bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supraglottic Airway Versus Tracheal Intubation for Airway Management in Out-of-Hospital Cardiac Arrest: A Systematic Review, Meta-Analysis, and Trial Sequential Analysis of Randomized Controlled Trials
Authors: Forestell Ben , Ramsden Sophie , Sharif Sameer , Centofanti John , Al Lawati Kumait , Fernando Shannon M. , Welsford Michelle , Nichol Graham , Nolan Jerry P. , Rochwerg Bram 
Published: November 2023

OBJECTIVES:
Given the uncertainty regarding the optimal approach for airway management for adult patients with out-of-hospital cardiac arrest (OHCA), we conducted a systematic review and meta-analysis to compare the use of supraglottic airways (SGAs) with tracheal intubation for initial airway management in OHCA.

DATA SOURCES:
We searched MEDLINE, PubMed, Embase, Cochrane Library, as well as unpublished sources, from inception to February 7, 2023.

STUDY SELECTION:
We included randomized controlled trials (RCTs) of adult OHCA patients randomized to SGA compared with tracheal intubation for initial prehospital airway management.

DATA EXTRACTION:
Reviewers screened abstracts, full texts, and extracted data independently and in duplicate. We pooled data using a random-effects model. We used the modified Cochrane risk of bias 2 tool and assessed certainty of evidence using the Grading Recommendations Assessment, Development, and Evaluation approach. We preregistered the protocol on PROSPERO (CRD42022342935).

DATA SYNTHESIS:
We included four RCTs (n = 13,412 patients). Compared with tracheal intubation , SGA use probably increases return of spontaneous circulation (ROSC) (relative risk [RR] 1.09; 95% CI, 1.02–1.15; moderate certainty) and leads to a faster time to airway placement (mean difference 2.5 min less; 95% CI, 1.6–3.4 min less; high certainty). SGA use may have no effect on survival at longest follow-up (RR 1.06; 95% CI, 0.84–1.34; low certainty), has an uncertain effect on survival with good functional outcome (RR 1.11; 95% CI, 0.82–1.50; very low certainty), and may have no effect on risk of aspiration (RR 1.04; 95% CI, 0.94 to 1.16; low certainty).

CONCLUSIONS:
In adult patients with OHCA, compared with tracheal intubation, the use of SGA for initial airway management probably leads to more ROSC, and faster time to airway placement, but may have no effect on longer-term survival outcomes or aspiration events.
Homoharringtonine promotes heart allograft acceptance by enhancing regulatory T cells induction in a mouse model
Authors: Qiu Xia , Zhang Hedong , Tang Zhouqi , Fan Yuxi , Yuan Wenjia , Feng Chen , Chen Chao , Cui Pengcheng , Cui Yan , Qi Zhongquan , Li Tengfang , Zhu Yuexing , Xie Liming , Peng Fenghua , Deng Tuo , Jiang Xin , Peng Longkai , Dai Helong 
Published: November 2023

Abstract

Background:
Homoharringtonine (HHT) is an effective anti-inflammatory, anti-viral, and anti-tumor protein synthesis inhibitor that has been applied clinically. Here, we explored the therapeutic effects of HHT in a mouse heart transplant model.

Methods:
Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver, kidney, and hematology. A mouse heart transplantation model was constructed, and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan–Meier analysis, immunostaining, and bulk RNA sequencing analysis. The HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells (Tregs) differentiation.

Results:
HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex vivo. Treatment of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days (P <0.001) without non-immune toxicity. The allografts had long-term survival after continuous HHT treatment for 28 days. HHT significantly reduced lymphocyte infiltration in the graft, and interferon-γ-secreting CD4+ and CD8+ T cells in the spleen (P <0.01). HHT significantly increased the number of peripheral Tregs (about 20%, P <0.001) and serum interleukin (IL)-10 levels. HHT downregulated the expression of T cell receptor (TCR) signaling pathway-related genes (CD4, H2-Eb1, TRAT1, and CD74) and upregulated the expression of IL-10 and transforming growth factor (TGF)-β pathway-related genes and Treg signature genes (CTLA4, Foxp3, CD74, and ICOS). HHT increased CD4+ Foxp3+ cells and Foxp3 expression ex vivo, and it enhanced the inhibitory function of inducible Tregs.

Conclusions:
HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels, thereby promoting mouse heart allograft acceptance. These findings may have therapeutic implications for organ transplant recipients, particularly those with viral infections and malignancies, which require a more suitable anti-rejection medication.
Neuromuscular Ultrasound Findings of Myokymia in a Young Woman With Generalized Anti-LGI-1 and Anti-Caspr2 Antibodies Negative Isaac Syndrome
Authors: Prado Mario B. , Moalong Kevin Michael C. , Adiao Karen Joy B. 
Published: November 2023

Abstract
Isaac syndrome is one of the rare peripheral nerve hyperexcitability (PNH) syndromes, which manifests with gross fasciculations, muscle undulation, twitching, and cramps, with or without autonomic and sensory symptoms. The diagnosis relies on characteristic electromyogram findings and the presence of anti–leucine-rich glial inactivated 1 and anti–contactin-associated protein 2 antibodies in the serum. Here, we report the case of a 21-year-old woman, who presented with extremities and tongue myokymia whose electromyogram findings were compatible with PNH, albeit seronegative for antibodies. Neuromuscular ultrasound was performed showing high-frequency rotatory, to-and-fro, high-amplitude movement of superficial and deep muscle fascicles, more prominent in the proximal than distal muscles. Neuromuscular ultrasound may be a useful adjunct in the diagnosis of PNH.
Patterns of Clinical Progression Among Patients With Autosomal Recessive Limb-Girdle Muscular Dystrophy: A Systematic Review
Authors: Cheung Antoinette , Audhya Ivana F. , Szabo Shelagh M. , Friesen Michael , Weihl Conrad C. , Gooch Katherine L. 
Published: November 2023

Abstract

Objectives:
As the clinical course of autosomal recessive limb–girdle muscular dystrophy (LGMDR) is highly variable, this study characterized the frequency of loss of ambulation (LOA) among patients by subtype (LGMDR1, LGMDR2, LGMDR3–6, LGMDR9, LGMDR12) and progression to cardiac and respiratory involvement among those with and without LOA.

Methods:
Systematic literature review.

Results:
From 2929 abstracts screened, 418 patients were identified with ambulatory status data (LOA: 265 [63.4%]). Cardiac and/or respiratory function was reported for 142 patients (34.0%; all with LOA). Among these, respiratory involvement was most frequent in LGMDR3–6 (74.1%; mean [SD] age 23.9 [11.0] years) and cardiac in LGMDR9 (73.3%; mean [SD] age 23.7 [17.7] years). Involvement was less common in patients without LOA except in LGMDR9 (71.4% respiratory and 52.4% cardiac).

Conclusions:
This study described the co-occurrence of LOA, cardiac, and respiratory involvement in LGMDR and provides greater understanding of the clinical progression of LGMDR.
Aggressive Acquired Demyelinating Neuropathy Caused by NF-155: Initially Treatment-Resistant
Authors: Jamall Selene , Baker Nancy , Peterson Gordon , Tsao Bryan , Rosenfeld Jeffrey 
Published: November 2023

Objectives:
Anti–neurofascin-155 IgG4 (NF-155) antibody disease has previously been associated with a subset of patients with chronic inflammatory demyelinating polyradiculoneuropathy. We report a case of NF-155 positive polyneuropathy that initially presented as an acute inflammatory demyelinating polyradiculoneuropathy. The patient responded appropriately to treatment but subsequently progressed over a 3-month period, resulting in quadriplegia, areflexia, and oculobulbar paralysis.

Methods:
Case report and literature review.

Results:
A 40-year-old male presented with acute bilateral arm and thigh weakness, areflexia, and distal sensory loss. Treatment with intravenous immunoglobulin (IVIg) for acute acquired demyelinating neuropathy resulted in initial improvement but subsequent decline. Lack of response to additional IVIg and plasmapheresis (PLEX) prompted testing for NF-155. Treatment with rituximab and steroids resulted in virtually complete recovery.

Conclusions:
Early testing for nodal and paranodal proteins is indicated in patients who present with acute acquired demyelinating neuropathy but fail to respond to conventional treatments, such as IVIg or PLEX. Identification of nodal and paranodal antibodies should prompt treatment with rituximab and steroids to increase likelihood of recovery.
The Severity of Fecal Problems Is Negatively Associated With Quality of Life in a Non-Patient Dutch Population
Authors: ten Hoor Maaike B.C. , Trzpis Monika , Broens Paul M.A. 
Published: November 2023

BACKGROUND:
Constipation and fecal incontinence have a negative influence on quality of life. The association between the severity of fecal problems and quality of life has not been investigated in a non-patient population.

OBJECTIVE:
To investigate the association between the severity of constipation and fecal incontinence and quality of life in non-patients.

DESIGN:
A population-based, cross-sectional study.

SETTINGS:
The study involved 3668 Dutch non-patients.

PATIENTS:
A survey company conducted a population-wide study of the general Dutch population. Altogether, 5000 Dutch citizens completed the Groningen Defecation and Fecal Continence and Short-Form 36 questionnaires. The data on 3668 respondents without comorbidities that could influence bowel function were included for analysis.

MAIN OUTCOME MEASURES:
The severity of constipation (Agachan score) and fecal incontinence (Wexner score) in relation to the quality-of-life scores.

RESULTS:
In the non-patient population (n = 3668), 487 (13.3%) had constipation, 116 (3.2%) had fecal incontinence, and the two fecal problems coexisted in 64 (1.7%). In the multivariable analysis, all quality-of-life domains were negatively associated with the severity of constipation and fecal incontinence. The associations between the severity of constipation and quality of life were stronger (highest: ß = -2.413, 95% CI, -2.681 to -2.145, p = < 0.001) than those of fecal incontinence (highest: ß = -1.280, 95% CI, -1.681 to -.880, p = < 0.001). We also found that a longer duration of bowel complaints coincided with higher severity scores, especially for constipation. Mostly, respondents rated their defecation health as positive, regardless of the severity of their fecal problems.

LIMITATIONS:
Cross-sectional design.

CONCLUSIONS:
The severity of constipation and fecal incontinence is significantly associated with reduced quality of life, with the severity of constipation having stronger associations than fecal incontinence. Given respondents' unawareness of their fecal problems and the progressive character thereof, timely intervention is advocated.
Modified Approach for Extraperitoneal Colostomy Creation in Laparoscopic Abdominoperineal Resection
Authors: Zhang Xiang , Li Xin , Cheng Zhiqiang , Wang Kexin , Dai Yong , Wang Yanlei 
Published: November 2023

BACKGROUND:
Parastomal hernia is a major long-term complication after abdominoperineal resection. Extraperitoneal colostomy has been proposed as an effective step for parastomal hernia prevention but it has not been widely used as it is technically-demanding and time-consuming. We proposed a modified approach for extraperitoneal colostomy creation by entering the extraperitoneal space through the arcuate line of the posterior rectus sheath.

OBJECTIVE:
To evaluate the safety, difficulty and efficacy for long-term parastomal hernia prevention of the modified approach for extraperitoneal colostomy creation compared with conventional transperitoneal colostomy approach.

DESIGN:
This was a retrospective evaluation of a surgical and video database.

SETTINGS:
This was a single-institution retrospective study.

PATIENTS:
Clinical data of 74 patients who underwent laparoscopic abdominoperineal resection surgery from January 2019 to January 2020 in the Department of General Surgery, Qilu Hospital of Shandong University were retrospectively reviewed.

MAIN OUTCOME MEASURES:
Baseline characteristics, time required for colostomy creation (from skin incision to colostomy maturation), perioperative complications, and long-term colostomy-related complications were compared.

RESULTS:
Baseline characteristics did not differ between the 2 approaches. The body mass index level ranged from 19.5 to 29.4 kg/m 2 for patients undergoing extraperitoneal approach. Time required for colostomy creation [22 (21-25) min for extraperitoneal vs. 23 (21-25) min for transperitoneal, p = 0.861] were comparable between the two approaches. The cumulative incidence of parastomal hernia was significantly greater with transperitoneal colostomy than extraperitoneal colostomy at 2 and 3 years postoperatively (16.2% vs. 0, p = 0.025, and 21.6% vs. 0, p = 0.005). The rest perioperative complications and long-term colostomy-related complications did not differ between the two approaches.

LIMITATIONS:
This study is limited by its retrospective design and small sample size.

CONCLUSIONS:
The modified approach for extraperitoneal colostomy creation is safe, technically simple and effective for long-term parastomal hernia prevention in patients with a body mass index of 19.5 - 29.4 kg/m 2.
The Novel Checkpoint Target Lymphocyte-Activation Gene 3 Is Highly Expressed in Cutaneous Squamous Cell Carcinoma
Authors: Dany Mohammed , Doudican Nicole , Carucci John 
Published: November 2023

BACKGROUND
Lymphocyte activation-gene 3 (LAG-3) is an emerging next-generation immune checkpoint molecule. We aim to define the expression pattern of LAG-3 in cutaneous squamous cell carcinoma (cSCC) as a first step to understand the role of LAG-3 in cSCC prognosis and therapy.

OBJECTIVE
To define the expression pattern of LAG-3 in cSCC as a first step to understand the role of LAG-3 in cSCC prognosis and therapy.

METHODS
To test whether LAG-3 is expressed on cSCC infiltrating lymphocytes, we isolated CD8+ T lymphocytes from three SCC tumors using flow cytometry and performed single-cell RNA sequencing for LAG-3 and programmed cell death protein -1 (PD-1). In addition, we evaluated LAG-3 mRNA expression in formalin-fixed, paraffin-embedded tissue using NanoString technology.

RESULTS
Single-cell RNA sequencing showed that LAG-3 is expressed more than PD-1 in CD8+ tumor infiltrating lymphocytes (50.8% vs 35.2%, respectively). Quantifying LAG-3 mRNA expression showed that compared with normal skin, LAG-3 mRNA is approximately 8 fold higher in immunocompetent associated SCC tumors and approximately 2 fold higher in transplant associated SCC tumors (p-values <.05). In addition, LAG-3 mRNA was expressed 7.2 fold higher in T2a SCC tumors compared with normal skin (p-value <.05).

CONCLUSION
Lymphocyte activation-gene 3 is expressed on SCC infiltrating T lymphocytes at a higher percentage than PD-1. In addition, LAG-3 mRNA expression is significantly higher in SCC tumors. Ongoing studies will be performed to define its role as an immune-related biomarker and as a therapeutic target.
Incidence and Survival Outcomes of Dermatofibrosarcoma Protuberans From 2000 to 2020: A Population-Based Retrospective Cohort Analysis
Authors: Xiong David D. , Bordeaux Jeremy S. 
Published: November 2023

BACKGROUND
Recent changes in the incidence and survival of dermatofibrosarcoma protuberans (DFSP) have not been described.

OBJECTIVE
To characterize the incidence and survival of DFSP.

MATERIALS AND METHODS
A retrospective cohort study of patients with DFSP from 2000 to 2020 in the Surveillance, Epidemiology, and End Results database was performed. Cox and Fine–Gray regression models were used to assess overall and DFSP-specific survival.

RESULTS
The incidence of DFSP has not changed from 2000 to 2020 with 4.6 cases/million person-years, with higher rates in dark-skinned and middle-age individuals. Factors associated with overall mortality in DFSP patients include advanced age (p < .0001), male sex (hazard ratio [HR] 1.8, p < .0001), larger tumors (HR 1.002 per millimeter, p < .001), lower household income (HR 1.8, p = .0002), and lower extremity location (HR 1.7, p = .008). Mohs surgery is associated with improved overall survival (HR 0.4, p = .02). Large tumor size (6.0+ cm, HR 6.7, p = .01) and advanced age (age 80+ years, HR 21.3, p = .003) were associated with worse DFSP-specific mortality.

CONCLUSION
Dermatofibrosarcoma protuberans incidence has remained constant from 2000 to 2020. Increasing age and tumor size, decreased income, male sex, and lower extremity location are associated with worsened survival. Mohs surgery is associated with improved overall survival. Increased age and tumor size are associated with worsened DFSP-specific mortality.
Intraocular lens power calculation: angle κ and ocular biomechanics
Authors: Marques João Heitor , Baptista Pedro Manuel , Ribeiro Bruno , Menéres Pedro , Beirão João Melo 
Published: November 2023

Purpose:
To study the effect of ocular biomechanics on the prediction error of intraocular lens (IOL) power calculation.

Setting:
Centro Hospitalar Universitário do Porto, Porto, Portugal.

Design:
Prospective longitudinal study.

Methods:
This study included 67 subjects. Before cataract surgery subjects underwent biometry with IOLMaster 700 and biomechanical analysis with Corvis Scheimpflug technology. The targeted spherical equivalent was calculated with SRK-T and Barrett Universal II. Associations between prediction error (PE), absolute prediction error (AE), and biometric and biomechanical parameters were performed with stepwise multivariate linear correlation analysis.

Results:
Using the SRKT formula, there was association between PE and Corvis Biomechanical Index (CBI, B = −0.531, P = .011) and between AE and the horizontal offset between the center of the pupil and the visual axis (angle κ, B = −0.274, P = .007). Considering the Barret Universal II formula, PE was independently associated with anterior chamber depth (B = −0.279, P = .021) and CBI (B = −0.520, P = .013) and AE was associated with angle κ (B = −0.370, P = .007).

Conclusions:
A large angle κ may reduce the predictability of IOL power calculation. Ocular biomechanics likely influence the refractive outcomes after IOL implantation. This study showed that eyes with softer corneal biomechanics had more myopic PE. This may relate to anteriorization of the effective lens position. Dynamic measurements may be the way to progress into future formulas.
Effects of a fortified balanced salt solution and Ringer’s lactate solution on anterior chamber inflammation after phacoemulsification in diabetes
Authors: Ma Mingming , Wang Manqiao , Zhang Xiaomin , Shao Yan , Li Xiaorong 
Published: November 2023

Purpose:
To compare the effects of a fortified balanced salt solution (fSS) and Ringer's lactate solution (Ringer) on anterior chamber (AC) inflammation in patients undergoing phacoemulsification.

Setting:
Tianjin Medical University Eye Hospital, Tianjin, China.

Design:
Prospective masked controlled trial.

Methods:
80 patients (40 patients with regular cataract and 40 cataract patients with diabetes mellitus [DM]) were randomized to receive either fSS (n = 40) or Ringer's solution (n = 40). Anterior-segment optical coherence tomography was used to evaluate AC cells and flare. Transepithelial electrical resistance (TEER) and zonula occludens-1 (ZO-1) immunofluorescence were used for tight junction examination. Monocytic leukemia cell line (Tohoku Hospital Pediatrics-1 [THP-1]) transmigration assay was performed to observe the effects of the 2 perfusates on the inflammatory response in vitro.

Results:
In patients with regular cataracts, postoperative AC cells and flare on the 1st and 7th days were not significantly different between the Ringer and fSS groups. However, in cataract patients with DM, AC cells were higher in the Ringer group than in the fSS group (P = .003) on postoperative day 1. The AC flare was also significantly higher in the Ringer group than in the fSS group (P < .0001). No significant differences between the groups were observed on day 7. Compared with Ringer, fSS increased the TEER value and ZO-1 content and reduced the adhesion of THP-1 cells.

Conclusions:
The results of this study indicated that early postoperative AC inflammation is more severe in patients with cataracts and DM. In addition, fSS attenuates inflammation by protecting the blood–aqueous barrier and inhibiting the exudation of inflammatory cells.
A phenotypic screening platform for chronic pain therapeutics using all-optical electrophysiology
Authors: Liu Pin W. , Zhang Hongkang , Werley Christopher A. , Pichler Monika , Ryan Steven J. , Lewarch Caitlin L. , Jacques Jane , Grooms Jennifer , Ferrante Jean , Li Guangde , Zhang Dawei , Bremmer Nate , Barnett Adam , Chantre Romina , Elder Amy E. , Cohen Adam E. , Williams Luis A. , Dempsey Graham T. , McManus Owen B. 
Published: November 2023

Abstract
Chronic pain associated with osteoarthritis (OA) remains an intractable problem with few effective treatment options. New approaches are needed to model the disease biology and to drive discovery of therapeutics. We present an in vitro model of OA pain, where dorsal root ganglion (DRG) sensory neurons were sensitized by a defined mixture of disease-relevant inflammatory mediators, here called Sensitizing PAin Reagent Composition or SPARC. Osteoarthritis-SPARC components showed synergistic or additive effects when applied in combination and induced pain phenotypes in vivo. To measure the effect of OA-SPARC on neural firing in a scalable format, we used a custom system for high throughput all-optical electrophysiology. This system enabled light-based membrane voltage recordings from hundreds of neurons in parallel with single cell and single action potential resolution and a throughput of up to 500,000 neurons per day. A computational framework was developed to construct a multiparameter OA-SPARC neuronal phenotype and to quantitatively assess phenotype reversal by candidate pharmacology. We screened ∼3000 approved drugs and mechanistically focused compounds, yielding data from over 1.2 million individual neurons with detailed assessment of functional OA-SPARC phenotype rescue and orthogonal “off-target” effects. Analysis of confirmed hits revealed diverse potential analgesic mechanisms including ion channel modulators and other mechanisms including MEK inhibitors and tyrosine kinase modulators. Our results suggest that the Raf-MEK-ERK axis in DRG neurons may integrate the inputs from multiple upstream inflammatory mediators found in osteoarthritis patient joints, and MAPK pathway activation in DRG neurons may contribute to chronic pain in patients with osteoarthritis.