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Various cellular processes (including cell motility) are driven by the regulated, polarized assembly of actin filaments into distinct force-producing arrays of defined size and architecture. Branched, linear, contractile and cytosolic arrays coexist in vivo, and cells intricately control the number, length and assembly rate of filaments in these arrays. Recent in vitro and in vivo studies have revealed novel molecular mechanisms that regulate the number of filament barbed and pointed ends and their respective assembly and disassembly rates, thus defining classes of dynamically different filaments, which coexist in the same cell. We propose that a global treadmilling process, in which a steady-state amount of polymerizable actin monomers is established by the dynamics of each network, is responsible for defining the size and turnover of coexisting actin networks. Furthermore, signal-induced changes in the partitioning of actin to distinct arrays (mediated by RHO GTPases) result in the establishment of various steady-state concentrations of polymerizable monomers, thereby globally influencing the growth rate of actin filaments.
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Actinas/metabolismo , Actinas/genética , Animais , Humanos , Transdução de Sinais/genética , Transdução de Sinais/fisiologiaRESUMO
BACKGROUND: Gestational diabetes mellitus (GDM) is frequently misdiagnosed during pregnancy. There is an abundance of evidence, but little is known regarding the regional prevalence estimates of GDM in India. This systematic review and meta-analysis aims to provide valuable insights into the national and regional prevalence of GDM among pregnant women in India. METHODS: We conducted an initial article search on PubMed, Scopus, Google Scholar, and ShodhGanga searches to identify quantitative research papers (database inception till 15th June,2022). This review included prevalence studies that estimated the occurrence of GDM across different states in India. RESULTS: Two independent reviewers completed the screening of 2393 articles, resulting in the identification of 110 articles that met the inclusion criteria, which collectively provided 117 prevalence estimates. Using a pooled estimate calculation (with an Inverse square heterogeneity model), the pooled prevalence of GDM in pregnant women was estimated to be 13%, with a 95% confidence interval (CI) ranging from 9 to 16%.. In India, Diabetes in Pregnancy Study of India (DIPSI) was the most common diagnostic criteria used, followed by International Association of Diabetes and Pregnancy Study Groups (IADPSG) and World Health Organization (WHO) 1999. It was observed that the rural population has slightly less prevalence of GDM at 10.0% [6.0-13.0%, I2=96%] when compared to the urban population where the prevalence of GDM was 12.0% [9.0-16.0%, I2 = 99%]. CONCLUSIONS: This review emphasizes the lack of consensus in screening and diagnosing gestational diabetes mellitus (GDM), leading to varied prevalence rates across Indian states. It thoroughly examines the controversies regarding GDM screening by analyzing population characteristics, geographic variations, diagnostic criteria agreement, screening timing, fasting vs. non-fasting approaches, cost-effectiveness, and feasibility, offering valuable recommendations for policy makers. By fostering the implementation of state-wise screening programs, it can contribute to improving maternal and neonatal outcomes and promoting healthier pregnancies across the country.
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Diabetes Gestacional , Humanos , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/diagnóstico , Gravidez , Feminino , Prevalência , Índia/epidemiologiaRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) is known to increase the risk of venous thromboembolism (VTE) and arterial thromboembolism (ATE). However, the incidence, predictors, and outcomes of clinical thrombosis for inpatients with COVID-19 are not well known. This study aimed to enhance our understanding of clinical thrombosis in COVID-19, its associated factors, and mortality outcomes. METHOD: Hospitalised adult (≥18 years of age) patients with COVID-19 in 2020 were retrospectively identified from the US National Inpatient Sample database. Clinical characteristics, incident VTE, ATE, and in-hospital mortality outcomes were recorded. Multivariable logistic regression was performed to identify clinical factors associated with thrombosis and in-hospital mortality in COVID-19 inpatients. RESULTS: A total of 1,583,135 adult patients with COVID-19 in the year 2020 were identified from the National Inpatient Sample database; patients with thrombosis were 41% females with a mean age of 65.4 (65.1-65.6) years. The incidence of thrombosis was 6.1% (97,185), including VTE at 4.8% (76,125), ATE at 3.0% (47,790), and the in-hospital mortality rate was 13.4% (212,785). Patients with thrombosis were more likely to have respiratory symptoms of COVID-19 (76.7% vs 75%, p<0.001) compared with patients without thrombosis. The main factors associated with overall thrombosis, VTE, and ATE were paralysis, ventilation, solid tumours without metastasis, metastatic cancer, and acute liver failure. Although all thrombosis categories were associated with higher in-hospital mortality for COVID-19 inpatients in univariable analyses (p<0.001), they were not in multivariable analyses-thrombosis (odds ratio [OR] 1.24; 95% confidence interval [CI] 0.90-1.70; p=0.19), VTE (OR 0.70; 95% CI 0.52-1.00; p=0.05), and ATE (OR 1.07; 95% CI 0.92-1.25; p=0.36). CONCLUSIONS: The association of COVID-19 with thrombosis and VTE increases with increasing severity of the COVID-19 disease. Risk stratification of thrombosis is crucial in COVID-19 patients to determine the necessity of thromboprophylaxis.
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The dynamic control of the actin cytoskeleton is a key aspect of essentially all animal cell movements. Experiments in single migrating cells and in vitro systems have provided an exceptionally deep understanding of actin dynamics. However, we still know relatively little of how these systems are tuned in cell-type-specific ways, for example in the context of collective cell movements that sculpt the early embryo. Here, we provide an analysis of the actin-severing and depolymerization machinery during vertebrate gastrulation, with a focus on Twinfilin1 (Twf1) in Xenopus. We find that Twf1 is essential for convergent extension, and loss of Twf1 results in a disruption of lamellipodial dynamics and polarity. Moreover, Twf1 loss results in a failure to assemble polarized cytoplasmic actin cables, which are essential for convergent extension. These data provide an in vivo complement to our more-extensive understanding of Twf1 action in vitro and provide new links between the core machinery of actin regulation and the specialized cell behaviors of embryonic morphogenesis.
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Actinas , Gastrulação , Citoesqueleto de Actina , Actinas/genética , Animais , Pseudópodes , Xenopus laevisRESUMO
PURPOSE OF REVIEW: Stroke remains a leading disabling condition, and many survivors have permanent disability despite acute stroke treatment and subsequent standard-of-care rehabilitation therapies. Adjunctive neuromodulation is an emerging frontier in the field of stroke recovery. In this narrative review, we aim to highlight and summarize various neuromodulation techniques currently being investigated to enhance recovery and reduce impairment in patients with stroke. RECENT FINDINGS: For motor recovery, repetitive transcranial magnetic simulation (rTMS) and direct current stimulation (tDCS) have shown promising results in many smaller-scale trials. Still, their efficacy has yet to be proven in large-scale pivotal trials. A promising large-scale study investigating higher dose tDCS combined with constraint movement therapy to enhance motor recovery is currently underway. MRI-guided tDCS studies in subacute and chronic post-stroke aphasia showed promising benefits for picture-naming recovery. rTMS, particularly inhibitory stimulation over the contralesional homolog, could represent a pathway forward in post-stroke motor recovery in the setting of a well-designed and adequately powered clinical trial. Recently evidenced-based guideline actually supported Level A (definite efficacy) for the use of low-frequency rTMS of the primary motor cortex for hand motor recovery in the post-acute stage of stroke based on the meta-analysis result. Adjunctive vagal nerve stimulation has recently received FDA approval to enhance upper limb motor recovery in chronic ischemic stroke with moderate impairment, and progress has been made to implement it in real-world practice. Despite a few small and large-scale studies in epidural stimulation (EDS), further research on the utilization of EDS in post-stroke recovery is needed. Deep brain stimulation or stent-based neuromodulation has yet to be further tested regarding safety and efficacy. Adjunctive neuromodulation to rehabilitation therapy is a promising avenue for promoting post-stroke recovery and decreasing the overall burden of disability. The pipeline for neuromodulation technology remains strong as they span from the preclinical stage to the post-market stage. We are optimistic to see that more neuromodulation tools will be available to stroke survivors in the not-to-distant future.
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Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Magnética Transcraniana/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Estimulação Transcraniana por Corrente Contínua/métodos , Extremidade Superior , Recuperação de Função FisiológicaRESUMO
Gramicidin S, natural antimicrobial peptide is used commercially in medicinal lozenges for sore throat and Gram-negative and Gram-positive bacterial infections. However, its clinical potential is limited to topical applications because of its high red blood cells (RBC) cytotoxicity. Given the importance of developing potential antibiotics and inspired by the cyclic structure and druggable features of Gramicidin S, we edited proline α-carbon with stereodynamic nitrogen to examine the direct impact on biological activity and cytotoxicity with respect to prolyl counterpart. Natural Gramicidin S (12), proline-edited peptides 13-16 and wild-type d-Phe-d-Pro ß-turn mimetics (17 and 18) were synthesized using solid phase peptide synthesis and investigated their activity against clinically relevant bacterial pathogens. Interestingly, mono-proline edited analogous peptide 13 showed moderate improvement in antimicrobial activity against E. coli ATCC 25922 and K.pneumoniae BAA 1705 as compared to Gramicidin S. Furthermore, proline edited peptide 13 exhibited equipotent antimicrobial effect against MDR S. aureus and Enterococcus spp. Analysis of cytotoxicity against VERO cells and RBC, reveals that proline edited peptides showed two-fivefold lesser cytotoxicity than the counterpart Gramicidin S. Our study suggests that introducing single azPro/Pro mutation in Gramicidin S marginally improved the activity and lessens the cytotoxicity as compared with the parent peptide.
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Gramicidina , Prolina , Animais , Chlorocebus aethiops , Gramicidina/farmacologia , Gramicidina/química , Prolina/farmacologia , Prolina/química , Escherichia coli , Staphylococcus aureus , Células Vero , Antibacterianos/farmacologia , Antibacterianos/química , PeptídeosRESUMO
The prevalence of valvular heart disease in the United States has been estimated at 4.2-to-5.6 million, with mitral regurgitation (MR) being the most common lesion. Significant MR is associated with heart failure (HF) and death if left untreated. When HF is present, renal dysfunction (RD) is common and is associated with worse outcomes (ie, it is a marker of HF disease progression). Additionally, a complex interplay exists in patients with HF who also have MR, as this combination further impairs renal function, and the presence of RD further worsens prognosis and often limits guideline-directed management and therapy (GDMT). This has important implications in secondary MR because GDMT is the standard of care. However, with the development of minimally invasive transcatheter mitral valve repair, mitral transcatheter edge-to-edge repair (TEER) has become a new treatment option for secondary MR that is now incorporated into current guidelines published in 2020 that listed mitral TEER as a class 2a recommendation (moderate recommendation with benefit >> risk) as an addition to GDMT in a subset of patients with left ventricular ejection fraction <50%. The Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial, which demonstrated favorable outcomes in secondary MR by adding mitral TEER to GDMT versus GDMT alone, was the evidence base for these guidelines. Considering these guidelines and the understanding that concomitant RD often limits GDMT in secondary MR, there is emerging research studying the renal outcomes from the COAPT trial. This review analyzes this evidence, which could further influence current decision-making and future guidelines.
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Insuficiência Cardíaca , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Humanos , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/complicações , Implante de Prótese de Valva Cardíaca/efeitos adversos , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Insuficiência da Valva Mitral/complicações , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda , Ensaios Clínicos como AssuntoRESUMO
PURPOSE: The objective of the study was to see the difference in expulsion rates of two types of Copper containing intrauterine contraceptive devices (IUCDs): Cu 375 & CuT 380 A, within or at 6 weeks after insertion. METHODS: It was a randomised control trial. A total of 396 pregnant women were recruited. Ultrasonography was done to look for the position of the IUCD at the time of discharge and at six weeks follow-up and the expulsion rate was calculated. RESULTS: Amongst 396 participants, 22 PPIUCDs were expelled completely at 6 weeks (modified intention to treat analysis [ITA]), 10 (5.3%) and 12 (6.7%) in the Cu 375 and CuT 380 A groups respectively. The expulsion rate was 6.02%. However, this difference was not statistically significant. When ultrasonologically assessed partial expulsions were also considered, the total expulsion rate in both groups (14.3% and 14.1% respectively) was also not significantly different. The expulsion rate was higher in the vaginal delivery group (10.7%) than in the caesarean section (3.6%) group (p = 0.007) and early postpartum insertion 12.3% than in the immediate post-placental insertion group, 3.7% (p = 0.002). CONCLUSIONS: The study concluded that the altered shape of Cu 375 has effectively no role in decreasing the expulsion rate. Placement of IUCD at or near the uterine fundus immediately after delivering the placenta (post-placental) decreases the expulsion rate, thereby increasing the contraceptive efficacy.SHORT CONDENSATIONThe altered shape of Cu 375 has effectively no role in decreasing the expulsion rate. Placement of IUCD at or near the uterine fundus immediately after delivering the placenta (post-placental) decreases the expulsion rate, thereby increasing the contraceptive efficacy.
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Dispositivos Intrauterinos de Cobre , Dispositivos Intrauterinos , Gravidez , Feminino , Humanos , Cobre , Cesárea , Estudos Prospectivos , Placenta , Período Pós-Parto , Anticoncepcionais , Expulsão de Dispositivo IntrauterinoRESUMO
BACKGROUND: The newest-generation balloon-expandable valve, SAPIEN 3 Ultra (S3U), is expected to function well with the enhanced sealing skirt compared with SAPIEN 3 (S3). However, current literature on the comparison between these two valves is limited to short-term follow-ups. Therefore, we aimed to evaluate the 1-year outcomes and echocardiographic changes of S3U compared with S3. METHODS: We retrospectively identified patients who underwent transfemoral-transcatheter aortic valve replacement with S3U or S3 (20/23/26 mm) at our institution in 2018-2020. Outcomes were 1-year clinical events and echocardiographic parameters, and were compared between S3U and S3 after adjustment with inverse probability of treatment weighting. RESULTS: The S3U and S3 groups included 297 (25.7%) and 858 (74.3%) patients, respectively. There were no significant differences between the two groups in clinical events (death 5.8% vs. 5.5%, hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.81-1.90; death or heart failure hospitalization 10.3% vs. 10.1%, HR 1.04, 95% CI 0.67-1.62). The S3U group had a lower prevalence of mild paravalvular leakage (PVL) (13.7% vs. 22.3%, p = 0.044), with similar moderate PVL (0.7% vs. 1.2%, p > 0.99). No significant differences were observed in aortic valve mean gradient and Doppler velocity index at 1 year. However, the S3U group had a larger increase in mean gradient from implantation to 1 year (median +4.70 vs. +1.63 mmHg, p < 0.001). CONCLUSIONS: S3U and S3 carried similarly favorable clinical event risks. Nonetheless, S3U was associated with less frequent mild PVL but a larger increase in transprosthetic gradient. Further studies are needed to determine the prognostic impact of these hemodynamic differences.
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OBJECTIVES: This study sought to examine the association of hospital procedural volume with the incidence and outcomes of surgical bailout (SB) in patients who undergo transcatheter aortic valve replacement (TAVR). BACKGROUND: SB is required for serious complications during or after TAVR. It remains unclear whether hospital experiences affect the incidence and outcomes of SB. METHODS: We retrospectively identified patients who underwent endovascular TAVR using the Nationwide Readmissions Database 2012-2017. We examined the association of annual hospital procedural volume (annual number of endovascular TAVR cases in each hospital in each year) with the incidence and in-hospital mortality of SB using multivariable logistic regressions and restricted cubic splines. RESULTS: Among 82,764 eligible patients, the incidence of SB was 0.95% (n = 789) and decreased from 2012 to 2017 (from 2.66% to 0.49%; Ptrend < 0.001), while in-hospital mortality of SB remained high over years (from 26.0% to 23.5%; Ptrend = 0.773). Very-high-volume hospitals (≥200 cases/year), as compared with low-volume hospitals (≤49 cases/year), showed significantly a lower incidence of SB (0.49% vs. 1.81%; adjusted OR = 0.28, 95% CI = 0.21-0.38), but similar in-hospital mortality of SB (26.2% vs. 25.6%; adjusted OR = 0.88, 95% CI = 0.47-1.66). There was a significant nonlinear, inverse association of hospital volume with the incidence of SB, but not with the in-hospital mortality of SB. CONCLUSIONS: Hospitals with higher TAVR volumes have a lower risk of SB, but the in-hospital mortality after SB does not change with hospital TAVR volume. Our findings highlight the importance that physicians should always be aware of the high mortality risk of SB following TAVR regardless of hospital procedural experiences.
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Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Mortalidade Hospitalar , Hospitais com Baixo Volume de Atendimentos , Humanos , Incidência , Estudos Retrospectivos , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVES: This study aimed to evaluate the incidence, treatment, and outcomes of acute myocardial infarction (AMI) following transcatheter or surgical aortic valve replacement (TAVR or SAVR). BACKGROUND: Coronary artery disease is common in patients who undergo aortic valve replacement. However, little is known about differences in clinical features of post-TAVR or post-SAVR AMI. METHODS: We retrospectively identified post-TAVR or post-SAVR (including isolated and complex SAVR) patients admitted with AMI using the Nationwide Readmissions Database 2012-2017. Incidence, invasive strategy (coronary angiography or revascularization), and in-hospital outcomes were compared between post-TAVR and post-SAVR AMIs. RESULTS: The incidence of 180-day AMI was higher post-TAVR than post-SAVR (1.59% vs. 0.72%; p < 0.001). Post-TAVR AMI patients (n = 1315), compared with post-SAVR AMI patients (n = 1344), were older, had more comorbidities and more frequent non-ST-elevation AMI (NSTEMI: 86.6% vs. 78.0%; p < 0.001). After propensity-score matching, there was no significant difference in in-hospital mortality between post-TAVR and post-SAVR AMIs (14.7% vs. 16.1%; p = 0.531), but the mortality was high in both groups, particularly in ST-elevation AMI (STEMI: 38.8% vs. 29.2%; p = 0.153). Invasive strategy was used less frequently for post-TAVR AMI than post-SAVR AMI (25.6% vs. 38.3%; p < 0.001). Invasive strategy was associated with lower mortality in both post-TAVR (adjusted odds ratio = 0.40; 95% confidence interval = [0.24-0.66]) and post-SAVR groups (0.60 [0.41-0.88]). CONCLUSIONS: AMI, albeit uncommon, was more frequent post-TAVR than post-SAVR. Patients commonly presented with NSTEMI, but the mortality of STEMI was markedly high. Further studies are needed to understand why a substantial percentage of patients do not receive invasive coronary treatment, particularly after TAVR, despite seemingly better outcomes with invasive strategy.
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Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Infarto do Miocárdio com Supradesnível do Segmento ST , Substituição da Valva Aórtica Transcateter , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Mortalidade Hospitalar , Humanos , Incidência , Estudos Retrospectivos , Fatores de Risco , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Transcatheter aortic valve-in-valve implantation (ViV-TAVI) has emerged in recent years as a safe alternative to redo surgery in high-risk patients. Although early results are encouraging, data beyond short-term outcomes are lacking. Herein, we aimed to assess the 2-year outcomes after ViV-TAVI. METHODS: Patients undergoing ViV-TAVI for degenerated surgical valves between 2013 and 2019 at the Cleveland Clinic were reviewed. The coprimary endpoints were all-cause mortality and congestive heart failure (CHF) hospitalizations. We used time-to-event analyses to assess the primary outcomes. Further, we measured the changes in transvalvular gradients and the incidence of structural valve deterioration (SVD). RESULTS: One hundred and eighty-eight patients were studied (mean age = 76 years; 65% males). At 2 years of follow-up, all-cause mortality and CHF hospitalizations occurred in 15 (8%) and 28 (14.9%) patients, respectively. On multivariable analysis, the postprocedural length of stay was a significant predictor for both all-cause mortality (hazard ratio [HR] = 1.1; 95% confidence interval [CI]: 1.01, 1.19) and CHF hospitalization (HR = 1.16; 95% CI: 1.07, 1.27). However, the internal diameter of the surgical valve was not associated with significant differences in both primary endpoints. For hemodynamic outcomes, nine patients (4.8%) developed SVD. The mean and peak transvalvular pressure gradients remained stable over the follow-up period. CONCLUSION: ViV-TAVI for degenerated surgical valves was associated with favorable 2-year clinical and hemodynamic outcomes. Further studies are needed to better understand the role of ViV-TAVI as a treatment option in the life management of aortic valve disease.
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Estenose da Valva Aórtica , Bioprótese , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Masculino , Humanos , Idoso , Feminino , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Próteses Valvulares Cardíacas/efeitos adversos , Bioprótese/efeitos adversos , Falha de Prótese , Reoperação/métodos , Resultado do Tratamento , Substituição da Valva Aórtica Transcateter/efeitos adversos , Substituição da Valva Aórtica Transcateter/métodos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/etiologia , Implante de Prótese de Valva Cardíaca/métodosRESUMO
BACKGROUND: Measures were undertaken at the Cleveland Clinic to reduce radiation exposure to patients and personnel working in the catheterization laboratories. We report our experience with these improved systems over a 7-year period in patients undergoing diagnostic catheterization (DC) and percutaneous coronary interventions (PCIs). METHODS: Patients were categorized into preinitiative (2009-2012) and postinitiative (2013-2019) groups in the DC and PCI cohorts. Propensity score matching was done between the pre- and postinitiative groups for both cohorts based on age, sex, body surface area, total fluoroscopy time, and total acquisition time. The effectiveness of radiation reduction measures was assessed by comparing the total air kerma (Ka,r ), and fluoroscopy- and acquisition-mode air kerma in patients in the two groups. RESULTS: In the DC cohort, there was a significant reduction in Ka,r in the postinitiative group in comparison to the preinitiative group (median, 396 vs. 857 mGy; p < 0.001). In the PCI cohort, Ka,r in the postinitiative group was 1265 mGy, which was significantly lower than the corresponding values in the preinitiative group (1994 mGy; p < 0.001). We also observed a significant reduction in fluoroscopy- and acquisition-based air kerma rates, and air kerma area product in the postinitiative group in comparison to the preinitiative group in both matched and unmatched DC and PCI cohorts after the institution of radiation reduction measures. CONCLUSION: There was a significant and sustained reduction in radiation exposure to patients in the catheterization laboratory with the implementation of advanced protocols. Similar algorithms can be applied in other laboratories to achieve a similar reduction in radiation exposure.
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Intervenção Coronária Percutânea , Exposição à Radiação , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/métodos , Fluoroscopia/efeitos adversos , Fluoroscopia/métodos , Humanos , Laboratórios , Intervenção Coronária Percutânea/efeitos adversos , Doses de Radiação , Exposição à Radiação/efeitos adversos , Exposição à Radiação/prevenção & controle , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The cerebral embolic protection (CEP) device captures embolic debris during transcatheter aortic valve replacement (TAVR). However, the impact of CEP on stroke severity following TAVR remains unclear. Therefore, we aimed to examine whether CEP was associated with reduced severity of stroke following TAVR. METHODS: This was a retrospective cohort study of 2839 consecutive patients (mean age: 79.2 ± 9.5 years, females: 41.5%) who underwent transfemoral TAVR at our institution between 2013 and 2020. We categorized patients into Sentinel CEP users and nonusers. Neuroimaging data were reviewed and the final diagnosis of a cerebrovascular event was adjudicated by a neurologist blinded to the CEP use or nonuse. We compared the incidence and severity (assessed by the National Institutes of Health Stroke Scale [NIHSS]) of stroke through 72 h post-TAVR or discharge between the two groups using stabilized inverse probability of treatment weighting (IPTW) of propensity scores. RESULTS: Of the eligible patients, 1802 (63.5%) received CEP during TAVR and 1037 (36.5%) did not. After adjustment for patient characteristics by stabilized IPTW, the rate of overall stroke was numerically lower in CEP users than in CEP nonusers, but the difference did not reach statistical significance (0.49% vs. 1.18%, p = 0.064). However, CEP users had significantly lower rates of moderate-or-severe stroke (NIHSS ≥ 6: 0.11% vs. 0.69%, p = 0.013) and severe stroke (NIHSS ≥ 15: 0% vs. 0.29%, p = 0.046). Stroke following CEP use (n = 8), compared with stroke following CEP nonuse (n = 15), tended to carry a lower NIHSS (median [IQR], 4.0 [2.0-7.0] vs. 7.0 [4.5-19.0], p = 0.087). Four (26.7%) out of 15 patients with stroke following CEP nonuse died within 30 days, with no death after stroke following CEP use. CONCLUSIONS: CEP use may be associated with attenuated severity of stroke despite no significant difference in overall stroke incidence compared with CEP nonuse. This finding is considered hypothesis-generating and needs to be confirmed in large prospective studies.
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Estenose da Valva Aórtica , Dispositivos de Proteção Embólica , Embolia Intracraniana , Acidente Vascular Cerebral , Substituição da Valva Aórtica Transcateter , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Substituição da Valva Aórtica Transcateter/efeitos adversos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/epidemiologia , Embolia Intracraniana/etiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Fatores de RiscoRESUMO
Chromatin modification through histone acetylation/deacetylation is important for the regulation of transcription as well as DNA replication in eukaryotes. PfGCN5 and PfMYST are two well-studied histone acetyltransferases in Plasmodium. PfMYST containing the MYST domain, zinc finger domain, and the chromodomain primarily acetylates histone 4. Here, we show that PfMYST is expressed in two isoforms, a long version (â¼72 kDa) and a short version (â¼45 kDa) of the protein, while the shorter version is predominantly present in the nucleus. Further, the association of PfMYST with the putative Plasmodium autonomously replicating sequences (PfARS) was found to be much stronger than the binding of PfGCN5 in these regions with concomitant enrichment of the H4 acetylation level. The binding of PfMYST at these sites was also correlated with another replication protein PfORC1 as well as with the replicating stage (trophozoite) of the parasite. Collectively these results show for the first time the potential role of PfMYST in parasite DNA replication through chromatin modification that may be found useful for the intervention of parasite growth.
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Plasmodium falciparum , Proteínas de Protozoários , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Histonas/metabolismo , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Cromatina , Replicação do DNARESUMO
Adult congenital heart disease (ACHD) is a rising concern for the current healthcare system, with a prevalence that is anticipated to steadily increase through the year 2050. It is estimated that there are >1.4 million adults in the United States living with a congenital heart defect. Despite significant advances in medical and surgical therapy, most of these patients progress to advanced heart failure due to the unique anatomic, physiological, and hemodynamic abnormalities associated with the disease. Patient awareness of the disease coupled with advances in the diagnosis and treatment has led to a significant increase in the surgical treatment of CHD in adults. The authors aim to summarize and critically appraise the current literature on the morbidity, mortality, and risk scores associated with ACHD.
Assuntos
Cardiopatias Congênitas , Insuficiência Cardíaca , Adulto , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/cirurgia , Insuficiência Cardíaca/cirurgia , Humanos , Morbidade , Medição de Risco , Fatores de Risco , Estados UnidosRESUMO
OBJECTIVES: Despite the rising use of MC, the impact of preexisting AF, a common comorbidity, on short-term postprocedural outcomes is poorly defined. We sought to assess outcomes between patients with and without atrial fibrillation (AF) who underwent percutaneous mitral valve repair with MitraClip (MC). METHODS: In this retrospective cohort study, the Nationwide Readmissions Database was queried for patients who underwent MC between 2014-2017. Groups were stratified based on the presence of AF. Multivariable logistic regression analyses were performed to identify the association between AF and in-hospital stroke and mortality. RESULTS: Of the 15,570 patients who underwent MC, 7,740 (49.7%) had AF. AF patients were older (82 vs. 79 years, p < .001) and more comorbid. Patients with AF relative to without AF demonstrated increased rates of in-hospital ischemic (1.3% vs .0.7%, p < .001) and hemorrhagic stroke (0.3% vs. 0.1%, p = .007), longer duration of hospitalization (median 3 vs. 2 days, p < .001), and similar in-hospital mortality (2.8% vs. 2.6%, p = .52). After adjusting for comorbidities, age, sex, hospital procedural volume, and CHA2DS2-VASc, the presence of AF was associated with higher in-hospital stroke (OR = 2.096, 95%CI[1.503-2.921], p < .001) but not in-hospital mortality (OR = 1.012, 95%CI[0.828-1.238], p = .904). AF patients were more likely to be readmitted (16.8% vs.14.1%, p < .001) and die (1.5% vs. 0.9%, p = .005) within 30 days of discharge despite similar incidences of stroke (0.7% vs. 0.6%, p = .53). CONCLUSIONS: The increased risk of in-hospital stroke, 30-day mortality, and longer hospitalization suggest the need for increased preprocedural optimization by means of stroke prevention strategies in those with AF undergoing MC.
Assuntos
Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Acidente Vascular Cerebral , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Resultado do TratamentoRESUMO
OBJECTIVE: We aimed to compare short-term outcomes between transcatheter aortic valve replacement (TAVR) for pure aortic regurgitation (AR) and TAVR for aortic stenosis (AS). BACKGROUND: In patients with severe pure AR for whom surgical valve replacement is infeasible, TAVR is sometimes used off-label. METHODS: Using the Nationwide Readmissions Database 2016-2017, we retrospectively identified patients without prior valve surgery who underwent endovascular TAVR. We compared in-hospital and 30-day outcomes according to the type of aortic valve disease. RESULTS: A total of 81,542 eligible patients were divided into the pure AR (n = 1,222, 1.50%), pure AS (n = 72,690, 89.1%), and AS + AR (n = 7,630, 9.36%) groups. In unadjusted analyses, the pure AR group, compared with the pure AS and AS + AR groups, showed a higher incidence of acute kidney injury (16.8% vs. 9.8% vs. 12.1%, respectively; p < .001) and need of surgical bailout (1.4% vs. 0.4% vs. 0.6%; p < .01). The pure AR group also showed higher in-hospital mortality than the pure AS group (2.4% vs. 1.4%; p = .005). After multivariable adjustment, TAVR for pure AR was significantly associated with a higher risk of acute kidney injury (odds ratio [OR] = 1.64, 95% confidence interval [CI] = 1.33-2.02; p < .001), cardiac tamponade (OR = 1.98, 95% CI = 1.00-3.92; p = .0498), and prolonged hospital stay (OR = 1.59, 95% CI = 1.29-1.95; p < .001) compared with TAVR for pure AS, whereas it was not significantly associated with in-hospital mortality (OR = 1.55, 95% CI = 0.99-2.45; p = .058) and other outcomes. CONCLUSIONS: TAVR may be a reasonable treatment option for selected patients with pure AR with regard to short-term outcomes. However, additional techniques or devices may be necessary to reduce periprocedural risk.
Assuntos
Insuficiência da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/cirurgia , Humanos , Estudos Retrospectivos , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The use of transcatheter aortic valve replacement (TAVR) has expanded to patient populations of varying surgical risk in light of recent clinical trials, yet its role in patients with aortic stenosis and coexisting thoracic aortic aneurysm (TAA) is not well-delineated. We aimed to evaluate whether risk factors and in-hospital outcomes vary between TAVR patients with and without an unruptured TAA. METHODS: The Nationwide Readmissions Database was queried for patients hospitalized between January 2012 and December 2017 who underwent TAVR with and without an unruptured TAA. In-hospital outcomes were compared between cohorts after adjusting for sex, comorbidities, and TAVR approach, and in a subgroup analysis that excluded those with bicuspid aortic valves. RESULTS: Among 171,011 TAVR patients, 1,677 (1%) presented with TAA. Patients with TAA were younger (median age 80 vs. 82 years, p < .001) and more likely to have bicuspid aortic valves (9.3% vs. 0.9%, p < .001). Among patients with aneurysm, 2.6% died, 2.2% developed stroke, 1% developed aortic dissection, and 1.4% experienced cardiac tamponade while hospitalized. After adjusting for age, sex, bicuspid aortic valve, and all comorbidities, TAA was associated with significantly higher risk of post-TAVR aortic dissection (OR = 2.117, 95% CI [1.304-3.435], p = .002) and cardiac tamponade (OR = 1.682, 95% CI [1.1-2.572], p = .02). CONCLUSIONS: While the overall incidence of post-TAVR complications is low, patients with an unruptured TAA should be carefully considered by the Heart Team in weighing the additional risks of aortic dissection and cardiac tamponade after TAVR with those associated with surgery.
Assuntos
Aneurisma da Aorta Torácica , Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Idoso de 80 Anos ou mais , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/epidemiologia , Aneurisma da Aorta Torácica/cirurgia , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Estudos de Coortes , Humanos , Complicações Pós-Operatórias , Fatores de Risco , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVES: This study sought to investigate the incidence and outcomes of surgical bailout (SB) after transcatheter mitral valve repair (TMVr) with MitraClip. BACKGROUND: TMVr poses a risk of serious procedural complications, possibly requiring urgent open surgery for SB. However, little is known about the risk of SB cases after TMVr. METHODS: We retrospectively identified patients who underwent TMVr using the Nationwide Readmissions Database 2014-2017. SB was defined as open thoracotomy for heart and aorta during the same hospitalization. Annual hospital volume was defined as the annual number of TMVr cases in each hospital in each year. RESULTS: Among 15,032 eligible patients, SB was required in 214 (1.42%), of whom 134 (62.6%) underwent mitral valve surgery (113 replacements; 21 repairs). The incidence of SB was decreasing significantly over the 4 years (5.26% in 2014; 0.43% in 2017; ptrend < .001). There was a significant nonlinear, inverse association of annual hospital volume with the incidence of SB. In-hospital death (15.0 vs. 2.1%; p < .001) and other in-hospital adverse events were significantly more frequent in patients with than without SB, whereas the 30-day readmission rate was similar (13.2 vs. 15.1%; p = .572). After adjustment for patient and hospital characteristics, SB was significantly associated with higher in-hospital mortality (odds ratio = 6.67, 95% confidence interval = 4.35, 10.23, p < .001). CONCLUSIONS: This study suggests that although the incidence of SB after TMVr is decreasing, SB is required more frequently in lower-volume hospitals and carries high in-hospital mortality. Further efforts are needed to understand the reasons for SB and improve outcomes in patients needing SB.