bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innate lymphoid cells in asthma: pathophysiological insights from murine models to human asthma phenotypes
Authors: Jonckheere Anne-Charlotte , Bullens Dominique M.A. , Seys Sven F. 
Published: December 2018

Purpose of review
The current review describes the role of different types of innate lymphoid cells (ILCs) in the pathogenesis of asthma inflammatory phenotypes by linking findings from murine asthma models with human studies. Novel treatment options are needed for patients with steroid-insensitive asthma. Strategies targeting ILCs, or their upstream or downstream molecules are emerging and discussed in this review.

Recent findings
In eosinophilic asthma, ILCs, and especially type 2 ILCs (ILC2s), are activated by alarmins such as IL-33 upon allergen triggering of the airway epithelium. This initiates IL-5 and IL-13 production by ILC2, resulting in eosinophilic inflammation and airway hyperreactivity. Type 3 ILCs (ILC3s) have been shown to be implicated in obesity-induced asthma, via IL-1β production by macrophages, leading ILC3 and release of IL-17. ILC1s might play a role in severe asthma, but its role is currently less investigated.

Summary
Several studies have revealed that ILC2s play a role in the induction of eosinophilic inflammation in allergic and nonallergic asthmatic patients mainly via IL-5, IL-13, IL-33 and thymic stromal lymphopoietin. Knowledge on the role of ILC3s and ILC1s in asthmatic patients is lagging behind. Further studies are needed to support the hypothesis that these other types of ILCs contribute to asthma pathogenesis, presumably in nonallergic asthma phenotypes.
Risk Factors for New-Onset Atrial Fibrillation in Patients With Sepsis: A Systematic Review and Meta-Analysis
Authors: Bosch Nicholas A. , Cohen David M. , Walkey Allan J. 
Published: December 2018

Objective:
Atrial fibrillation frequently develops in patients with sepsis and is associated with increased morbidity and mortality. Unfortunately, risk factors for new-onset atrial fibrillation in sepsis have not been clearly elucidated. Clarification of the risk factors for atrial fibrillation during sepsis may improve our understanding of the mechanisms of arrhythmia development and help guide clinical practice.

Data Sources:
Medline, Embase, Web of Science, and Cochrane CENTRAL.

Study Selection:
We conducted a systematic review and meta-analysis to identify risk factors for new-onset atrial fibrillation during sepsis.

Data Extraction:
We extracted the adjusted odds ratio for each risk factor associated with new-onset atrial fibrillation during sepsis. For risk factors present in more than one study, we calculated pooled odds ratios (meta-analysis). We classified risk factors according to type and quantified the factor effect sizes. We then compared sepsis-associated atrial fibrillation risk factors with risk factors for community-associated atrial fibrillation.

Data Synthesis:
Forty-four factors were examined as possible risk factors for new-onset atrial fibrillation in sepsis, 18 of which were included in meta-analyses. Risk factors for new-onset atrial fibrillation included demographic factors, comorbid conditions, and most strongly, sepsis-related factors. Sepsis-related factors with a greater than 50% change in odds of new-onset atrial fibrillation included corticosteroid use, right heart catheterization, fungal infection, vasopressor use, and a mean arterial pressure target of 80–85 mm Hg. Several cardiovascular conditions that are known risk factors for community-associated atrial fibrillation were not identified as risk factors for new-onset atrial fibrillation in sepsis.

Conclusions:
Our study shows that risk factors for new-onset atrial fibrillation during sepsis are mainly factors that are associated with the acute sepsis event and are not synonymous with risk factors for community-associated atrial fibrillation. Our results provide targets for future studies focused on atrial fibrillation prevention and have implications for several key areas in the management of patients with sepsis such as glucocorticoid administration, vasopressor selection, and blood pressure targets.
Concurrent Radiation and Immunotherapy
Authors: Amin Neha P. , Remick Jill , Agarwal Manuj , Desai Nina A. , Bergom Carmen , Simone Charles B. 
Published: December 2018

Objective:
The objective of this study was to report on US radiation oncologists’ (ROs) practice patterns and perceptions of concurrent radiation (RT) and immunotherapy (IT) (CRI).

Methods:
A 22-question survey was emailed to radiation oncologists in February 2018. CRI was defined as RT completed within 1 week before initial IT infusion through 4 weeks after final IT infusion.

Results:
Of the 323 respondents from 45 states, 88% had experience treating a patient with CRI, including 51% private and 48% academic physicians. The most common reason for not offering CRI was concerns of increased toxicity (50%). Although 84% to 94% of respondents did not change RT dose, more ROs decreased dose when treating central structures (chest/abdomen/pelvis) versus noncentral structures (brain/head and neck/extremities): 13% to 15% versus 4% to 8%, P<0.001. The majority (58% to 80%) of respondents would not delay RT from last IT infusion. Moderate and significant actual toxicities were rare (medical intervention 6%, hospitalization/death <1%). 97.5% of ROs did not routinely prescribed prophylactic steroids for CRI. More ROs believed CRI with SBRT/SRS versus palliative RT had better local control (35% vs. 25%, P<0.05) and higher rates of abscopal responses (41% vs. 25%, P<0.01).

Conclusions:
Despite concerns for toxicity, ROs with CRI experience reported minimal toxicities. Most ROs do not alter RT dose, use prophylactic steroids, or delay starting RT from last IT infusion. Uncertainty remains about improved local control outcomes and abscopal responses from CRI, with a perception that concurrent SBRT offers better outcomes than palliative RT. These survey results may help guide ROs until more definitive data are available.
Bisphosphonate-loaded Bone Cement as a Local Adjuvant Therapy for Giant Cell Tumor of Bone
Authors: Greenberg David D. , Lee Francis Y. 
Published: December 2018

Background:
Historically, nontargeted adjuvant therapies such as liquid nitrogen, phenol, argon beam, and alcohol have been applied locally after curettage of giant cell tumors (GCT) in the extremities. Systemic bisphosphonates (BP) and denosumab have emerged as osteoclast-targeting therapies because osteoclast-like giant cells, responsible for aggressive bone resorption, are susceptible to BP or denosumab. However, such drugs may cause systemic side effects. We examined the effects of an alternative intraoperative local delivery of BP on GCTs.

Materials and Methods:
In total, 17 patients with GCTs underwent extended surgical curettage procedures consisting of high-speed burring, traditional adjuvant therapy, and application of BP-loaded polymethylmethacrylate bone cement. Clinical data and follow-up radiographs were reviewed to investigate local recurrence (LR) rate and complications in a retrospective manner.

Results:
There were 6 males and 11 females (mean age, 33.7 y). There were no cases of pulmonary metastases. Patient follow-up ranged from 1 to 12 years. There was 1 LR during the follow-up period for an LR rate of 5.9%. The mean final Musculoskeletal Tumor Society (MSTS) score was 29. There were no systemic or localized avascular necrosis or atypical fractures related to BPs noted.

Conclusions:
BP-loaded polymethylmethacrylate is a targeted local adjuvant therapy that is feasible, safe, and may reduce LRs while alleviating the risk of systemic side effects of BPs such as avascular necrosis of jaw and atypical femur fractures. Future prospective randomized clinical trials will strengthen the level of evidence of this proposed targeted therapy.

Level of Evidence:
Therapeutic level IV—see instructions for authors for a complete description of evidence.
Simultaneous Quantification of 13 Cannabinoids and Metabolites in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry in Adult Epilepsy Patients
Authors: Roslawski Michaela J. , Remmel Rory P. , Karanam Ashwin , Leppik Ilo E. , Marino Susan E. , Birnbaum Angela K. 
Published: December 2018

Background:
A sensitive, robust method was developed and validated to quantitate 13 major natural cannabinoid parent and metabolite compounds in human plasma at or below 0.5 ng/mL.

Methods:
A liquid chromatography tandem mass spectrometry method was developed and validated to measure 13 cannabinoid compounds: cannabidiol (CBD), cannabidiolic acid, cannabidivarin, cannabinol, cannabigerol, cannabigerolic acid, cannabichromene, Δ9-tetrahydocannabinol (THC), Δ9-tetrahydrocannabinolic acid A (THCA), Δ9-tetrahydrocannabivarin (THCV), 11-hydroxy-Δ9-tetrahydrocannbinol (11-OH-THC), 11-nor-9-carboxy-Δ9-tetrahydrocannbinol (THC-COOH), and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol glucuronide (THC-COOH-glu). Samples (200 µL) were extracted through protein precipitation and separated with a Kinetex EVO C18 column and a 65%–95% gradient of methanol and 0.2% ammonium hydroxide/H2O at a flow rate of 0.4 mL/min. Samples were obtained from patients with epilepsy receiving cannabis for the treatment of seizures.

Results:
The extracted lower limit of quantification was 0.05 ng/mL for CBD, cannabidivarin, cannabinol, and 11-OH-THC; 0.10 ng/mL for cannabidiolic acid, cannabigerol, cannabichromene, cannabigerolic acid, THC, THCA, and THCV; and 0.50 ng/mL for THC-COOH and THC-COOH-glu. Mean quality control intraday accuracy and precision for all analytes ranged 96.5%–104% and 2.7%–4.9%, respectively, whereas interday accuracy and precision ranged 98%–103.3% and 0.2%–3.6%, respectively. An absolute matrix effect was observed for some analytes, however, with minimal relative matrix effect. Lack of nonspecific drug binding to extraction glass and plasticware was verified. Patient CBD levels ranged from 0.135 to 11.13 ng/mL.

Conclusions:
The validated method met FDA guidelines for bioanalytical assays precision and accuracy criteria. The assay reliably confirmed the use of particular medical cannabis formulations in patient samples as well as reliably measured low CBD concentrations from single-dose CBD exposure.
Rapid Quantitation of Flecainide in Human Plasma for Therapeutic Drug Monitoring Using Liquid Chromatography and Time-of-Flight Mass Spectrometry
Authors: Rahman Mohammed , Couchman Lewis , Povstyan Valentyna , Bainbridge Verity , Kipper Karin , El-Nahhas Toqa , Johnston Atholl , Holt David 
Published: December 2018

Background:
Measurement of flecainide is useful to optimize dosage and minimize risks of toxicity. Furthermore, there is a need for urgent sample analysis when flecainide is used in transplacental therapy for fetal tachycardia. To this end, we have developed and validated a rapid assay for the measurement of flecainide in human plasma or serum, using a small sample volume (50 µL).

Methods:
After a simple deproteination with zinc sulfate and methanol, prepared samples were injected onto a short (30 mm) analytical column and eluted using a rapid gradient elution. Detection was performed using time-of-flight mass spectrometry. Flecainide was quantified using flecainide-D4 as internal standard, with both compounds extracted from the total ion chromatogram using a ±5 ppm extraction window based on the theoretical m/z values for the protonated ions.

Results:
The assay was linear over a putative therapeutic range (100–1500 mcg/L). Between- and within-assay imprecision and accuracy were <4.6% and 94.8%–110.0%, respectively. Matrix effects were minimal and were compensated for by flecainide-D4. There were no effects due to hemolysis or lipemia, and no carryover was apparent. Total analysis time was just 1.2 minutes (72 seconds).

Conclusions:
We have developed and validated a rapid method for the analysis of flecainide. The method is particularly suited for flecainide therapeutic drug monitoring, when analyzing samples from mothers receiving flecainide for the treatment of fetal tachycardia.
Translational highlights in breast cancer research and treatment: recent developments with clinical impact
Authors: Fasching Peter A. , Schneeweiss Andreas , Kolberg Hans-Christian , Ettl Johannes , Fehm Tanja N. , Overkamp Friedrich , Lüftner Diana 
Published: December 2018

Purpose of review
Over the last decades the time which is needed to translate a preclinical finding or idea in the clinic has reduced continuously. Especially but not only for breast cancer the number of tested drugs and targeted pathways have increased immensely. In addition, the introduction of immune-oncological treatments has further advanced the possibilities for future treatments. This review focuses on recent developments in the prevention and treatment of breast cancer including results from major clinical trials and recent conferences.

Recent findings
Many pathways involved in the progression or treatment of breast cancer have been also identified in the cause and pathogenesis of breast cancer. Therefore, breast cancer risk can be described in much more detail, possibly leading to new prevention strategies. In breast cancer treatment the introduction of PARP inhibitors has begun. Recent trials will lead to a better understanding whether PI3K inhibitors can be developed for application in the clinic and first large randomized trials show the superiority of anti PD-1/PD-L1 treatments.

Summary
Treatment strategies which were developed over the last decade are moving rapidly into the clinical use. The understanding of treatment targets and involved side effects will be important for the safe implementation of these treatments into routine practice.
Cyclin-dependent kinase 4/6 inhibitors: what have we learnt across studies, therapy situations and substances
Authors: Banys-Paluchowski Malgorzata , Krawczyk Natalia , Paluchowski Peter 
Published: December 2018

Purpose of review
Cyclin-dependent kinases (CDK) are key regulatory enzymes that control cell cycle and cell division. In the recent years, new therapeutic options selectively targeting CDK 4 and 6 have shown promising clinical activity in several solid tumors. Since 2015, three CDK 4/6 inhibitors have been approved for treatment of hormone receptor-positive HER2-negative metastatic breast cancer: palbociclib, ribociclib and abemaciclib. These drugs share a common mechanism of action and have been evaluated in studies with a similar design. The following review gives a clinical overview of the CDK 4/6 inhibitors in breast cancer therapy and highlight current study data with regard to their antitumor efficacy and toxicities.

Recent findings
In clinical trials in the first-line and later-line setting, palbociclib, ribociclib and abemaciclib in combination with endocrine therapy significantly prolonged progression-free survival. The most common adverse events during treatment with CDK 4/6 inhibitors are neutropenia, fatigue and gastrointestinal symptoms.

Summary
CDK 4/6 inhibitors represent a valuable treatment option for patients with metastatic hormone receptor-positive HER2-negative breast cancer. Although the clinical efficacy of the three agents seems similar, their toxicity profiles differ. Therefore, the choice of a CKD 4/6 inhibitor depends on patient's characteristics and individual preferences.

Video abstract
In the video, the author describes the content of the review and present the main topics discussed in the article (http://links.lww.com/COOG/A44).
A Multicenter Study Evaluating the Risk Factors and Outcomes of Repeat Descemet Stripping Endothelial Keratoplasty
Authors: Thompson Jordan M. , Truong Alexander H. , Stern Hudson D. , Djalilian Ali , Cortina M. Soledad , Tu Elmer Y. , Johnson Paula , Verdier David D. , Rafol Lorene , Lubeck David , Spektor Tatyana , Jorgensen Colin , Rubenstein Jonathan B. , Majmudar Parag A. , Talati Rushi , Basti Surendra , Feder Robert , Sugar Alan , Mian Shahzad I. , Balasubramanian Neelam , Sandhu Jasmin , Gaynes Bruce I. , Bouchard Charles S. 
Published: December 2018

Purpose:
Descemet stripping endothelial keratoplasty (DSEK), currently the most common procedure for managing corneal endothelial dysfunction, may be repeated following DSEK failure from a variety of causes. This multicenter study reports the risk factors and outcomes of repeat DSEK.

Methods:
This was an institutional review board-approved multicenter retrospective chart review of patients who underwent repeat DSEK. Twelve surgeons from 5 Midwest academic centers and 3 private practice groups participated. The Eversight Eye Bank provided clinical indication and donor graft data. We also assessed the role of the learning curve by comparing cohorts from the first and second 5-year periods.

Results:
A total of 121 eyes from 121 patients who underwent repeat DSEK were identified. The average age of the patients was 70 ± 12 years. The most common indication for repeat DSEK was late endothelial graft failure without rejection (58%, N = 63). Average preoperative and 12-month postoperative repeat DSEK corrected distance visual acuities were 20/694 and 20/89, respectively. Visual acuity outcomes, endothelial cell density, and cell loss did not significantly vary between the 2 cohorts. Initial graft rebubble rates for the first and second cohorts were 51% and 25%. The presence of glaucoma, prior glaucoma surgery, or a history of penetrating (full thickness) keratoplasty did not significantly affect visual outcomes. The median, mean, and range of intraocular pressures before repeat DSEK were 15.0, 15.7, and 6 to 37 mm Hg, respectively. Patients with higher intraocular pressures before repeat DSEK had improved postoperative corrected distance visual acuities.

Conclusions:
Repeating DSEK improves vision following failed or decompensated DSEK surgery. Higher preoperative repeat DSEK IOPs were associated with improved visual outcomes, and initial graft rebubble rates, which decreased over time, were likely due to surgeon experience.
Outcomes of Combined Ahmed Glaucoma Valve and Trabeculectomy Revision With Adjunctive Antimetabolite
Authors: Lin Mark , Alizadeh Reza , Law Simon K. 
Published: December 2018

Purpose:
Evaluate the intraocular pressure (IOP) control in combined Ahmed Glaucoma Valve (AGV) implantation and trabeculectomy revision with adjunctive antimetabolite compared with AGV alone in patients who failed prior trabeculectomy.

Methods:
Consecutive cases of combined AGV implantation and trabeculectomy revision with adjunctive antimetabolite (combined group) after January 3, 2014 were case-matched to cases of AGV implantation alone (AGV-alone group) before January 3, 2014. Primary outcome measures were qualified success with stratified IOP targets based on criteria: (A) IOP≤18 mm Hg and 20% IOP reduction; (B) IOP≤15 mm Hg and 25% IOP reduction; (C) IOP≤12 mm Hg and 30% IOP reduction, and hypertensive phase (HP) rate. Secondary outcome measures were 1-year postoperative IOP and number of glaucoma medications and complications.

Results:
Twenty eyes (20 patients) in each group were included. Cumulative success for combined group and AGV-alone group at 1-year were: 74.0% versus 59.2% (criterion A, P=0.221), 61.9% versus 49.5% (B, P=0.183), and 54.2% versus 30.0% (C, P=0.033), respectively. In total, 50% (10 eyes) in the AGV-alone group developed HP compared with 15% (3 eyes) in the combined group (P=0.041). At 1-year follow-up, combined group had statistically significantly lower IOP than AGV-alone group (10.1±4.4, 13.3±2.9 mm Hg, respectively; P=0.028). There were no cases of bleb-related infections, choroidal effusion or hemorrhage, persistent hypotony, or hypotony maculopathy in either group.

Conclusions:
Combining AGV implantation with trabeculectomy revision with antimetabolite was associated with better tonometric success compared with AGV implantation alone in patients with previously failed trabeculectomy, particularly when a low IOP target (≤12 mm Hg) is required. Revised trabeculectomy may provide complimentary outflow facility to AGV.
Changes in Intraocular Pressure and Angle Status After Phacoemulsification in Primary Angle Closure Hypertension
Authors: Selvan Harathy , Angmo Dewang , Tomar Ankit S. , Yadav Suresh , Sharma Arpit , Dada Tanuj 
Published: December 2018

Purpose:
To study the change in intraocular pressure (IOP) and angle status after phacoemulsification in a cohort of primary angle closure hypertension (PACHT) patients.

Setting:
Tertiary Eye Care, India.

Design:
Prospective interventional case-series.

Methods:
Case-series of 18 eyes of 18 patients. Preoperative biometry including axial length, anterior chamber depth (ACD), lens thickness, and central corneal thickness were studied. Preoperative and postoperative IOP, number of topical glaucoma medications, angle swept source optical coherence tomography (SS-OCT) parameters of nasal and temporal angle opening distance, trabecular iris space area, scleral spur angle, lens vault and circumferential iridotrabecular contact (ITC) were studied and their correlations derived.

Results:
The mean preoperative IOP, 31±6 mm Hg, decreased to 14±1 mm Hg at 6-months postoperative period, P<0.001, a fall by 58±14%. The number of glaucoma medications reduced from 4(3-5) to 2(1-3), P<0.001. All SS-OCT studied parameters denoted significant angle widening postsurgery. The ITC% reduced from 52(16-100) to 19(0-97), P<0.001. The preoperative ITC showed moderate to strong correlation with all preoperative nasal and temporal angle parameters. It also showed moderate positive correlation with percentage fall in IOP at 1-month postoperative period. The preoperative ACD showed significant negative correlation with preoperative and postoperative ITC.

Conclusions:
PACHT patients benefit significantly from cataract surgery with marked angle widening, IOP reduction and a decrease in the number of glaucoma medications. The SS-OCT derived circumferential iridotrabecular contact index can be used as the single best parameter to indicate the preoperative angle status and predict postoperative change in IOP, as against the numerous single section measured angle parameters.
Determining Optic Nerve Cupping Using Optical Coherence Tomography (OCT) Versus a New Electronic Mobile Device
Authors: Sarmento Andrea G.L. , Sarmento Adriano , Souza Luiz L. , Oliveira Luiz A. , Rios Marcus F.R. , Domingues Thiago A.L. , Paula Jayter S. , Lira Rodrigo P.C. 
Published: December 2018

Purpose:
We present a new device that may aid in glaucoma screening. The vertical cup-to-disc ratio (CDR) obtained from a new electronic mobile device (EMD) was compared with that obtained from a spectral-domain optical coherence tomography. In addition, results from examiner’s evaluations were compared with the results mentioned above.

Methods:
A single-masked study was performed to evaluate the CDR results from 110 eyes from 110 subjects whose ages ranged between 18 and 60 years (39±13 y old), of whom 66 (60%) were female individuals. Vertical CDR was analyzed 5 times with each device in a single visit and evaluated by 3 different ophthalmologists. The Spearman correlation test and Bland-Altman analysis were used to evaluate the correlation and agreement between methods.

Results:
The CDR average using spectral-domain optical coherence tomography was 0.47±0.04, whereas the CDR average using EMD was 0.42±0.02. The clinical evaluation resulted in an average of 0.34±0.27. The Spearman test showed a strong correlation between vertical CDR obtained with both devices (r=0.8319; P<0.0001) and between EMD and the examiners (r=0.7156; P>0.001). Bland-Altman analysis showed good agreement between both devices as well as between EMD and the examiners (95% limits of agreement from −0.20 to 0.10 and from −0.15 to 0.30, respectively).

Conclusions:
We present a low-cost, reliable EMD that may serve as an alternative to subjectively measuring vertical CDR in face-to-face consultations and hence increase the general public’s access to glaucoma screening. This may be especially useful for patients who live in remote areas.