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The aim of this study was to investigate the effect of hesperidin on the liver and kidney dysfunctions induced by nickel. The mice were divided into six groups: nickel treatment with 80 mg/kg, 160 mg/kg, 320 mg/kg hesperidin groups, 0.5% CMC-Na group, nickel group, and blank control group. Histopathological techniques, biochemistry, immunohistochemistry, and the TUNEL method were used to study the changes in structure, functions, oxidative injuries, and apoptosis of the liver and kidney. The results showed that hesperidin could alleviate the weight loss and histological injuries of the liver and kidney induced by nickel, and increase the levels of lactate dehydrogenase (LDH), alanine aminotransferase (GPT), glutamic oxaloacetic transaminase (GOT) in liver and blood urea nitrogen (BUN), creatinine (Cr) and N-acetylglucosidase (NAG) in kidney. In addition, hesperidin could increase the activities of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione peroxidase (GSH-Px) in the liver and kidney, decrease the content of malondialdehyde (MDA) and inhibit cell apoptosis. It is suggested that hesperidin could help inhibit the toxic effect of nickel on the liver and kidney.
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Recent studies suggest that PARP inhibitors and POLQ inhibitors confer synthetic lethality in BRCA1-deficient tumors by accumulation of single-stranded DNA (ssDNA) gaps at replication forks. Loss of USP1, a deubiquitinating enzyme, is also synthetic lethal with BRCA1 deficiency, and USP1 inhibitors are now undergoing clinical development for these cancers. Here, we show that USP1 inhibitors also promote the accumulation of ssDNA gaps during replication in BRCA1-deficient cells, and this phenotype correlates with the drug sensitivity. USP1 inhibition increased monoubiquitinated PCNA at replication forks, mediated by the ubiquitin ligase RAD18, and knockdown of RAD18 caused USP1 inhibitor resistance and suppression of ssDNA gaps. USP1 inhibition overcame PARP inhibitor resistance in a BRCA1-mutated xenograft model and induced ssDNA gaps. Furthermore, USP1 inhibition was synergistic with PARP and POLQ inhibition in BRCA1-mutant cells, with enhanced ssDNA gap accumulation. Finally, in patient-derived ovarian tumor organoids, sensitivity to USP1 inhibition alone or in combination correlated with the accumulation of ssDNA gaps. Assessment of ssDNA gaps in ovarian tumor organoids therefore represents a rapid approach for predicting response to USP1 inhibition in ongoing clinical trials.
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OBJECTIVE: To investigate the safety and efficacy of mitoxantrone liposome in the treatment of children with high-risk acute myeloid leukemia (AML). METHODS: The children with high-risk AML who received the mitoxantrone liposome regimen at Wuhan Children's Hospital from January 2022 to February 2023 were collected as the observation group, and the children with high-risk AML who received idarubicin regimen were enrolled as controls, and their clinical data were analyzed. Time to bone marrow recovery, the complete remission rate of bone marrow cytology, the clearance rate of minimal residual disease, and treatment-related adverse reactions were compared between the two groups. RESULTS: The patients treated with mitoxantrone liposome showed shorter time to recovery of leukocytes(17 vs 21 day), granulocytes(18 vs 24 day), platelets(17 vs 24 day), and hemoglobin(20 vs 26 day) compared with those treated with idarubicin, there were statistical differences (P <0.05). The effective rate and MRD turning negative rate in the observation group were 90.9% and 72.7%, respectively, while those in the control group were 94.1% and 76.4%, with no statistical difference (P >0.05). The overall response rate of the two groups of patients was similar. CONCLUSION: The efficacy of mitoxantrone liposome is not inferior to that of idarubicin in children with high-risk AML, but mitoxantrone liposome allows a significantly shorter duration of bone marrow suppression and the safety is better.
Subject(s)
Leukemia, Myeloid, Acute , Liposomes , Mitoxantrone , Humans , Mitoxantrone/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Child , Idarubicin/administration & dosage , Male , Female , AdolescentABSTRACT
Raman spectroscopy has been widely used for label-free biomolecular analysis of cells and tissues for pathological diagnosis in vitro and in vivo. AI technology facilitates disease diagnosis based on Raman spectroscopy, including machine learning (PCA and SVM), manifold learning (UMAP), and deep learning (ResNet and AlexNet). However, it is not clear how to optimize the appropriate AI classification model for different types of Raman spectral data. Here, we selected five representative Raman spectral data sets, including endometrial carcinoma, hepatoma extracellular vesicles, bacteria, melanoma cell, diabetic skin, with different characteristics regarding sample size, spectral data size, Raman shift range, tissue sites, Kullback-Leibler (KL) divergence, and significant Raman shifts (i.e., wavenumbers with significant differences between groups), to explore the performance of different AI models (e.g., PCA-SVM, SVM, UMAP-SVM, ResNet or AlexNet). For data set of large spectral data size, Resnet performed better than PCA-SVM and UMAP. By building data characteristic-assisted AI classification model, we optimized the network parameters (e.g., principal components, activation function, and loss function) of AI model based on data size and KL divergence etc. The accuracy improved from 85.1 to 94.6% for endometrial carcinoma grading, from 77.1 to 90.7% for hepatoma extracellular vesicles detection, from 89.3 to 99.7% for melanoma cell detection, from 88.1 to 97.9% for bacterial identification, from 53.7 to 85.5% for diabetic skin screening, and mean time expense of 5 s.
Subject(s)
Spectrum Analysis, Raman , Spectrum Analysis, Raman/methods , Humans , Female , Endometrial Neoplasms/pathology , Endometrial Neoplasms/diagnosis , Endometrial Neoplasms/chemistry , Machine Learning , Melanoma/pathology , Melanoma/diagnosis , Melanoma/classification , Extracellular Vesicles/chemistry , Support Vector Machine , Bacteria/classification , Bacteria/isolation & purification , Artificial IntelligenceABSTRACT
Efforts to develop a range of HIV prevention products that can serve as behaviorally congruent viable alternatives to consistent condom use and oral pre-exposure prophylaxis (PrEP) remain crucial. MTN-035 was a randomized crossover trial seeking to evaluate the safety, acceptability, and adherence to three placebo modalities (insert, suppository, enema) prior to receptive anal intercourse (RAI). If participants had no RAI in a week, they were asked to use their assigned product without sex. We hypothesized that the modalities would be acceptable and safe for use prior to RAI, and that participants would report high adherence given their behavioral congruence with cleansing practices (e.g., douches and/or enemas) and their existing use to deliver medications (e.g., suppositories; fast-dissolving inserts) via the rectum. Participants (N = 217) were sexual and gender minorities enrolled in five different countries (Malawi, Peru, South Africa, Thailand, and the United States of America). Mean age was 24.9 years (range 18-35 years). 204 adverse events were reported by 98 participants (45.2%); 37 (18.1%) were deemed related to the study products. The proportion of participants reporting "high acceptability" was 72% (95%CI: 65% - 78%) for inserts, 66% (95%CI: 59% - 73%) for suppositories, and 73% (95%CI: 66% - 79%) for enemas. The proportion of participants reporting fully adherent per protocol (i.e., at least one use per week) was 75% (95%CI: 69% - 81%) for inserts, 74% (95%CI: 68% - 80%) for suppositories, and 83% (95%CI: 77% - 88%) for enemas. Participants fully adherent per RAI-act was similar among the three products: insert (n = 99; 58.9%), suppository (n = 101; 58.0%) and enema (n = 107; 58.8%). The efficacy and effectiveness of emerging HIV prevention drug depends on safe and acceptable delivery modalities that are easy to use consistently. Our findings demonstrate the safety and acceptability of, and adherence to, enemas, inserts, and suppositories as potential modalities through which to deliver a rectal microbicide.
Subject(s)
Anti-Infective Agents , HIV Infections , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Male , Humans , Adolescent , Young Adult , Adult , Rectum , HIV Infections/prevention & control , HIV Infections/drug therapy , Homosexuality, Male , Suppositories , Sexual Behavior , Anti-Infective Agents/therapeutic useABSTRACT
BACKGROUND: Targeted therapy combined with immune checkpoint inhibitors is considered a promising treatment for primary advanced hepatocellular carcinoma (HCC). Nevertheless, the difference between synchronous and asynchronous treatment of lenvatinib with programmed death receptor-1 (PD-1) inhibitor in advanced HCC is still unclear. The aim of this investigation is to evaluate the effectiveness of synchronous and asynchronous of lenvatinib and PD-1 inhibitor on the advanced HCC beyond oligometastasis. METHODS: In this study, 213 patients from four institutions in China were involved. Patients were split into two collections: (1) lenvatinib plus PD-1 inhibitor were used synchronously (synchronous treatment group); (2) patients in asynchronous treatment group received PD-1 inhibitor after 3 months of lenvatinib treatment prior to tumour progression. To analyse progression-free survival (PFS), overall survival (OS), efficacy and safety of patients in both groups, we employed propensity score matching (PSM). RESULTS: The 6-, 12- and 24-month OS rates were 100%, 93.4% and 58.1% in the synchronous treatment group and 100%, 71.5% and 25.3% in the asynchronous treatment group, respectively. In contrast to the asynchronous treatment group, the group treated synchronously exhibited a substantially enhanced OS (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.30-0.66; p < .001). The 6-, 12- and 18-month PFS rates were 82.6%, 42.6% and 10.8% in the synchronous treatment group and 63.3%, 14.2% and 0% in the asynchronous treatment group, respectively. A significant difference was observed in the PFS rate (HR, 0.46; 95% CI, 0.33-0.63; p < .001) between the two collections. CONCLUSIONS: Patients with advanced HCC beyond oligometastasis, simultaneous administration of lenvatinib and PD-1 inhibitor led to significant improvements in survival.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/therapeutic use , Liver Neoplasms/drug therapy , Phenylurea Compounds/pharmacology , Phenylurea Compounds/therapeutic useABSTRACT
In the aorta of mid-gestational mouse embryos, a specialized endothelial subpopulation termed hemogenic endothelial cells (HECs) develops into hematopoietic stem and progenitor cells (HSPCs), through a conserved process of endothelial-to-hematopoietic transition (EHT). EHT is tightly controlled by multiple intrinsic and extrinsic mechanisms. Nevertheless, the molecular regulators restraining this process remain poorly understood. Here, it is uncovered that, one of the previously identified HEC signature genes, Nupr1, negatively regulates the EHT process. Nupr1 deletion in endothelial cells results in increased HSPC generation in the aorta-gonad-mesonephros region. Furthermore, single-cell transcriptomics combined with serial functional assays reveals that loss of Nupr1 promotes the EHT process by promoting the specification of hematopoiesis-primed functional HECs and strengthening their subsequent hematopoietic differentiation potential toward HSPCs. This study further finds that the proinflammatory cytokine, tumor necrosis factor α (TNF-α), is significantly upregulated in Nupr1-deficient HECs, and the use of a specific TNF-α neutralizing antibody partially reduces excessive HSPC generation in the explant cultures from Nupr1-deficient embryos. This study identifies a novel negative regulator of EHT and the findings indicate that Nupr1 is a new potential target for future hematopoietic stem cell regeneration research.
Subject(s)
Endothelial Cells , Mesonephros , Animals , Mice , Aorta , Gonads , Tumor Necrosis Factor-alphaABSTRACT
BACKGROUND: Mitral valve stenosis (MS) is the primary pathologic feature of rheumatic mitral valve disease, and the complex repair affects its clinical outcome. This study aimed to examine the efficacy of the 4-step commisuroplasty "SCORe" procedure by assessing changes in the mobility of mitral valve leaflets and its clinical effects. METHODS: From September 1, 2018, to January 13, 2019, patients with MS who underwent mitral valve repair with the SCORe procedure in the study center were analyzed in this prospective study. Mitral valve structure was assessed by transthoracic echocardiography pre- and postoperatively as well as during follow-up. RESULTS: In total, 60 consecutive patients were examined. In 56 patients (93.3%), mitral valve orifice area (MVOA) was less than 1.5 cm2, and mean (SD) MVOA for the whole cohort was 1.20 (0.34) cm2. The mobility of the anterior leaflet was improved (P < .001) during the cardiac cycle postsurgery, but that of the posterior leaflet was not (P = .591). The mean (SD) coaptation length was increased significantly from 6.69 (1.32) mm to 7.92 (1.24) mm (P < .001) postoperatively. Mean (SD) MVOAs increased to 2.24 (0.38) cm2 postoperatively (P < .001). During the 1-year follow-up, there were no deaths or reoperations. Follow-up echocardiography revealed minor or mild regurgitation in 98.3% of patients. CONCLUSION: These findings demonstrated that the SCORe procedure can effectively improve the mobility of mitral leaflets and enlarge the valve orifice area in patients with rheumatic MS in China, with minimal complications and promising results.
Subject(s)
Cardiac Surgical Procedures , Heart Valve Diseases , Mitral Valve Stenosis , Humans , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Prospective Studies , Cardiac Surgical Procedures/adverse effects , Mitral Valve Stenosis/diagnostic imaging , Mitral Valve Stenosis/surgeryABSTRACT
Multipurpose prevention technologies (MPT) have been increasingly researched for their dual-purpose preventative properties against HIV and other STIs. The acceptability of PC-1005, a topical MPT candidate, was explored among men and women participating in the MTN-037 Phase I trial at two U.S. sites (Pittsburgh, PA, and Birmingham, AL). We triangulated quantitative and qualitative assessments of the acceptability of three volumes (4 mL, 16 mL, 32 mL) of PC-1005 administered rectally (N = 12; 6 males, 6 females). Participants rated overall gel acceptability on a scale of 1-10, with a median of 7.17 (SD = 2.04) and had positive feelings about all three dose volumes, citing them to be very comfortable or comfortable (dose 1 = 91.7%; dose 2 = 91.7%; dose 3 = 83.3%). High acceptability of and comfort with all three dose volumes shows promise for PC-1005 as an MPT to prevent HIV and STIs, warranting future clinical development.
Subject(s)
HIV Infections , HIV Seropositivity , HIV-1 , Sexually Transmitted Diseases , Adult , Female , HIV Infections/prevention & control , Humans , Male , Sexually Transmitted Diseases/prevention & controlABSTRACT
Background: Lenvatinib combined with a PD-1 inhibitor has obtained a satisfactory antitumor effect in several solid tumors. However, the efficacy and tumor response of lenvatinib with a PD-1 inhibitor in advanced intrahepatic cholangiocarcinoma still need further exploration. Methods: This is a single-arm study for the assessment of the efficacy and tolerability of lenvatinib with a PD-1 inhibitor in intrahepatic cholangiocarcinoma patients who had chemotherapy failure. Efficacy was evaluated based on the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1). Results: A total of 40 patients with advanced intrahepatic cholangiocarcinoma were enrolled after the chemorefractory effect. The median progression-free survival was 5.83 ± 0.76 months. The 3-month and 6-month progression-free survival rates were 80.0% and 32.5%, respectively. The median overall survival was 14.30 ± 1.30 months. The 12-month and 18-month overall survival rates were 61.4% and 34.7%. The 3-month RECIST 1.1 evaluation was that seven patients (17.5%) showed partial response, 23 patients (57.5%) had stable disease, and 10 patients (25.0%) had progressive disease. The objective response rate was 17.5%, and the disease control rate was 75.0%. All the recorded any-grade adverse events inducing treatment termination were controllable, and there were no AE-related deaths. Conclusion: Our study showed that a combination of lenvatinib with the PD-1 inhibitor could be an effective treatment for advanced intrahepatic cholangiocarcinoma after the chemorefractory effect.
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BACKGROUND: Despite being one of the few chronic secondary heart diseases that can be prevented, current epidemiological data on rheumatic heart disease (RHD) in China are unavailable. This study examined mitral valve (MV) surgery trends in a large Chinese cardiovascular center over the last 10 years and provided insight into the distribution of RHDs and their changes. METHODS: Medical records of patients who underwent cardiac surgery, MV surgery, and MV surgery for rheumatic MV (rMV) disease at Beijing Anzhen Hospital between January 2010 and December 2019 were retrospectively reviewed. Patients' demographic and clinical characteristics were statistically analyzed among age groups. RESULTS: Overall, 7,736 patients underwent rMV surgery and 87.5% were aged 40-70 years. The proportion of patients aged >60 years increased annually (P<0.05), and the proportion of patients in all other age groups decreased. The proportion of patients with rMV diseases among those with cardiac or mitral valve diseases decreased each year, but the absolute number of patients with rMV disease remained stable. Approximately 90% of patients who underwent rMV surgery were from northern China. The incidence of rMV disease among patients with mitral valve disease moderately correlated with the per capita gross regional product (Per-GRP), an indicator of living standards (r=-0.517, P<0.05). CONCLUSIONS: RHD still exists in northern China and requires adequate resources for its management. The number of older patients with rMV disease presents a challenge for mitral valve surgery.
Subject(s)
Cardiac Surgical Procedures , Heart Valve Diseases , Rheumatic Heart Disease , China/epidemiology , Heart Valve Diseases/epidemiology , Heart Valve Diseases/surgery , Humans , Mitral Valve/surgery , Retrospective Studies , Rheumatic Heart Disease/epidemiology , Rheumatic Heart Disease/surgeryABSTRACT
BACKGROUND: Two phase 3 clinical trials showed that use of a monthly vaginal ring containing 25 mg dapivirine was well tolerated and reduced HIV-1 incidence in women by approximately 30% compared with placebo. We aimed to evaluate use and safety of the dapivirine vaginal ring (DVR) in open-label settings with high background rates of HIV-1 infection, an important step for future implementation. METHODS: We did a phase 3B open-label extension trial of the DVR (MTN-025/HIV Open-label Prevention Extension [HOPE]). Women who were HIV-1-negative and had participated in the MTN-020/ASPIRE phase 3 trial were offered 12 months of access to the DVR at 14 clinical research centres in Malawi, South Africa, Uganda, and Zimbabwe. At each visit (monthly for 3 months, then once every 3 months), women chose whether or not to accept the offer of the ring. Used, returned rings were tested for residual amounts of dapivirine as a surrogate marker for adherence. HIV-1 serological testing was done at each visit. Dapivirine amounts in returned rings and HIV-1 incidence were compared with data from the ASPIRE trial, and safety was assessed. This study is registered with ClinicalTrials.gov, NCT02858037. FINDINGS: Between July 16, 2016, and Oct 10, 2018, of 1756 women assessed for eligibility, 1456 were enrolled and participated in the study. Median age was 31 years (IQR 27-37). At baseline, 1342 (92·2%) women chose to take the DVR; ring acceptance was more than 79% at each visit up until 12 months and 936 (73·2%) of 1279 chose to take the ring at all visits. 12â530 (89·3%) of 14â034 returned rings had residual dapivirine amounts consistent with some use during the previous month (>0·9 mg released) and the mean dapivirine amount released was greater than in the ASPIRE trial (by 0·21 mg; p<0·0001). HIV-1 incidence was 2·7 per 100 person-years (95% CI 1·9-3·8, 35 infections), compared with an expected incidence of 4·4 per 100 person-years (3·2-5·8) among a population matched on age, site, and presence of a sexually transmitted infection from the placebo group of ASPIRE. No serious adverse events or grade 3 or higher adverse events observed were assessed as related to the DVR. INTERPRETATION: High uptake and persistent use in this open-label extension study support the DVR as an HIV-1 prevention option for women. With an increasing number of HIV-1 prophylaxis choices on the horizon, these results suggest that the DVR will be an acceptable and practical option for women in Africa. FUNDING: The Microbicide Trials Network and the National Institute of Allergy and Infectious Diseases, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health, all components of the US National Institutes of Health.
Subject(s)
Anti-HIV Agents/therapeutic use , Contraceptive Devices, Female , HIV Infections/prevention & control , Pyrimidines/therapeutic use , Tenofovir/therapeutic use , Administration, Intravaginal , Adult , Female , HIV Infections/diagnosis , HIV Infections/immunology , HIV Infections/virology , HIV-1/immunology , Humans , Malawi , Patient Compliance/statistics & numerical data , Patient Safety , Seroconversion , South Africa , Treatment Outcome , Uganda , ZimbabweABSTRACT
BACKGROUND: To identify the association between tricuspid annular circumference and secondary tricuspid regurgitation and analyze the risk factors of recurrent tricuspid regurgitation after concomitant tricuspid annuloplasty during left heart surgery. METHODS: From October 2018 to June 2019, a total of 117 patients receiving concomitant tricuspid annuloplasty within left heart surgery were enrolled. Severity of tricuspid regurgitation was classified as 4 subtypes: normal, mild, moderate and severe. Perioperative data and mid-term outcome were collected. Tricuspid annular circumference (TAC) was measured under cardiac arrest during surgery procedure by cardioplegia. Optimal TAC and TAC index (TAC/body surface area, BSA) cutoffs of significant tricuspid annulus dilatation (moderate and severe) were obtained. Univariable and multivariable logistic regression analyses were performed to identify the risk factors of postoperative recurrent tricuspid regurgitation. The follow up period is 13-19 months (mean 15.5 ± 3.2 months). RESULTS: There was 1 patient was excluded who died after surgery. A total of 116 patients receiving tricuspid annuloplasty were included. Optimal cutoffs of significant tricuspid annulus dilatation were recommended (TAC 11.45 cm, Sensitivity 82.89%, Specificity 73.68%, AUC 0.915; TAC index 7.09 cm/m2, Sensitivity 73.68%, Specificity 85%, AUC 0.825, respectively). Based on findings of multivariable logistic regression, it has been showed that TAC index and postoperative atrial fibrillation were the independent risk factors of recurrent regurgitation after surgery. Optimal TAC index cutoff to predict recurrent tricuspid regurgitation was 7.86 cm/m2 CONCLUSIONS: The severity of secondary tricuspid regurgitation is associated with the tricuspid annular circumference. The cut-offs of significant tricuspid regurgitation (more than moderate) were TAC 11.45 cm and TAC index 7.09 cm/m2, respectively. Clinically, concomitant tricuspid annuloplasty is relative safe and effective. TAC index ≥ 7.86 cm/m2 and postoperative atrial fibrillation are the risk factors of recurrent significant tricuspid regurgitation after concomitant tricuspid annuloplasty during left heart surgery.
Subject(s)
Cardiac Valve Annuloplasty/adverse effects , Postoperative Complications/etiology , Tricuspid Valve Insufficiency/surgery , Tricuspid Valve/surgery , Aged , Echocardiography , Female , Humans , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Postoperative Complications/physiopathology , Recurrence , Risk Assessment , Risk Factors , Severity of Illness Index , Time Factors , Treatment Outcome , Tricuspid Valve/diagnostic imaging , Tricuspid Valve/physiopathology , Tricuspid Valve Insufficiency/diagnostic imaging , Tricuspid Valve Insufficiency/physiopathologyABSTRACT
OBJECTIVE: Whether mitral valve repair is superior to replacement in the population with rheumatic heart disease has been debated. This study aims to compare outcomes of repair with replacement by the propensity score method. METHODS: This observational, prospective study enrolled patients with rheumatic heart disease who underwent mitral valve repair and replacement from January 2011 to April 2019. The propensity score method was used to select 2 groups with similar baseline characteristics. Baseline, clinical, and follow-up data were collected. Clinical outcomes included death from any cause, reoperation, and valve-related complications. RESULTS: The overall population before matching (N = 1644) included 612 patients who underwent repair and 1032 patients who underwent replacement. The propensity score analysis generated matches for 1058 patients (529 pairs). The median follow-up time was 4.12 years. Early mortality and death from any cause during follow-up were significantly lower in the repair group compared with the replacement group (hazard ratio, 0.19; 95% confidence interval [CI], 0.05-0.64; P = .003; hazard ratio, 0.38; 95% CI, 0.19-0.74; P = .003, respectively). Patients in the repair group had a lower risk of valve-related complications compared with patients in the replacement group (subhazard ratio, 0.44; 95% CI, 0.21-0.90; P = .025). In terms of reoperation, no significant difference was observed between the repair and replacement groups (subhazard ratio, 2.54; 95% CI, 0.89-7.22; P = .081). CONCLUSIONS: The results suggest that rheumatic mitral valve repair in select patients is superior to mitral valve replacement with regard to lower mortality and fewer valve-related complications; meanwhile, it has a comparable risk of reoperation compared with replacement.
Subject(s)
Heart Valve Prosthesis Implantation , Mitral Valve/surgery , Rheumatic Heart Disease/surgery , Adult , Aged , Cardiac Surgical Procedures/adverse effects , Cardiac Surgical Procedures/methods , Cardiac Surgical Procedures/mortality , Female , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/methods , Heart Valve Prosthesis Implantation/mortality , Humans , Male , Middle Aged , Mitral Valve Insufficiency/surgery , Postoperative Complications , Propensity Score , Prospective Studies , Reoperation/statistics & numerical data , Treatment OutcomeABSTRACT
BACKGROUND: The elevation of troponin after coronary artery bypass grafting (CABG) is common This study aimed to investigate the association between very early cardiac troponin I (cTnI) concentration and its longitudinal change within 24 hours after CABG and 30-day adverse events. METHODS: This study prospectively enrolled 633 patients who underwent isolated off-pump CABG from January 2019 to May 2019. Serum cTnI levels were measured in all patients at two examinations within 24 hours postoperatively (1 hour and 12-18 hours), and a proportional hazards model was used to determine the association between cTnI levels and their change with adverse events, which were defined as a composite of 30-day mortality, stroke, heart failure, myocardial infarction (MI), and ventricular fibrillation. RESULTS: cTnI levels of the two examinations and absolute change of cTnI levels were significantly higher in the event group than in the non-event group (P<0.01, both). Earlier and later cTnI concentrations were associated with 30-day complications [adjusted hazard ration (HR) 1.598, 95% confidence interval (CI), 1.158-2.204 and HR 1.499, 95% CI, 1.228-1.831, respectively]. With regard to longitudinal change in cTnI levels, participants with persistently high levels of cTnI and those with progression from a low level to high level concentration experienced a significantly increased risk of adverse events than did participants who had a trend of persistently low cTnI levels (HR 3.105, 95% CI, 1.748-5.517 versus HR 2.944, 95% CI, 1.488-5.824). CONCLUSIONS: Longitudinal change in cTnI levels within 24 hours and early cTnI concentrations, even less than 1 hour after CABG, are associated with adverse events. These data will be useful in identifying patients at an increased risk of complications.
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BACKGROUND: Many comparative studies of percutaneous balloon mitral valvuloplasty (PBMV) and surgical mitral commissurotomy (SMC) in rheumatic mitral stenosis (MS) were done in the last few decades. With the development of valve repair techniques, various surgical rheumatic valve repair techniques have been applied in clinic, but there is a lack of comparison with PBMV. Our study was designed to compare the perioperative and mid-term outcomes of PBMV and mitral valve repair with "four-step" procedure in the treatment of rheumatic MS. METHODS: Patients with MS were treated with PBMV or rheumatic mitral valve repair (rMVP) at Beijing Anzhen Hospital between January 1, 2013 and September 30, 2018 were selected. By using propensity score matching (PSM) method, we compared the changes in post-operation clinical outcomes between the two matched groups. Kaplan-Meier analyses was used for survival analysis and drawing the curve, and log-rank test were used to compare intergroup differences. RESULTS: A total of 252 cases were enrolled after selection, 74 cases in PBMV and 178 cases in rMVP. Seventy-four pairs were matched successfully after PSM. There were 53 females in PBMV and 54 in rMVP. The mean age of two groups was 46.95±12.50 and 47.55±11.91 years respectively. There was no significantly differences in mitral valve orifice area (MVOA) (1.05±0.32 vs. 0.97±0.24 cm2, P=0.12) and left ventricular ejection fraction (EF) (62.36%±5.17% vs. 62.52%±4.94%, P=0.76) between two groups preoperatively. Baseline characteristics were basically balanced after PSM. In each group, there was one case transferred to surgical mitral valve replacement due to the failure of valvuloplasty before discharge. All patients survived the interventions and no severe complications were found. MVOA were significantly increased in rMVP compared with PBMV postoperatively, as well as grading of MS and tricuspid regurgitation (TR) were significantly improved in rMVP. Three cases in PBMV were lost during the follow-up. Mitral replacement was performed in 11 patients and one of them died in PBMV, while none of patients underwent re-intervention in rMVP, but one patient died of pneumonia. CONCLUSIONS: For selected patients with rheumatic MS in China, our study shows that there are comparable clinical outcomes in terms of operative, mid-term mortality and complications between PBMV and surgical rMVP with "four-step" procedure. Surgical rMVP shows more advantageous in the correction of valve stenosis and the management of concomitant tricuspid valve lesions and atrial fibrillation (AF).
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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BACKGROUND: Rheumatic mitral valve repair and replacement techniques are frequently used with excellent outcomes in experienced centers. This study aims to evaluate the impact of procedural types on left ventricular function in quinquagenarians. METHODS: Between January 2018 and September 2019, patients with severe rheumatic mitral stenosis were prospectively recruited. Propensity score matching was performed to reduce the selection bias. We compared the strain, twist and synchrony parameters of left ventricle in 70 quinquagenarian patients who underwent rheumatic mitral valve repair and replacement 12 hours before surgery, at 7 days and 6 months postoperatively. RESULTS: The overall group displayed significant improvement of left ventricular deformation after rheumatic mitral valve surgery. Compared with patients undergoing posterior chordal-sparing mitral valve replacement, patients undergoing rheumatic mitral valve repair showed more significant amelioration in global longitudinal strain (-18.6% versus -16.2%, P<0.001), twist (18.2° versus 15.9°, P<0.001), torsion (1.8°/cm versus 1.3°/cm, P<0.001), apical rotation (10.5° versus 8.8°, P<0.001), basal rotation (-7.7° versus -7.1°, P=0.049), systolic dyssynchrony index (4.7% versus 5.1%, P=0.021), standard deviation of time to peak longitudinal (46.9 ms versus 49.3 ms, P=0.024) and radial strain (15.8 ms versus 17.1 ms, P=0.037) at 6-month follow-up. CONCLUSIONS: Rheumatic mitral valve repair might provide patients with better postoperative left ventricular performance than posterior chordal-sparing mitral valve replacement. Longer follow-up is required to compare long-term outcomes.
Subject(s)
Cardiac Surgical Procedures , Mitral Valve Insufficiency/surgery , Rheumatic Heart Disease/surgery , Ventricular Function, Left , Echocardiography, Three-Dimensional , Female , Heart Valve Prosthesis , Heart Valve Prosthesis Implantation , Humans , Male , Middle Aged , Mitral Valve/diagnostic imaging , Mitral Valve/surgery , Mitral Valve Insufficiency/diagnostic imaging , Propensity Score , Prospective Studies , Reproducibility of Results , Rheumatic Heart Disease/diagnostic imagingABSTRACT
Optical read-out of motion is widely used in sensing applications. Recent developments in micro- and nano-optomechanical systems have given rise to on-chip mechanical sensing platforms, potentially leading to compact and integrated optical motion sensors. However, these systems typically exploit narrow spectral resonances and therefore require tuneable lasers with narrow linewidth and low spectral noise, which makes the integration of the read-out extremely challenging. Here, we report a step towards the practical application of nanomechanical sensors, by presenting a sensor with ultrawide (â¼80 nm) optical bandwidth. It is based on a nanomechanical, three-dimensional directional coupler with integrated dual-channel waveguide photodiodes, and displays small displacement imprecision of only 45 fm/Hz1/2 as well as large dynamic range (>30 nm). The broad optical bandwidth releases the need for a tuneable laser and the on-chip photocurrent read-out replaces the external detector, opening the way to fully-integrated nanomechanical sensors.
ABSTRACT
BACKGROUND: We compared and analyzed differences between repair vs. replacement of mitral valves on severe rheumatic mitral stenosis by looking at mid-term clinical outcomes. METHODS: Patients with severe rheumatic mitral stenosis (mitral valve area ≤1.5 cm2, with or without mitral valve regurgitation) from January 2011 to September 2017 were divided into two groups: a mitral valve repair group (MVP) and a mitral valve replacement group (MVR). After propensity score matching between the two groups, we compared changes in post-operation clinical outcomes. We also monitored changes in left ventricular longitudinal and circumferential strain in successfully matched patients (20 pairs) by echocardiography speckle tracing. RESULTS: A total of 921 patients were recruited (221 in MVP and 700 in MVR). After a propensity score matching, 216 cases were selected with 108 patients in each group. With a follow-up period of 3 months to 7.1 years, the incidence of heart failure was observed to be significantly higher in the MVR group than in the MVP group (P<0.05). Echocardiographic speckle tracking imaging analysis showed that left ventricular longitudinal strain decreased in the MVR group, suggesting that a change of cardiac structure may affect the cardiac function. CONCLUSIONS: Selecting suitable patients for mitral valve repair is feasible even for patients with severe rheumatic mitral stenosis. In our study, compared with prosthetic valve replacement in these patients, valve repair still significantly reduced the valve-related complications rates and improved the quality of life during the follow-up.