Comparison of miscarriage rates in low prognosis patients according to the POSEIDON criteria.

OBJECTIVE: The POSEIDON criteria stratified patients with poor ovarian response into four subgroups with exclusive characteristics and assisted reproductive technology success rates. However, limited studies focused on miscarriage in the POSEIDON population. This study aimed to explore whether the miscarriage rate different among low prognosis patients according to POSEIDON criteria. MATERIALS AND METHODS: This is a retrospective observational study. All clinical pregnancies achieved after in vitro fertilization or intracytoplasmic sperm injection treatment between January 1998 and April 2021 were analyzed. The primary outcome was miscarriage, defined as the pregnancy loss before 20 weeks of gestation age. Miscarriage rate was estimated per clinical pregnancy and gestational sac. RESULTS: A total of 1222 clinical pregnancies from 1088 POSEIDON patients met the inclusion criteria. The miscarriage rates per clinical pregnancy in each POSEIDON subgroup were as follows: Group 1: 11.7 %, Group 2: 26.5 %, Group 3: 20.9 %, and Group 4: 37.5 %. The miscarriage rate per gestational sac showed a similar trend as the clinical miscarriage rate. Multivariate regression analysis showed that advanced maternal age is an independent factor for miscarriage (Group 2 vs. 1: OR 2.476; Group 4 vs. 3: OR 2.252). Patients with diminished ovarian reserve (DOR) have higher miscarriage risks but without significance (Group 3 vs. 1: OR 1.322; Group 4 vs. 2: OR 1.202). CONCLUSION: Miscarriage rates differed among low prognosis patients according to the POSEIDON criteria. Age remains a determined risk for miscarriage. DOR might be a potential factor for miscarriage, but it didn't account for a significant impact in POSEIDON patients.

Machine Learning Radiomics Signature for Differentiating Lymphoma versus Benign Splenomegaly on CT.

BACKGROUND: We aimed to develop and validate a preoperative CT-based radiomics signature for differentiating lymphoma versus benign splenomegaly. METHODS: We retrospectively analyzed CT studies from 139 patients (age range 26-93 years, 43% female) between 2011 and 2019 with histopathological diagnosis of the spleen (19 lymphoma, 120 benign) and divided them into developing (n = 79) and testing (n = 60) datasets. The volumetric radiomic features were extracted from manual segmentation of the whole spleen on venous-phase CT imaging using PyRadiomics package. LASSO regression was applied for feature selection and development of the radiomic signature, which was interrogated with the complete blood cell count and differential count. All p values < 0.05 were considered to be significant. RESULTS: Seven features were selected for constructing the radiomic signature after feature selection, including first-order statistics (10th percentile and Robust Mean Absolute Deviation), shape-based (Surface Area), and texture features (Correlation, MCC, Small Area Low Gray-level Emphasis and Low Gray-level Zone Emphasis). The radiomic signature achieved an excellent diagnostic accuracy of 97%, sensitivity of 89%, and specificity of 98%, distinguishing lymphoma versus benign splenomegaly in the testing dataset. The radiomic signature significantly correlated with the platelet and segmented neutrophil percentage. CONCLUSIONS: CT-based radiomics signature can be useful in distinguishing lymphoma versus benign splenomegaly and can reflect the changes in underlying blood profiles.

Comparing Magnetic Resonance Fingerprinting (MRF) and the MAGiC Sequence for Simultaneous T1 and T2 Quantitative Measurements in the Female Pelvis: A Prospective Study.

The aim of this study was to explore the potential of magnetic resonance fingerprinting (MRF), an emerging quantitative MRI technique, in measuring relaxation values of female pelvic tissues compared to the conventional magnetic resonance image compilation (MAGiC) sequence. The study included 32 female patients who underwent routine pelvic MRI exams using anterior and posterior array coils on a 3T clinical scanner. Our findings demonstrated significant correlations between MRF and MAGiC measured T1 and T2 values (p < 0.0001) for various pelvic tissues, including ilium, femoral head, gluteus, obturator, iliopsoas, erector spinae, uterus, cervix, and cutaneous fat. The tissue contrasts generated from conventional MRI and synthetic MRF also showed agreement in bone, muscle, and uterus for both T1-weighted and T2-weighted images. This study highlights the strengths of MRF in providing simultaneous T1 and T2 mapping. MRF offers distinct tissue contrast and has the potential for accurate diagnosis of female pelvic diseases, including tumors, fibroids, endometriosis, and pelvic inflammatory disease. Additionally, MRF shows promise in monitoring disease progression or treatment response. Overall, the study demonstrates the potential of MRF in the field of female pelvic organ imaging and suggests that it could be a valuable addition to the clinical practice of pelvic MRI exams. Further research is needed to establish the clinical utility of MRF and to develop standardized protocols for its implementation in clinical practice.

Generalizable transfer learning of automated tumor segmentation from cervical cancers toward a universal model for uterine malignancies in diffusion-weighted MRI.

PURPOSE: To investigate the generalizability of transfer learning (TL) of automated tumor segmentation from cervical cancers toward a universal model for cervical and uterine malignancies in diffusion-weighted magnetic resonance imaging (DWI). METHODS: In this retrospective multicenter study, we analyzed pelvic DWI data from 169 and 320 patients with cervical and uterine malignancies and divided them into the training (144 and 256) and testing (25 and 64) datasets, respectively. A pretrained model was established using DeepLab V3 + from the cervical cancer dataset, followed by TL experiments adjusting the training data sizes and fine-tuning layers. The model performance was evaluated using the dice similarity coefficient (DSC). RESULTS: In predicting tumor segmentation for all cervical and uterine malignancies, TL models improved the DSCs from the pretrained cervical model (DSC 0.43) when adding 5, 13, 26, and 51 uterine cases for training (DSC improved from 0.57, 0.62, 0.68, 0.70, p < 0.001). Following the crossover at adding 128 cases (DSC 0.71), the model trained by combining data from adding all the 256 patients exhibited the highest DSCs for the combined cervical and uterine datasets (DSC 0.81) and cervical only dataset (DSC 0.91). CONCLUSIONS: TL may improve the generalizability of automated tumor segmentation of DWI from a specific cancer type toward multiple types of uterine malignancies especially in limited case numbers.

Oxidized-LDL Deteriorated the Renal Residual Function and Parenchyma in CKD Rat through Upregulating Epithelial Mesenchymal Transition and Extracellular Matrix-Mediated Tubulointerstitial Fibrosis-Pharmacomodulation of Rosuvastatin.

This study tested the hypothesis that intrarenal arterial transfusion of oxidized low-density lipoprotein (ox-LDL) jeopardized the residual renal function and kidney architecture in rat chronic kidney disease ((CKD), i.e., induced by 5/6 nephrectomy) that was reversed by rosuvastatin. Cell culture was categorized into A1 (NRK-52E cells), A2 (NRK-52E + TGF-ß), A3 (NRK-52E + TGF-ß + ox-LDL) and A4 (NRK-52E + TGF-ß + ox-LD). The result of in vitro study showed that cell viability (at 24, 48 and 72 h), NRK-52E ox-LDL-uptake, protein expressions of epithelial−mesenchymal−transition (EMT) markers (i.e., p-Smad2/snail/α-SMA/FSP1) and cell migratory and wound healing capacities were significantly progressively increased from A1 to A4 (all p < 0.001). SD rats were categorized into group 1 (sham-operated control), group 2 (CKD), group 3 (CKD + ox-LDL/0.2 mg/rat at day 14 after CKD induction) and group 4 (CKD + ox-LDL-treated as group 3+ rosuvastatin/10 mg/kg/day by days 20 to 42 after CKD induction) and kidneys were harvested at day 42. The circulatory levels of BUN and creatinine, ratio of urine-protein to urine-creatinine and the protein expressions of the above-mentioned EMT, apoptotic (cleaved-caspase3/cleaved-PARP/mitochondrial-Bax) and oxidative-stress (NOX-1/NOX-2/oxidized-protein) markers were lowest in group 1, highest in group 3 and significantly higher in group 4 than in group 2 (all p < 0.0001). Histopathological findings demonstrated that the kidney injury score, fibrotic area and kidney injury molecule-1 (KIM-1) displayed an identical pattern, whereas the cellular expression of podocyte components (ZO-1/synaptopodin) exhibited an opposite pattern of EMT markers (all p < 0.0001). In conclusion, ox-LDL damaged the residual renal function and kidney ultrastructure in CKD mainly through augmenting oxidative stress, EMT and fibrosis that was remarkably reversed by rosuvastatin.

Disposition of embryos from women who only produced morphologically poor embryos on day three.

BACKGROUND: The presence of only morphologically poor embryos (MPEs) on day3 is common in autologous in vitro fertilization (IVF), particularly among p Tel: 886-7-7317123 Ext. 8916. Fax: 886-7-7322915.atients who have advanced maternal age or are poor responders. However, there are limited data regarding the disposition of embryos from patients who only produced MPEs on day3. The present study was designed to investigate the possible benefits of extended culturing MPEs. Try to detect whether the extended culture (day4 or day5 culture) can improve the live birth rate per cycle? METHODS: This retrospective, observational, single-center, cohort study examined 224 IVF/intracytoplasmic sperm injection (ICSI) cycles between January 2010 and June 2015, in which women only produced MPEs on day3. A total of 544 MPEs were analyzed. The defines a day3 embryo as an MPE if it fails to develop to eight cells, blastomeres of equal size, and less than 20% cytoplasmic fragments. Of the 224 cycles, 89 (39.7%) underwent fresh embryo transfer on day3, and 135 (60.3%) underwent extended culture. Of the 135 extended cultures, 54 cycles (40.0%) experienced day4, or day5 embryo transfer, 16 cycles (11.9%) had all embryos frozen, and 65 cycles (48.1%) had total embryo arrest. RESULTS: Analysis of patient baseline demographic data, cycle characteristics, and cycle outcomes for day3 transfer group and extended culture group indicated that a higher body mass index in the day3 transfer group was the only significant difference (p = 0.006). Both fresh transfer groups had low live birth rates (LBRs) (4.5% vs. 7.4% p = 0.46). After extended culture, 65 cycles (48.1%) were cancelled because the embryos exhibited developmental arrest and 70 cycles (51.9%) grew to day4 or day5. Thirteen frozen embryo transfer (FET) cycles and 22 frozen blastocysts derived from MPEs were thawed. There were more high-quality embryos (p < 0.001), higher implantation rates (IRs) (p = 0.038), and higher LBRs (p = 0.042) for embryos that underwent FET cycles. MPES in extended culture transfer have favorable survival than MPES in day3 transfer. CONCLUSION: The extended culture of MPEs in fresh transfer cycles did not increase the LBR. However, younger females with the extended culture of MPEs followed by FET resulted in significantly higher LBRs and may be a feasible strategy to improve outcomes for patients with poor embryo quality. However, day3 embryo transfer may be a better choice if a fresh transfer is unrestricted and avoid the cycle cancellation. Extended culture may decrease to the transfer of developmental potential arrest embryos to patients.

Monopronucleated (1PN) and tripronuclear (3PN) zygotes formation during assisted reproduction in POSEIDON group 4 patients: Emphasizing on polar bodies.

AIM: Abnormal fertilization (1PN/3PN) and its accompanying polar body (PB) conditions have been less discussed in poor ovarian responders. By observing the PBs, we analyzed the mechanisms of abnormal fertilization and aimed to explore the role of intracytoplasmic sperm injection/in vitro fertilization (ICSI/IVF) in POSEIDON group 4 patients. METHODS: An observational study. All fresh IVF/ICSI cycles from January 2018 to December 2019 were evaluated. The inclusion criteria were POSEIDON group 4. Fertilization and PB conditions were assessed 16-18 h post-insemination. Primary observation endpoints including normal fertilization, abnormal fertilization, and total fertilization failure rate. RESULTS: A total of 351 cycles involving 180 patients met the inclusion criteria. Of these, 15 cycles reported no retrieved oocytes. Finally, 336 cycles (IVF, n = 267; ICSI, n = 69) were included. A total of 1005 oocytes and 939 embryos were assessed. The mean female age was 40.8 years, and the mean AMH level was 0.6 ng/mL. The normal fertilization rate was 69.7%. The zygote distribution was 18.7% 0PN, 3.9% 1PN, 66.9% 2PN, 9.5% 3PN, and 1.0% ≥4PN. For 1PN zygotes, 59% were denoted as 1PN2PB. The mean 3PN rate was 8.9%. CONCLUSIONS: In POSEIDON group 4, most of the monopronucleated zygotes were 1PN2PB. Digyny (3PN1PB), due to failure to extrude the second PB, was the major cause of triploidy in which ICSI could not circumvent. The distribution of abnormally fertilized zygotes was similar in IVF and ICSI. To investigate the mechanisms of abnormal fertilization and assess whether ICSI is necessary, analysis of PB will provide important clues.

Investigation of echocardiographic characteristics and predictors for persistent defects of patent foramen ovale or patent ductus arteriosus in Chinese newborns.

BACKGROUND: Persistent patent foramen ovale (PFO) and patent ductus arteriosus (PDA) increase the adult risk of cryptogenic embolic stroke and chronic pulmonary hypertension. To understand the characteristics of PFO and PDA in newborns, we investigated the spontaneous closure rate and derived the determinants for residual defects. METHODS: We utilized the database of congenital heart disease (CHD) in Xiamen ChangGung Memorial Hospital from 2015 to 2017 and allocated 2523 eligible newborns into four groups according to PDA, PFO, both or neither at birth. A total of 574, 1229, 202 and 518 newborns were assigned into the group of PFO and PDA, PFO alone, PDA alone and non-PFO/non-PDA, respectively. Regular echocardiographic follow-ups at baseline, 6, 12 and 24 months after birth were performed for evaluating the spontaneous closure rate in the subjects. Regression analysis was carried out to study the risk factors of residual congenital defects. RESULTS: Newborns with PFO alone had the youngest birth age and lowest birth weight among the four groups. About one in four PDA-alone newborns had concomitant small ASD, i.e., <5 mm in diameter. Echocardiographic study showed that 71.3% and 30.8% of CHD newborns had PFO and PDA, respectively, compared to less than 10% of them having ASD or VSD. However, more than 95% of newborns with PFO or PDA closed spontaneously at 6 months, in contrast to about 30% of newborns with ASD or VSD had persistent existence of the intracardiac defects. Complex CHD significantly linked to persistent PFO or PDA at 6 and 12 months, with an adjusted hazard ratio of 9.03 (95% CI 1.97-41.46) and 12.11 (95% CI 2.11-69.72), respectively. CONCLUSIONS: Chinese newborns with PFO or PDA expressed differences in characteristics and concomitant congenital defects. Additionally, persistent PFO or PDA is strongly associated with complex CHD and requires long-term regular monitoring for future associated complications.

Computer-Aided Segmentation and Machine Learning of Integrated Clinical and Diffusion-Weighted Imaging Parameters for Predicting Lymph Node Metastasis in Endometrial Cancer.

Precise risk stratification in lymphadenectomy is important for patients with endometrial cancer (EC), to balance the therapeutic benefit against the operation-related morbidity and mortality. We aimed to investigate added values of computer-aided segmentation and machine learning based on clinical parameters and diffusion-weighted imaging radiomics for predicting lymph node (LN) metastasis in EC. This prospective observational study included 236 women with EC (mean age ± standard deviation, 51.2 ± 11.6 years) who underwent magnetic resonance (MR) imaging before surgery during July 2010-July 2018, randomly split into training (n = 165) and test sets (n = 71). A decision-tree model was constructed based on mean apparent diffusion coefficient (ADC) value of the tumor (cutoff, 1.1 × 10-3 mm2/s), skewness of the relative ADC value (cutoff, 1.2), short-axis diameter of LN (cutoff, 1.7 mm) and skewness ADC value of the LN (cutoff, 7.2 × 10-2), as well as tumor grade (1 vs. 2 and 3), and clinical tumor size (cutoff, 20 mm). The sensitivity and specificity of the model were 94% and 80% for the training set and 86%, 78% for the independent testing set, respectively. The areas under the receiver operating characteristics curve (AUCs) of the decision-tree was 0.85-significantly higher than the mean ADC model (AUC = 0.54) and LN short-axis diameter criteria (AUC = 0.62) (both p < 0.0001). We concluded that a combination of clinical and MR radiomics generates a prediction model for LN metastasis in EC, with diagnostic performance surpassing the conventional ADC and size criteria.

Reduced effects of cardiac extracorporeal shock wave therapy on angiogenesis and myocardial function recovery in patients with end-stage coronary artery and renal diseases.

BACKGROUND: Growing evidence have shown cardiac extracorporeal shock wave therapy (ESWT) improve clinical symptoms and left ventricular ejection fraction (LVEF) for patients with end-stage diffuse coronary artery disease (EnD-CAD) unsuitable for coronary interventions. However, little is known whether cardiac ESWT remains effective on symptomatic relief and improvement of LVEF for the EnD-CAD patients with end-stage renal disease (ESRD). METHODS: This was a small-scale prospective study. Between August 2016 and January 2019, a total of 16 subjects received cardiac ESWT for their EnD-CAD. They were divided into two groups according to ESRD or not, i.e., EnD-CAD group (n = 8) and EnD-CAD/ESRD group (n = 8). Clinical symptoms including angina and dyspnea, levels of circulating endothelial progenitor cells (EPC), LVEF, and adverse events were regularly followed up for one year to compare safety and efficacy of cardiac ESWT between the EnD-CAD patients with or without ESRD. RESULTS: All participants tolerated cardiac ESWT without any relevant side effects such as skin allergic reaction, local redness/tenderness or cardiac arrhythmia. There were similar baseline comorbidities and clinical features between two groups, but the EnD-CAD/ESRD group had significantly higher serum potassium level as well as lower renal function and lipid profile (all p-values <0.03). After cardiac ESWT, the patients in both groups had significant improvement in angina and dyspnea at 1 year (all p-values <0.03). However, the EnD-CAD/ESRD group did not have increase in either circulating EPC levels or LVEF at 6 months (mean change in LVEF: -4.00% ± 8.32%, p = 1.000). In contrast, the EnD-CAD group had gradually improving levels of circulating EPC surface markers and increased LV systolic function (mean change in LVEF: +4.87% ± 8.76%, p = 0.092). Notably, patients in the EnD-CAD/ESRD group suffered from high incidental clinical adverse events before and after enrollment into the ESWT study (75% vs. 25%, p = 0.132). CONCLUSION: Although cardiac ESWT provided improvement of clinical symptoms in the EnD-CAD patients, its long-term effects on the angiogenesis and LVEF were reduced for those high-risk patients with concomitant EnD-CAD and ESRD. TRIAL REGISTRATION: none.

Association between paternal age and risk of schizophrenia: a nationwide population-based study.

PURPOSE: To study the association between paternal age and schizophrenia in offspring. METHODS: This report describes a nationwide population-based cohort study from 1997 to 2013. Data from Taiwan's National Health Insurance Research Database were utilized to answer the research question. A total of 17,649 offspring with schizophrenia were selected from 11 million offspring in the general population. Additionally, we established the offspring without schizophrenia as the comparison group by matching the study cohort by age, gender in a 1:4 ratio (n = 70,596). RESULTS: The median age at first presentation with schizophrenia was 20 years (interquartile range (IQR), 17 to 24). Comparison of the schizophrenia and non-schizophrenia groups indicated that father's age at birth (30.0 (IQR), 27 to 33 vs. 29.0 (IQR), 26 to 32 years), mother's age at birth (26.0 (IQR), 24 to 29 vs. 26.0 (IQR), 23 to 29 years), paternal schizophrenia (2.6% vs. 0.6%), and maternal schizophrenia (4.4% vs. 0.7%) were all significantly greater in the schizophrenia group. In addition, each 5-year increase in father's age increased the odds of being diagnosed with schizophrenia (model 1: aOR = 1.22; 95% CI 1.20, 1.24; model 2: aOR = 1.20; 95% CI 1.18, 1.23). Subgroup analysis showed that each 5-year increase in father's age increased the odds of being diagnosed with schizophrenia in male and female offspring, as well as in offspring of mothers and fathers with or without schizophrenia (aOR = 1.20 to 2.20, all p values < 0.01). CONCLUSION: This study indicated that advanced paternal age increased the risk of schizophrenia in offspring. Offspring born to fathers older by 5-year increments were at heightened risk of schizophrenia.

Risk of major adverse cardiovascular and cerebrovascular events in Taiwanese women with endometriosis.

BACKGROUND/PURPOSE: Endometriosis (EM) is linked to cardiovascular disease (CVD). However, whether this finding can be applied to the Taiwanese population remained unanswered. To investigate the association between EM and major adverse cardiovascular and cerebrovascular events (MACCE) and the therapeutic effect on the risk of MACCE in Asian women with EM. A retrospective population-based cohort study was performed. METHODS: A total of 17 543 patients with EM aged between 18 and 50 years were identified from a general population of 1 million Taiwanese after excluding diagnoses of major CVD and cerebrovascular accident (CVA) prior to EM. The comparison group (n = 70 172) without EM was selected by matching the study cohort with age, sex, and income and urbanization levels in a 4:1 ratio. RESULTS: During a median follow-up period of 9.2 years, Taiwanese women with EM had a significantly higher frequency of comorbidities, medical and surgical treatment, and MACCE than did their non-EM counterparts (2.76% vs 2.18%, P < .0001). After adjustment for comorbidities, patients with EM had an approximately 1.2-fold increased risk of MACCE (95% CI 1.05-1.29; P = .0053) and a higher cumulative incidence of MACCE compared with the normal population. Neither medical nor surgical treatment increased the risk of MACCE. Furthermore, medical treatment for EM appeared to be protective against MACCE. CONCLUSION: Taiwanese women with EM not only had a substantially higher frequency of comorbidities but also an increased risk of MACCE compared with the general population.

Baseline factors identified for the prediction of good responders in patients with end-stage diffuse coronary artery disease undergoing intracoronary CD34+ cell therapy.

BACKGROUND: Treating patients with end-stage diffuse coronary artery disease (EnD-CAD) unsuitable for coronary intervention remains a clinical challenge. They usually express refractory angina and have a high risk of mortality. Although growing data have indicated cell therapy is an alternative solution to medical or invasive therapy, there are still lacking useful markers to predict whether heart function will improve in the EnD-CAD patients who underwent circulatory-derived CD34+ cell therapy. By utilizing the baseline variables and results from our previous phase I/II clinical trials, the aim of this study tried to elucidate the variables predictive of the "good response" to CD34+ cell therapy. METHODS: This retrospective study included 38 patients in phase I clinical trial (2011-2014), and 30 patients in phase II clinical trial (2013-2017). These patients were categorized into "good responders" and "non-responders" according to their 1-year improvement of LVEF ≥ 7.0% or < 7.0% after intracoronary CD34+ cell therapy. Univariate and multivariate logistic regression models were performed to identify potential independent predictors of a good responder to cell therapy, followed by Hosmer-Lemeshow (H-L) test for goodness of fit and prediction power. RESULTS: Among baseline data, multivariate analysis demonstrated that the history of a former smoker was independently predictive of good responders (p = 0.006). On the other hand, male gender, the baseline Canadian Cardiovascular Society angina score ≥ 3, and grades of LV diastolic dysfunction ≥ 2 were significantly negative predictors of good responders (all p < 0.01). After administration of subcutaneous granulocyte-colony stimulating factor (G-CSF), a higher post-G-CSF neutrophil count in addition to the above four baseline variables also played crucial roles in early prediction of good response to CD34+ cell therapy for EnD-CAD (all p < 0.03). The H-L test displayed a good prediction power with sensitivity 83.3%, specificity 85.3%, and accuracy 84.4%. CONCLUSIONS: Using the results of our phase I/II clinical trials, previous smoking habit, female sex, lower grades of angina score, and diastolic dysfunction were identified to be independently predictive of "good response" to CD34+ cell therapy in the patients with EnD-CAD. TRIAL REGISTRATION: This is a retrospective analysis based on phase I ( ISRCTN72853206 ) and II ( ISRCTN26002902 ) clinical trials.

Intracoronary Injection of Autologous CD34+ Cells Improves One-Year Left Ventricular Systolic Function in Patients with Diffuse Coronary Artery Disease and Preserved Cardiac Performance-A Randomized, Open-Label, Controlled Phase II Clinical Trial.

This phase II randomized controlled trial tested whether intracoronary autologous CD34+ cell therapy could further improve left ventricular (LV) systolic function in patients with diffuse coronary artery disease (CAD) with relatively preserved LV ejection fraction (defined as LVEF >40%) unsuitable for coronary intervention. Between December 2013 and November 2017, 60 consecutive patients were randomly allocated into group 1 (CD34+ cells, 3.0 × 107/vessel/n = 30) and group 2 (optimal medical therapy; n = 30). All patients were followed for one year, and preclinical and clinical parameters were compared between two groups. Three-dimensional echocardiography demonstrated no significant difference in LVEF between groups 1 and 2 (54.9% vs. 51.0%, respectively, p = 0.295) at 12 months. However, compared with baseline, 12-month LVEF was significantly increased in group 1 (p < 0.001) but not in group 2 (p = 0.297). From baseline, there were gradual increases in LVEF in group 1 compared to those in group 2 at 1-month, 3-months, 6-months and 12 months (+1.6%, +2.2%, +2.9% and +4.6% in the group 1 vs. -1.6%, -1.5%, -1.4% and -0.9% in the group 2; all p < 0.05). Additionally, one-year angiogenesis (2.8 ± 0.9 vs. 1.3 ± 1.1), angina (0.4 ± 0.8 vs. 1.8 ± 0.9) and HF (0.7 ± 0.8 vs. 1.8 ± 0.6) scores were significantly improved in group 1 compared to those in group 2 (all p < 0.001). In conclusion, autologous CD34+ cell therapy gradually and effectively improved LV systolic function in patients with diffuse CAD and preserved LVEF who were non-candidates for coronary intervention (Trial registration: ISRCTN26002902 on the website of ISRCTN registry).

Soluble ST2 is a Useful Biomarker for Grading Cerebral-Cardiac Syndrome in Patients after Acute Ischemic Stroke.

This study tested whether the soluble (s)ST2 is a superb biomarker predictive of moderate to severe cerebral-cardiac syndrome (CCS) (defined as coexisting National Institute of Health Stroke Scale (NIHSS) >8 and left-ventricular ejection fraction (LVEF) <60%) in patients after acute ischemic stroke (IS). Between November 2015 and October 2017, a total of 99 IS patients were prospectively enrolled and categorized into three groups based on NIHSS, i.e., group 1 (NIHSS ≤ 8, n = 66), group 2 (NIHSS = 9-15, n = 14) and group 3 (NIHSS ≥ 16, n = 19), respectively. Blood samples were collected immediately after hospitalization, followed by transthoracic echocardiographic examination. The results showed that the flow cytometric analysis for assessment of inflammatory biomarkers of TLR2+/CD14+cells, TLR4+/CD14+cells, Ly6g+/CD14+cells, and MPO+/CD14+cells, and ELISA assessment for circulatory level of sST2 were significantly higher in groups 2/3 than in group 1 (all p < 0.01). However, these parameters did not show significant differences between groups 2 and 3 (all p > 0.05). The LVEF was significantly lower in group 3 than in group 1 (p < 0.001), but it displayed no difference between groups 1/2 or between groups 2/3. These inflammatory biomarkers ((TLR2+/CD14+cells// TLR4+/CD14+cells// MPO+/CD14+cells) and sST2)) were significantly positively correlated to NIHSS and strongly negatively correlated to LVEF (all p < 0.05). Multivariate analysis demonstrated that both MPO/CD14+cells >20% (p = 0.027) and sST2 ≥ 17,600 (p = 0.004) were significantly and independently predictive of moderate-severe CCS after acute IS. Receiver operating characteristic curve analysis demonstrated that sST2 was the most powerful predictor of CCS with a sensitivity of 0.929 and a specificity of 0.731 (p < 0.001). In conclusion, sST2 is a useful biomarker for prediction of CCS severity in patients after acute IS.

Deep learning for fully automated tumor segmentation and extraction of magnetic resonance radiomics features in cervical cancer.

OBJECTIVE: To develop and evaluate the performance of U-Net for fully automated localization and segmentation of cervical tumors in magnetic resonance (MR) images and the robustness of extracting apparent diffusion coefficient (ADC) radiomics features. METHODS: This retrospective study involved analysis of MR images from 169 patients with cervical cancer stage IB-IVA captured; among them, diffusion-weighted (DW) images from 144 patients were used for training, and another 25 patients were recruited for testing. A U-Net convolutional network was developed to perform automated tumor segmentation. The manually delineated tumor region was used as the ground truth for comparison. Segmentation performance was assessed for various combinations of input sources for training. ADC radiomics were extracted and assessed using Pearson correlation. The reproducibility of the training was also assessed. RESULTS: Combining b0, b1000, and ADC images as a triple-channel input exhibited the highest learning efficacy in the training phase and had the highest accuracy in the testing dataset, with a dice coefficient of 0.82, sensitivity 0.89, and a positive predicted value 0.92. The first-order ADC radiomics parameters were significantly correlated between the manually contoured and fully automated segmentation methods (p < 0.05). Reproducibility between the first and second training iterations was high for the first-order radiomics parameters (intraclass correlation coefficient = 0.70-0.99). CONCLUSION: U-Net-based deep learning can perform accurate localization and segmentation of cervical cancer in DW MR images. First-order radiomics features extracted from whole tumor volume demonstrate the potential robustness for longitudinal monitoring of tumor responses in broad clinical settings. U-Net-based deep learning can perform accurate localization and segmentation of cervical cancer in DW MR images. KEY POINTS: • U-Net-based deep learning can perform accurate fully automated localization and segmentation of cervical cancer in diffusion-weighted MR images. • Combining b0, b1000, and apparent diffusion coefficient (ADC) images exhibited the highest accuracy in fully automated localization. • First-order radiomics feature extraction from whole tumor volume was robust and could thus potentially be used for longitudinal monitoring of treatment responses.

Risk of Venous Thromboembolic Events in Patients with Osteonecrosis of the Femoral Head Undergoing Primary Hip Arthroplasty.

Previous data have shown patients with osteonecrosis of the femoral head (ONFH) have increased lifelong risk of unprovoked venous thromboembolic events (VTE) as compared with the general population, according to sharing common pathological mechanism of endothelial dysfunction. However, whether the risk of VTE increases in those ONFH patients undergoing major hip replacement surgery remains unclear. This is a retrospective nationwide Asian population-based study. From 1997 to 2013, a total of 12,232 ONFH patients receiving partial or total hip replacement for the first time and revision surgeries were retrospectively selected from Taiwan Health Insurance surgical files. By 1:1 matching on age, sex, surgical types, and socioeconomic status, 12,232 subjects without ONFH undergoing similar hip surgery were selected as non-ONFH group. The incidence and risk of post-surgery VTE, including deep venous thrombosis (DVT) and pulmonary embolism (PE), were compared between the ONFH and non-ONFH groups. Results showed that 53.8% of ONFH patients were male and the median age was 61.9 years old. During the mean follow-up period of 6.4 years, the incidences of VTE (1.4% vs. 1.2%), DVT (1.1% vs. 0.9%), and PE (0.4% vs. 0.4%) were slightly but insignificantly higher in the ONFH than in the non-ONFH group undergoing the same types of major hip replacement surgery (all p-values > 0.250). Concordantly, we found no evidence that the risk of VTE was increased in the ONFH patients as compared with the non-ONFH counterparts (adjusted HR 1.14; 95% CI 0.91-1.42; p = 0.262). There were also no increased risks for DVT and PE in the ONFH subgroups stratified by comorbidities, drug exposure to pain-killer or steroid, and follow-up duration after surgery, either. In conclusion, hip arthroplasty in Asian patients with ONFH is associated with similar rates of VTE as compared to patients with non-ONFH diagnoses.

Developmental potential of surplus morulas with delayed and/or incomplete compaction after freezing-thawing procedures.

BACKGROUND: Morulas with delayed growth sometimes coexist with blastocysts. There is still limited evidence regarding the optimal disposal of surplus morulas. With the advancement of vitrification, the freezing-thawing technique has been widely applied to zygotes with 2 pronuclei, as well as embryos at the cleavage and blastocyst stages. The freezing of morulas, however, has rarely been discussed. The purpose of this study was to investigate whether these poor-quality and slow-growing morulas are worthy of cryopreservation. METHODS: This is a retrospective, observational, proof-of-concept study. A total of 1033 day 5/6 surplus morulas were cryopreserved from January 2015 to December 2018. The study included 167 women undergoing 180 frozen embryo transfer cycles. After the morulas underwent freezing-thawing procedures, their development was monitored for an additional day. The primary outcome was the blastocyst formation rate. Secondary outcomes were clinical pregnancy rate, live birth rate and abortion rate. RESULTS: A total of 347 surplus morulas were thawed. All studied morulas showed delayed compaction (day 5, n = 329; day 6, n = 18) and were graded as having low (M1, n = 54), medium (M2, n = 138) or high (M3, n = 155) fragmentation. The post-thaw survival rate was 79.3%. After 1 day in extended culture, the blastocyst formation rate was 66.6%, and the top-quality blastocyst formation rate was 23.6%. The day 5 morulas graded as M1, M2, and M3 had blastocyst formation rates of 88.9, 74.0, and 52.8% (p < 0.001), respectively, and the top-quality blastocyst formation rates were 64.8, 25.2, and 9.0% (p < 0.001), respectively. The clinical pregnancy rate was 33.6%. CONCLUSIONS: The post-thaw blastocyst formation rate was satisfactory, with approximately one-half of heavily fragmented morulas (M3) developing into blastocysts. Most of the poor-quality morulas were worth to freeze, with the reasonable goal of obtaining pregnancy and live birth. This alternative strategy may be a feasible approach for coping with poor-quality surplus morulas in non-PGS (preimplantation genetic screening) cycles.

Risk of New-Onset Atrial Fibrillation Among Asian Chronic Hepatitis C Virus Carriers: A Nationwide Population-Based Cohort Study.

Background Hepatitis C virus (HCV) infection not only links closely to systemic inflammation but also has numerous extrahepatic manifestations. Chronic inflammation also increases the risk of new-onset atrial fibrillation (AF). However, little is known regarding the clinical association between HCV infection and new-onset AF. Methods and Results We conducted a population-based cohort study using Taiwan's National Health Insurance Research Database during 1997 to 2013. A total of 11 771 HCV-infected patients were included in this study, and each of them was matched in a ratio of 1:4. Because of higher mortality among HCV cohorts, we used both Cox proportional hazard regression and competing risk regression models to compute the hazard ratios accompanying 95% CIs after adjustment for relevant confounder. The results demonstrated that the patients with chronic HCV infection had significantly higher incidence rate (332.0 versus 265.8 in 100 000 person-years, P<0.0001) of new-onset AF compared with the non-HCV population. The adjusted hazard ratio of HCV for new-onset AF was 1.32 (95% CI, 1.20-1.44; P<0.0001) and 1.20 (95% CI, 1.10-1.31; P=0.0001) while calculated with Cox proportional hazard regression model and competing risk model, respectively. Intriguingly, we observed that the patients with HCV treated with antiviral agents had significantly lower incidental AF than those without anti-HCV treatment (1.2% versus 6.0%; P<0.0001). Conclusions Chronic HCV infection was associated with an increased risk of incidental AF probably through sharing common pathology of chronic inflammation. Furthermore, a well-designed study is needed to clarify whether anti-HCV therapy can provide protection against the occurrence of AF.

Prognostic model based on magnetic resonance imaging, whole-tumour apparent diffusion coefficient values and HPV genotyping for stage IB-IV cervical cancer patients following chemoradiotherapy.

OBJECTIVES: To develop and validate a prognostic model of integrating whole-tumour apparent diffusion coefficient (ADC) from pretreatment diffusion-weighted (DW) magnetic resonance (MR) imaging with human papillomavirus (HPV) genotyping in predicting the overall survival (OS) and disease-free survival (DFS) for women with stage IB-IV cervical cancer following concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively analysed three prospectively collected cohorts comprising 300 patients with stage IB-IV cervical cancer treated with CCRT in 2007-2014 and filtered 134 female patients who underwent MR imaging at 3.0 T for final analysis (age, 24-92 years; median, 54 years). Univariate and multivariate Cox regression analyses were used to evaluate the whole-tumour ADC histogram parameters, HPV genotyping and relevant clinical variables in predicting OS and DFS. The dataset was randomly split into training (n = 88) and testing (n = 46) datasets for construction and independent bootstrap validation of the models. RESULTS: The median follow-up time for surviving patients was 69 months (range, 9-126 months). Non-squamous cell type, ADC10 <0.77 × 10-3 mm2/s, T3-4, M1 stage and high-risk HPV status were selected to generate a model, in which the OS and DFS for the low, intermediate and high-risk groups were significantly stratified (p < 0.0001). The prognostic model improved the prediction significantly compared with the International Federation of Gynaecology and Obstetrics (FIGO) stage for both the training and independent testing datasets (p < 0.0001). CONCLUSIONS: The prognostic model based on integrated clinical and imaging data could be a useful clinical biomarker to predict OS and DFS in patients with stage IB-IV cervical cancer treated with CCRT. KEY POINTS: • ADC 10 is the best prognostic factor among ADC parameters in cervical cancer treated with CCRT • A novel prognostic model was built based on histology, ADC 10 , T and M stage and HPV status • The prognostic model outperforms FIGO stage in the survival prediction.