Recurrent graft fibrosis after liver transplantation can threaten both graft and patient survival. Therefore, early detection of fibrosis is essential to avoid disease progression and the need for ...retransplantation. Non-invasive blood-based biomarkers of fibrosis are limited by moderate accuracy and high cost. We aimed to evaluate the accuracy of machine learning algorithms in detecting graft fibrosis using longitudinal clinical and laboratory data.
In this retrospective, longitudinal study, we trained machine learning algorithms, including our novel weighted long short-term memory (LSTM) model, to predict the risk of significant fibrosis using follow-up data from 1893 adults who had a liver transplantation between Feb 1, 1987, and Dec 30, 2019, with at least one liver biopsy post transplantation. Liver biopsy samples with indefinitive fibrosis stage and those from patients with multiple transplantations were excluded. Longitudinal clinical variables were collected from transplantation to the date of last available liver biopsy. Deep learning models were trained on 70% of the patients as the training set and 30% of the patients as the test set. The algorithms were also separately tested on longitudinal data from patients in a subgroup of patients (n=149) who had transient elastography within 1 year before or after the date of liver biopsy. Weighted LSTM model performance for diagnosing significant fibrosis was compared against LSTM, other deep learning models (recurrent neural network and temporal convolutional network), and machine learning models (Random Forest, Support vector machines, Logistic regression, Lasso regression, and Ridge regression) and aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and transient elastography.
1893 people who had a liver transplantation (1261 67% men and 632 33% women) with at least one liver biopsy between Jan 1, 1992, and June 30, 2020, were included in the study (591 31% cases and 1302 69% controls). The median age at liver transplantation was 53·7 years (IQR 47·3–59·0) for cases and 55·3 years (48·0 to 61·2) for controls. The median time interval between transplant and liver biopsy was 21 months (5 to 71). The weighted LSTM model (area under the curve 0·798 95% CI 0·790 to 0·810) consistently outperformed other methods, including unweighted LSTM (0·761 0·750 to 0·769; p=0·031) Recurrent Neural Network (0·736 0·721 to 0·744), Temporal Convolutional Networks (0·700 0·662 to 0·747, and Random Forest 0·679 0·652 to 0·707), FIB-4 (0·650 0·636 to 0·663) and APRI (0·682 0·671 to 0·694) when diagnosing F2 or worse stage fibrosis. In a subgroup of patients with transient elastography results, weighted LSTM was not significantly better at detecting fibrosis (≥F2; 0·705 0·687 to 0·724) than transient elastography (0·685 0·662 to 0·704). The top ten variables predictive for significant fibrosis were recipient age, primary indication for transplantation, donor age, and longitudinal data for creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, platelets, white blood cell count, and weight.
Deep learning algorithms, particularly weighted LSTM, outperform other routinely used non-invasive modalities and could help with the earlier diagnosis of graft fibrosis using longitudinal clinical and laboratory variables. The list of most important predictive variables for the development of fibrosis will enable clinicians to modify their management accordingly to prevent onset of graft cirrhosis.
Canadian Institute of Health Research, American Society of Transplantation, Toronto General and Western Hospital Foundation, and Paladin Labs.
Abstract Background The aim of the present study was to investigate the therapeutic effects of p75 tumor necrosis factor receptor monoclonal antibody D8F2 on a traumatic arthritis model in rats, and ...to explore the underlying mechanism. Methods Forty male Sprague Dawley rats were randomly divided into five groups: (A) sham operation control group, (B) traumatic arthritis model group, (C) low-dose D8F2 group (1 mg/kg), (D) medium-dose D8F2 group (3 mg/kg), and (E) high-dose D8F2 group (10 mg/kg). Joint fluid samples were collected at 72 h after surgery, and enzyme-linked immunosorbent assay was performed to measure the following inflammatory factors: tumor necrosis factor α (TNF-α) and interleukin 1β. One week after the surgery, rats were killed, and immunohistochemical staining was applied to detect the matrix metalloproteinase (MMP1 and MMP3) expression in the synovium. In cultured synovial fibroblast experiments, the D8F2-induced ubiquitination of TNF receptor–associated factor 2 (TRAF2) was examined by immunoprecipitation, and nuclear translocation of p65 nuclear factor-κB (p65NF-κB) mediated by TNF-α and D8F2 was analyzed by western blotting. Results In the traumatic arthritis model group, the inflammatory factors and MMPs were significantly increased relative to the sham operation control group ( P < 0.05), whereas D8F2 could downregulate these factors in a dose-dependent manner ( P < 0.05). The results from in vitro studies indicated that D8F2 can induce TRAF2 ubiquitination and inhibit the nuclear translocation of p65NF-κB mediated by TNF-α. Conclusions p75 Tumor necrosis factor receptor monoclonal antibody has a therapeutic effect on traumatic arthritis, which may occur via the downregulation of inflammatory factors and MMPs at the transcription level because of TRAF2 degradation and inhibited activation of NF-κB.
The demand for genital plastic surgery has increased dramatically among female patients globally. Although various labia minora reduction procedures have been applied with different indications, ...advantages, and disadvantages, none has been universally accepted as the best method. So, we presented an innovative strategy for this increasingly demanded reconstructive procedure.
In this retrospective study, we included 29 patients seen between November 2020 and May 2023 with hypertrophic labia minora. The patients with hypertrophic labia minora after serrated-shaped resection were included for analysis. Patient satisfaction and complications were evaluated through the follow-up after the operation.
Patients with a mean age of 27.1 years (range 19-47 y) performed labia minora reduction via serrated-shaped resection. One patient experienced incision dehiscence, requiring additional surgical revision. One patient experienced postoperative cosmetic asymmetry and also performed secondary repair surgery. One patient experienced urinary retention, which was relieved after urinary catheterization. High overall patient satisfaction has been achieved after a median follow-up of 6.7 months (range 1-24 months). No flap necrosis, sexual dysfunction, or hypertrophic scarring has been reported.
Results suggested that serrated-shaped resection is a novel technique for repairing hypertrophic labia minora with high efficiency and satisfaction. The procedure could effectively improve the appearance of the labia minora and reduce complications.
Purpose To determine the feasibility of implementing problem-based learning (PBL) in a large class and whether previous PBL experience is necessary. Materials and Methods A total of 236 students from ...2 large classes at China Medical University were enrolled. One class (118 students) had had a previous small-group PBL experience and another class (113 students) had not. Each class was subdivided into 15 groups (7 to 8 students/group) and took 2 separate 100-minute PBL sessions per week with the same teaching faculty. Each PBL class had 2 facilitators, 1 content expert facilitator, and 1 nonexpert facilitator. The results of the theoretical examination and case analysis examinations were analyzed using the t test. Questionnaires were used to evaluate both student and facilitator perceptions. Results The feedback from both students and facilitators was positive. According to the questionnaires, both experienced and non-experienced students acknowledged that the teaching method was enjoyable and functional. The test results showed students had achieved the learning objectives. The results of the theoretical and case analysis examinations showed no significant difference between the PBL experienced class and the non-experienced class. The mean study hours spent weekly by the students after class on the course were about 6.3 ± 1.1 hours for the non-experienced students and 4.7 ± 0.981 hours for the experienced students ( t = 11.94, P < .001). The non-experienced students showed more preference for the content expert tutor. Conclusion Implementing PBL in a large class is feasible without extracting great demand on limited educational resources. Previous PBL experience is helpful but not necessary.
Abstract Objective Infantile nystagmus (IN) is characterized by bilateral involuntary, periodic, and predominantly ocular oscillations. In this article, we describe a mutation screen conducted on a ...4-generation family in which 4 patients were affected with X-linked IN (XLIN). Design Experimental study. Participants A 4-generation Chinese Han family including 4 symptomatic members with IN and 200 normal male controls. Methods DNA was extracted from peripheral blood, and the FERM domain-containing 7 gene ( FRMD7 ) was amplified on DNA samples of all the available family members. The mutation screen was conducted by performing direct DNA sequencing. Results A nonsense mutation (R335X) in the FRMD7 gene was identified in 4 male patients and an asymptomatic female member. Conclusions Although the R335X mutation in the FRMD7 gene has been previously described, the clinical features, including both disease penetrance and severity, among individuals with FRMD7 mutation in our family vary greatly. One female member with the heterozygous R335X mutation had no clinical manifestation of the disease. This incomplete penetrance suggests that random X-chromosome inactivation may play a role in the pathogenesis of IN, and that loss of functional FRMD7 may account for the development of this disorder. Our findings may be helpful in the genetic counseling of patients with nystagmus.
Furthermore, Aung and coworkers3 found that patients with evolving ID who maintained their hemoglobin levels over time had a 2-fold greater risk of death than those whose hemoglobin levels declined ...without evolving ID. ...Jankowska and coworkers4 demonstrated that with increasing CHF severity, patients in advanced New York Heart Association classes had ID, and the progression of CHF is associated with the decline in circulating hepcidin and the development of ID.
Objectives The aim of this study was to understand the impact of attenuated plaque on distal embolization during stent implantation in patients with acute myocardial infarction (AMI). Background ...Attenuated plaques identified by grayscale intravascular ultrasound (IVUS) might predict transient deterioration in coronary flow and/or no-reflow during percutaneous coronary intervention (PCI). Methods We analyzed clinical, angiographic, and IVUS data from 364 patients (n = 364 infarct-related arteries) enrolled in the randomized HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial. No-reflow was final Thrombolysis In Myocardial Infarction (TIMI) flow grade ≤2 in the absence of mechanical obstruction. Attenuated plaque was hypoechoic or mixed atheroma with ultrasound attenuation without calcification. A mean attenuation score was created by measuring the angle of attenuation each 1 mm, scoring the angle as 1 to 4 (corresponding to <90°, 90° to 180°, 180° to 270°, or 270° to 360°, respectively), summing the scores, and normalizing for analysis length. Results Overall, 284 (78.0%) patients had attenuated plaques; no-reflow occurred in 37 (10.2%). Patients with no-reflow had a higher mean attenuation score (median interquartile range 2.2 0.0 to 2.8 vs. 1.3 0.7 to 1.8, p < 0.001), lower baseline left ventricular ejection fraction (52.8% 43.2% to 61.5% vs. 61.4% 52.2% to 68.1%, p = 0.002), and more baseline angiographic thrombus (89.2% vs. 74.1%, p = 0.043) with no differences in post-PCI stent expansion versus patients without no-reflow. Multivariate analysis indicated that mean attenuation score was the strongest predictor of no-reflow. The mean attenuation score that best predicted no-reflow was ≥2 points (90° to 180°, sensitivity of 81.5%, and specificity of 80.5%). Conclusions Attenuated plaque was present in three-quarters of patients with AMI. The amount of attenuated plaque strongly correlated with no-reflow; the larger the attenuated plaque, the greater the likelihood of no-reflow. (Dual Arm Factorial Randomized Trial in Patients w/ST Segment Elevation AMI to Compare the Results of Using Anticoagulation With Either Unfractionated Heparin + Routine GP IIb/IIIa Inhibition or Bivalirudin + Bail-out GP IIb/IIIa Inhibition; and Primary Angioplasty with stent implantation with Either a Slow Rate-release Paclitaxel-eluting Stent TAXUS™ or Uncoated Bare Metal Stent EXPRESS2™; NCT00433966 )
Background Treprostinil is a stable prostacyclin analog approved for the treatment of pulmonary arterial hypertension (PAH) as parenteral or inhaled therapy. Treprostinil diolamine, a ...sustained-release oral formulation of treprostinil, was studied to determine whether it could provide a more convenient prostacyclin treatment option for patients with less severe PAH. The objective of this study was to evaluate the efficacy and safety of oral treprostinil in patients with PAH receiving stable background endothelin receptor antagonist (ERA), phosphodiesterase type 5 inhibitor (PDE-5I) therapy, or both. Methods A 16-week, multicenter, double-blind, placebo-controlled study in 310 patients with PAH compared bid administration of oral treprostinil (n = 157) with placebo (n = 153). The primary end point was change in 6-min walk distance at week 16. Secondary efficacy end points were World Health Organization functional class, Borg dyspnea score, dyspnea-fatigue index, signs and symptoms of PAH, and clinical worsening. Results One hundred thirty-two patients (84%) receiving oral treprostinil and 138 (90%) receiving placebo completed the study. The mean ± SD dose of oral treprostinil at week 16 was 3.1 ± 1.9 mg bid. The Hodges-Lehmann placebo-corrected median difference in 6MWD at week 16 was 10.0 m (95% CI, −2 to 22 m; P = .089). There were no significant changes in secondary end points. The most common adverse events associated with oral treprostinil were headache (71%), diarrhea (55%), nausea (46%), flushing (35%), and jaw pain (25%). Conclusions The addition of oral treprostinil to background ERA and PDE-5I therapy did not result in a statistically significant improvement in exercise capacity. Side effects were common but tolerated by most subjects. Trial registry ClinicalTrials.gov ; No.: NCT00887978 ; URL: www.clinicaltrials.gov
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