bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of the multi-biomarker disease activity score with arterial 18-fluorodeoxyglucose uptake in rheumatoid arthritis
Authors: Giles Jon T , Solomon Daniel H , Liao Katherine P , Rist Pamela M , Fayad Zahi A , Tawakol Ahmed , Bathon Joan M 
Published: April 2024

Abstract

Objectives
Rheumatoid arthritis (RA) and atherosclerosis share many common inflammatory pathways. We studied whether a multi-biomarker panel for RA disease activity (MBDA) would associate with changes in arterial inflammation in an interventional trial.

Methods
In the TARGET Trial, RA patients with active disease despite methotrexate were randomly assigned to the addition of either a TNF inhibitor or sulfasalazine+hydroxychloroquine (triple therapy). Baseline and 24-week follow-up [18F]fluorodeoxyglucose–PET/CT scans were assessed for change in arterial inflammation measured as the maximal arterial target-to-blood background ratio of FDG uptake in the most diseased segment of the carotid arteries or aorta (MDS-TBRmax). The MBDA test, measured at baseline and weeks 6, 18 and 24, was assessed for its association with the change in MDS-TBRmax.

Results
Interpretable scans were available at baseline and week 24 for 112 patients. The MBDA score at week 24 was significantly correlated with the change in MDS-TBRmax (Spearman’s rho = 0.239; P = 0.011) and remained significantly associated after adjustment for relevant confounders. Those with low MBDA at week 24 had a statistically significant adjusted reduction in arterial inflammation of 0.35 units vs no significant reduction in those who did not achieve low MBDA. Neither DAS28-CRP nor CRP predicted change in arterial inflammation. The MBDA component with the strongest association with change in arterial inflammation was serum amyloid A.

Conclusion
Among treated RA patients, achieved MBDA predicts changes in arterial inflammation. Achieving low MBDA at 24 weeks was associated with clinically meaningful reductions in arterial inflammation, regardless of treatment.
Inhibition of Pck1 in intestinal epithelial cells alleviates acute pancreatitis via modulating intestinal homeostasis
Authors: Yin Nuoming , Xu Binqiang , Huang Zehua , Fu Yang , Huang Huizheng , Fan Junjie , Huang Chunlan , Mei Qixiang , Zeng Yue 
Published: April 2024

AbstractIntestinal barrier dysfunction usually occurred in acute pancreatitis (AP) but the mechanism remains unclear. In this study, RNA sequencing of ileum in L‐arginine‐induced AP mice demonstrated that phosphoenolpyruvate kinase 1 (Pck1) was significantly up‐regulated. Increased Pck1 expression in intestinal epithelial cells (IECs) was further validated in ileum of AP mice and duodenum of AP patients. In AP mice, level of Pck1 was positively correlated with pancreatic and ileal histopathological scores, serum amylase activity, and intestinal permeability (serum diamine oxidase (DAO), D‐lactate, and endotoxin). In AP patients, level of Pck1 had a positive correlation with Ranson scores, white blood cell count and C‐reactive protein. Inhibition of Pck1 by 3‐Mercaptopicolinic acid hydrochloride (3‐MPA) alleviated pancreatic and ileal injuries in AP mice. AP + 3‐MPA mice showed improved intestinal permeability, including less epithelial apoptosis, increased tight junction proteins (TJPs) expression, decreased serum DAO, D‐lactate, endotoxin, and FITC‐Dextran levels, and reduced bacteria translocation. Lysozyme secreted by Paneth cells and mucin2 (MUC2) secretion in goblet cells were also partly restored in AP + 3‐MPA mice. Meanwhile, inhibition of Pck1 improved intestinal immune response during AP, including elevation of M2/M1 macrophages ratio and secretory immunoglobulin A (sIgA) and reduction in neutrophils infiltration. In vitro, administration of 3‐MPA dramatically ameliorated inflammation and injuries of epithelial cells in enteroids treated by LPS. In conclusion, inhibition of Pck1 in IECs might alleviate AP via modulating intestinal homeostasis.
Preventing Iatrogenic Injury to the Vertebral Artery in Cervical Spine Surgery
Authors: Garg Sahil , Maniakhina Lana , Muir Sean M. , Gill Arianna K. , Gill Sonny S. 
Published: April 2024

Summary of Background Data:
Iatrogenic injury of the vertebral artery (VA) in the context of surgical approaches to the cervical spine has been cited as a relatively rare complication with varying degrees of severity ranging from minimal injury to acute stroke and can result in death. It is estimated that ~50% of cases of iatrogenic VA injury are preventable after postoperatively examining a patient’s preoperative imaging. Despite the low incidence (<2%) of this complication, the potential associated morbidity demonstrates the importance of meticulous preoperative vascular consideration.

Objective:
This study aims to emphasize the importance of preoperative vascular screening during anterior cervical access planning visualized through a rare case of a VA aberration in a 47-year-old patient.

Study Design:
This study is designed as a retrospective case report.

Methods:
A thorough chart review was performed for this subject including all prior medical records, imaging studies, imaging reports, operative notes, and communication records.

Results:
The subject was found to have a history of patent foramen ovale (PFO) repair with a rare vertebral artery malformation described as a medial transposition of the vertebral artery out of the vertebral artery foramen between C3 and C4.

Conclusions:
Consideration of cervical anatomy, particularly the VA, is key to minimizing the risk of adverse surgical outcomes in both anterior and posterior approaches to the cervical spine. During the workup process, the patient’s primary care providers, radiologists, and surgeons should be aware of the potential variations of the VA with particular attention given to the course of the VA on MR imaging.

Level of Evidence:
Level IV.
Oral lasofoxifene's effects on moderate to severe vaginal atrophy in postmenopausal women: two phase 3, randomized, controlled trials
Authors: Kagan Risa , Simon James A. , Goldstein Steven R. , Komm Barry S. , Jenkins Simon N. , Portman David J. 
Published: April 2024

Abstract

Objective
The aim of this study was to demonstrate whether lasofoxifene improves vaginal signs/symptoms of genitourinary syndrome of menopause.

Methods
Two identical, phase 3 trials randomized postmenopausal women with moderate to severe vaginal symptoms to oral lasofoxifene 0.25 or 0.5 mg/d, or placebo, for 12 week. Changes from baseline to week 12 in most bothersome symptom, vaginal pH, and percentages of vaginal parabasal and superficial cells were evaluated. These coprimary endpoints were analyzed using analysis of covariance, except superficial cells, which were analyzed by the nonparametric, rank-based Kruskal-Wallis test.

Results
The two studies enrolled 444 and 445 women (mean age, ~60 y), respectively. Coprimary endpoints at week 12 improved with lasofoxifene 0.25 and 0.5 mg/d greater than with placebo (P < 0.0125 for all). Study 1: most bothersome symptom (least square mean difference from placebo: −0.4 and −0.5 for 0.25 and 0.5 mg/d, respectively), vaginal pH (−0.65, −0.58), and vaginal superficial (5.2%, 5.4%), and parabasal (−39.9%, −34.9%) cells; study 2: most bothersome symptom (−0.4, −0.5), vaginal pH (−0.57, −0.67), and vaginal superficial (3.5%, 2.2%) and parabasal (−34.1%, −33.5%) cells. Some improvements occurred as early as week 2. Most treatment-emergent adverse events were mild or moderate and hot flushes were most frequently reported (lasofoxifene vs placebo: 13%–23% vs 9%–11%). Serious adverse events were infrequent and no deaths occurred.

Conclusions
In two phase 3 trials, oral lasofoxifene 0.25 and 0.5 mg/d provided significant and clinically meaningful improvements in vaginal signs/symptoms with a favorable safety profile, suggesting beneficial effects of lasofoxifene on genitourinary syndrome of menopause.
The Posthyaluronidase Syndrome: Dosing Strategies for Hyaluronidase in the Dissolving of Facial Filler and Independent Predictors of Poor Outcomes
Authors: Wilde Caroline L. , Jiang Kailun , Lee Sieun , Ezra Daniel G. 
Published: April 2024

Background:
Hyaluronic acid dermal fillers are used extensively in periocular aesthetic medicine, and the incidence of filler-related complications is increasing. This study aimed to investigate the optimal dosing strategy for hyaluronidase and to identify predictors of poor outcomes.

Methods:
We performed a retrospective review of 157 orbits of 90 patients treated with hyaluronidase over a 4-year period. Demographic data, indication, and details of hyaluronidase treatment and outcomes were recorded.

Results:
The primary indication for dissolving filler was swelling in 52%, lumpiness in 20%, and before surgical blepharoplasty in 17%. The most frequently used hyaluronidase concentration was 150 U per mL in 66%, followed by 75 U per mL in 31%, 37.5 U per mL in 3%, and 100 U per mL in 1%. Outcomes were characterized as follows: 59% with a satisfactory result; 24% as insufficient treatment requiring further hyaluronidase; and 18% complaining of facial changes such as hollowing, indicating a post hyaluronidase syndrome. There was no statistical difference in outcomes between the 75 and 150 U per mL dosage groups (P = 0.625). A significant correlation was identified between posthyaluronidase syndrome and duration of filler in situ (P = 0.00019) and volume of filler (P = 0.000017).

Conclusions:
The posthyaluronidase syndrome may be related to previous filler volume and duration, rather than the concentration or dose of hyaluronidase used. All patients should be informed about the risks of adverse effects after hyaluronidase treatment; patients with longer histories of filler use and higher total volumes should be advised of the increased risk.
PNPLA3 rs738409, age, diabetes, sex, and advanced fibrosis jointly contribute to the risk of major adverse liver outcomes in metabolic dysfunction-associated steatotic liver disease
Authors: Chalasani Naga , Vilar-Gomez Eduardo , Loomba Rohit , Yates Katherine P. , Diehl Anna Mae , Neuschwander-Tetri Brent A. , Dasarathy Srinivasan , Kowdley Kris V. , Terrault Norah , Wilson Laura A. , Tonascia James , Sanyal Arun J. 
Published: April 2024

Background and Aims:
The patatin-like phospholipase domain-containing protein 3 (PNPLA3) rs738409 variant is associated with steatotic liver disease and its progression. We examined the association between PNPLA3 and the development of major adverse liver outcomes (MALOs) and how nonmodifiable and modifiable conditions modify this relationship.

Approach and Results:
A total of 2075 adults with biopsy-confirmed metabolic dysfunction-associated steatotic liver disease (MASLD) were enrolled in the metabolic dysfunction-associated steatohepatitis Clinical Research Network (MASH CRN) studies and followed prospectively until death, transplant, or withdrawal of consent. One hundred four MALOs were recorded during an average of 4.3 years. PNPLA3 G-allele (Adj. sub-hazard ratio (sHR): 1.4, 95% CI: 1.07–1.8), advanced fibrosis (AF) (Adj. sHR: 7.8, 95% CI: 4.4–13.8), age >60 years (Adj. sHR: 2.9, 95% CI: 1.3–6.8), and type 2 diabetes mellitus (Adj. sHR: 2.8, 95% CI: 1.8–4.2) were associated with MALO. Among participants with AF, those carrying the G-allele displayed the highest cumulative incidence of MALO (85%) versus noncarriers (53%), p=0.03, and p-value for interaction <0.01. The strength of the association between PNPLA3 and MALO was statistically significantly greater among older than 60 years (sHR: 2.1, 95% CI: 1.5–2.8), women (sHR: 1.4, 95% CI: 1.1–1.9), and those with AF (sHR: 1.9, 95% CI: 1.5–2.4) or type 2 diabetes mellitus (sHR: 2.1, 95% CI: 1.5–2.8) as compared with their counterparts, p-value for interaction between PNPLA3 and each factor<0.01.

Conclusions:
The deleterious effects of PNPLA3 rs738409 on the risk of MALO are significantly worsened by AF, age, type 2 diabetes mellitus, and sex.
The Value of Warning Signs From the WHO 2009 Dengue Classification in Detecting Severe Dengue in Children
Authors: Karyanti Mulya Rahma , Uiterwaal Cuno S. P. M. , Hadinegoro Sri Rezeki , Widyahening Indah Suci , Saldi Siti Rizny F. , Heesterbeek J. A. P. Hans , Hoes Arno W. , Bruijning-Verhagen Patricia 
Published: April 2024

Background:
World Health Organization proposed 7 warning signs to identify the risk of severe dengue in 2009. This study aimed to evaluate the value of these warning signs in detecting severe dengue in children.

Material and Methods:
A cross-sectional study was conducted utilizing data of children with clinical dengue infection obtained from medical records between January 2009 and December 2018 in Jakarta. Children with confirmed dengue were analyzed and stratified into 3 age groups: infants less than 1 year old, children 1–14 years and adolescents 15–18 years of age. Positive predictive value, negative predictive value (NPV), sensitivity and specificity of each warning sign present or absent on admission in detecting severe dengue were computed.

Results:
Six hundred ninety-nine children with clinical dengue infection were enrolled, among whom 614 (87.8%) had confirmed dengue infection, either by antigen or antibody serological tests. Severe dengue occurred in 211/614 (34.4%) cases. In infants, important warning signs on admission to detect or exclude severe dengue were liver enlargement (NPV 80.8%) and clinical fluid accumulation (NPV 75%). In children and adolescents, warning sign with highest NPV (in children 76.6% and in adolescents 91.9%) was increase in hematocrit concurrent with a rapid decrease in platelet count. Other warning signs with high NPV values in children were abdominal pain (72%), vomiting (70%), clinical fluid accumulation (69.3%), and in adolescents’ abdominal pain (80.7%), vomiting (75.7%), clinical fluid accumulation (82.7%). NPVs increase with more than 1 warning sign in all age groups.

Conclusion:
In infants, liver enlargement or clinical fluid accumulation are important warning signs for severe dengue, when both are absent, severe dengue is unlikely. In older children and adolescents, an increase in hematocrit with the concurrent rapid decrease in platelet count is most discriminative; followed by the absence of abdominal pain, vomiting or fluid accumulation are unlikely severe dengue.
Flange depth for scleral pocket vs no pocket techniques for intrascleral intraocular lens fixation
Authors: Amado Sebastian F. , Amado Norberto M. , Hermosa Luciano 
Published: April 2024

Purpose:
To compare flange depth for a modified scleral pocket (SP) vs no scleral pocket (NSP) technique (Yamane technique) for intrascleral intraocular lens (IOL) fixation.

Setting:
Instituto de Oftalmología Santa Fe, Santa Fe, Argentina.

Design:
Prospective, randomized, single-surgeon, observational study.

Methods:
Eyes with aphakia and no capsular support were included. They were divided into 2 groups: one was programmed for a double-needle flanged intrascleral IOL fixation as originally described by Shin Yamane with NSP and the second group had a modified SP technique. Flange depth was measured with anterior-segment optical coherence tomography (AS-OCT) at 1 month, 3 months, 6 months, and 12 months postoperatively, and the results were compared.

Results:
Each group comprised 18 eyes of 18 patients, giving a total of 36 flanges per group. The groups were comparable preoperatively. At 12 months, uncorrected distance visual acuity and corrected distance visual acuity (CDVA) were not statistically different for both groups (P = .333; P = .448). Spherical equivalent (SEQ) was not significantly different between groups at 12 months postoperatively (P = .078). AS-OCT revealed a significantly deeper flange position for the SP group at 1 month, 3 months, 6 months, and 12 months postoperatively (P < .05).

Conclusions:
When performing a double-needle intrascleral IOL fixation in aphakic eyes with no capsular support, a modified scleral pocket technique provides a significantly deeper flange position with no difference in CDVA or SEQ 12 months postoperatively.
Severely subluxated cataract
Authors: Chee Soon-Phaik , McKee Yuri , Snyder Michael E. , Lockington David , Vasavada Abhay , Vasavada Vaishali , Daoud Yassine J. , Rodgers Emily Grace , Al-Mohtaseb Zaina 
Published: April 2024

A 56-year-old man with a history of myopic LASIK presented with left eye gradual blurring of vision over 3 months. There was no history of trauma. His uncorrected visual acuities were 20/25 in the right eye and 20/400 in the left eye. The right eye was normal except for an early cataract. The left eye had a moderate cataract that was phacodonetic. Vitreous was present in the shallow anterior chamber (AC) (Figure 1

JOURNAL/jcrs/04.03/02158034-202405000-00018/figure1/v/2024-04-22T135154Z/r/image-tiff

). The fundus was normal. The intraocular pressures (IOPs) were 14 mm Hg in the right eye and 20 mm Hg in the left eye.
Ultrasound biomicroscopy of the anterior segment in the left eye revealed near total zonular loss with few intact zonular strands at the 6 and 10 o'clock regions (Figure 2

JOURNAL/jcrs/04.03/02158034-202405000-00018/figure2/v/2024-04-22T135154Z/r/image-tiff

). Vitreous was observed in the AC, herniating mostly from the 3 o'clock region. The endothelial cell density and optical coherence tomography (OCT) of the macular and disc in both eyes were normal. Central corneal thickness was 527 µm in the right eye and 520 µm in the left eye.
Describe how you would manage this case surgically. Optical biometry had been obtained, and the axial length in both eyes was similar. Discuss how you would select the monofocal intraocular lens (IOL) diopter (D) targeted for −1.50 D if the AC depth in the left eye was 2.48 mm and in the right eye was 3.25 mm.
Long-term outcomes of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): a randomized, multicenter, prospective, phase III trial
Authors: Zhang Rong-xin , Wu Xiao-jun , Wan De-sen , Lin Jun-zhong , Ding Pei-rong , Liao Le-en , Lei Jian , Lu Zhen-hai , Li Li-ren , Chen Gong , Kong Ling-heng , Wang Fu-long , Zhang Jian , Fan Wen-hua , Jiang Wu , Zhou Wen-hao , Li Cong , Li Yuan , Li Xue-ying , Peng Jian-hong , Pan Zhi-zhong 
Published: April 2024

Background:
The authors aimed to compare combined intraoperative chemotherapy and surgical resection with curative surgical resection alone in colorectal cancer patients.

Methods:
The authors performed a multicenter, open-label, randomized, phase III trial. All eligible patients were randomized and assigned to intraoperative chemotherapy and curative surgical resection or curative surgical resection alone (1:1). Survival after long-term follow-up was performed in patients analyzed on an intention-to-treat basis.

Results:
From January 2011 to January 2016, 696 colorectal cancer patients were enrolled and randomly assigned to intraoperative chemotherapy and radical surgical resection (n=341) or curative surgical resection alone (n=344). Intraoperative chemotherapy with surgical resection showed no significant survival benefit over surgical resection alone in colorectal cancer patients [3-year disease-free survival (DFS): 91.1 vs. 90.0%, P=0.328; 3-year OS: 94.4 vs. 95.9%, P=0.756). However, colon cancer patients benefitted from intraoperative chemotherapy, with a relative 4% reduction in liver and peritoneal metastasis (HR=0.336, 95% CI: 0.148–0.759, P=0.015) and a 6.5% improvement in 3-year DFS (HR=0.579, 95% CI: 0.353–0.949, P=0.032). Meanwhile, patients with colon cancer and abnormal pretreatment carcinoembryonic antigen (CEA) levels achieved significant survival benefits from intraoperative chemotherapy (DFS: HR=0.464, 95% CI: 0.233–0.921, P=0.029 and OS: HR=0.476, 95% CI: 0.223–1.017, P=0.049).

Conclusions:
Intraoperative chemotherapy showed no significant extra prognostic benefit in total colorectal cancer patients who underwent radical surgical resection; however, in colon cancer patients with abnormal pretreatment serum CEA levels (> 5 ng/ml), intraoperative chemotherapy could improve long-term survival.
Surgical Management of Airway Obstruction following Posterior Pharyngeal Flap
Authors: Li Yanan , Yin Xing , Shi Bing , Li Jingtao 
Published: April 2024

Background:
The posterior pharyngeal flap (PPF) is effective in managing velopharyngeal insufficiency but is associated with airway obstruction risk. This study compared the effectiveness and complications of 2 PPF revision procedures and screened potential prognostic factors to postoperative hypernasality and persistent obstruction.

Methods:
Patients who received flap division (FD) or port enlargement (PE) for airway obstruction following PPF were reviewed. Ventilation status was assessed using the Nasal Obstruction Symptom Evaluation scale, and velopharyngeal closure was assessed using subjective speech evaluation and nasopharyngoscopy. The effectiveness of ventilation relief and complication rate (hypernasality and persistent obstruction) of the 2 techniques were compared. A comprehensive panel of factors—including age, velopharyngeal mobility, obstruction laterality, body mass index, jaw relationship, and adenoid hypertrophy—was evaluated for correlation with complications.

Results:
A total of 79 patients were enrolled, with 51 undergoing FD and 28 undergoing PE. Both techniques significantly improved ventilation dysfunction and hyponasality. Mild hypernasality occurred in 10 cases in the FD group and 3 in the PE group. Age at surgery was significantly associated with persistent obstruction after PPF revision. The occurrence of persistent obstruction was significantly higher among patients younger than 12 years than those older than 12 years. Obstruction laterality was suggested in significant correlation with hypernasality after PPF revision. Among patients with unilateral port obstruction, the occurrence of hypernasality after FD was significantly higher than after PE.

Conclusions:
Both flap division and port enlargement are effective revision procedures to relieve airway obstruction after PPF. Patients younger than 12 years are more likely to experience persistent ventilation problems after PPF revision.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, II.