bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Post Hoc Analysis of Osmotherapy Use in the Erythropoietin in Traumatic Brain Injury Study—Associations With Acute Kidney Injury and Mortality
Authors: Skrifvars Markus B. , Bailey Michael , Moore Elizabeth , Mårtensson Johan , French Craig , Presneill Jeffrey , Nichol Alistair , Little Lorraine , Duranteau Jacques , Huet Olivier , Haddad Samir , Arabi Yaseen M. , McArthur Colin , Cooper David James , Bendel Stepani , Bellomo Rinaldo 
Published: January 2021

OBJECTIVES:
Mannitol and hypertonic saline are used to treat raised intracerebral pressure in patients with traumatic brain injury, but their possible effects on kidney function and mortality are unknown.

DESIGN:
A post hoc analysis of the erythropoietin trial in traumatic brain injury (ClinicalTrials.gov NCT00987454) including daily data on mannitol and hypertonic saline use.

SETTING:
Twenty-nine university-affiliated teaching hospitals in seven countries.

PATIENTS:
A total of 568 patients treated in the ICU for 48 hours without acute kidney injury of whom 43 (7%) received mannitol and 170 (29%) hypertonic saline.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
We categorized acute kidney injury stage according to the Kidney Disease Improving Global Outcome classification and defined acute kidney injury as any Kidney Disease Improving Global Outcome stage-based changes from the admission creatinine. We tested associations between early (first 2 d) mannitol and hypertonic saline and time to acute kidney injury up to ICU discharge and death up to 180 days with Cox regression analysis. Subsequently, acute kidney injury developed more often in patients receiving mannitol (35% vs 10%; p < 0.001) and hypertonic saline (23% vs 10%; p < 0.001). On competing risk analysis including factors associated with acute kidney injury, mannitol (hazard ratio, 2.3; 95% CI, 1.2–4.3; p = 0.01), but not hypertonic saline (hazard ratio, 1.6; 95% CI, 0.9–2.8; p = 0.08), was independently associated with time to acute kidney injury. In a Cox model for predicting time to death, both the use of mannitol (hazard ratio, 2.1; 95% CI, 1.1–4.1; p = 0.03) and hypertonic saline (hazard ratio, 1.8; 95% CI, 1.02–3.2; p = 0.04) were associated with time to death.

CONCLUSIONS:
In this post hoc analysis of a randomized controlled trial, the early use of mannitol, but not hypertonic saline, was independently associated with an increase in acute kidney injury. Our findings suggest the need to further evaluate the use and choice of osmotherapy in traumatic brain injury.
Congenital vascular lesions, could MAPK and PI3K inhibitors pave the way to new therapies?
Authors: Bisdorff-Bresson Annouk , Eyries Mélanie , Boccara Olivia 
Published: January 2021

Purpose of review
Superficial vascular anomalies are a heterogeneous group of malformative and tumoral lesions, developed from various types of abnormal lymphatic and/or blood vessels. They are mostly benign but their clinical evolution can lead to dramatic cosmetic concern, functional impairment and even life-threatening conditions. Until recently, treatments relied on invasive procedures such as embotherapy/sclerotherapy and/or surgery. Recent molecular findings pave the way of new medical therapies.

Recent findings
Two main signaling pathways PI3K-AKT-mTOR and RAS-MAPK-ERK are now identified to encounter for the causative pathogenic genetic variants of most vascular anomalies. Involved genes are also responsible for several common neoplasms for which targeted therapies are already available or under development. Repurposing treatment strategy is considered for vascular anomalies treatment with promising results.

Summary
The mTOR inhibitor sirolimus is the most used targeted therapy so far but new molecules are tested currently.
Extramedullary Blast Crisis of Chronic Myelogenous Leukemia With a Skin Lesion: A Case Report and Literature Review
Authors: Qi Jing , Zhang Fan , Liu Yinhua , Yao Junping , Xu Youhai , He Hesheng 
Published: January 2021

Abstract:
Extramedullary blast crisis of chronic myeloid leukemia (CML) is defined as extramedullary disease composed of blasts regardless of the proliferation of blasts in the bone marrow. The commonly affected sites are the lymph node, central nervous system, bone, skin, and soft tissue. However, skin infiltration of CML patients as the initial presentation while their bone marrow is still in the chronic phase is extremely rare. In this article, we present a case of a 51-year-old woman who was admitted to our hospital complaining about a skin nodule in her right calf and easy fatigability for 1 week. The peripheral blood and bone marrow analysis both supported the diagnosis of CML in the chronic phase, whereas the excisional biopsy specimen obtained from her right calf showed immature cells infiltration, and fluorescence in situ hybridization test was positive for p210 BCR/ABL1 gene rearrangement. Based on the presence of extramedullary myeloid sarcoma, the patient was diagnosed with extramedullary myeloid blast crisis of CML despite the chronic phase in the bone marrow.
Efficacy and Safety of a New Botulinum Toxin (HU-014) Versus Existing Onabotulinumtoxin A in Subjects With Moderate to Severe Glabellar Lines
Authors: Yoo Kwang Ho , Lee Yang Won , Lee Ji Su , Kwon Soon Hyo , Huh Chang Hun , Kim Beom Joon 
Published: January 2021

BACKGROUND
Recently, the safety of a new botulinum toxin (HU-014) was confirmed through animal experiments. The evaluation of the efficacy and safety of this newly introduced botulinum toxin is required considering the risk of adverse events (AEs) and need for standardization before its universal use.

OBJECTIVE
The aim of this multicenter, double-blind, randomized, parallel, active-controlled phase III clinical trial was to investigate the noninferiority of HU-014 versus existing onabotulinumtoxin A for the treatment of moderate to severe glabellar lines.

METHODS
In total, 267 subjects were randomized to either the test (HU-014) or control (onabotulinumtoxin A) group. At the baseline and at weeks 4, 8, 12, and 16, investigator's live assessment, independent photographic assessment, subjects' improvement assessment, subjects' satisfaction assessment, and safety assessment were performed.

RESULTS
At week 4, the response rate was 90.15% and 92.31% in the test and control groups, respectively, as per investigator's live assessment while frowning, without a significant difference. Both groups also showed no significant differences in response rates in the other assessments. In addition, no serious AEs were reported.

CONCLUSION
HU-014 was noninferior to existing onabotulinumtoxin A in the treatment of glabellar lines at a 1:1 dose ratio, and both products were well tolerated.
Pulse-Dye Laser Followed by Betamethasone-Calcipotriol and Fractional Ablative CO2-Laser-Assisted Delivery for Nail Psoriasis
Authors: Shehadeh Waseem , Matz Hagit , Ellenbogen Eran , Sprecher Eli , Artzi Ofir 
Published: January 2021

BACKGROUND
Nail psoriasis is a common and potentially debilitating condition for which no effective and safe nonsystemic therapy is currently available. Recently, laser-assisted drug delivery (LADD) is being increasingly used to facilitate transcutaneous penetration of topical treatments.

OBJECTIVES
We set to assess the efficacy and safety of combined pulse-dye laser and fractional CO2 laser-assisted betamethasonecalcipotriol gel delivery for the treatment of nail psoriasis.

MATERIAL AND METHODS
We conducted a prospective, intrapatient comparative study in a series of 22 patients with bilateral fingernail psoriasis. Nails on the randomized hand were treated with 3 monthly sessions of pulse-dye laser to the proximal and lateral nail folds followed by fractional ablative CO2 laser to the nail plate. Between treatments and one month following the last treatment, the participants applied betamethasone propionate-calcipotriol gel once daily to the nail plate. Clinical outcome was ascertained using nails photography, the Nail Psoriasis Severity Index (NAPSI) and patient satisfaction.

RESULTS
Seventeen completed the study. Three participants withdrew from the study because of treatment-associated pain. Treatment was associated with a statistically significant improvement of the NAPSI scale (p < .002). Patient satisfaction was high.

CONCLUSION
Combined PDL and fractional ablative CO2-LADD of betamethasone-calcipotriol gel should be considered for the treatment of nail psoriasis.
Safety and Efficacy of Dermal Fillers in Patients With Connective Tissue Disease: A Review
Authors: Gonzalez Cristian D. , Pamatmat Jarod John , Goff Heather W. 
Published: January 2021

BACKGROUND
Dermal fillers such as hyaluronic acid, poly-l-lactic acid, and polymethyl-methacrylate are often used to treat cutaneous defects such as lipoatrophy. However, concern exists regarding their use in patients with a connective tissue disease (CTD) because of a theoretical risk of disease reactivation or exacerbation. Evidence regarding their use in patients with CTD also remains limited.

OBJECTIVE
This review intends to summarize and evaluate the available literature regarding the use of dermal fillers in patients with CTD.

MATERIALS AND METHODS
A literature search until May 2020 was conducted through PubMed, Ovid MEDLINE, and Ovid Embase to identify articles discussing the treatment of cutaneous defects secondary to CTD. Articles discussing the use of autologous fat transfer alone were excluded.

RESULTS
Twenty-three articles were reviewed. The amount of available evidence varies between the type of CTD and type of filler with morphea having the most published evidence out of the CTDs discussed and hyaluronic acid having the most published evidence out of the fillers discussed. Most studies demonstrated positive results with no report of disease reactivation or exacerbation.

CONCLUSION
Despite limited available evidence, dermal fillers seem to be safe as an adjunctive treatment for cutaneous defects in patients with CTD.
Treatment of Cutaneous Squamous Cell Carcinoma In Situ With Curettage Followed by Topical Imiquimod 5% Cream
Authors: Ondo Andrew L. , Kerner James D. , Kerner Jacob V. , Ondo Isaac P. , Trainor Patrick , Shanler Stuart D. 
Published: January 2021

BACKGROUND
Treatment strategies for cutaneous squamous cell carcinoma in situ (cSCCIS) are many but reported cure rates are variable and few studies report 5-year follow-up data.

OBJECTIVE
To evaluate the treatment of cSCCIS by curettage followed by topical imiquimod 5% cream (C&I).

METHODS
We evaluated all immunocompetent patients with biopsy proven cSCCIS treated by C&I between January 2008 and December 2012.

RESULTS
A total of 861 patients with 1,198 cSCCIS were treated, with median follow-up of 71 months. The mean tumor diameter was 10.2 mm. The average duration of treatment with imiquimod 5% cream was 21 days. Kaplan–Meier estimated recurrence-free survival at 5-year follow-up was 99.71% with 95% CI (99.38%, 100.00%). A follow-up questionnaire returned by 45% of patients revealed that 94% were satisfied with their treatment. Six hundred eleven patients developed a new nonmelanoma skin cancer (NMSC) during the follow-up period, and 91% (556/611) of patients chose this combination treatment for at least one new NMSC.

CONCLUSION
The combination treatment for cSCCIS of C&I had less than 1% cumulative probability of treatment failure at 5 years. Patients tolerated the treatment well, with the majority choosing this method of treatment for at least one new NMSC.
AUTOLOGOUS POSTERIOR CAPSULE FLAP TRANSPLANTATION IN THE MANAGEMENT OF REFRACTORY MACULAR HOLE IN A PSEUDOPHAKIC EYE
Authors: Yuguchi Takaaki , Ogura Shuntaro , Hirano Yoshio , Suzuki Norihiro , Yasukawa Tsutomu , Ogura Yuichiro 
Published: January 2021

Purpose:
To report a case of refractory macular hole (MH) in pseudophakic eye treated with autologous posterior capsule flaps transplantation.

Methods:
Case report.

Results:
A 48-year-old man visited our hospital with visual loss in the right eye because of unclosed MH. The patient had undergone two previous surgeries in another hospital, that is, the first included a cataract surgery, vitrectomy, and internal limiting membrane peeling with sulfur hexafluoride (SF6) gas tamponade, and the second included an ineffective autologous internal limiting membrane flap technique and massaging the edges of the MH with a soft-tipped flute needle followed by the same gas, but the MH remained open. In our hospital, posterior capsule flaps were acquired from the same eye, inserted into the MH, and the same gas tamponade was performed, which was about four months after the disease onset (3 months after the prior second surgery). The patient kept face-down position for a week after the surgery and the MH was closed, which remained for over 12 months. The visual acuity improved from 20/250 to 20/60, and the retinal sensitivities around the MH gradually improved.

Conclusion:
An autologous posterior capsule flaps transplantation was effective in the management of refractory MH to not only close the MH but also improve the visual outcomes.
A Predictive Model for the Diagnostic and Therapeutic Yield of Colonoscopy Performed for Lower Gastrointestinal Bleeding
Authors: Chung Waihong , Rich Harlan , Wands Jack 
Published: January 2021

Background:
Although colonoscopy is routinely performed for the management of lower gastrointestinal bleeding (LGIB), the quality of evidence supporting its use is poor and its yield for active bleeding or malignancy is low in practice.

Methods:
We conducted a retrospective analysis of all adult patients who underwent colonoscopies for LGIB at our hospital system between January 1, 2015, and December 31, 2019. A statistical model was built on a cohort of 5195 cases using multiple logistic regressions to predict the detection of various colonoscopy findings and the use of different colonoscopy maneuvers. The model was converted into a risk scoring system, named the TYPICAL Index, and was validated against a separate cohort of 914 cases.

Results:
Active bleeding was only seen in 3.8% of colonoscopies performed for LGIB and endoscopic hemostasis was applied in 43.7% of actively bleeding lesions. Malignant-appearing lesions were detected in 2.5% of LGIB procedures and all cases of proximal colonic mass were identified in subjects age above 60. The TYPICAL Index, derived from age, gender, hemoglobin, creatinine, international normalized ratio, and prior colonoscopy for LGIB has a concordance statistic of 0.71 and a negative predictive value of 93.8% for potential bleeding sources requiring hemostasis, malignant-appearing lesions, or active bleeding on colonoscopy when applied using a threshold of 6.

Conclusions:
Active bleeding and malignancies are rarely encountered and endoscopic hemostasis is seldom required during colonoscopy performed for LGIB. We developed and validated a risk scoring system to identify cases of low predicted diagnostic and therapeutic yield and to guide clinical decision-making.
Oral Fecal Microbiota Transplant Capsules Are Safe and Effective for Recurrent Clostridioides difficile Infection
Authors: Du Charles , Luo Yuying , Walsh Samantha , Grinspan Ari 
Published: January 2021

Goals:
We performed a systematic review with meta-analysis to examine the efficacy and safety of oral fecal microbiota transplantation (FMT) capsules for recurrent Clostridioides difficile infection (rCDI).

Background:
FMT through colonoscopy is established as effective and safe in treating multiple recurrences of CDI, but consensus has not been established on delivery through oral capsules.

Study:
A systematic literature search was performed with multiple databases including MEDLINE and EMBASE to identify original studies including at least 10 patients that investigated the role of oral FMT capsules to treat rCDI. Cure rates were pooled by a random effects model and publication bias was assessed with the Egger test. Secondary analyses assessed for differences between capsule preparation (frozen vs. lyophilized stool) and delivery modality (capsule vs. colonoscopy).

Results:
Fifteen studies (12 case series and 3 randomized controlled trials) encompassing 763 patients were identified for inclusion. Significant variability existed in baseline patient characteristics and protocols. Meta-analysis of proportions showed efficacy of oral FMT capsules to be 0.821 (95% confidence interval: 0.762-0.874). No evidence for publication bias was found (P=0.51). Secondary analyses did not find significant differences in efficacy. Fourteen adverse events leading to death or hospitalization were noted, none of which were attributed to FMT.

Conclusions:
Oral FMT capsules for rCDI are promising because of ease of administration and noninvasive delivery. We found an overall efficacy of 82.1% with a low rate of serious adverse events. Further studies are needed to optimize protocols and outcomes.
Primary biliary cholangitis: treatment
Authors: Cazzagon Nora , Floreani Annarosa 
Published: January 2021

Purpose of review
To discuss the most recent data regarding treatment of patients with primary biliary cholangitis (PBC) with inadequate response to ursodeoxycholic acid (UDCA).

Recent findings
Patients with PBC at high-risk of progressive disease are younger, have advanced fibrosis and showed inadequate response to UDCA after 12 months of treatment. These patients need a second-line treatment in addition to UDCA. The goal of therapy should be the normalization of ALP and bilirubin below 0.6 the upper limit of normal. Obeticholic acid (OCA) has proven to be effective in improving surrogate markers of prognosis in PBC, also in real-life cohort. Pruritus is the most frequent adverse event during treatment with OCA. Bezafibrate is another option in patients with inadequate response to UDCA as it was proven to improve surrogate endpoints, pruritus and even, clinical outcome compared with UDCA monotherapy. Finally, budesonide may be considered in patients with marked portal inflammation. Triple therapy with UDCA, OCA and bezafibrate may be considered in patients showing inadequate response to dual therapy.

Summary
Patients with PBC need to be evaluated at baseline, and on-treatment, for the risk of progressive disease and eventually treated with second-line therapies in addition to UDCA.
The Effect of a Psychotherapy Protocol on Dream Awareness in Adults With Generalized Anxiety Disorder
Authors: Khodarahimi Siamak , Mirderikvand Fazlolah , Amraei Kourosh 
Published: January 2021

Abstract
This study aimed to examine the effect of an Affective and Sensory Psychotherapy Protocol (ASPP) on dream awareness in adults with generalized anxiety disorder (GAD). For this purpose, 60 self-referred male and female adults were studied within a randomized clinical trial. The Generalized Anxiety Disorder 7-Item Scale and the Mannheim Dream Questionnaire were used at baseline, posttreatment, and 3-month follow-up. No significant difference was observed between patients in the experimental and control groups at baseline. Findings showed that patients in the experimental group had a significant increase in dream recall, attitude toward dreams, and the total dream score than individuals in the control group. However, no sex difference was observed in the results for within-subject and between-group effects in the current study. The present research supported the influence of an ASPP on dream awareness in adults with GAD.
Integrating Focused Cardiac Ultrasound Into Pediatric Septic Shock Assessment*
Authors: Arnoldi Sara , Glau Christie L. , Walker Sarah B. , Himebauch Adam S. , Parikh Darshana S. , Udeh Simone C. , Weiss Scott L. , Fitzgerald Julie C. , Nishisaki Akira , Conlon Thomas W. 
Published: January 2021

Objectives:
To assess focused cardiac ultrasound impact on clinician hemodynamic characterization of patients with suspected septic shock as well as expert-generated focused cardiac ultrasound algorithm performance.

Design:
Retrospective, observational study.

Setting:
Single-center, noncardiac PICU.

Patients:
Less than 18 years old receiving focused cardiac ultrasound study within 72 hours of sepsis pathway initiation from January 2014 to December 2016.

Interventions:
Hemodynamics of patients with suspected septic shock were characterized as fluid responsive, myocardial dysfunction, obstructive physiology, and/or reduced systemic vascular resistance by a bedside clinician before and immediately following focused cardiac ultrasound performance. The clinician’s post-focused cardiac ultrasound hemodynamic assessments were compared with an expert-derived focused cardiac ultrasound algorithmic hemodynamic interpretation. Subsequent clinical management was assessed for alignment with focused cardiac ultrasound characterization and association with patient outcomes.

Measurements and Main Results:
Seventy-one patients with suspected septic shock (median, 4.7 yr; interquartile range, 1.6–8.1) received clinician performed focused cardiac ultrasound study within 72 hours of sepsis pathway initiation (median, 2.1 hr; interquartile range, –1.5 to 11.8 hr). Two patients did not have pre-focused cardiac ultrasound and 23 patients did not have post-focused cardiac ultrasound hemodynamic characterization by clinicians resulting in exclusion from related analyses. Post-focused cardiac ultrasound clinician hemodynamic characterization differed from pre-focused cardiac ultrasound characterization in 67% of patients (31/46). There was substantial concordance between clinician’s post-focused cardiac ultrasound and algorithm hemodynamic characterization (33/48; κ = 0.66; CI, 0.51–0.80). Fluid responsive (κ = 0.62; CI, 0.40–0.84), obstructive physiology (к = 0.87; CI, 0.64–1.00), and myocardial dysfunction (1.00; CI, 1.00–1.00) demonstrated substantial to perfect concordance. Management within 4 hours of focused cardiac ultrasound aligned with algorithm characterization in 53 of 71 patients (75%). Patients with aligned management were less likely to have a complicated course (14/52, 27%) compared with misaligned management (8/19, 42%; p = 0.25).

Conclusions:
Incorporation of focused cardiac ultrasound in the evaluation of patients with suspected septic shock frequently changed a clinician’s characterization of hemodynamics. An expert-developed algorithm had substantial concordance with a clinician’s post-focused cardiac ultrasound hemodynamic characterization. Management aligned with algorithm characterization may improve outcomes in children with suspected septic shock.
Pain during and after COVID-19 in Germany and worldwide: a narrative review of current knowledge
Authors: Meyer-Frießem Christine H. , Gierthmühlen Janne , Baron Ralf , Sommer Claudia , Üçeyler Nurcan , Enax-Krumova Elena K. 
Published: January 2021

Abstract
Pain is a common symptom accompanying the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Nonspecific discomfort such as sore throat and body ache are frequent. Parainfectious pain such as headache, myalgia, or neuropathic pain has also been reported. The latter seems to be associated with an autoimmune response or an affection of the peripheral neuromuscular system or the central nervous system because of the viral infection. Furthermore, chronic pain can be a complication of intensive care unit treatment due to COVID-19 itself (such as intensive care–acquired weakness) or of secondary diseases associated with the SARS-CoV-2 infection, including Guillain–Barré syndrome, polyneuritis, critical illness polyneuropathy, or central pain following cerebrovascular events. Data on long-lasting painful symptoms after clinically manifest COVID-19 and their consequences are lacking. In addition, preexisting chronic pain may be exacerbated by limited and disrupted health care and the psychological burden of the COVID-19 pandemic. Medical providers should be vigilant on pain during and after COVID-19.