving our understanding of cell death and clearance mechanisms in atherosclerosis, there still remains unanswered questions as to how these pathways can be harnessed using therapeutics to promote lesion regression and disease stability.

Summary
Improving our understanding of the mechanisms that regulate macrophage death in atherosclerosis, in particular apoptosis, necroptosis and efferocytosis, will provide novel therapeutic opportunities to resolve atherosclerosis and promote plaque stability.
Statin-associated immune-mediated myopathy: biology and clinical implications
Authors: Christopher-Stine Lisa , Basharat Pari 
Published: February 2017

Purpose of reviewIn the last 6 years, our understanding of statin-associated myopathy expanded to include not only a toxic myopathy with limited and reversible side-effects but also an autoimmune variety in which statins likely induce an autoimmune myopathy that is both associated with a specific autoantibody and responsive to immunosuppression and immune modulation. This review widens the reader's understanding of statin myopathy to include an autoimmune process.Recent findingsStatin-associated immune-mediated myopathy provides an example of an environmental trigger (statins) directly implicated in an autoimmune disease associated with a genetic predisposition as well as potential risk factors including concomitant diseases and specific statins. Given a median exposure to statins of 38 months, providers should be aware that anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) myopathy may occur even after several years of statin exposure.SummaryIt is important for the reader to understand the clinical presentation of statin-associated immune-mediated myopathy and the difference in its clinical presentation to that of statins as direct myotoxins. Prompt recognition of such an entity allows the clinician to immediately stop the offending agent if it has not already been discontinued as well as to recognize that statin rechallenge is not a likely option, and that prompt treatment with immunosuppression and/or immunomodulation is usually of enormous benefit to the patient in restoring muscle strength and physical function.Video abstracthttp://links.lww.com/COL/A15
Utilization of ultrasound for diagnostic evaluation and management of peritonsillar abscesses
Authors: Froehlich Michael H. , Huang Zhen , Reilly Brian K. 
Published: February 2017

Purpose of review
We outlined the management of peritonsillar abscess (PTA) through the use of ultrasound, an imaging modality that continues to emerge as a diverse diagnostic and treatment tool. Our review compares the use of ultrasound to alternative diagnostic modalities, particularly computed tomography (CT). Further, the review evaluates how ultrasound can be used to help facilitate guided drainage of PTA and serve as a suitable alternative to more invasive management options.

Recent findings
Studies over the past 5 years have demonstrated that the initial management of PTA with ultrasound is a more cost-efficient and lower-risk option than imaging with CT. Ultrasound possesses great specificity for PTA and may be more diagnostically accurate than previously thought. Ultrasound is particularly well tolerated in children and adults, avoids radiation exposure, as well as minimizes false-positive aspirations. In addition, the ability to utilize ultrasound from different approaches allows for flexibility in the management of PTA.

Summary
These findings illustrate that ultrasound is being increasingly considered in the management of stable patients presenting with PTA.
Genetic signature and profiling of head and neck cancer: where do we stand?
Authors: Paczkowska Julia , Szyfter Krzysztof , Giefing Maciej , Wierzbicka Malgorzata 
Published: February 2017

Purpose of review
To focus on two novel aspects of head and neck squamous cell carcinoma (HNSCC) genetics of special interest: the epithelial–mesenchymal transition (EMT) process, an initial step in tumor progression that finally leads to metastasis formation, by explaining how genes as well as epigenetic factors control this process, and the new diagnostic options based on the analysis of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) that could revolutionize diagnosis in the coming years.

Recent findings
We present an intriguing recently described group of factors, namely miRNAs, deregulated during EMT. MiRNAs could serve as novel markers of EMT and metastasis formation and are also a potential therapeutic target. Second, we show recent findings on CTC and cfDNA analysis in HNSCC that demonstrate the usefulness of this new diagnostic approach.

Summary
We stress the importance of EMT in the context of metastasis formation and the potential of liquid biopsies in clinical practice.
Second‐line Agents in Pediatric Patients With Autoimmune Hepatitis
Authors: Zizzo Andréanne N. , Valentino Pamela L. , Shah Prakesh S. , Kamath Binita M. 
Published: February 2017

ABSTRACTBackground and Aims:Ten percent to 20% of children with autoimmune hepatitis (AIH) require second‐line therapy to achieve remission. Although current guidelines exist on first‐line management, evidence for second‐line therapy in treatment‐refractory patients is lacking. Our aim was to perform a systematic review and meta‐analysis of the efficacy and safety of second‐line treatments used in this population.Methods:Electronic and manual searches were used to identify potential studies for inclusion. Studies were selected based on reported response rates to second‐line therapies in children who failed response to prednisone and azathioprine. Data extraction and risk of bias assessment were performed independently by 2 reviewers. Meta‐analysis using weighted estimate of response rates at 6 months was performed for each treatment option. Heterogeneity was assessed.Results:Fifteen studies of 76 pediatric patients with AIH were included in the review. Overall response rates at 6 months were estimated as 36% for mycophenolate mofetil (MMF) (N = 34, 95% confidence interval [CI] (16–57)), and 50% for tacrolimus (N = 4, 95% CI (0–100%)) and 83% for cyclosporine (N = 15, 95% CI (66%–100%)). Adverse effects were most frequent with cyclosporine (64% experiencing at least 1 adverse effect) followed by tacrolimus (54%) and MMF (48%). Pooled estimates of adverse events were 78% for cyclosporine (95% CI (54%–100%)), 42% for tacrolimus (95% CI (0%–85%)) and 45% for MMF (95% CI (25%–68%)). Sensitivity analyses were not performed due to small sample size.Conclusions:Cyclosporine had the highest response rate at 6 months in children with standard‐treatment‐refractory AIH; however, it also had the highest rate of adverse events. MMF was the second most efficacious option with a low adverse effect rate.