bluuebunny/crossref_metadata_2025_split huggingface dataset:
New drugs in gastrointestinal stromal tumors
Authors: Martin-Broto Javier , Moura David S. 
Published: May 2020

Purpose of review
Tyrosine kinase inhibitors (TKIs) are the backbone for advanced gastrointestinal stromal tumor (GIST) treatment. The increasing knowledge concerning the structure and the changing conformational status because of some mutations in KIT and PDGFRα, allowed the development of new efficient compounds, with the main goal to overcome resistance in GIST. This review summarizes the latest developments in the treatment of GIST patients.

Recent findings
Amongst the several TKIs currently being studied in GIST, ripretinib, avapritinib and crenolanib had shown promising potent activity in preclinical studies and clinical trials. Ripretinib is a type II inhibitor that exerts its main action in the switch pocket of the activation loop, by mimicking the inhibition exerted by the regulatory region in this domain. Ripretinib is considered the new standard in the fourth line in advanced GIST. Avapritinib is a type I inhibitor synthesized to exerts its activity in the active conformation of the activation loop of KIT and PDFGRα. The relevant activity reported with avapritinib in patients carrying the D842 v mutation represents, for first time, an active therapeutic option in this resistant mutant. Crenolanib is a type I selective inhibitor of PDGFRα-resistant mutants, mainly D842 V, which is currently under clinical trial.

Summary
New potent TKIs are being approved, adding value to the already three registered drugs. Other agents, such as MEK inhibitors, immunotherapy and TRK-targeted therapy are potential new options in specific subsets of GIST patients.
1α, 25-dihydroxyvitamin D3 inhibits transforming growth factor β1-induced epithelial-mesenchymal transition via β-catenin pathway
Authors: Xiong Xin-Rong , Tian Xin-Li , Huo Ru-Jie , Dong Yan-Ting , Liu Dai , Bai Jing-Cui , Qi Yun-Feng , Tian Xin-Rui 
Published: May 2020

AbstractBackground:The transforming growth factor β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) has been proven associated with the pathogenesis of asthmatic airway remodeling, in which the Wnt/β-catenin pathway plays an important role, notably with regard to TGF-β1. Recent studies have shown that 1α, 25-dihydroxyvitamin D3(1α, 25(OH)2D3) inhibits TGF-β1-induced EMT, although the underlying mechanism have not yet been fully elucidated.Methods:Alveolar epithelial cells were exposed to 1α, 25(OH)2D3, ICG-001, or a combination of both, followed by stimulation with TGF-β1. The protein expression of E-cadherin, α-smooth muscle actin, fibronectin, and β-catenin was analyzed by western blotting and immunofluorescence analysis. The mRNA transcript of Snail was analyzed using RT-qPCR, and matrix metalloproteinase 9 (MMP-9) activity was analyzed by gelatin zymogram. The activity of the Wnt/β-catenin signaling pathway was analyzed using the Top/Fop flash reporters.Results:Both 1α, 25(OH)2D3and ICG-001 blocked TGF-β1-induced EMT in alveolar epithelial cells. In addition, the Top/Fop Flash reporters showed that 1α, 25(OH)2D3suppressed the activity of the Wnt/β-catenin pathway and reduced the expression of target genes, including MMP-9 and Snail, in synergy with ICG-001.Conclusion:1α, 25(OH)2D3synergizes with ICG-001 and inhibits TGF-β1-induced EMT in alveolar epithelial cells by negatively regulating the Wnt/β-catenin signaling pathway.
Primary central nervous system lymphoma: status and advances in diagnosis, molecular pathogenesis, and treatment
Authors: Zhang Yan , Zhou Dao-Bin 
Published: May 2020

Abstract
Primary central nervous system lymphoma (PCNSL) is a rare group of extra-nodal non-Hodgkin lymphoma which is confined to the central nervous system or eyes. This article aims to present a brief profile of PCNSL diagnosis and treatment in immunocompetent patients. The authors retrieved information from the PubMed database up to September 2019. The annual incidence of PCNSL increased over the last four decades. The prognosis of PCNSL has improved mainly due to the introduction and wide-spread use of high-dose methotrexate, which is now the backbone of all first-line treatment polychemotherapy regimens. Gene expression profiling and next-generation sequencing analyses have revealed mutations that induce activation of nuclear factor-κB, B cell antigen receptor, and Janus kinases/signal transducer and activator of transcription proteins signal pathways. Some novel agents are investigated in the treatment of relapsed PCNSL including immunotherapy and targeted therapy. In particular, lenalidomide and ibrutinib have demonstrated durable efficiency. Treatment of PCNSL has evolved in the last 40 years and survival outcomes have improved in most patient groups, but there is still room to improve outcome by optimizing current chemotherapy and novel agents.
Far from MCAR
Authors: Balzer Laura B. , Ayieko James , Kwarisiima Dalsone , Chamie Gabriel , Charlebois Edwin D. , Schwab Joshua , van der Laan Mark J. , Kamya Moses R. , Havlir Diane V. , Petersen Maya L. 
Published: May 2020

Background:
Population-level estimates of disease prevalence and control are needed to assess prevention and treatment strategies. However, available data often suffer from differential missingness. For example, population-level HIV viral suppression is the proportion of all HIV-positive persons with suppressed viral replication. Individuals with measured HIV status, and among HIV-positive individuals those with measured viral suppression, likely differ from those without such measurements.

Methods:
We discuss three sets of assumptions to identify population-level suppression in the intervention arm of the SEARCH Study (NCT01864603), a community randomized trial in rural Kenya and Uganda (2013–2017). Using data on nearly 100,000 participants, we compare estimates from (1) an unadjusted approach assuming data are missing-completely-at-random (MCAR); (2) stratification on age group, sex, and community; and (3) targeted maximum likelihood estimation to adjust for a larger set of baseline and time-updated variables.

Results:
Despite high measurement coverage, estimates of population-level viral suppression varied by identification assumption. Unadjusted estimates were most optimistic: 50% (95% confidence interval [CI] = 46%, 54%) of HIV-positive persons suppressed at baseline, 80% (95% CI = 78%, 82%) at year 1, 85% (95% CI = 83%, 86%) at year 2, and 85% (95% CI = 83%, 87%) at year 3. Stratifying on baseline predictors yielded slightly lower estimates, and full adjustment reduced estimates meaningfully: 42% (95% CI = 37%, 46%) of HIV-positive persons suppressed at baseline, 71% (95% CI = 69%, 73%) at year 1, 76% (95% CI = 74%, 78%) at year 2, and 79% (95% CI = 77%, 81%) at year 3.

Conclusions:
Estimation of population-level disease burden and control requires appropriate adjustment for missing data. Even in large studies with limited missingness, estimates relying on the MCAR assumption or baseline stratification should be interpreted cautiously.
The Left-handed Plastic Surgery Trainee: Perspectives and Recommendations
Authors: Savetsky Ira L. , Cammarata Michael J. , Kantar Rami S. , Diaz-Siso J. Rodrigo , Avashia Yash J. , Rohrich Rod J. , Saadeh Pierre B. 
Published: May 2020

Background:
Left-handed surgeons experience difficulty with tools designed for use in the right hand. The purpose of this study was to examine instrument laterality and to survey the experiences of left-handed plastic surgery trainees.

Methods:
Count sheets for plastic surgery trays (reconstructive, microsurgery, rhinoplasty, craniofacial) were acquired from Tisch Hospital, NYU Langone Health. Instruments with right-handed laterality were tallied. A survey was also distributed to plastic surgery residents and fellows to determine hand preference for surgical tasks, and those who identified as left-handed described how handedness impacted their training.

Results:
Right-handed laterality was seen in 15 (31.3%) of the 48 reconstructive instruments, 17 (22.7%) of the 75 rhinoplasty instruments, and 22 (31.0%) of the 71 craniofacial instruments. One-hundred percent of the 25 microsurgery instruments were ambidextrous. There were 97 survey responses. Trainees (17.5%) were identified as left-handed and were more likely than right-handed trainees to report operating with both hands equally or with the opposite hand (47.1% versus 1.3%; P < 0.001). Left-handed trainees were significantly more likely than right-handed trainees to use their nondominant hand with scissors (P < 0.001), electrocautery (P = 0.03), and needle drivers (P < 0.001) and when performing tissue dissection (P < 0.001) and microsurgery (P = 0.008). There was no difference in use of the nondominant hand between right and left-handed trainees for knot tying (P = 0.83) and in use of the scalpel (P = 0.41).

Conclusions:
Left-handed plastic surgery trainees frequently encounter instruments designed for the nondominant hand, with which they adaptively perform several surgical tasks. Mentoring may help trainees overcome the laterality-related challenges of residency.
Perioperative Thromboprophylaxis in Digital Replantation: A Systematic Review
Authors: Reissis Dimitris , Geoghegan Luke , Sarsam Raghda , Young Sing Quillan , Nikkhah Dariush 
Published: May 2020

Background:
There is no international consensus on the use of perioperative thromboprophylaxis in digital replantation. Suboptimal perioperative management may lead to replant failure, which compromises extremity function, worsens psychosocial outcomes for patients, and incurs significant cost. This systematic review evaluates and compares the efficacy and safety of perioperative antithrombotic protocols used in digital replantation.

Methods:
A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)--compliant prospectively registered (PROSPERO, CRD42018108695) systematic review was conducted. Cochrane Central Register of Controlled Trials, Medline, EMBASE, and Scopus were searched up until December 2019. Articles were assessed for eligibility in duplicate by 2 independent reviewers. All comparative studies that examined the use of perioperative thromboprophylaxis in digital replantation were eligible for inclusion.

Results:
Collectively, 1,025 studies were identified of which 7 met full inclusion criteria reporting data from 635 patients (908 digital replants, 86% men, average age 37.3 years). Laceration was the most commonly reported mechanism of injury (68%), with 33% of replantation occurring in Tamai zone III. Fourteen distinct perioperative protocols were identified. One study reported significantly higher digital survival with continuous heparin infusion versus bolus heparin. Five studies demonstrated a significantly higher incidence of complications among patients treated with systemic heparin.

Conclusions:
The clinical efficacy and safety of perioperative antithrombotic therapy following digital replantation remains equivocal. The perceived benefits of improved digital survival must be tempered against the adverse systemic side effects of antithrombotic and anticoagulant therapies until further prospectively collected data sets become available.
Articulating the “So, What?” in Clinical Research: Insight from the M-CHOIR Group
Authors: Kim You J. , Mack Shale J. , Chung Kevin C. 
Published: May 2020

Summary:
With the academic culture of “publish or perish,” authors must ensure that they are delivering high-quality data with a meaningful impact on clinical practice. Even for physician–scientists at the top of their fields, establishing the relevance of a study to clinical practice is a challenge. Thus, it is essential that research proposals ask questions that are clinically important, use appropriate methodologies, and examine outcomes that are relevant to both the physicians and the patients. The question of “so, what?” or in other words, “who cares?” is one that can make or break a study’s impact on clinical practice. Researchers should use models such as PICOS (Population, Intervention, Comparison, Outcomes, and Study design) and FINER (Feasible, Interesting, Novel, Ethical, Relevant) and ask why readers will care about their study’s findings before the study is conducted. By doing so, researchers can ensure the successful execution of their study and a meaningful impact of their findings, in both academia and clinical practice. This Special Topic article aims to guide researchers in producing relevant, impactful conclusions of their studies by providing input and resources from the Michigan Center for Hand Outcomes and Innovation (M-CHOIR) group.
TOPOGRAPHIC CHANGES IN CHOROIDAL THICKNESS IN AGE-RELATED MACULAR DEGENERATION DURING THE DEVELOPMENT OF ACTIVE CHOROIDAL NEOVASCULARIZATION
Authors: Park Jae Yong , Kang Min-Ji , Kim Bum Gi , Chung Kyu Ho , Sim Ha Eun , Lee Seong Woo , Kim Jae Suk , Lee Hyeon Seok , Hwang Je Hyung 
Published: May 2020

Purpose:
To evaluate topographic changes in choroidal thickness during development of choroidal neovascularization (CNV) in treatment-naive age-related macular degeneration (AMD) and to test the value of such changes as a predictive tool of CNV development.

Methods:
This retrospective cohort included 86 eyes that developed CNV from intermediate AMD, 43 eyes with intermediate AMD, and 36 eyes without AMD. Patients with intermediate AMD underwent spectral domain optical coherence tomography using enhanced depth imaging mode every 6 months until CNV was detected. Choroidal neovascularization was localized to one of the subfields of Early Treatment of Diabetic Retinopathy Study grid on fluorescein angiography. Average choroidal thickness of each subfield was calculated.

Results:
Choroidal thickness of the subfield where CNV developed at first clinical detection significantly increased compared with that 6 months before (P = 0.000 for central, P = 0.001 for superior parafoveal, P = 0.002 for temporal parafoveal, P = 0.002 for inferior parafoveal, and P = 0.001 for nasal parafoveal subfield). In eight patients who visited unexpectedly 3 months before CNV development in central subfield, choroidal thickness of central subfield increased significantly compared with that 6 months before CNV development (P = 0.001).

Conclusion:
Choroidal neovascularization development accompanied choroidal thickening of the corresponding subfield. Regular measurement of choroidal thickness may assist in prediction of CNV.
PERFLUOROCARBON LIQUID–ASSISTED INVERTED INTERNAL LIMITING MEMBRANE FLAP TECHNIQUE VERSUS INTERNAL LIMITING MEMBRANE PEELING FOR HIGHLY MYOPIC MACULAR HOLE RETINAL DETACHMENT
Authors: Gu Xunyi , Hu Zizhong , Qian Huiming , Fransisca Silvia , Mugisha Aime , Wang Jingfan , Zhang Zhengyu , Zhang Weiwei , Ji Jiangdong , Liu Qinghuai , Xie Ping 
Published: May 2020

Purpose:
To compare the efficacy of a modified perfluorocarbon liquid–assisted inverted internal limiting membrane (ILM) flap technique with the standard ILM peeling for the treatment of macular hole retinal detachment in highly myopic eyes.

Methods:
This was a retrospective, consecutive, nonrandomized comparative study. Forty-two macular hole retinal detachment eyes of 42 patients were included into either a perfluorocarbon liquid–assisted inverted ILM flap technique group (n = 22, inverted group) or standard ILM removal group (n = 20, peeling group). Outcomes measured were macular hole closure, retinal reattachment, and best-corrected visual acuity at least 6 months after surgery.

Results:
Macular hole closure was achieved in 20 eyes (90.9%) in the inverted group and in eight eyes (40%) in the peeling group (P < 0.01). Reattachment rates were 100% in the inverted group and 95% in the peeling group (P = 0.476). The mean best-corrected visual acuity improvement from baseline was 27.4 ± 19.9 Early Treatment Diabetic Retinopathy Study letters in the inverted group while the best-corrected visual acuity improvement was 13.6 ± 22.5 Early Treatment Diabetic Retinopathy Study letters in the peeling group (P = 0.044).

Conclusion:
The perfluorocarbon liquid–assisted inverted ILM flap technique was effective in sealing the macular hole, reattaching retina, and improving visual function postoperatively in highly myopic macular hole retinal detachment.
Descemet Membrane Endothelial Keratoplasty in Asian Eyes: Intraoperative and Postoperative Complications
Authors: Ang Marcus , Ting Darren S. J. , Kumar Ashish , May Khin Oo , Htoon Hla Myint , Mehta Jodhbir S. 
Published: May 2020

Purpose:
To describe intraoperative and postoperative complications of Descemet membrane endothelial keratoplasty (DMEK) in Asian eyes.

Methods: A
prospective comparative study of consecutive cases of DMEK cases between January 2016 and January 2018. A subgroup of consecutive patients were optimized with preoperative topical eye drops and modification of donor insertion. Main outcome measures were intraoperative complications and total surgical time. Secondary outcome measures were postoperative complications and endothelial cell loss (ECL) at the 6-month follow-up.

Results:
We included 50 consecutive patients in this study; mean age of 66 ± 9 years old with 70% women. The indications for DMEK were Fuchs endothelial dystrophy (82%) and bullous keratopathy (18%). When compared with the standard group (n = 24 eyes), the optimized DMEK group (n = 26 eyes) was associated with a significantly reduced surgical time (33.9 ± 12.7 vs. 26.9 ± 7.6 minutes; P = 0.041), lower ECL at 6 months (27.2 ± 17.1% vs. 13.7 ± 9.7%; P = 0.012) and lower risk of high vitreous pressure causing iris prolapse (16.7% vs. 0%; P = 0.046). Multivariate analysis revealed a shorter surgical time (Odds Ratio [OR]: 0.924; 95% confidence interval: 0.858–0.995; P = 0.036) and reduced ECL (OR: 0.907; 95% confidence interval: 0.843–0.977; P = 0.01) in the optimized group.

Conclusions:
We observed intraoperative challenges such as difficulty with donor insertion with increased vitreous pressure in Asian eyes by performing DMEK surgery, which may be reduced with anticipated preoperative and postoperative measures.
The Keratoconus Outcome Research Questionnaire: A Cross-Cultural Validation Study of the Danish Version
Authors: Bak-Nielsen Sashia , Groenborg Therese K. , Ivarsen Anders , Hjortdal Jesper 
Published: May 2020

Purpose:
To evaluate the psychometric properties of the Danish Keratoconus Outcome Research Questionnaire (KORQ).

Methods:
Phase 1: Rasch analysis assessed the original Danish KORQ. Phase 2: Reengineering of the Danish KORQ to optimize the psychometric properties and functioning of the KORQ.

Results:
The KORQ was self-administered by 195 patients. Phase 1 displayed trouble with local dependency and poor item fit. In phase 2, local dependency was addressed, and acceptable item fit was obtained for both subscales by collapsing item pairs into superitems (A6+A7, A9+A17, and S6+S9) and deleting 2 items (S4 and S2). After these corrections, the inter-item range was 0.28 to 0.72 for activity limitation scale (AL-S) and 0.14 to 0.54 for symptoms scale (S-S). Ordered thresholds were present, except in items A11, S5, and S10. No differential item functioning was present. Person separation reliability was 0.93 for AL-S and 0.81 for S-S. The person–item maps showed that the target was slightly above the study population. The maximal corneal curvature was the clinical measure of keratoconus with the highest correlation of 0.33 for AL-S and 0.24 for S-S. Evaluating individual questions showed that patients had the most trouble seeing at distance, driving at night, and wearing rigid gas-permeable lenses, whereas the least troublesome areas were walking up/downstairs, doing household tasks, avoiding objects on their path, and doing their job.

Conclusions:
The revised Danish KORQ largely fulfilled the assumptions of the Rasch model and displayed satisfactory psychometric properties. The need to revise the Danish KORQ highlights that cross-cultural validation is of key importance when working with patient-reported outcomes.
Spontaneous Descemet Membrane Detachment After Penetrating Keratoplasty—Clinical Presentation and Outcome of Air/Gas Descemetopexy
Authors: Nahum Yoav , Gal-Or Orly , Dadon Judith , Greenbaum Aharon , Israeli David , Melles Gerrit R. J. , Bahar Irit , Livny Eitan 
Published: May 2020

Purpose:
To describe the clinical characteristics and treatment of spontaneous Descemet membrane (DM) detachment occurring decades after penetrating keratoplasty (PK).

Methods:
A multicenter interventional case series design was used. We reviewed the medical records of 4 patients with a history of PK presenting with spontaneous DM detachment at 3 university hospitals in Israel and an ocular surgery institute in The Netherlands in 2016 to 2019. Patient demographic and clinical data, postoperative best corrected visual acuity, findings on preoperative and postoperative anterior segment optical coherence tomography (AS-OCT), and graft survival were recorded.

Results:
Patients were aged 46 to 50 years. All had undergone PK for keratoconus 20 to 26 years previously. Patients presented within 18 to 180 days of onset of visual disturbance. Symptoms included sudden painless visual loss (2 patients), gradual visual loss and foreign body sensation (1 patients), and visual loss not otherwise specified (1 patient). Slit-lamp examination showed corneal edema, and AS-OCT showed DM detachment of variable extent. In 2 patients, the initial diagnosis was graft rejection and failure. Treatment consisted of anterior chamber injection of air (n = 3) or 20% SF6 (n = 1). In 3 patients, the DM reattached and the cornea regained its clarity. The fourth patient had persistent DM detachment that required repeated PK.

Conclusions:
Spontaneous DM detachment can mimic late graft failure in patients after PK. If diagnosed early, DM reattachment may be performed by air/gas injection, avoiding repeated keratoplasty. Eyes with presumed late penetrating graft rejection or failure should be examined by AS-OCT to exclude DM detachment.
Simultaneous Penetrating Keratoplasty and Implantation of a New Scleral-Fixated, Sutureless, Posterior Chamber Intraocular Lens (Soleko, Carlevale): A Novel Technique
Authors: Petrelli Myrsini , Schmutz Lydia , Gkaragkani Evangelia , Droutsas Konstantinos , Kymionis George D. 
Published: May 2020

Purpose:
To describe a novel technique of combined penetrating keratoplasty (PKP) with implantation of a new scleral-fixated, sutureless, posterior chamber intraocular lens (PC-IOL) (Soleko, Carlevale).

Methods:
New surgical approach description.

Results:
We describe a novel technique for the management of PKP graft failure and posttraumatic aphakia with repeat-PKP and simultaneous implantation of a new scleral-fixated, sutureless PC-IOL. The postoperative course was uneventful, and the patient reported marked improvement in his vision. Up to 6 months postoperatively, the graft showed no signs of failure or rejection, the intraocular lens remained well-positioned, and no complications were observed.

Conclusions:
The favorable final outcome of our patient suggests that simultaneous PKP and implantation of this new scleral-fixated, sutureless PC-IOL may represent an efficient and effective method for the management of aphakia combined with corneal scarring.