bluuebunny/crossref_metadata_2025_split huggingface dataset:
Third Place Award: Reconstruction of metastatic bone loss of the proximal femur and acetabulum: A literature review
Authors: Mayassi Hani A. , Zeitlinger Lauren N. , Aboulafia Albert J. , Wallace Matthew T. 
Published: June 2020

Background:
Improved rates of long-term survival in cancer patients has led to an increasing prevalence of metastatic disease, notably to osseous structures. The proximal femur and acetabulum are vital weight-bearing surfaces of the lower extremity and common regions of metastatic spread. There are many reconstructive options that depend on several factors including the location of the lesion, type of lesion, and the prognosis of the patient.

Methods:
An extensive literature review was conducted searching Pubmed.gov with the key words metastatic, proximal femur, acetabulum, reconstruction, and fixation. This identified pathologic characteristics for various metastatic processes, anatomic considerations for the proximal femur, and periacetabular metastatic lesions. This also identified treatment-sensitive tumors compared to treatment-resistant conditions. Reconstruction was usually recommended specifically considering renal, lung, and gastrointestinal carcinomas as well as previously irradiated bone where healing was unlikely. In addition, this study provides a technique guide for implementation of a proximal femoral prosthetic replacement (PFR).

Results:
The management of femoral head or neck lesions are frequently managed by hemiarthroplasty with overall reasonable outcomes. In intertrochanteric or subtrochanteric regions, there have been high failure rates of intramedullary fixation, and 2-year reoperation rate of up to 35% was reported with conversion to endoprosthesis. In comparison to an 85% implant survival in intramedullary constructions, there was a 100% 5-year survival in endoprosthesis reconstruction. Periacetabular lesions that do not impact structural stability can be managed with palliative measures. Those patients experiencing significant pain with contained defects may be managed with cement augmentation. Support of the columns may be required with fixation into the ilium, and those with extensive disease may require en bloc internal hemipelvectomy.

Conclusions:
Management of lesions of the proximal femur and acetabulum can be managed with a variety of treatment constructions. The utilization of PFR is increasingly more common especially in the setting of destructive metastatic lesions in the proximal femur as soft-tissue repairs improve ambulatory function. Additionally, the survivorship of endoprosthesis is greater than intramedullary fixation and is recommended for reconstruction for individuals with an expected survivorship greater than 7 mo. Lesions within the periacetabular region that are refractory to nonoperative management may benefit anywhere on the spectrum from intralesional cementation to en bloc hemipelvectomy depending the primary tumor type and degree of osseous involvement.

Level of Evidence:
Level IV.
Comparison of Radiation Treatment Volumes for Borderline Resectable Pancreatic Cancer in Contemporary Clinical Trials
Authors: Bluemel Trevor S. , Kharofa Jordan 
Published: June 2020

Objectives:
Optimal radiation target volumes for neoadjuvant therapy in patients with borderline resectable pancreatic cancer (BRPCa) are undefined. Most local recurrences are near the celiac axis and superior mesenteric artery. Methods for generating radiation target volumes include symmetric expansion around the tumor or a customized vascular based approach. We investigated 3 current prospective trials’ coverage of vascular regions at increased risk of recurrence by comparing them to 2 reference standards.

Materials and Methods:
Fourteen computed tomography simulation scans from an institutional prospective trial on BRPCa were used to replicate distinct volumes corresponding to each of 3 contemporary BRPCa trials. Trial volumes were compared with 2 reference volumes (vascular planning target volume and Hopkins planning target volume), which were both based on vascular regions at increased risk of recurrence. Boolean operators and DICE analyses were performed to evaluate trial volume coverage of reference standards.

Results:
A total of 42 target volumes and 28 reference volumes were created using the 14-patient data set. DICE coefficients were highly variable ranging from 0.11 to 0.99. Mean % coverage of reference volumes ranged from 5.8% to 98.6%.

Conclusions:
The wide range of DICE coefficients and coverage indicate heterogeneity in high risk vascular target coverage using symmetric Boolean expansions from the primary tumor. This approach may inadequately cover regions at high risk of local recurrence in BRPCa. A customized clinical target volume that specifically includes the superior mesenteric artery and celiac axis will improve coverage to this region and will account for individual and tumor variability.
Neonatal Autoimmune Subepidermal IgG/IgA Blistering Disease With Severe Laryngeal and Esophageal Involvement: A Report of a Case and Review of the Literature
Authors: Raiber Sofia , Sezin Tanya , Sadik Christian D. , Bergman Reuven , Avitan-Hersh Emily 
Published: June 2020

Abstract:
Neonatal autoimmune subepidermal blistering disease is rare. Mucosal involvement is more common in neonatal linear immunoglobulin A (IgA) bullous dermatosis. We describe a neonate with subepidermal cutaneous blistering disease with severe laryngeal and esophageal involvement leading to acute respiratory distress. Histopathology demonstrated a subepidermal blister with neutrophils and eosinophils at the dermal base. Collagen IV was detected at the dermal floor, and direct immunofluorescence showed linear IgG, IgA, and C3 deposits at the basement membrane zone. The patient demonstrated markedly increased serum levels of anti-BP180 NC16A and anti-BP230 IgG antibodies (Abs) but failed to show anti-LAD-1 IgA Abs. His healthy mother showed serum anti-LAD-1 IgA Abs but did not show anti-BP180 and anti-BP230 Abs. The neonate responded promptly to systemic corticosteroid therapy. A review of the literature detected 11 cases of neonatal subepidermal blistering disease with linear IgA deposits. Nine of these cases demonstrated coexisting linear IgG deposits, often with C3. Respiratory compromise was present in most of the cases. Neutrophils and eosinophils were commonly present in the inflammatory cell infiltrates. Besides our case, 2 cases of neonatal IgG/IgA subepidermal blistering disease with esophageal involvement were previously described. IgA Abs were present in the sera of both cases. Anti-LAD-1 IgA Abs were detected in the mother's serum of our case alone, but IgA Abs do not cross the placenta. Our case was consistent with neonatal IgG/IgA pemphigoid. Neonatal IgG/IgA subepidermal blistering disease may be associated with severe laryngeal and esophageal involvement leading to respiratory compromise. Expedited diagnosis and prompt treatment are warranted.
Indeterminate Dendritic Cell Tumor as Cutaneous Involvement of Chronic Myelomonocytic Leukemia Successfully Treated With Phototherapy
Authors: Santos-Briz Angel , Medina-Miguelañez Mario , Moyano-Bueno David , Viñolas-Cuadros Alex , Martínez Teresa G. , Izquierdo Marta M. , García-Sánchez Maria S. 
Published: June 2020

Abstract:
Indeterminate dendritic cell tumor (IDCT) is a rare disease composed of so-called indeterminate cells, a dendritic cell subset displaying histological and some ultrastructural and immunophenotypic features of Langerhans cells, but lacking Birbeck granules. We report a case of cutaneous IDCT occurring in a patient with chronic myelomonocytic leukemia (CMML) successfully treated with UV-A phototherapy. Next-generation sequencing studies of the CMML demonstrated mutations in TET2, ASXL1, and ZRS2 genes, also detected in the IDCT, demonstrating a clonal relationship between both tumors and confirming IDCT as a specific subtype in the spectrum of CMML-related cutaneous lesions.
Dihydroartemisinin Attenuates Pulmonary Hypertension Through Inhibition of Pulmonary Vascular Remodeling in Rats
Authors: Tang Ming , Wang Ruiyu , Feng Panpan , Dong Qian , Chen Wanshi , Zhao Yongpeng , Li Ailing , Li Haibin , Chen Jiwang , Huang Wei 
Published: June 2020

Abstract:
Pulmonary arterial hypertension (PAH) is a malignant disease characterized by pulmonary arterial remodeling because of the abnormal proliferation and migration of pulmonary arterial smooth muscle cells. Dihydroartemisinin (DHA), an artemisinin derivative used to treat malaria, is able to inhibit fibrosis, neovascularization, and tumor proliferation. In this study, we hypothesized that DHA can be beneficial in treating PAH. To test this hypothesis, a rat model of pulmonary hypertension induced with monocrotaline (MCT) was used. Compared with MCT treatment alone, treatment with 50 or 100 mg/kg DHA significantly reduced the mean pulmonary arterial pressure (30.11 ± 2.48 mm Hg vs. 21.35 ± 3.04 mm Hg and 19.18 ± 1.98 mm Hg, respectively, both P < 0.01), right ventricular transverse diameter (4.36 ± 0.41 mm vs. 3.72 ± 0.24 mm and 3.67 ± 0.27 mm, respectively, both P < 0.01), pulmonary artery medial wall thickness (57.93 ± 11.14% vs. 34.45 ± 4.39% and 25.01 ± 6.66%, respectively, both P < 0.01), and increased tricuspid annular plane systolic excursion (1.34 ± 0.17 mm vs. 1.62 ± 0.3 mm and 1.62 ± 0.16 mm, respectively, both P < 0.05). We also found that DHA inhibited platelet-derived growth factor-BB-mediated pulmonary arterial smooth muscle cells proliferation and migration in a dose-dependent manner. Moreover, DHA downregulated β-catenin levels while upregulating the levels of axis inhibition protein 2 (Axin2) and glycogen synthase kinase 3β (GSK-3β). Our findings suggest that DHA, which may be a potential candidate for PAH therapy, attenuates experimental pulmonary hypertension possibly by inhibiting pulmonary vascular remodeling.
CEACAM1 Inhibited IκB-α/NF-κB Signal Pathway Via Targeting MMP-9/TIMP-1 Axis in Diabetic Atherosclerosis
Authors: Yu Jie , Sun Guihu , Chen Yu , Li Lin , Wang Huawei , Tu Dong , Li Longjun , Meng Zhaohui , Wang Yan 
Published: June 2020

Abstract:
Atherosclerosis (AS) is the most common and serious complication in type 2 diabetes mellitus (T2DM). Recent studies have emphasized that inflammation is the main cause of atherosclerosis. Studies have shown that carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1) regulates the expression of matrix metallopeptidase 9 (MMP-9) after ischemic stroke to reduce inflammation. The aim of this study was to elucidate potential molecular mechanism of CEACAM1 on the inflammatory response in atherosclerosis. The serum levels of CEACAM1, MMP-9, and tissue inhibitors of metalloproteinase 1 (TIMP-1) in T2DM patients and healthy control was detected. The results showed that the levels of CEACAM1 and TIMP-1 were significantly decreased, and the levels of MMP-9 were significantly higher than those in the control group. Moreover, we also observed the effect of CEACAM1 on atherosclerosis in T2DM rats. Hematoxylin & eosin (HE) staining and oil red staining showed that CEACAM1 recombinant protein reduced intima-media thickness and the area of atherosclerotic plaques. To further explore the molecular mechanism of CEACAM1 regulating MMP-9/TIMP-1, we conducted experiments in rat aorta vascular endothelial cells and rat aorta smooth muscle cells. The result showed that CEACAM1 inhibits inflammatory response via MMP-9/TIMP-1 axis. Taken together, CEACAM1 attenuates diabetic atherosclerosis by inhibition of IκB/NF-κB signal pathway via MMP-9/TIMP-1 axis, which indicate that CEACAM1 is potentially amenable to therapeutic manipulation for clinical application in atherosclerosis in T2DM.
ABUNDANCE AND MULTIMODAL VISIBILITY OF SOFT DRUSEN IN EARLY AGE-RELATED MACULAR DEGENERATION
Authors: Chen Ling , Messinger Jeffrey D. , Sloan Kenneth R. , Wong Jessica , Roorda Austin , Duncan Jacque L. , Curcio Christine A. 
Published: June 2020

Purpose:
To determine the abundance and multimodal visibility of drusen and basal linear deposit (BLinD) in early age-related macular degeneration.

Methods:
A 69-year-old white man was imaged by color fundus photography and red free photography, fundus autofluorescence, and optical coherence tomography. From en face images, we determined the drusen field, drusen area, and equivalent diameters of individual drusen. From high-resolution light-microscopic histology (6 months after the last clinic visit), we determined the area of drusen, BLinD, and pre-BLinD in a subretinal pigment epithelium-basal lamina lipid field.

Results:
In right and left eyes, respectively, BLinD covered 40% and 46% of the lipid field, versus 21% and 14% covered by drusen. The lipid field was covered 60% to 61% by Drusen + BLinD and 65% to 72% by BLinD + pre-BLinD. In the left eye, the drusen area on color fundus photography (0.18 mm2) and red free (0.28 mm2) was smaller than the drusen area on histology (1.16 mm2). Among drusen confirmed by optical coherence tomography, 55.1% and 56.6% were observed on red free and fundus autofluorescence, respectively.

Conclusion:
Basal linear deposit covered 1.9 and 3.4-fold more fundus area than soft drusen, silently increasing progression risk. Improved visualization of BLinD and readouts of the retinal pigment epithelium health over lipid will assist population surveillance, early detection, and trial outcome measures.
Corneal Elevation, Power, and Astigmatism to Assess Toric Orthokeratology Lenses in Moderate-to-High Astigmats
Authors: Tomiyama Erin S. , Logan Anna-Kaye , Richdale Kathryn 
Published: June 2020

Objectives:
Fitting philosophies for toric orthokeratology are based on elevation or corneal astigmatism, but it is unclear which is more effective. The purpose of this analysis was to further understand corneal shape and the relationship between peripheral elevation and central astigmatism in moderate-to-high astigmats.

Methods:
Corneal tomography was measured three times on the right eyes of 25 moderate-to-high refractive myopic astigmatic adults. Corneal astigmatism and elevation were calculated at 4-, 6-, and 8-mm chords. Subjects were fitted with toric orthokeratology lenses following the manufacturer's guidelines based on elevation. Twenty subjects completed 10 days of wear. A masked examiner assessed movement and centration via slitlamp videos and quantified treatment zone and decentration from tangential power difference tomography maps. Correlations between variables were assessed.

Results:
Average corneal astigmatism was 2.20±0.70 DC and peripheral elevation was 50.88±18.92 μm and they were strongly correlated (4 mm R2=0.96, 6 mm R2=0.92, 8 mm R2=0.86, all P<0.001). Each diopter of astigmatism equated to 25 μm of elevation at an 8-mm chord. Via slitlamp, average treatment zone area was 12.73±4.62 mm2 and 13 lenses decentered. From tomography, average treatment zone area was 7.16±2.56 mm2 and 17 were decentered. Tomography treatment zone area was negatively correlated with central corneal astigmatism (R2=0.60) and elevation at an 8-mm chord (R2=0.64, both P<0.001).

Conclusions:
For tomography images, central corneal astigmatism was highly correlated with peripheral elevation and may be a more expedient measure for clinical use. Treatment area decreased as corneal astigmatism and elevation increased.
Review of Gamma-Irradiated Sterile Cornea: Properties, Indications, and New Directions
Authors: Kuo Irene C. 
Published: June 2020

Abstract:
Gamma-irradiated sterile cornea (GISC) is a relatively new graft tissue that follows the 30-year success of irradiation to other tissues (bone and sclera) to lessen antigenic load and infection transmission. It can serve as a graft to cover glaucoma drainage devices, as graft tissue for frank or impending corneal perforations in tectonic keratoplasty, as graft tissue in lamellar keratoplasty, and as carrier tissue for keratoprosthesis. With the limited availability of fresh corneal tissue in less developed countries, GISC may fill a need for corneal tissue worldwide. It can be used in situations where corneal endothelium is not needed and with a greatly reduced risk of rejection and infection because of the effect of irradiation on corneal tissue.
Laser Iridoplasty to Treat Iris-occluded XEN Gel Stent
Authors: Tadrosse Abanoob F. , Khouri Albert S. 
Published: June 2020

Purpose:
To provide the first report on argon laser peripheral iridoplasty (ALPI) to restore XEN-45 Gel stent patency after iris occlusion.

Methods:
Case description, laser technique, and relevant clinical imaging.

Results:
A 53-year-old African American male patient presented with progressive advanced stage primary open-angle glaucoma. Initial intraocular pressure (IOP) was 40 mm Hg, which continued to be elevated despite maximal medical therapy and selective laser trabeculoplasty. The patient underwent an uncomplicated XEN-45 Gel stent implantation and presented with an IOP of 4 mm Hg 5 days postoperatively with a functioning bleb. On postoperative day 10, the XEN lumen was found to be occluded by the iris with an IOP spike of 39 mm Hg. Anti-glaucoma treatment to induce miosis and liberate the stent was unsuccessful. ALPI was attempted to relieve the obstruction. IOP dropped to 26 mm Hg immediately post-ALPI and continued to be well-controlled 6 months later (11 mm Hg).

Conclusions:
ALPI can effectively restore XEN Gel stent patency if occluded by the iris and should be considered before attempting more invasive surgical revisions.
Twelve-month outcomes of an ab interno gelatin stent combined with cataract surgery or as a standalone procedure in pseudophakic eyes with open-angle glaucoma
Authors: Rather Peyton A. , Vold Steven , McFarland Michael 
Published: June 2020

Purpose:
To provide safety and effectiveness outcomes at 12 months postsurgery for an ab interno transscleral gelatin stent in patients with advanced refractory glaucoma or intolerant of medical therapy.

Setting:
Multisubspecialty ophthalmology practice and surgery center.

Design:
Retrospective, single-arm, cohort study.

Methods:
All patients implanted with the gelatin stent either combined with cataract surgery or as a solo procedure between February 2017 and April 2018 and meeting eligibility criteria were included. Outcome measures included proportion of patients achieving a 20% reduction in intraocular pressure (IOP), proportions at or below 12 mm Hg, 15 mm Hg, and 18 mm Hg, IOP, medication usage, needling rate, and adverse events.

Results:
The study included 92 eyes of 69 patients. Mean preoperative IOP and medications were 16.6 mm Hg on 2.1 medications. Average visual field mean deviation was −13.7 dB. Half (48%) of the patients achieved the primary endpoint of 20% reduction while medication use decreased by −1.7 medications. Most patients at 12 months had IOP of 18 mm Hg or less on zero medications (74%), whereas 34% were medication free and had IOP of 12 mm Hg or less. Bleb needling was required for only 14% of patients. There were few adverse events (13% of eyes), the most common being corrected distance visual acuity loss and hyphema.

Conclusions:
Eyes with advanced glaucoma despite maximum tolerated medical therapy achieved lower target IOP on fewer medications after implantation with the gelatin microstent.
Microglial annexin A3 downregulation alleviates bone cancer-induced pain through inhibiting the Hif-1α/vascular endothelial growth factor signaling pathway
Authors: Zhang Zengli , Deng Meiling , Huang Jiangju , Wu Jing , Li Zhengyiqi , Xing Manyu , Wang Jian , Guo Qulian , Zou Wangyuan 
Published: June 2020

Abstract
Bone cancer-induced pain (BCP) is a challenging clinical problem because traditional therapies are often only partially effective. Annexin A3 (ANXA3) is highly expressed in microglia in the spinal cord, and its expression is upregulated during BCP. However, the roles of microglial ANXA3 in the development and maintenance of BCP and the underlying molecular mechanisms remain unclear. This study was performed on male mice using a metastatic lung BCP model. Adeno-associated virus shANXA3 (AAV-shANXA3) was injected intrathecally 14 days before and 7 days after bone cancer induction, and relevant pain behaviors were assessed by measuring the paw withdrawal mechanical threshold, paw withdrawal thermal latency, and spontaneous hind limb lifting. ANXA3 protein expression was downregulated in microglial N9 cells by lentiviral transfection (LV-shANXA3). ANXA3, hypoxia-inducible factor-1α (Hif-1α), vascular endothelial growth factor (VEGF) expression levels, and Hif-1α transactivation activity regulated by ANXA3 were measured. As a result, ANXA3 was expressed in microglia, and its expression significantly increased during BCP. ANXA3 knockdown reversed pain behaviors but did not prevent pain development. Moreover, ANXA3 knockdown significantly reduced Hif-1α and VEGF expression levels in vitro and in vivo. And overexpression of Hif-1α or VEGF blocked the effects of AAV-shANXA3 on BCP. ANXA3 knockdown in N9 cells significantly decreased the p-PKC protein expression in the cocultured neurons. Finally, ANXA3 overexpression significantly increased Hif-1α transactivation activity in 293T cells. Therefore, microglial ANXA3 downregulation alleviates BCP by inhibiting the Hif-1α/VEGF signaling pathway, which indicates that ANXA3 may be a potential target for the treatment of BCP.
Acute orofacial pain leads to prolonged changes in behavioral and affective pain components
Authors: Araya Erika Ivanna , Baggio Darciane Favero , Koren Laura de Oliveira , Andreatini Roberto , Schwarting Rainer K. W. , Zamponi Gerald W. , Chichorro Juliana Geremias 
Published: June 2020

Abstract
Acute pain that persists for a few days is associated with a reduction in patients' quality of life. Orofacial persistent pain promotes psychological disorders such as anxiety, impairs daily essential activities such as eating, and results in decreased social interaction. Here, we investigated whether rats subjected to orofacial formalin injection or intraoral incision surgery display persistent facial heat hyperalgesia, ongoing pain, anxiety-like behavior, and changes in ultrasonic vocalization. Orofacial formalin injection or intraoral incision caused facial heat hyperalgesia for 3 days compared with saline-injected and sham animals. In addition, both experimental groups showed a reduction in the number of entries and in the time spent in the open arms in the elevated plus maze test on day 3, suggesting that anxiety-like behavior developed as a consequence of persistent pain. At this time point, both groups also displayed a reduction in the number of 50-kHz calls, specifically in the flat subtype, which suggests a decrease in social communication. Moreover, on day 3 after surgery, systemic morphine produced robust conditioned place preference in rats subjected to intraoral incision compared with sham, and the former group also presented increased spontaneous facial grooming, revealing the presence of ongoing pain. Finally, Western blot and immunohistochemistry analysis showed a reduction in tyrosine hydroxylase expression in the nucleus accumbens, which may reflect a decrease in mesolimbic dopaminergic activity. Altogether, the results demonstrate that acute orofacial pain causes prolonged changes in behavioral and affective pain components, which may be related to dopaminergic changes in the nucleus accumbens.