bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term Outcomes for the Treatment of Paragangliomas in the Upfront, Adjuvant, and Salvage Settings With Stereotactic Radiosurgery and Intensity-modulated Radiotherapy
Authors: Anderson Joshua L. , Khattab Mohamed H. , Anderson Chelsea , Sherry Alexander D. , Luo Guozhen , Manzoor Nauman , Attia Albert , Netterville James , Cmelak Anthony J. 
Published: November 2019

Objective:
To analyze local control (LC) and toxicity rates between stereotactic radiosurgery (SRS) and intensity-modulated radiotherapy (IMRT) in relation to reported surgical rates in the treatment of paragangliomas (PG) in the upfront, adjuvant, and salvage settings, and to explore factors affecting tumor size reduction, toxicity rates, and symptom control.

Study Design:
Retrospective cohort analysis.

Setting:
Tertiary referral center.

Patients and Interventions:
Thirty patients treated with either linear accelerator-based SRS or IMRT in the definitive, planned adjuvant, or unplanned salvage postsurgery settings.

Main Outcome Measures:
Local control, toxicities, symptom control, tumor size reduction, and factors affecting each.

Results:
Median follow-up was 4.16 years. LC rates were 100%. Acute grade >3 toxicity rate was 6.7%, 86.7% of tumors had a reduction in volume, and 76.7% of patients had improvement in at least one tumor-induced symptom by last follow-up. Larger tumor size at presentation and longer time to last follow-up were significantly associated with greater tumor size reduction on multivariate analysis.

Conclusions:
SRS and IMRT are safe and effective treatment for PG with high efficacy and low morbidity rates in the upfront, planned adjuvant, and unplanned salvage settings.
Quantifying Tertiary Referral Center Bias in Vestibular Schwannoma Research
Authors: Saba Elias S. , Marinelli John P. , Lohse Christine M. , Link Michael J. , Carlson Matthew L. 
Published: November 2019

Objective:
The majority of research influencing our understanding of vestibular schwannoma (VS) comes from large tertiary referral centers, and as a consequence, is inherently prone to referral bias. The objective of the current study was to characterize tertiary referral center bias in VS research.

Study design:
Single-institution retrospective clinical, audiometric, and radiologic review.

Setting:
One tertiary referral center.

Patients:
One hundred twenty-three patients with sporadic VS treated at our institution, consisting of a local cohort of all 41 VS patients residing in the same US county as our medical center and a referral cohort of 82 patients from outside counties matched 2:1 based on age, sex, and year of diagnosis.

Intervention:
Surgical resection, stereotactic radiosurgery (SRS), observation.

Main outcome measures:
Clinical manifestations, audiometric and radiologic findings, elected treatment modality.

Results:
Local patients had significantly longer follow-up after initial presentation compared to referral patients (median 4.0 vs 2.2 yr; p = 0.007). Referral patients were significantly less likely to have an incidental VS diagnosis (1% vs. 29%; p < 0.001) and presented with worse symptomatology such as hearing loss (80% vs. 54%; p = 0.002), dizziness (72% vs. 44%; p = 0.002), headache (29% vs. 15%; p = 0.075), and other cranial nerve dysfunction (11% vs. 0%; p = 0.029). Audiometrically, referral patients had significantly poorer word recognition scores at presentation (median 70% vs. 90%; p = 0.043). Local patients were more likely to have tumors confined to the IAC compared with referral patients, and had significantly smaller tumors when restricted to this region (median 4.0 vs 6.5 mm; p = 0.005). Referral patients were significantly more likely to undergo definitive management with either radiosurgery or microsurgery following primary evaluation compared to local patients (48% vs. 24%; p = 0.013).

Conclusion:
These data suggest that the majority of existing literature surrounding VS likely suffers from referral bias, whereby disease characteristics and management decisions are distinct from that of the general VS patient population.
Performance of liver biomarkers, in patients at risk of nonalcoholic steato-hepatitis, according to presence of type-2 diabetes
Authors: Poynard Thierry , Peta Valentina , Deckmyn Olivier , Pais Raluca , Ngo Yen , Charlotte Frederic , Ngo An , Munteanu Mona , Imbert-Bismut Françoise , Monneret Denis , Housset Chantal , Thabut Dominique , Valla Dominique , Boitard Christian , Castera Laurent , Ratziu Vlad 
Published: November 2019

Objective
There is a controversy about the performance of blood tests for the diagnostic of metabolic liver disease in patients with type-2-diabetes in comparison with patients without type-2-diabetes. These indirect comparisons assumed that the gold-standard is binary, whereas fibrosis stages, steatosis and nonalcoholic-steato-hepatitis (NASH) grades use an ordinal scale. The primary aim was to compare the diagnostic performances of FibroTest in type-2-diabetes vs. controls matched on gender, age, fibrosis stages and obesity, and taking into account the spectrum effect by Obuchowski measure.

Methods
Data were retrospectively compared among patients prospectively included, with simultaneous biopsy and blindly assessed FibroTest, SteatoTest-2 and NashTest-2. The secondary aim was to construct an index (SpectrumF3F4-Index) to predict an adjusted-area under the receiver operating curve (AUROC) for F3F4 diagnosis from the prevalences of fibrosis stages, permitting to reduce the spectrum effect when performances of FibroTest, transient elastography and magnetic resonance elastography are indirectly compared.

Results
In 505 patients at risk of NASH, the Obuchowski measures [95% confidence interval (CI)] of FibroTest, SteatoTest-2 and NashTest-2 were all equivalent in 136 type-2-diabetes cases vs. 369 matched controls: 0.871 (0.837–0.905), vs. 0.880 (0.879–0.881), 0.835 (0.797–0.873) vs. 0.806 (0.780–0.832) and 0.829 (0.793–0.865) vs. 0.855 (0.829–0.869), respectively. Standard-AUROCs (95% CI) were 0.932 (0.898–0.965), 0.872 (0.837–0.907) and 0.834 (0.699–0.969) and reduced after adjustment by SpectrumF3F4-Index to 0.794 (0.749–0.838), 0.767 (0.750–0.783) and 0.773 (0.725–0.822) for transient, magnetic resonance elastography and FibroTest, respectively.

Conclusions
When compared by Obuchowski measures, the performances of tests were not different in patients with T2-diabetes vs. patients without T2-diabetes. When individual data are not available, adjusted-AUROCs reduced the spectrum effect.
Metabolomic and gene expression analysis to study the effects of dietary saturated and polyunsaturated fats
Authors: Ulven Stine M. , Holven Kirsten B. 
Published: November 2019

Purpose of review
Give an update on recent dietary intervention studies that have used peripheral blood mononuclear cell gene expression analysis and/or metabolic profiling to understand how intake of polyunsaturated and saturated fat affects and biological pathways linked to cardiovascular disease.

Recent findings
Several studies showed that intake of fish oil and vegetable oil, high in omega-3 fatty acids, reduced expression level of genes involved in inflammation. One intervention study showed that gene transcripts encoding genes involved inflammation and lipid metabolism increased after intake of polyunsaturated fat (mainly omega-6 fatty acids) compared to saturated fat. Additionally, using targeted metabolomics, the concentrations of atherogenic lipoprotein particles and several metabolites including palmitoylcarnitine, myristoylcarnitine, and kynurenine were reduced after intake of polyunsaturated fat compared to saturated fat, whereas acetate and acetoacetate were increased. The use of targeted metabolomics showed that overfeeding with polyunsaturated fat reduced the serum concentration of ceramides, dihydroceramides, glucosylceramides, and lactosylceramides, whereas overfeeding with saturated fat increased serum concentration of these metabolites.

Summary
The use of gene expression profiling and metabolomics are promising tools to identify possible new biomarkers linking fat quality to cardiovascular disease risk.
Fatty liver, cardiometabolic disease and mortality
Authors: Bedogni Giorgio , Gastaldelli Amalia , Foschi Francesco G. 
Published: November 2019

Purpose of review
We discuss the findings of the most recent metanalyses on the association between nonalcoholic fatty liver disease (NAFLD), cardiometabolic disease and mortality.

Recent findings
Recent metanalyses have shown that NAFLD is associated with incident type 2 diabetes mellitus (T2DM) and incident cardiovascular disease (CVD). Nonalcoholic steatohepatitis, which can be diagnosed by liver biopsy only in tertiary care centers, is often associated with liver fibrosis, which has been shown by metanalyses to increase both cardiovascular and liver-related mortality. Hyperlipidemia, lipotoxicity and impaired insulin secretion are among the possible mechanisms underlying the association of NAFLD with T2DM and CVD. Metanalyses of the association between NAFLD and mortality in the general population, where risk stratification cannot be performed on the basis of liver biopsy, have given contradictory results.

Summary
To establish conclusively whether NAFLD adds to known prognostic factors of death in the general population will require a shared operational definition of NAFLD, purposefully designed cohort studies, and the use of clinically relevant measures of effect size.
Advances in vaccinating immunocompromised children
Authors: Miller Katrina , Leake Katelyn , Sharma Tanvi 
Published: November 2019

Purpose of review
Immunocompromised children are a largely under-vaccinated population and are vulnerable to acquiring vaccine-preventable infections (VPIs). A variety of factors contribute to poor vaccine coverage including: severity of underlying illness, sporadic contact with primary care physicians, and lack of awareness among specialty providers regarding vaccination status. In this review, we report recent data regarding incidence of VPIs, new approaches to vaccine use, rates of vaccine coverage, and strategies to optimize vaccine administration in immunocompromised populations.

Recent findings
Pediatric transplant recipients and patients with autoimmune disorders receiving novel biological therapies, represent growing immunocompromised patient populations. VPIs continue to be a concern for such patients. Underlying disease severity may limit efforts to immunize pediatric patients early in their disease process, prior to immunosuppression. Inactive vaccines are safe and immunogenic after the introduction of immunosuppression, but live vaccines are typically contraindicated. Emerging data support the safety and effectiveness of live vaccines in certain immunocompromised individuals. Care providers must remain vigilant in maintaining patients’ vaccination status based on current vaccination guidelines, and create a multidisciplinary approach to optimizing vaccination.

Summary
Immunocompromised children remain under-vaccinated and vulnerable to VPIs. Optimizing vaccines should be a priority for every provider caring for this population.
Targeting metabolic dependencies in pediatric cancer
Authors: Issaq Sameer H. , Heske Christine M. 
Published: November 2019

Purpose of review
In an attempt to identify potential new therapeutic targets, efforts to describe the metabolic features unique to cancer cells are increasingly being reported. Although current standard of care regimens for several pediatric malignancies incorporate agents that target tumor metabolism, these drugs have been part of the therapeutic landscape for decades. More recent research has focused on the identification and targeting of new metabolic vulnerabilities in pediatric cancers. The purpose of this review is to describe the most recent translational findings in the metabolic targeting of pediatric malignancies.

Recent findings
Across multiple pediatric cancer types, dependencies on a number of key metabolic pathways have emerged through study of patient tissue samples and preclinical modeling. Among the potentially targetable vulnerabilities are glucose metabolism via glycolysis, oxidative phosphorylation, amino acid and polyamine metabolism, and NAD+ metabolism. Although few agents have yet to move forward into clinical trials for pediatric cancer patients, the robust and promising preclinical data that have been generated suggest that future clinical trials should rationally test metabolically targeted agents for relevant disease populations.

Summary
Recent advances in our understanding of the metabolic dependencies of pediatric cancers represent a source of potential new therapeutic opportunities for these diseases.
Challenges and solutions to the study of rare childhood tumors
Authors: Fair Douglas , Potter Samara L. , Venkatramani Rajkumar 
Published: November 2019

Purpose of review
The majority of progress made in pediatric oncology over the past 50 years has been achieved in the most common cancers. Rare pediatric cancers, which collectively comprise more than 10% of all pediatric cancers, pose multiple challenges to researchers and clinicians, all which stem from the infrequency of these cancers. There has been a tremendous increase in focus on rare pediatric cancers by international consortia and registries, disease-specific clinics, and divisions of academic children's hospitals in the last 10 years. This focus, along with the progress made in cancer genomics, has changed the landscape for the study and treatment of rare pediatric cancers. This review focuses on the past, present, and future of the study and treatment of rare pediatric cancers.

Recent findings
Cancer genomics is changing the way some cancers are being diagnosed, categorized, and treated. Rare pediatric cancers potentially stand to greatly benefit from advances in precision diagnosis and treatment.

Summary
The challenges of studying rare pediatric cancers are well known. By utilizing similar techniques that allowed for progress in the common pediatric malignancies, namely collaboration, increased focus, greater funding, and utilization of cancer genomics, progress in the study and treatment of rare pediatric cancers is promising.
Self-Contempt as a Predictor of Suicidality
Authors: Rüsch Nicolas , Oexle Nathalie , Thornicroft Graham , Keller Johannes , Waller Christiane , Germann Ines , Regelmann Christina A. , Noll-Hussong Michael , Zahn Roland 
Published: November 2019

Abstract
People with mental illness can internalize public prejudice and negative emotional reactions to their group, leading to self-contempt. This study examined self-contempt related to having a mental illness as predictor of suicidality among 77 people with mental illness in Southern Germany. Self-contempt, depressive symptoms, hopelessness, and suicidality were assessed at baseline; suicidality was measured again 3 months later. High self-contempt at baseline predicted increased suicidality at follow-up, adjusting for baseline suicidality, symptoms, diagnosis, age, sex, and hopelessness. These results suggest that self-contempt may be a risk factor for suicidality and call for specific interventions targeting self-stigma and its emotional consequences.
Long-Term Results and Reconstruction Failure in Patients Receiving Postmastectomy Radiation Therapy with a Temporary Expander or Permanent Implant in Place
Authors: Dicuonzo Samantha , Leonardi Maria Cristina , Radice Davide , Morra Anna , Gerardi Marianna Alessandra , Rojas Damaris Patricia , Surgo Alessia , Dell’Acqua Veronica , Luraschi Rosa , Cattani Federica , Rietjens Mario , De Lorenzi Francesca , Veronesi Paolo , Galimberti Viviana , Marvaso Giulia , Fodor Cristiana , Orecchia Roberto , Jereczek-Fossa Barbara Alicja 
Published: November 2019

Background:
This study investigated the risk of reconstruction failure after mastectomy, immediate breast reconstruction, and radiotherapy to either a temporary tissue expander or permanent implant.

Methods:
Records of women treated at a single institution between June of 1997 and December of 2011 were reviewed. Two patient groups were identified based on type of immediate breast reconstruction: tissue expander followed by exchange with a permanent implant and permanent implant. The study endpoint was rate of reconstruction failure, defined as a replacement, loss of the implant, or conversion to flap.

Results:
The tissue expander/permanent implant and the permanent implant groups consisted of 63 and 75 patients, respectively. The groups were well balanced for clinical and treatment characteristics. With a median follow-up of 116 months, eight implant losses, 50 implant replacements, and four flap conversions were recorded. Reconstruction failure occurred in 22 of 63 patients in the expander/implant group and in 40 of 75 patients in the permanent implant group. A traditional proportional hazards model showed a higher risk of reconstruction failure for the expander/implant group (hazard ratio, 2.01) and a significantly shorter time to reconstruction failure compared with the permanent implant group (109.2 months versus 157.7 months; p = 0.03); however, according to a competing risk model, the between-groups cumulative incidences were not significantly different (hazard ratio, 1.09).

Conclusions:
Radiotherapy to either a tissue expander or a permanent implant presented a fairly large risk of reconstruction failure over time. The expander/implant group was not more likely to develop reconstruction failure compared to permanent implant group, but the timing of onset was shorter. More complex techniques should be investigated to lower the risk of reconstruction failure.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
The KS-Pexy: A Novel Method to Manage Horizontal Lower Eyelid Laxity
Authors: Van Slyke Aaron C. , Carr Lauren A. , Carr Nicholas J. 
Published: November 2019

Background:
Patients with horizontal lower lid laxity undergoing lower lid blepharoplasty are at a high risk for lid malposition. Prophylactic correction of horizontal lower lid laxity during blepharoplasty may alleviate this risk. In this article, the authors describe a novel lower lid blepharoplasty technique, the KS-pexy (named after its originators, Kuhnt and Szymanowski), for correcting horizontal lower lid laxity.

Methods:
All cases of KS-pexy between September of 2009 and June of 2018 from an aesthetic practice were reviewed retrospectively. All patients were diagnosed with horizontal lower lid laxity and requested lower lid blepharoplasty for aesthetic concerns. Patient demographics, clinical presentation, procedure details, and intraoperative findings were analyzed.

Results:
Sixty-two patients underwent KS-pexy performed by the senior author. The average follow-up was 41.1 months, ranging from 2 to 107 months. Thirteen patients had a negative vector, 54 patients received a KS-pexy in combination with another facial procedure, and 14 patients had their KS-pexy as a secondary procedure. The overall success rate was 96.8 percent. The complication profile was as follows: chemosis (27.4 percent), new-onset dry eyes persisting longer than 8 weeks (6.5 percent), temporary lower eyelid malposition (4.8 percent), lower eyelid malposition requiring surgical intervention (3.2 percent), poor scar quality (1.6 percent), lower lid abscess (1.6 percent), transient conjunctivitis (1.6 percent), lateral fat compartment swelling (1.6 percent), canthopexy dehiscence (1.6 percent), hordeolum (1.6 percent), and temporary V2 paresthesia (1.6 percent).

Conclusion:
The KS-pexy is an effective means to treat horizontal eyelid laxity prophylactically in patients requesting lower eyelid blepharoplasty for aesthetic reasons.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, IV.
Probiotics to manage inflammation in HIV infection
Authors: Reikvam Dag Henrik , Meyer-Myklestad Malin Holm , Trøseid Marius , Stiksrud Birgitte 
Published: November 2019

Purpose of review
To evaluate the current scientific basis for administering probiotics to people living with HIV (PLHIV) to alleviate chronic inflammation and subsequently improve their prognosis.

Recent findings
The gut microbiome is a potential contributing factor to low-grade inflammation in HIV infection, and there is a scientific rationale for attempting to attenuate inflammation by administering probiotics. Sixteen reports from clinical studies in antiretroviral therapy (ART)-treated PLHIV assessing inflammation after probiotic intervention have been identified; half of them randomized control trials (RCT). Some of the studies report improvement in some parameters of inflammation, but results are inconsistent. No studies report improvement of CD4 counts. None of the RCTs report improvements in any markers of inflammation when analyzed according to protocol.

Summary
Current scientific evidence does not support the use of probiotics to alleviate inflammation in HIV infection. The potential effect of probiotic intervention in ART-treated PLHIV with high risk for inflammation remains to be investigated.
Ocular and neurosyphilis: epidemiology and approach to management
Authors: Singh Ameeta E. 
Published: November 2019

Purpose of review
In the context of a resurgence of syphilis worldwide, it can be anticipated that a rise in cases of ocular, otic, and neurosyphilis will also be seen. This article reviews the current epidemiology, manifestations, and approach to management and treatment.

Recent findings
Although studies continue investigating alternate approaches and new diagnostic tests for ocular and neurosyphilis, few data exist to change current diagnostic algorithms and approaches to diagnosis, management, or follow up.

Summary
The diagnosis of neurologic and eye/ear involvement with syphilis may be delayed because of a lack of specificity of findings, low suspicion for syphilis, fluctuation in symptoms, and/or similarities in presentation to other diseases. A high index of suspicion for syphilis and re-education about the protean manifestations of syphilis by all clinicians is required provide timely diagnosis and management of ocular, otic, and neurosyphilis.
Periarticular Neurofascial Dextrose Prolotherapy Versus Physiotherapy for the Treatment of Chronic Rotator Cuff Tendinopathy
Authors: Kazempour Mofrad Morteza , Rezasoltani Zahra , Dadarkhah Afsaneh , Kazempour Mofrad Reza , Abdorrazaghi Fateme , Azizi Sirous 
Published: November 2019

Background/Objective
Rotator cuff tendinopathy is a common cause of shoulder pain. We aimed to compare periarticular (neurofascial) dextrose prolotherapy versus physiotherapy for treatment of chronic rotator cuff tendinopathy in the short term.

Methods
We carried out a randomized clinical trial with 2 arms at a university hospital. In total, 66 patients with chronic rotator cuff tendinopathy, proven by magnetic resonance imaging, were randomly allocated to 2 groups. The outcomes were change in shoulder pain intensity (primary) and disability (secondary) index using a questionnaire for Shoulder Pain and Disability Index. For physiotherapy, participants received superficial heat, transcutaneous electrical nerve stimulation, and pulsed ultrasound. Also, they carried out an exercise program, 10 sessions of 30 minutes for 3 weeks. For prolotherapy, we used 8 mL of 12.5% dextrose and 40 mg of 2% lidocaine. The mixture was injected 2 times with 1-week interval superficially around the shoulder joint and to tender points along the suprascapular nerve.

Results
Neurofascial dextrose was more effective than physiotherapy for alleviating pain in 2 weeks (p < 0.001), and they were similar 3 months after the interventions (p = 0.055). For disability, dextrose was more effective than physiotherapy 2 weeks and 3 months (both p < 0.001) after the interventions. However, the changes in the physiotherapy group seemed to be more sustained.

Conclusions
Both interventions are effective for the short-term management of rotator cuff tendinopathy. However, prolotherapy is more successful as the initial treatment. Besides, the treatment time is much shorter for dextrose prolotherapy compared with physiotherapy.