bluuebunny/crossref_metadata_2025_split huggingface dataset:
Life-Threatening Bleeding in Children: A Prospective Observational Study
Authors: Leonard Julie C. , Josephson Cassandra D. , Luther James F. , Wisniewski Stephen R. , Allen Christine , Chiusolo Fabrizio , Davis Adrienne L. , Finkelstein Robert A. , Fitzgerald Julie C. , Gaines Barbara A. , Goobie Susan M. , Hanson Sheila J. , Hewes Hilary A. , Johnson Laurie H. , McCollum Mark O. , Muszynski Jennifer A. , Nair Alison B. , Rosenberg Robert B. , Rouse Thomas M. , Sikavitsas Athina , Singleton Marcy N. , Steiner Marie E. , Upperman Jeffrey S. , Vogel Adam M. , Wills Hale , Winkler Margaret K. , Spinella Philip C. 
Published: May 2021

OBJECTIVES:
The purpose of our study was to describe children with life-threatening bleeding.

DESIGN:
We conducted a prospective observational study of children with life-threatening bleeding events.

SETTING:
Twenty-four childrens hospitals in the United States, Canada, and Italy participated.

SUBJECTS:
Children 0–17 years old who received greater than 40 mL/kg total blood products over 6 hours or were transfused under massive transfusion protocol were included.

INTERVENTIONS:
Children were compared according bleeding etiology: trauma, operative, or medical.

MEASUREMENTS AND MAIN RESULTS:
Patient characteristics, therapies administered, and clinical outcomes were analyzed. Among 449 enrolled children, 55.0% were male, and the median age was 7.3 years. Bleeding etiology was 46.1% trauma, 34.1% operative, and 19.8% medical. Prior to the life-threatening bleeding event, most had age-adjusted hypotension (61.2%), and 25% were hypothermic. Children with medical bleeding had higher median Pediatric Risk of Mortality scores (18) compared with children with trauma (11) and operative bleeding (12). Median Glasgow Coma Scale scores were lower for children with trauma (3) compared with operative (14) or medical bleeding (10.5). Median time from bleeding onset to first transfusion was 8 minutes for RBCs, 34 minutes for plasma, and 42 minutes for platelets. Postevent acute respiratory distress syndrome (20.3%) and acute kidney injury (18.5%) were common. Twenty-eight–day mortality was 37.5% and higher among children with medical bleeding (65.2%) compared with trauma (36.1%) and operative (23.8%). There were 82 hemorrhage deaths; 65.8% occurred by 6 hours and 86.5% by 24 hours.

CONCLUSIONS:
Patient characteristics and outcomes among children with life-threatening bleeding varied by cause of bleeding. Mortality was high, and death from hemorrhage in this population occurred rapidly.
Tropomyosin receptor kinases in sarcomas – of joy and despair
Authors: Dieckmann Nils , Schildhaus Hans-Ulrich , Bauer Sebastian 
Published: May 2021

Purpose of review
The relatively recent discovery of neurotrophic tropomyosin receptor kinase (NTRK) gene arrangements as pan-tumor predictive biomarkers has led to impressive novel treatments for patients with TRK fusions. Although the number of patients who qualify for treatment is vanishingly small for cancer patients in general, a few histological subsets of sarcomas exhibit NTRK fusions more commonly leading to large expectations within the sarcoma community.

Recent findings
Larotrectenib and entrectenib have recently been approved based on durable responses in TRK positive cancers with nonresectable or metastatic disease, including many sarcomas. Identification of resistance mutations to TRKi has led to the development of novel salvage therapies which may soon further expand the armamentarium of treatments. The greatest barrier and frustration to date is the actual identification of patients who harbor the fusion. The dimension of rarity in sarcomas remains difficult to comprehend for both patients and caregivers. Diagnosis of NTRK fusions is complex, particularly in the context of sarcomas and can involve immunohistochemistry as a screening tool but frequently requires fluorescence-in-situ hybridization or next-generation sequencing (NGS) to confirm the diagnosis.

Summary
The growing evidence on subtype-specific incidence of NTRK fusions will help to improve strategic prioritization or exclusion of subtypes to reduce the burden of negative testing. Next-generation inhibitors provide potential salvage treatment options for patients failing first-line therapy.
Preferentially Expressed Antigen in Melanoma Immunostaining in a Series of Melanocytic Neoplasms
Authors: Googe Paul B. , Flanigan Kendall L. , Miedema Jayson R. 
Published: May 2021

Abstract:
In their 2018 article, Lezcano et al [AJSP 2018(11):1456] show that diffuse tumor cell nuclear reactivity for Preferentially expressed Antigen in Melanoma (PRAME) is a feature of melanoma and that benign and atypical melanocytic tumors are PRAME negative or show only focal positivity for PRAME. We report our observations of PRAME staining in 253 melanocytic tumors. Tumors were classified by hematoxylin and eosin sections. The nuclear PRAME staining of neoplastic melanocytes in each case was categorized as absent, focally present, or diffusely present. The results were compared with those of Lezcano et al 105 of 134 (78%) melanocytic nevi were completely PRAME negative. Of the 29 PRAME-positive benign lesions, 28 exhibited focal but not diffuse positivity, including atypical (n = 11) and dysplastic nevi (n = 11). One of 11 Spitz nevi showed diffuse positivity (9%). Thirty-nine of 51 (76%) invasive melanomas, 41 of 50 (82%) melanoma in situ, and 15 of 18 (83%) metastatic melanomas were diffusely PRAME positive. Excluding desmoplastic melanomas, 39 of 49 (80%) primary melanomas were diffusely PRAME positive. Our findings of PRAME staining in melanocytic neoplasia are in general agreement with those of Lezcano et al. Diffuse PRAME reactivity in neoplastic melanocytes is a feature of malignancy and was only otherwise seen in 1 Spitz nevus. Caution is advised in interpretation of PRAME reactivity in melanocytic tumors of uncertain classification because melanoma arising in association with nevus and some atypical melanocytic tumors may show focal or incomplete PRAME staining. Routine histopathological findings, clinical information, PRAME staining, and judicious application of molecular studies are steps leading to accurate classification of melanocytic neoplasia.
Case of Symptomatic Dermal Neurofibroma With Microcystic Features
Authors: Pak Kaitlynne Y. , Pun Stacey , Cassarino David S. 
Published: May 2021

Abstract:
A neurofibroma is a benign neural tumor arising within a peripheral nerve sheath composed of Schwann cells, fibroblasts, and immune cells involved in the nerve. Microcystic elements have been rarely described in these tumors. Neurofibromas are classically described as unencapsulated tumors of interspersed spindle cells and mast cells in a hypocellular, myxoid stroma. These tumors are most commonly dermal and seen in almost all patients with neurofibromatosis type 1; however, they may also occur sporadically, as seen in our case here. We report a 23-year-old patient with no significant medical history who presented with a dome-shaped papule on her cheek. This slow-growing mass had been present for multiple years and was soft, inflamed, and painful. Shave biopsy was collected and sent for evaluation. The shave biopsy diagnosed a benign neural tumor with features of a rare microcystic neurofibroma. This unencapsulated tumor consisted of microcystic spaces lined by oval-shaped to spindle-shaped cells in a matrix of myxoid to collagenous-like areas. Scattered lymphocytes and mast cells were noted, with few true vessels enclosing red blood cells. The stromal cells and cells lining the microcystic spaces stained S100 and SOX-10 positive. These cells had limited CD34 staining; however, most microcystic spaces were negative. Only the few true vessels stained CD31 positive. It is important to distinguish the prominent microcystic features in neurofibromas versus schwannomas by the lack of encapsulation or Antoni A features with Verocay bodies, which are typical of the latter. Further differentiating neurofibromas versus malignant peripheral nerve sheath tumors is required, where the latter should exhibit much greater nuclear atypic, higher cellularity, necrosis, hemorrhage, and increased mitotic activity. Excision of this benign microcystic neurofibroma was not deemed necessary because of lack of clinical concern and recurrent lesions.
L-Lift Technique Using Poly-l-Lactic Acid: A Pilot Study
Authors: Hexsel Doris , Camozzato Fernanda , Valente-Bezerra Indira , Silva Aline F. , Siega Carolina 
Published: May 2021

BACKGROUND
Minimally invasive procedures that prevent and delay the aging process can be an alternative to more invasive surgical procedures.

OBJECTIVE
To assess the efficacy and safety of L-Lift technique to improve skin firmness, facial global aesthetics, and the patient and investigator satisfaction.

METHODS
Prospective, open, single-center study. Thirty participants underwent 3 treatment sessions 1 month apart and were assessed 8, 16, and 24 weeks after first injections. Assessments included the Facial Laxity Rating Scale (FLRS), Global Aesthetic Improvement Scale (GAIS), objective measurement of skin elasticity, and the Skin Distension Test.

RESULTS
At Week 24, 60% of the patients had at least 1-class improvement in the FLRS for the middle face and 33% for the lower face. At Week 24, investigators considered that 90.0% of the patients improved according to the GAIS and 90.0% of the subjects considered they have improved. Skin elasticity (at Week 8 and at Week 16) and Skin Distension Test (at Week 24) assessments indicated improvement in skin firmness. Both patients and investigators were satisfied with the treatment at the study end.

CONCLUSION
The technique is safe and efficacious. It may be particularly suitable for patients presenting initial signs of facial skin laxity.
Increasing a Dermatologist's Footprint on Instagram: An Analysis of Top Influencers Performing Nonsurgical Cosmetic Procedures
Authors: O'Brien Kathleen F. , Newsom Emily C. , Park Joyce H. , Lawrence Naomi 
Published: May 2021

BACKGROUND
Patients use social media to find information about cosmetic procedures, yet dermatologists historically lack a social media presence. Misleading information from nonexperts is potentially harmful.

OBJECTIVE
To identify the top influencers posting about nonsurgical cosmetic procedures on Instagram, verify their credentials, and analyze their content to empower dermatologists to effectively join the online conversation, combat harmful misinformation, and preserve the expertise and influence of board-certified dermatologists.

METHODS AND MATERIALS
Using the Klear marketing platform, Instagram influencers with more than 50,000 followers were identified. Influence rating, top posts, and other metrics were extracted using proprietary algorithms.

RESULTS
Ninety nine influencers were identified. Of the top 10, 70% were board-certified plastic surgeons. Physicians not board-certified in a core cosmetic specialty had the highest influencer rating and number of followers. The most popular posts were of before and after photographs and personal posts.

CONCLUSION
Dermatologists may be able to increase their Instagram footprint by posting frequently, especially of before and after and personal photographs, using hashtags, Instagram live and Instagram television, and Instagram stories. It is important for the dermatology community to find a way to ethically navigate social media to have a seat at the table and meet patients where they are.
Posteromedial quadratus lumborum block versus wound infiltration after caesarean section
Authors: Stopar-Pintaric Tatjana , Blajic Iva , Visic Uros , Znider Manja , Plesnicar Ana , Vlassakov Kamen , Lucovnik Miha 
Published: May 2021

BACKGROUND
Reducing pain and minimising the use of opioids after caesarean section are crucial to enhancing maternal recovery and promoting mother-newborn interaction. Various techniques have been implemented to improve analgesia. We compared the analgesic efficacy of posteromedial quadratus lumborum block with that of wound infiltration following elective caesarean section.

OBJECTIVE
We hypothesised that within a multimodal analgesia approach, posteromedial quadratus lumborum block would, due to its potential to relieve visceral pain, result in a 15% reduction in 24-h postoperative opioid consumption compared with wound infiltration.

DESIGN
A double-blind, randomised, placebo-controlled clinical study.

SETTING
A single-centre study between August 2019 and May 2020.

PATIENTS
One hundred and sixteen women were randomly allocated into two groups. In the quadratus lumborum group, 20 ml 0.9% saline was injected into the surgical wound followed by bilateral posteromedial quadratus lumborum block using 20 ml 0.25% levobupivacaine per side. In the wound infiltration group, 20 ml of 0.25% levobupivacaine was injected into the surgical wound followed by a bilateral posteromedial quadratus lumborum injection with 20 ml 0.9% saline per side.

MAIN OUTCOME MEASURES
The primary outcome was opioid (piritramide) consumption at 24 h. Secondary outcomes were piritramide consumption at 48 h, time-to-first analgesic request, pain scores at rest and with movement, surgery-to-first-ambulation time, surgery-to-breastfeeding time, sedation, pruritus and complications.

RESULTS
Piritramide consumption in 24 h was significantly lower with posteromedial quadratus lumborum block (1.5 ± 1.8 mg) than with wound infiltration (2.2 ± 1.7 mg) (P = 0.04), mean difference of -0.7 mg, (95% CI -1.3 to -0.03). In those who required piritramide, time-to-first analgesic request was significantly longer with posteromedial quadratus lumborum block 11 [7 to 14] h, than with wound infiltration 7 [5 to 11] h (P = 0.02). Pain scores were low, with no differences recorded at rest and with movement. There were no differences in time-to-ambulation and time-to-breastfeed between the groups.

CONCLUSION
As a component of multimodal post-caesarean section analgesia, posteromedial quadratus lumborum block was associated with lower 24-h opioid consumption compared with wound infiltration.

TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT04000308
Designing devices for global surgery: evaluation of participatory and frugal design methods
Authors: Marriott Webb Millie , Bridges Philippa , Aruparayil Noel , Mishra Anurag , Bains Lovenish , Hall Richard , Gnanaraj Jesudian , Culmer Peter 
Published: May 2021

Introduction:
Most people living in low- and middle-income countries have no access to surgical care. Equipping under-resourced health care contexts with appropriate surgical equipment is thus critical. “Global” technologies must be designed specifically for these contexts. But while models, approaches and methods have been developed for the design of equipment for global surgery, few studies describe their implementation or evaluate their adequacy for this purpose.

Methods:
A multidisciplinary team applied participatory and frugal design methods to design a surgical device for gasless laparoscopy. The team employed a formal roadmap, devised to guide the development of global surgical equipment, to structure the design process into phases. Phases 0–1 comprised primary research with surgeons working in low-resource settings and forming collaborative partnerships with key stakeholders. These participated in phases 2–3 through design workshops and video events. To conclude, surgical stakeholders (n=13) evaluated a high-fidelity prototype in a cadaveric study.

Results:
The resulting design, “RAIS” (Retractor for Abdominal Insufflation-less Surgery), received positive feedback from rural surgeons keen to embrace and champion innovation as a result of the close collaboration and participatory design methods employed. The roadmap provided a valuable means to structure the design process but this evaluation highlighted the need for further development to detail specific methodology. The project outcomes were used to develop recommendations for innovators designing global surgical equipment.
To inform early phases in the design roadmap, engaging a variety of stakeholders to provide regular input is crucial. Effective communication is vital to elucidate clear functional design requirements and hence reveal opportunities for frugal innovation. Finally, responsible innovation must be embedded within the process of designing devices for global surgery.

Conclusion:
A community-wide effort is required to formally evaluate and optimize processes for designing global surgical devices and hence accelerate adoption of frugal surgical technologies in low-resource settings.
MASSIVE ADVANCING NONEXUDATIVE TYPE 1 CHOROIDAL NEOVASCULARIZATION IN CTRP5 LATE-ONSET RETINAL DEGENERATION
Authors: Keenan Tiarnan D. L. , Vanderford Elliott K. , de Silva Tharindu , Sieving Paul A. , Cukras Catherine A. 
Published: May 2021

Purpose:
To describe longitudinal multimodal imaging findings of nonexudative choroidal neovascularization in CTRP5 late-onset retinal degeneration.

Methods:
Four patients with CTRP5-positive late-onset retinal degeneration underwent repeated ophthalmoscopic examination and multimodal imaging. All four patients (two siblings and their cousins, from a pedigree described previously) had the heterozygous S163R mutation.

Results:
All four patients demonstrated large subretinal lesions in the mid-peripheral retina of both eyes. The lesions were characterized by confluent hypercyanescence with hypocyanescent borders on indocyanine green angiography, faintly visible branching vascular networks with absent/minimal leakage on fluorescein angiography, Type 1 neovascularization on optical coherence tomography angiography, and absent retinal fluid, consistent with nonexudative choroidal neovascularization. The neovascular membranes enlarged substantially over time and the birth of new membranes was observed, but all lesions remained nonexudative/minimally exudative. Without treatment, all involved retinal areas remained free of atrophy and subretinal fibrosis.

Conclusion:
We report the existence of massive advancing nonexudative Type 1 choroidal neovascularization in CTRP5 late-onset retinal degeneration. These findings have implications for age-related macular degeneration. They provide a monogenic model system for studying the mechanisms underlying the distinct events of choroidal neovascularization development, enlargement, progression to exudation, and atrophy in age-related macular degeneration. They suggest that choroidal hypoperfusion precedes neovascularization and that nonexudative neovascularization may protect against atrophy.
CILIORETINAL ARTERIES INFLUENCE OPTIC NERVE HEAD, PERIPAPILLARY, AND MACULAR VESSEL DENSITIES IN HEALTHY EYES
Authors: Diener Raphael , Leclaire Martin D. , Eckardt Franziska , Lauermann Jost L. , Alnawaiseh Maged , Eter Nicole , Treder Maximilian 
Published: May 2021

Background/Purpose:
To analyze the influence of a cilioretinal artery (CRA) on macular and peripapillary vessel density in healthy eyes as measured using optical coherence tomography angiography.

Methods:
A total of 83 eyes of 83 patients were included in this study. Optical coherence tomography angiography was performed using the RTVue XR Avanti with AngioVue (Optovue Inc). The macula was imaged with a 3 × 3-mm scan, whereas for the optic nerve head a 4.5 × 4.5-mm scan was taken. Optical coherence tomography angiography images of the optic nerve head were screened for the presence of a CRA.

Results:
In 31 eyes, a CRA was detected (37.3%). The vessel density in eyes with a CRA was significantly lower within the optic nerve head (P = 0.005) but higher in the peripapillary capillary network (P < 0.001) and (whole en face) macular superficial capillary plexus (P = 0.025), when compared with eyes with no CRA.

Conclusion:
Our findings reveal that in eyes with a CRA, the vessel density in the peripapillary and macular superficial capillary plexus is increased, whereas the optic nerve head perfusion (as indicated by vessel density in the inside disk region) is decreased. This has to be considered when analyzing quantitative optical coherence tomography angiography parameters in scientific and clinical applications.
COVID-19 and Dry Eye
Authors: Koh Shizuka , Rhee Michelle K. 
Published: May 2021

Abstract:
The aim of this article is to review the literature on the impact of coronavirus disease 2019 (COVID-19) on dry eye disease (DED). A literature search on dry eye and COVID-19 was performed. Most current studies focus on DED in patients diagnosed with COVID-19 or dry eye symptoms in random populations of students and medical staff. Real-world dry eye practices revealed a variety of responses, possibly related to local environmental factors and lifestyle. Patients recovered from COVID-19 warrant ocular surface surveillance for DED. Pandemic mitigation strategies including remote work/school/leisure and mask wearing affect dry eye practices globally. Heightened reiteration of dry eye management for environmental and behavioral modifications, visual display terminals, and mask wearing with attention to its effects on the ocular surface is increasingly important as this pandemic continues.
Investigating the specificity of the neurologic pain signature against breathlessness and finger opposition
Authors: Harrison Olivia K. , Hayen Anja , Wager Tor D. , Pattinson Kyle T.S. 
Published: May 2021

Abstract
Brain biomarkers of pain, including pain-predictive “signatures” based on brain activity, can provide measures of neurophysiological processes and potential targets for interventions. A central issue relates to the specificity of such measures, and understanding their current limits will both advance their development and explore potentially generalizable properties of pain to other states. Here, we used 2 data sets to test the neurologic pain signature (NPS), an established pain neuromarker. In study 1, brain activity was measured using high-field functional magnetic resonance imaging (7T fMRI, N = 40) during 5 to 25 seconds of experimental breathlessness (induced by inspiratory resistive loading), conditioned breathlessness anticipation, and finger opposition. In study 2, we assessed anticipation and breathlessness perception (3T, N = 19) under blinded saline (placebo) and remifentanil administration. The NPS responded to breathlessness, anticipation, and finger opposition, although no direct comparisons with painful events were possible. Local NPS patterns in anterior or midinsula, S2, and dorsal anterior cingulate responded to breathlessness and finger opposition and were reduced by remifentanil. Local NPS responses in the dorsal posterior insula did not respond to any manipulations. Therefore, significant global NPS activity alone is not specific for pain, and we offer insight into the overlap between NPS responses, breathlessness, and somatomotor demand.