Formation of Different Polyploids Through Disrupting Meiotic Crossover Frequencies Based on cntd1 Knockout in Zebrafish.

Polyploidy, a significant catalyst for speciation and evolutionary processes in both plant and animal kingdoms, has been recognized for a long time. However, the exact molecular mechanism that leads to polyploid formation, especially in vertebrates, is not fully understood. Our study aimed to elucidate this phenomenon using the zebrafish model. We successfully achieved an effective knockout of the cyclin N-terminal domain containing 1 (cntd1) using CRISPR/Cas9 technology. This resulted in impaired formation of meiotic crossovers, leading to cell-cycle arrest during meiotic metaphase and triggering apoptosis of spermatocytes in the testes. Despite these defects, the mutant (cntd1-/-) males were still able to produce a limited amount of sperm with normal ploidy and function. Interestingly, in the mutant females, it was the ploidy not the capacity of egg production that was altered. This resulted in the production of haploid, aneuploid, and unreduced gametes. This alteration enabled us to successfully obtain triploid and tetraploid zebrafish from cntd1-/- and cntd1-/-/- females, respectively. Furthermore, the tetraploid-heterozygous zebrafish produced reduced-diploid gametes and yielded all-triploid or all-tetraploid offspring when crossed with wild-type (WT) or tetraploid zebrafish, respectively. Collectively, our findings provide direct evidence supporting the crucial role of meiotic crossover defects in the process of polyploidization. This is particularly evident in the generation of unreduced eggs in fish and, potentially, other vertebrate species.

The global incidence of adverse events associated with fecal microbiota transplantation in children over the past 20 years: A systematic review and meta-analysis.

OBJECTIVES: To understand the global incidence of the adverse events associated with fecal microbiota transplantation (FMT) in children over the past 20 years. METHODS: We searched PubMed, Web of Science, Embase, and three Chinese databases (CNKI, Wanfang, and Chongqing Weipu) for high-quality articles written over the past 20 years and made selections based on the quality standard score. The study characteristics and incidences of adverse events were extracted from each article, meta-analysis was performed using the R.3.6.3 software, and randomized-effect or fixed-effect meta-analyses were used to determine the incidence of adverse events. Subgroup analysis was performed to determine heterogeneity. RESULTS: A total of 18 articles involving 681 children were included in the analysis. The total effective rate of FMT in children was 85.75% (95% CI: 76.23-93.15%), of which the overall efficacy of FMT for the treatment of Clostridium difficile infection was 91.22% (95% CI: 83.49-96.68%) and the overall adverse event rate was 28.86% (95% CI: 19.56-39.15%), with a mild to moderate adverse event rate of 27.72% (95% CI: 17.86-38.83%) and a severe adverse event rate of 0.90% (95% CI: 0.33-1.76%). The most common mild to moderate adverse events were as follows: bellyache, 14.02% (95% CI: 5.43-25.77%); diarrhea, 7.75% (95% CI: 2.69-15.11%); and bloating, 7.36% (95% CI: 1.79-16.28%). Other adverse events included fever, 2.34%; vomiting, 3.12%; nausea, 1.50%; hematochezia, 2.30%; anorexia, 1.94%; and fatigue, 0.03%. The only death reported was in a study from China, in which the patient died of sepsis and liver failure 4 weeks after FMT. The other serious adverse event was an immunodeficiency patient with severe hematochezia. Another study in the United States described seven serious adverse events including one death that was not considered to be related to FMT; however, they did not describe the events in detail. There was no difference in the incidence of adverse events between the upper and lower gastrointestinal tracts (OR = 0.61, 95% CI: 0.02-15.42, P = 0.76). CONCLUSION: Adverse events related to FMT in children are mostly mild to moderate, of short duration, and self-limiting. Therefore, the use of FMT in children is safe and worthy of widespread promotion.

A CT-based nomogram for differentiating invasive fungal disease of the lung from bacterial pneumonia.

BACKGROUND: There is an annual increase in the incidence of invasive fungal disease (IFD) of the lung worldwide, but it is always a challenge for physicians to make an early diagnosis of IFD of the lung. Computed tomography (CT) may play a certain role in the diagnosis of IFD of the lung, however, there are no specific imaging signs for differentiating IFD of lung from bacterial pneumonia (BP). METHODS: A total of 214 patients with IFD of the lung or clinically confirmed BP were retrospectively enrolled from two institutions (171 patients from one institution in the training set and 43 patients from another institution in the test set). The features of thoracic CT images of the 214 patients were analyzed on the picture archiving and communication system by two radiologists, and these CT images were imported into RadCloud to perform radiomics analysis. A clinical model from radiologic analysis, a radiomics model from radiomics analysis and a combined model from integrating radiologic and radiomics analysis were constructed in the training set, and a nomogram based on the combined model was further developed. The area under the ROC curve (AUC) of the receiver operating characteristic (ROC) curve was calculated to assess the diagnostic performance of the three models. Decision curve analysis (DCA) was conducted to evaluate the clinical utility of the three models by estimating the net benefit at a range of threshold probabilities. RESULTS: The AUCs of the clinical model for differentiating IFD of lung from BP in the training set and test sets were 0.820 and 0.827. The AUCs of the radiomics model in the training set and test sets were 0.895 and 0.857. The AUCs of the combined model in the training set and test setswere 0.944 and 0.911. The combined model for differentiating IFD of lung from BP obtained the greatest net benefit among the three models by DCA. CONCLUSION: Our proposed nomogram, based on a combined model integrating radiologic and radiomics analysis, has a powerful predictive capability for differentiating IFD from BP. A good clinical outcome could be obtained using our nomogram.

A CT-based technique to predict optimal projection for self-expanding TAVI in patients with different aortic valve anatomies.

BACKGROUND: Optimal projection is essential for valve deployment during transcatheter aortic valve implantation (TAVI). The purpose of this study was to propose an approach to predict optimal projection in TAVI candidates with different aortic valve anatomies. METHODS: 331 patients undergoing self-expanding TAVI were included and the so-called non-coronary cusp (NCC)-parallel technique was utilized, which generated the predicted projection by connecting NCC commissures on the transverse plane on the pre-procedural computed tomography images. RESULTS: 37.8% of the study cohort were bicuspid aortic valve (BAV) patients. Around 80% of both NCC-parallel views and final views were in the right anterior oblique (RAO) and caudal (CAU) quadrant. There was less than 5° change required from the NCC-parallel view to the final implanted view in 79% of tricuspid aortic valve (TAV) patients but only in 27% (13/48) of type 0 BAV patients with coronary arteries originated from the different cusps. After excluding the above mentioned BAV patients, 62.3% (48/77) of BAV patients needed less than 5° change to achieve optimal projection and only in 8 patients, the angular change was larger than 10° in either left/right anterior oblique or cranial/caudal direction. CONCLUSIONS: The NCC-parallel technique provides reliable prediction for optimal projection in self-expanding TAVI in all TAV and most BAV patients, with a vast majority of views in the RAO and CAU quadrant.

Reshaping bicuspid aortic valve stenosis with an hourglass-shaped balloon for transcatheter aortic valve replacement: A pilot study.

OBJECTIVES: We evaluated the safety and usefulness of preparatory anatomical reshaping with a geometric hourglass-shaped balloon to optimize transcatheter aortic valve replacement (TAVR) outcomes in bicuspid aortic valve (BAV) stenosis. BACKGROUND: TAVR has been increasingly performed for BAV stenosis; however, technical challenges remain. Procedural results are suboptimal given unfavorable valvular anatomies. METHODS: Eligible patients with BAV stenosis were enrolled to undergo aortic valve predilatation with the hourglass-shaped TAV8 balloon before TAVR using the self-expandable Venus A-Valve. Procedural details and outcomes were compared to a sequential group of patients with BAV who underwent TAVR with the same device following preparatory dilatation using a cylindrical balloon. RESULTS: A total of 22 patients were enrolled in the TAV8 group and 53 were included in the control group. Valve downsizing was less common in the TAV8 group (36.4 vs. 67.9%; p = .012). Stable valve release and optimal implant depth were consistently achieved in the TAV8 group with no requirement for a second valve (0 vs. 17.0%; p = .039) and with higher device success rates (100.0 vs 77.4%; p = .014). Residual aortic regurgitation graded as ≥mild was less common in the TAV8 group (13.6 vs 45.3%; p = .009). Mortality was similar (0 vs. 3.8%; p = 1); no major/disabling stroke or conversion to open-heart surgery was seen in either group within 30 days. CONCLUSIONS: Compared with standard cylindrical balloon valvuloplasty, preparatory reshaping with the hourglass-shaped balloon before self-expandable TAVR in BAV was associated with significantly better procedural results and may encourage more promising outcomes.

Transcatheter Aortic Valve Replacement in Patients with Aortic Stenosis Having Coronary Cusp Fusion versus Mixed Cusp Fusion Nonraphe Bicuspid Aortic Valve.

OBJECTIVES: We aimed to assess the procedural and clinical results of transcatheter aortic valve replacement (TAVR) for nonraphe bicuspid aortic stenosis (AS) with coronary vs mixed cusp fusion. BACKGROUND: It remains unclear whether cusp fusion morphology affects TAVR outcomes in patients with nonraphe bicuspid AS. METHODS: This retrospective study enrolled consecutive patients with severe symptomatic AS and type-0 bicuspid aortic valve, who underwent TAVR at our institution between 2012 and 2017. TAVR outcomes were defined based on the Valve Academic Research Consortium-2 recommendations. RESULTS: Compared to patients with mixed cusp fusion (44/71), those with coronary cusp fusion (27/71) had a larger ellipticity index for the aortic annulus (21.9% ± 9.0% vs 15.6% ± 9.3%, p=0.007) and increased left ventricular outflow tract obstruction (31.1% ± 9.4% vs 26.9% ± 7.5%, p=0.04) but comparable rates of second valve implantation (15.9% vs 14.8%), mild paravalvular leakage (PVL, 38.5% vs 30.2%), permanent pacemaker implantation (PPM, 25.9% vs 15.9%), and 30-day mortality (7.4% vs 6.8%). Use of a first-generation transcatheter heart valve was associated with higher risk for mild PVL (odds ratio (OR) = 4.37; 95% confidence interval (95% CI) = 1.14-16.75; p=0.03) but not PPM (OR = 0.77; 95% CI = 0.22-2.62; p=0.67), whereas a larger oversizing ratio tended to be associated with a higher PPM rate (OR = 1.49; 95% CI = 0.46-4.86; p=0.51) but lower incidence of mild PVL (OR = 0.51; 95% CI = 0.19-1.35; p=0.17). CONCLUSIONS: In AS patients with type-0 bicuspid valves, cusp fusion morphology does not affect the procedural or clinical results of TAVR. Use of second-generation transcatheter heart valves may provide more favorable results in such patients. This trial is registered with NCT01683474.

The impact of age on the implementation of evidence-based medications in patients with coronary artery disease and its prognostic significance: a retrospective cohort study.

BACKGROUND: Elderly patients with coronary artery disease (CAD) frequently complicated with more cardiovascular risk factors, but received fewer evidence-based medications (EBMs). This study explored the association of EBMs compliance in different age groups and the risk of long-term death. METHODS: A retrospective analysis was conducted from a single registered database. 2830 consecutive patients with CAD were enrolled and grouped into 3 categories by age. The primary end point was all-cause mortality and secondary endpoint is cardiovascular mortality. RESULTS: The mean follow-up time was 30.25 ± 11.89 months and death occurred in 270 cases,including 150 cases of cardiac death. Cumulative survival curves indicated that the incidence rates of all-cause death and cardiovascular death increased with age (older than 75 years old vs. 60 to 75 years old vs. younger than 60 years old, mortality: 18.7% vs. 9.6% vs. 4.1%, p < 0.001; cardiovascular mortality: 10.3% vs. 5.1% vs. 2.7%, p < 0.001). The percentage of elderly patients using no EBMs was significantly higher than the percentages in the other age group (7.7% vs. 4.6% vs. 2.2%,p < 0.05). Cox regression analysis revealed the benefit of combination EBMs (all-cause mortality: hazard ratio [HR] 0.15, 95% CI 0.08-0.27; cardiac mortality: HR 0.08, 95% CI 0.04-0.19) for older CAD patients. Similar trends were found about different kinds of EBMs in elderly patients. CONCLUSIONS: Elderly patients with CAD had higher risk of death but a lower degree of compliance with EBMs usage. Elderly CAD patients could receive more clinical benefits by using EBMs.

Genetic structure and differentiation analysis of a Eurasian Uyghur population by use of 27 continental ancestry-informative SNPs.

Previously, we developed and validated a multiplex assay of 27 ancestry-informative markers (AIMs) for analyzing African (AFR), European (EUR), and East Asian (EAS) ancestry components. In this study, we typed and collectively analyzed a large Uyghur sample of 979 individuals to estimate the genetic coefficients of the 27 AIMs and investigate differentiation parameters between Uyghur and Han. The Uyghur allele frequencies ranged from 0.243 to 0.952, and heterozygosities ranged from 0.091 to 0.500. Values of F st 3 and I n 3 for EUR, Uyghur, and EAS ranged from 0.028 to 0.550 and 0.0002 to 0.345, respectively. The Uyghur population displays a substantial ancestry contribution of 50.3:49.7 (EUR:EAS) and was efficiently discriminated from Han Chinese with an accuracy of 99.285 %. All populations were clustered into AFR, EUR, EAS, and admixture groups of these three ancestries. Central Asian was obviously stratified from the other admixture populations of South Asians, North Asians, and the Americans. The 27 SNPs yield a circle with an average distance of 0.936 from the center (0, 0) in PCA analysis. Using this set, Chinese Uyghur and Han populations achieved accurate differentiation, and our updated genotype database (by citing 1000 Genomes data) of 43 worldwide populations is a useful resource for forensic applications and disease association studies.

[Construction of a 15-plex Rapid STR Multiplex Amplification System].

OBJECTIVE: To establish a 15-plex rapid STR multiplex amplification system. METHODS: Fourteen auto-chromosome loci and one sex-chromosome were selected to compare the situations of allelic losses and nonspecific amplication under different conditions. FastStart Taq DNA polymerase and DNA standard sample 9947A were used during amplification and optimization process.15-plex rapid STR amplification system was achieved by performing various experiments including selection of amplification conditions and the volume of DNA polymerase, adjustment of inter-locus balance, optimization of rapid amplification, screening of reaction buffers, selection of reaction volume, and a variety of additives. RESULTS: Using 10 µL rapid PCR system, including 1 ng DNA templates, 0.4 µL polymerase and 10xFastStart high fidelity reaction buffer, a complete and well-balance DNA profile of 15 STR loci for standard genomic DNA was obtained in 32 minutes, without the allele drop-out and non-specific amplicons. Meanwhile, 5% glycerinum, 0.01% gelatin, 0.05% gelatin and 5 mmol/L ammonium sulfate could be used as the reactive additive during the amplification procedure. CONCLUSION: The 15-plex rapid STR multiplex amplification system can be used to decrease reaction time and enhance sample throughput.

Donor lymphocytes may acquire cytolytic specificity to donor's engrafted hematopoietic cells after a hematopoietic stem cell allograft resulting in marrow failure.

BACKGROUND: Secondary rejection sometimes occurs after engraftment of allogeneic hematopoietic stem cell transplantation (allo-HSCT), which results in marrow failure. To clear possible reasons for BM failure, we observed a patient with acute myeloblastic leukemia who died of hematopoietic failure one year after apparently successful allo-HSCT. METHODS: The patient was a 44 year old male. Allo-HSCT was successful after 40 days, and 100% of marrow cells were of donor's origin. Graft-versus-host disease (GVHD) began at the 60th day with involvement of multiple organs. He died of marrow failure on the 360th day after allo-HSCT. RESULTS: We identified the origin of the patient's lymphocytes by a donor's specific HLA locus, and a dominant T-cell clone by spectratyping of the TCRVB subfamily on T-cells. The patient's dominant CD8+ cells were separated by magnetic beads and incubated with donor's cells or patient's leukemic cells to evaluate their cytolytic specificity. TCRalpha and TCRbeta cDNAs were cloned from the dominant CD8+ T-cells, transfected into Jurkat cells, and characterized the cytolytic specificity of the transfected Jurkat cells. In the period of 60 to 120th day after allo-HSCT, blood CD3+CD8+ cytotoxic T lymphocytes (CTLs) gradually increased and fluctuated in the range of 60 to 90%, CD3+CD4+ cells fluctuated in the range of 5 to 18%, and CD4+CD25+ cells accounted for between 3 to 13%. Spectratyping of the 24 TCRVbeta subfamilies in blood lymphocytes demonstrated a dominant TCRVbeta13.1 clone with HLA-A*0201 of donor origin. The dominant CD8+ cells separated by magnetic beads showed cytolytic specificity to donor's blood mononuclear cells (BMCs), but not to patient's fibroblasts. Jurkat cells containing the cDNAs of TCRalpha and TCRbeta chains cloned from the dominant CD8+ cell clone had cytolytic activity against donor's BMCs, patient's leukemic cells, and BMCs from an unrelated subject accounting for 43%, 15%, and 0.42%, respectively. The dominant lymphocyte clone of donor's origin with CD3+CD8+ TCRVbeta13.1 markers in the patient may have been determinant in the hematopoiesis failure. CONCLUSIONS: Donor's lymphocytes changed in the recipient, acquiring the cytolytic specificity to donor's hematopoietic cells and presumably leading to marrow failure.

Peri-implantation estradiol level has no effect on pregnancy outcome in vitro fertilization- embryo transfer.

Background: The necessity of monitoring luteal endocrine functions in in vitro fertilization- embryo transfer (IVF-ET) remains uncertain. Specifically, the significance of luteal phase estradiol (E2) levels is a matter of debate in current literature. Objective: To assess the impact of luteal phase (day 11 after HCG trigger) estradiol levels on IVF-ET outcomes. Design: Twelve thousand five hundred and thirty-five (n = 12,535) IVF-ET cycles performed in our center between 2015 and 2021 were divided into 5 groups based on the middle and late luteal phase serum E2 (MllPSE2) level percentiles as follows: Group A < 50 pg/mL (N=500), group B 50 pg/mL≤E2<150 pg/mL (N=2545), group C 150 pg/mL≤E2<250 pg/mL (N=1327), group D 250 pg/mL≤E2<500 pg/mL (N=925), group E E2≥500 pg/mL (n=668). The clinical pregnancy rates, abortion rates, and live birth rates of each group were compared. Binary logistic regression analysis was carried out to assess the potential impact of MllPSE2 on the live birth rate (LBR). Results: No significant differences were found in various parameters when comparing the five groups. The level of MllPSE2 showed no significant difference between the pregnant group and the non-pregnant group. The binary logistic regression analysis model demonstrated that MllPSE2 was not significantly related to LBR. Conclusion: The influence of E2 during the peri-implantation period (day 11) on clinical outcome in IVF-ET is not affected, even if E2<50 pg/mL. It is speculated that ovarian-derived E2 in MllPSE2 is not deemed necessary for endometrial receptivity. Although caution is warranted due to the retrospective nature of the analysis and the potential for unmeasured confounding, it is argued that the need for luteal E2 monitoring in IVF-ET may be of questionable value.

Ccdc57 is required for straightening the body axis by regulating ciliary motility in the brain ventricle of zebrafish.

Recently, cilia defects have been proposed to contribute to scoliosis. Here, we demonstrate that coiled-coil domain-containing 57 (Ccdc57) plays an essential role in straightening the body axis of zebrafish by regulating ciliary beating in the brain ventricle (BV). Zygotic ccdc57 (Zccdc57) mutant zebrafish developes scoliosis without significant changes in their bone density and calcification, and the maternal-zygotic ccdc57 (MZccdc57) mutant embryos display curved bodies since the long-pec stage. The expression of ccdc57 is enriched in ciliated tissues and immunofluorescence analysis reveals colocalization of Ccdc57-HA with acetylated α-tubulin, implicating it in having a role in ciliary function. Further examination reveals that it is the coordinated cilia beating of multiple cilia bundles (MCB) in the MZccdc57 mutant embryos that is affected at 48 hours post fertilization, when the compromised cerebrospinal fluid flow and curved body axis have already occurred. Either ccdc57 mRNA injection or epinephrine treatment reverses the spinal curvature in MZccdc57 mutant larvae from ventrally curly to straight or even dorsally curly and significantly upregulates urotensin signaling. This study reveals the role of ccdc57 in maintaining coordinated cilia beating of MCB in the BV.

Outcomes Following Transcatheter Aortic Valve Replacement for Aortic Stenosis in Patients With Type 0 Bicuspid, Type 1 Bicuspid, and Tricuspid Aortic Valves.

BACKGROUND: Data concerning the outcomes of transcatheter aortic valve replacement in type 0 bicuspid aortic stenosis (AS) are scarce. The study aims to compare the outcomes of transcatheter aortic valve replacement for AS in patients with type 0 bicuspid, type 1 bicuspid, and tricuspid aortic valve anatomy. METHODS: We enrolled consecutive patients undergoing transcatheter aortic valve replacement for severe AS between 2012 and 2022 in this single-center retrospective cohort study. The primary outcome was mortality, while secondary outcomes included in-hospital complications such as stroke and pacemaker implantation and transcatheter heart valve hemodynamic performance. RESULTS: The number of patients with AS with type 0 bicuspid, type 1 bicuspid, and tricuspid aortic valve anatomy was 328, 302, and 642, respectively. Self-expanding transcatheter heart valves were used in the majority of patients (n=1160; 91.4%). In the matched population, differences in mortality (30 days: 4.2% versus 1.7% versus 1.7%, Poverall=0.522; 1 year: 10% versus 2.3% versus 6.2%, Poverall=0.099) and all stroke (30 days: 1.0% versus 0.9% versus 0.0%, Poverall=0.765; 1 year: 1.4% versus 1.6% versus 1.3%, Poverall=NS) were nonsignificant, and the incidence of overall in-hospital complications was comparable among groups. Ascending aortic diameter was the single predictor of 1-year mortality in type 0 bicuspid patients (hazard ratio, 1.59 [95% CI, 1.03-2.44]; P=0.035). The proportion of patients with a mean residual gradient ≥20 mm Hg was the highest in those with type 0 bicuspid anatomy, although the need for permanent pacemaker implantation was the lowest in this group. CONCLUSIONS: Major clinical outcomes of transcatheter aortic valve replacement for AS in patients with type 0 bicuspid, type 1 bicuspid, and tricuspid aortic valve anatomy are equivalent at short- and mid-term follow-up. These observations merit further exploration in prospective international registries and randomized controlled trials.

Sex Difference in Outcomes Following Transcatheter Aortic Valve Replacement in Bicuspid Aortic Stenosis.

BACKGROUND: It is unknown whether the sex difference whereby female transcatheter aortic valve replacement (TAVR) candidates had a lower risk profile, a higher incidence of in-hospital complications, but more favorable short- and long-term survival observed in tricuspid cohorts undergoing TAVR would persist in patients with bicuspid aortic valves (BAVs). OBJECTIVES: The aim of this study was to reexamine the impact of sex on outcomes following TAVR in patients with BAVs. METHODS: In this single-center study, patients with BAVs undergoing TAVR for severe aortic stenosis from 2012 to 2021 were retrospectively included. Baseline characteristics, aortic root anatomy, and in-hospital and 1-year valve hemodynamic status and survival were compared between sexes. RESULTS: A total of 510 patients with BAVs were included. At baseline, women presented with fewer comorbidities. Men had a greater proportion of Sievers type 1 BAV, higher calcium volumes (549.2 ± 408.4 mm3 vs 920.8 ± 654.3 mm3; P < 0.001), and larger aortic root structures. Women experienced more vascular complications (12.9% vs 4.9%; P = 0.002) and bleeding (11.1% vs 5.3%; P = 0.019) and higher residual gradients (16.9 ± 7.7 mm Hg vs 13.2 ± 6.4 mm Hg; P < 0.001), while men were more likely to undergo second valve implantations during index TAVR (6.3% vs 15.9%; P = 0.001). Death at 1 year was not significantly different between sexes (HR: 1.15; 95% CI: 0.56-2.35; P = 0.70). Bleeding (adjusted HR: 4.62; 95% CI: 1.51-14.12; P = 0.007) was the single independent predictor of 1-year death for women. CONCLUSIONS: In patients with BAVs undergoing TAVR, women presented with fewer comorbidities, while men had a greater proportion of type 1 BAV, more calcification, and larger aortic roots. In-hospital outcomes favored men, with fewer complications except for the need for second valve implantation, but 1-year survival was comparable between sexes.

The incidence and predictors of high-degree atrioventricular block in patients with bicuspid aortic valve receiving self-expandable transcatheter aortic valve implantation.

BACKGROUND: The high-degree atrioventricular block (HAVB) in patients with bicuspid aortic valve (BAV) treated with transcatheter aortic valve implantation (TAVI) remains high. The study aims to explore this poorly understood subject of mechanisms and predictors for HAVB in BAV self-expandable TAVI patients. METHODS: We retrospectively included 181 BAV patients for analysis. Using computed tomography data, the curvature of ascending aorta (AAo) was quantified by the angle (AAo angle) between annulus and the cross-section at 35 mm above annulus (where the stent interacts with AAo the most). The valvular anatomy and leaflet calcification were also characterized. RESULTS: The 30-day HAVB rate was 16.0% (median time to HAVB was three days). Type-1 morphology was found in 79 patients (43.6%) (left- and right-coronary cusps fusion comprised 79.7%). Besides implantation below membrane septum, large AAo angle [odds ratio (OR) = 1.08, P = 0.016] and type-1 morphology (OR = 4.97, P = 0.001) were found as the independent predictors for HAVB. Together with baseline right bundle branch block, these predictors showed strong predictability for HAVB with area under the cure of 0.84 (sensitivity = 62.1%, specificity = 92.8%). Bent AAo and calcified raphe had a synergistic effect in facilitating high implantation, though the former is associated with at-risk deployment (device implanted above annulus + prothesis pop-out, versus straight AAo: 9.9% vs. 2.2%, P = 0.031). CONCLUSIONS: AAo curvature and type-1 morphology are novel predictors for HAVB in BAV patients following self-expandable TAVI. For patients with bent AAo or calcified raphe, a progressive approach to implant the device above the lower edge of membrane septum is favored, though should be done cautiously to avoid pop-out.

Quantitative measurement of cartilage volume with automatic cartilage segmentation in knee osteoarthritis.

PURPOSE: To determine the reproducibility of the automatic cartilage segmentation method using a prototype KneeCaP software (version 1.3; Siemens Healthcare, Erlangen, Germany) and to compare the difference in cartilage volume (CV) between the normal knee joint and knee osteoarthritis (KOA) of different degrees by using the above software. MATERIALS AND METHODS: The study included 62 subjects with knee OA and 29 healthy control subjects. The cartilage lesion patients were divided into a mild-to-moderate OA group (n = 29) and severe OA group (n = 33). Automatic cartilage segmentation was performed on all the subjects, and among them, 19 knee cases were randomly selected to also do the manual cartilage segmentation. Statistical significance was determined with one-way analysis of variance (ANOVA), intraclass correlation coefficient (ICC), and Pearson correlation coefficient. Automatic segmentation was compared with the manual one. The relative cartilage volume percentages of the femur, tibia, and patella in the normal control/mild-to-moderate/severe OA groups were assessed. RESULTS: Comparing the cartilage volumes derived by manual and automatic segmentation, the ICC value for the knee joint, patella, femur, or tibia was 0.784, 0.815, 0.740, and 0.797. The relative cartilage volume percentages of the femur, tibia, and patella in the normal control/mild-to-moderate/severe OA groups were 57.28%/59.30%/62.45% (femur), 25.35%/23.46%/21.84% (tibia), and 17.37%/17.24%/15.71% (patella), respectively. Compared with the normal control group, the relative tibia cartilage volume percentage was lower in the mild-to-moderate OA group and the severe OA group. Corresponding index showed a similar difference between the mild-to-moderate OA group and the severe OA group (p < 0.001). CONCLUSION: This study demonstrated that the relative cartilage volume percentage is correlated with the semi-quantitative systems and may be a preferred outcome measure in clinical studies of OA. Automatic cartilage segmentation using KneeCaP delivered reliable results on high-spatial-resolution 3 T MR images for the healthy, mild-moderate OA patients. Key Points • The cartilage automatic segmentation has excellent reproducibility and was not affected by inter-observer variation. • The relative cartilage volume percentage is correlated with the semi-quantitative systems and may be a preferred outcome measure in clinical studies of OA.

Pulmonary invasive fungal disease and bacterial pneumonia: a comparative study with high-resolution CT.

BACKGROUND: Early diagnosis of invasive fungal disease (IFD) is challenging. High-resolution computed tomography (CT) may improve IFD diagnosis; however, there are no definitive imaging signs for differentiating between bacterial pneumonia and IFD. METHODS: We retrospectively evaluated CT images of 208 patients with IFD (n = 102) or bacterial pneumonia (n = 106). We classified pulmonary opacities as consolidations, ground-glass opacities (GGOs), or nodules and recorded the presence of perinodular ground-glass halos, reversed halo sign (RSH), and cavitation (crescent-shaped or not). RESULTS: Consolidation appeared in 83.3% and 92.5% of patients with IFD and bacterial pneumonia, respectively. Multifocal non-segmental consolidation was more common in IFD (48%) than bacterial pneumonia (22.6%; P < 0.05). Segmental or subsegmental consolidation was more common in bacterial pneumonia (43.4%) than IFD (7.8%; P < 0.01). GGOs and nodules were more common in IFD than bacterial pneumonia (60.8% vs. 24.5% and 54.9% vs. 15.1%, respectively; each P < 0.05). Consolidation combined with GGO, nodules, or both GGO and nodules was more frequent in IFD than in bacterial pneumonia (each P < 0.05). Nodules with halo sign (n = 23) appeared in 22.5% and 3.8% of patients with IFD and bacterial pneumonia, respectively. Nodules with RSH appeared only in IFD, and those with cavitation appeared in 11.8% and 1.9% of patients with IFD and bacterial pneumonia, respectively. CONCLUSIONS: Consolidation plus GGO and nodules or consolidation plus nodules is suggestive for IFD. Segmental or subsegmental consolidations are more frequent in bacterial pneumonia than in IFD. Large nodules, as well as nodules with halo sign or both small and large nodules, are related to IFD.

Progression of the Ascending Aortic Diameter After Transcatheter Aortic Valve Implantation: Based on Computed Tomography Images.

OBJECTIVES: The natural history of ascending aortic diameter after transcatheter aortic valve implantation (TAVI) has not been investigated. Our aim was to determine the progression of ascending aortic diameter in patients undergoing TAVI. METHODS: We retrospectively included 134 patients undergoing TAVI for aortic stenosis at our institution from June 2012 to November 2016, including 79 patients with bicuspid aortic valve (BAV) and 55 patients with tricuspid aortic valve (TAV). Preoperative measurements of the ascending aorta were compared with aortic measurements at 1-year follow-up based on computed tomography images. RESULTS: A very slight decrease in median aortic diameter was identified in overall patients: 4.07 cm (interquartile range [IQR], 3.76-4.54 cm) vs 4.06 cm (IQR, 3.74-4.51 cm); P=.04. Further subgroup analysis found that the decrease remained statistically significant in the subgroup of TAV and mild aortic dilation. In addition, no aortic events occurred during long-term follow-up (median, 27 months; IQR, 20-42 months). CONCLUSIONS: TAVI could prevent a further progression of aortic diameter for both BAV or TAV patients by correcting hemodynamic derangements, especially for patients with TAV, mild aortic dilation, and small annulus angles. Aortic events appeared rarely during long-term follow-up after TAVI. However, our results need further confirmation with future investigations in a larger population with longer-term follow-up.

The impact of renal function on the prognostic value of N-terminal pro-B-type natriuretic peptide in patients with coronary artery disease.

BACKGROUND: The impact of renal function on the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) remains unclear in coronary artery disease (CAD). This study sought to investigate the value of using NT-proBNP level to predict prognoses of CAD patients with different estimated glomerular filtration rates (eGFRs). METHODS: A retrospective analysis was conducted from a single registered database. 2087 consecutive patients with CAD confirmed by coronary angiography were enrolled. The primary endpoint was allcause mortality. RESULTS: The mean follow-up time was 26.4 ± 11.9 months and death events occurred in 197 cases. The NT-proBNP levels increased with the deterioration of renal function, as well as the optimal cutoff values based on eGFR stratification to predict endpoint outcome (179.4 pg/mL, 1443.0 pg/mL, 3478.0 pg/mL, for eGFR ≥ 90, 60-90 and < 60 mL/min/1.73 m2, respectively). Compared with the routine cut-off value or overall optimal one, stratified optimal ones had superior predictive ability for endpoint in each eGFR group (all with the highest Youden's J statistics). And the prognostic value became weaker as eGFR level decreased (eGFR ≥ 90 vs. 60-90 vs. < 60 mL/min/1.73 m2, odds ratio [OR] 7.7; 95% confidence interval [CI] 1.7-33.9 vs. OR 4.8; 95% CI 2.7-8.5 vs. OR 3.0; 95% CI 1.5-6.2). CONCLUSIONS: This study demonstrated that NT-proBNP exhibits different predictive values for prognosis for CAD patients with different levels of renal function. Among the assessed values, the NT-proBNP cut-off value determined using renal function improve the accuracy of the prognosis prediction of CAD. Moreover, lower eGFR is associated with a higher NT-proBNP cut-off value for prognostic prediction.

Enzyme/pH-sensitive polyHPMA-DOX conjugate as a biocompatible and efficient anticancer agent.

In this study, to enhance the therapeutic function and reduce the side-effects of doxorubicin (DOX), a biodegradable N-(2-hydroxypropyl) methacrylamide (HPMA) polymer-DOX conjugate has been prepared through reversible addition fragmentation chain transfer (RAFT) polymerization and conjugation chemistry, and the anticancer agent DOX was covalently linked to the polymeric vehicle through a pH-responsive hydrazone bond. The cellular mechanisms of the conjugate were explored, and the therapeutic indexes were studied as well. The high molecular weight (MW) polymeric conjugate (94 kDa) was degraded into products with low MW (45 kDa) in the presence of lysosomal cathepsin B and also showed pH-responsive drug release behavior. In vitro cellular mechanism studies revealed that the polymeric conjugate was uptaken by the 4T1 cells, leading to cell apoptosis and cytotoxicity to cancer cells, while the polymeric conjugate demonstrated excellent in vivo biosafety even at a high dose. Compared to free DOX, the conjugate has a much longer half-life in pharmacokinetics and accumulates in tumors with a much higher amount. The conjugate therefore has a much greater in vivo anticancer efficacy against 4T1 xenograft tumors and shows subtle side-effects, which were confirmed via tumor size and weight, immunohistochemistry and histological studies. Overall, this polymeric conjugate may be used as an enzyme/pH-sensitive anticancer agent.