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Background: Although the incidence of osteochondritis dissecans (OCD) of the knee may be low, an overview and comparison of sports-related outcomes with current surgical management techniques are needed. Purpose: To summarize the available evidence regarding outcomes for different surgical treatment options for unstable OCD of the knee in both skeletally mature and immature patients by calculating the return to sports (RTS) rate, the mean RTS time, and other sports-related postoperative outcome measures. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review of studies on RTS after surgical correction of unstable OCD within the knee was conducted utilizing PubMed, Embase, and the Cochrane databases. Included were studies discussing the treatment of unstable OCD with minimum 1-year follow-up outcomes. Multivariate analysis was used to compare studies grouped together based on RTS and skeletal maturity. Results: Of 2229 articles, 6 studies (197 patients; 198 knees) met the inclusion criteria and were included in our analysis. The percentage of patients who returned to the previous level of sport ranged from 52% to 100%; those returning to any level of sport ranged from 87% to 100%. Clinical outcomes did not differ between patients with open versus closed physes. Osteochondral Autograft Transfer System (OATS) procedures had a 100% RTS rate across several studies with skeletally mature and mixed cohorts, and microfracture had the lowest overall RTS rate (52%). For skeletally immature patients, all examined studies that utilized either open or arthroscopic reduction and internal fixation, 77% and 78%, respectively, had acceptable RTS rates. Arthroscopic fixation had a higher rate of revision surgery in both skeletally mature and immature patients. Conclusion: Our analysis indicated that the treatment of unstable OCD lesions using the OATS technique demonstrated high RTS rates across several studies, while microfracture alone exhibited the lowest RTS rate. Both arthroscopic and open internal fixation utilizing bioabsorbable screws yielded satisfactory RTS rates for juvenile patients with OCD.
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Background: Hemostasis for transfemoral transcatheter aortic valve replacement (TAVR) is typically achieved using a suture-mediated vascular closure device (VCD) prior to large-bore sheath insertion (preclosure technique). Recently, the addition of a hybrid closure technique using a preclose technique with the addition of a collagen-plug VCD after sheath removal in cases of failed hemostasis has been utilized. Methods: Data were collected from the Northwell TAVR registry, including 3 high-volume TAVR centers. We evaluated a preclose strategy with suture-mediated vascular closure alone ("legacy strategy") and standard bailout techniques versus a contemporary hybrid strategy of suture-mediated closure with collagen-mediated closure bailout. The primary end point was major or minor vascular complications as defined by the VARC-3 criteria. Results: A total of 1327 patients were included, of which 791 patients underwent TAVR with suture-mediated closure alone and 536 with contemporary strategy. The primary end point (major or minor vascular complication) was lower in the contemporary strategy (5.44% vs 1.31%; P < .001). Both minor (3.92% vs 1.12%; P = .002) and major (1.14% vs 0.19%; P = .0196) vascular complications were reduced and the total length of stay was less in the contemporary strategy (median of 3 days vs 2 days; P < .0001). Using multivariable analysis, we observed that vascular management strategy significantly improved the composite primary outcome when adjusted for sheath size, peripheral artery disease, carotid disease, and site of procedure. In the contemporary group, bailout collagen-plug VCD with an Angio-Seal (Terumo Medical) was used in 68 patients (12.69%) and bailout MANTA (Teleflex) was required in 4 patients (0.75%). There were no major or minor vascular complications among the patients who received bailout collagen-plug VCD. Conclusions: A contemporary hybrid strategy of suture-mediated closure with collagen-mediated closure bailout reduces the risk of vascular complications among patients undergoing transfemoral TAVR.
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PURPOSE: Chronic, high-altitude hypoxic exposure increases the risk of high-altitude pulmonary hypertension (PH). Emerging evidence shows maternal exercise may improve offspring resistance to disease throughout life. The purpose of this study is to determine if maternal exercise mitigates chronic hypoxic-induced changes in the offspring indicative of high-altitude pulmonary hypertension development. METHODS: Female adult C57BL/6 J mice were randomly allocated to nonexercise or exercise conditions. Exercise consisted of voluntary running wheel exercise for four weeks during the perinatal period. Three days after birth, the pups remained at low altitude (normoxia) or were exposed to hypobaric hypoxia of 450 mmHg to simulate ~4500 m altitude exposure until 8 weeks of age. The study consisted of 4 groups: Hypoxia + Nonexercise pregnancy, Hypoxia + Exercise, or the respective, normoxia conditions (Normoxia + Nonexercise or Normoxia + Exercise). Offspring body size, motor function, right ventricular systolic pressure (RVSP), and cardiopulmonary morphology were assessed after 8 weeks in normoxia or hypoxia. RESULTS: Both hypoxic groups had smaller body sizes, reduced motor function, increased hematocrit, RVSP, muscularization in medium-sized pulmonary arteries, as well as right ventricular hypertrophy and contractility compared to the normoxic groups ( p < 0.05). CONCLUSIONS: Chronic hypoxia simulating 4500 m attenuated growth, lowered motor function, and elicited PH development. Voluntary maternal exercise did not significantly decrease RVSP in the offspring, which aligned with a lack of effect to attenuate abnormal body size and cardiopulmonary development due to chronic hypoxia. These findings are preliminary in nature and more powered studies through larger group sizes are required to generalize the results to the population.
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Although the gasotransmitter hydrogen sulfide (H2S) is well known for its vasodilatory effects, H2S also exhibits vasoconstricting properties. Herein, it is demonstrated that administration of H2S as intravenous sodium sulfide (Na2S) increased blood pressure in sheep and rats, and this effect persisted after H2S has disappeared from the blood. Inhibition of the L-type calcium channel (LTCC) diminished the hypertensive effects. Incubation of Na2S with whole blood, red blood cells, methemoglobin, or oxyhemoglobin produced a hypertensive product of H2S, which is not hydrogen thioperoxide, metHb-SH- complexes, per-/poly- sulfides, or thiolsulfate, but rather a labile intermediate. One-electron oxidation of H2S by oxyhemoglobin generated its redox cousin, sulfhydryl radical (HSâ¢). Consistent with the role of HS⢠as the hypertensive intermediate, scavenging HS⢠inhibited Na2S-induced vasoconstriction and activation of LTCCs. In conclusion, H2S causes vasoconstriction that is dependent on the activation of LTCCs and generation of HS⢠by oxyhemoglobin.
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Pressão Sanguínea , Canais de Cálcio Tipo L , Sulfeto de Hidrogênio , Oxiemoglobinas , Animais , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Oxiemoglobinas/metabolismo , Oxiemoglobinas/farmacologia , Ratos , Canais de Cálcio Tipo L/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Ovinos , Masculino , Hipertensão/metabolismo , Modelos Animais de Doenças , Sulfetos/farmacologia , Sulfetos/metabolismoRESUMO
BACKGROUND: Recent randomized studies have broadened the indication of transcatheter aortic valve replacement (TAVR) to also include low-surgical-risk patients. However, the data on self-expanding (SE) and balloon-expandable (BE) valves in low-risk patients remain sparse. METHODS: The current study is a post hoc analysis of combined data from both LRT 1.0 and 2.0 trials comparing BE and SE transcatheter heart valves. RESULTS: A total of 294 patients received a BE valve, and 102 patients received an SE valve. The 30-day clinical outcomes were similar across both groups except for stroke (4.9% vs. 0.7%, p = 0.014) and permanent pacemaker implantation (17.8% vs. 5.8%, p < 0.001), which were higher in the SE cohort than the BE cohort. No difference was observed in terms of paravalvular leak (≥moderate) between the groups (0% vs. 1.5%, p = 0.577). SE patients had higher aortic valve area (1.92 ± 0.43 mm2 vs. 1.69 ± 0.45 mm2, p < 0.001) and lower mean gradient (8.93 ± 3.53 mmHg vs. 13.41 ± 4.73 mmHg, p < 0.001) than BE patients. In addition, the rate of subclinical leaflet thrombosis was significantly lower in SE patients (5.6% vs. 13.8%, p = 0.038). CONCLUSION: In this non-randomized study assessing SE and BE valves in low-risk TAVR patients, SE valves are associated with better hemodynamics and lesser leaflet thrombosis, with increased rates of stroke and permanent pacemaker implantation at 30 days; however, this could be due to certain patient-dependent factors not fully evaluated in this study. The long-term implications of these outcomes on structural valve durability remain to be further investigated. CLINICAL TRIAL REGISTRY: LRT 1.0: NCT02628899 LRT 2.0: NCT03557242.
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Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Acidente Vascular Cerebral , Trombose , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/etiologia , Acidente Vascular Cerebral/etiologia , Trombose/etiologia , Resultado do Tratamento , Desenho de Prótese , Fatores de RiscoRESUMO
Purpose: The purpose of this study was to evaluate patient outcomes and satisfaction after arthroscopic portal closure with absorbable versus nonabsorbable sutures after knee arthroscopy. Methods: Patients undergoing primary knee arthroscopy were identified during procedure scheduling. Exclusion criteria included revision procedures, concomitant ligament reconstruction, or meniscal repair surgery. Before surgery, enrolled patients were randomly assigned to undergo closure with either 3-0 Monocryl absorbable or 3-0 nylon non-absorbable sutures. Postoperative evaluation at 2, 6, and 12 weeks included a Visual Analogue Cosmesis scale, a 10-point visual analogue scale (VAS) for pain, patient scar assessment, and customized questionnaire assessing scar satisfaction. Results: Between January 2019 and August 2022, 247 were included for analysis: 145 in the absorbable group and 129 in the non-absorbable group. There was no significant difference between groups in terms of age, sex, body mass index, race, smoking status, or laterality of procedure. Patients in the nonabsorbable group reported higher overall satisfaction at week 6 follow-up (9.12 ± 1.85 vs 8.44 ± 2.49, P = .019) and week 12 follow-up (9.13 ± 1.76 vs 8.54 ± 2.50, P = .048). There was no difference in pain, swelling, itching, numbness, incisional pain, or burning at any time. Patients in the nonabsorbable group observed more skin discoloration at 2 weeks (3.00 ± 2.33 vs 2.41 ± 1.80, P = .026) and 6 weeks (3.74 ± 2.82 vs 2.98 ± 2.45, P = .032) follow-up with no significant difference at 12 weeks. Conclusion: In this study, patients were more satisfied with nonabsorbable sutures for portal wound closure after knee arthroscopy despite early reporting of increased skin discoloration relative to absorbable sutures. Level of Evidence: Level I, randomized controlled trial.
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Introduction: The COVID-19 pandemic has exacerbated mental health issues among adolescents. Exercise is well-regarded for boosting mental health. Riding for Focus (R4F) is a 6-8 week cycling education program designed to equip middle school adolescents with basic cycling skills and introduce students to lifetime physical activity. A secondary goal of the R4F program is to improve adolescent mental health and psychosocial well-being. This study aimed to quantify the change in adolescent psychosocial well-being associated with the R4F program during the COVID-19 pandemic. Program evaluation also examined associations between participating in the R4F and mental health outcomes in the context of established risk factors, including gender, race, socioeconomic status, involvement in IEP programs, participation in after-school clubs, screen time, hours of sleep, and physical activity levels. Methods: Anonymous surveys were collected before and after the program in 20 schools in North America, with psychosocial well-being quantified using WHO-5 and PSC-17-Y. 1,148 middle school students, aged 11-14, completed pre intervention surveys. 815 students also completed post intervention surveys. Results: There was a general increase in psychosocial well-being after the R4F program and positive psychosocial well-being changes in students that identified as female, non-white, physically active, part of an IEP program, meeting screentime recommendations, and engaged in school programs, though effect sizes were small. Despite mental health improvements among underrepresented groups, relative risk assessments still indicated that males, white students, those from high socioeconomic status families still had reduced relative risk of developing psychosocial disorders post intervention. Discussion: These analyses illustrate the feasibility of cycling as a viable PE elective and the need for further, more robust studies to better assess the positive impacts of the R4F scholastic cycling program on the psychological health and well-being of middle school age children.
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Phosphatidylinositol transfer proteins (PITPs) are ubiquitous in eukaryotes and are involved in the regulation of phospholipid metabolism, membrane trafficking, and signal transduction. Sec14 is a yeast PITP that has been shown to transfer phosphatidylinositol (PI) or phosphatidylcholine (PC) from the endoplasmic reticulum to the Golgi. It is now believed that Sec14 may play a greater role than just shuttling PI and PC throughout the cell. Genetic evidence suggests that retrieval of membrane-bound PI by Sec14 also manages to present PI to the phosphatidylinositol-4-kinase, Pik1, to generate phosphatidylinositol-4-phosphate, PI(4)P. To test this hypothetical model, we designed a photocleavable bolalipid to span the entire membrane, having one phosphatidylcholine or phosphatidylinositol headgroup on each leaflet connected by a photocleavable diacid. Sec14 should not be able to present the bola-PI to Pik1 for phosphorylation as the head group will be difficult to lift from the bilayer as it is tethered on the opposite leaflet. After photocleavage the two halves would behave as a normal phospholipid, thus phosphorylation by Pik1 would resume. We report here the synthesis of a photocleavable bola-PC, a precursor to the desired bola-PI. The mono-photocleavable bola-PC lipid was designed to contain two glycerol molecules with choline head groups connected through a phosphodiester bond at the sn3 position. Each glycerol was acylated with palmitic acid at the sn1 position. These two glycerol moieties were then connected through their respective sn2 hydroxyls via a photocleavable dicarboxylic acid containing a nitrophenyl ethyl photolabile protecting group. The bola-PC and its precursors were found to undergo efficient photocleavage when irradiated in solution or in vesicles with 365 nm light for two minutes. Treatment of the bola-PC with a mutant phospholipase D and myo-inositol produced a mono-inositol bola-PC-PI.
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Glicerol , Fosfatidilcolinas , Fosforilação , Fosfolipídeos , FosfatidilinositóisRESUMO
IMPORTANCE: In order to grow, bacterial cells must both create and break down their cell wall. The enzymes that are responsible for these processes are the target of some of our best antibiotics. Our understanding of the proteins that break down the wall- cell wall hydrolases-has been limited by redundancy among the large number of hydrolases many bacteria contain. To solve this problem, we identified 42 cell wall hydrolases in Bacillus subtilis and created a strain lacking 40 of them. We show that cells can survive using only a single cell wall hydrolase; this means that to understand the growth of B. subtilis in standard laboratory conditions, it is only necessary to study a very limited number of proteins, simplifying the problem substantially. We additionally show that the ∆40 strain is a research tool to characterize hydrolases, using it to identify three "helper" hydrolases that act in certain stress conditions.
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Bacillus subtilis , Hidrolases , Hidrolases/genética , Hidrolases/metabolismo , N-Acetil-Muramil-L-Alanina Amidase/genética , N-Acetil-Muramil-L-Alanina Amidase/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Parede Celular/metabolismo , Peptidoglicano/metabolismoRESUMO
22 June 2023: This article was published in error while under embargo and has been temporarily removed.
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Intracellular Ca2+ signals are key for the regulation of cellular processes ranging from myocyte contraction, hormonal secretion, neural transmission, cellular metabolism, transcriptional regulation, and cell proliferation. Measurement of cellular Ca2+ is routinely performed using fluorescence microscopy with biological indicators. Analysis of deterministic signals is reasonably straightforward as relevant data can be discriminated based on the timing of cellular responses. However, analysis of stochastic, slower oscillatory events, as well as rapid subcellular Ca2+ responses, takes considerable time and effort which often includes visual analysis by trained investigators, especially when studying signals arising from cells embedded in complex tissues. The purpose of the current study was to determine if full-frame time-series and line-scan image analysis workflow of Fluo-4 generated Ca2+ fluorescence data from vascular myocytes could be automated without introducing errors. This evaluation was addressed by re-analyzing a published "gold standard" full-frame time-series dataset through visual analysis of Ca2+ signals from recordings made in pulmonary arterial myocytes of en face arterial preparations. We applied a combination of data driven and statistical approaches with comparisons to our published data to assess the fidelity of the various approaches. Regions of interest with Ca2+ oscillations were detected automatically post hoc using the LCPro plug-in for ImageJ. Oscillatory signals were separated based on event durations between 4 and 40 s. These data were filtered based on cutoffs obtained from multiple methods and compared to the published manually curated "gold standard" dataset. Subcellular focal and rapid Ca2+ "spark" events from line-scan recordings were examined using SparkLab 5.8, which is a custom automated detection and analysis program. After filtering, the number of true positives, false positives, and false negatives were calculated through comparisons to visually derived "gold standard" datasets. Positive predictive value, sensitivity, and false discovery rates were calculated. There were very few significant differences between the automated and manually curated results with respect to quality of the oscillatory and Ca2+ spark events, and there were no systematic biases in the data curation or filtering techniques. The lack of statistical difference in event quality between manual data curation and statistically derived critical cutoff techniques leads us to believe that automated analysis techniques can be reliably used to analyze spatial and temporal aspects to Ca2+ imaging data, which will improve experiment workflow.
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Sinalização do Cálcio , Miócitos Cardíacos , Fluxo de Trabalho , Miócitos Cardíacos/metabolismo , Contração Muscular , Processamento de Imagem Assistida por Computador , Cálcio/metabolismoRESUMO
BACKGROUND: The LRT trial (Low-Risk Transcatheter Aortic Valve Replacement [TAVR]) demonstrated the safety and feasibility of TAVR in low-risk patients, with excellent 1- and 2-year outcomes. The objective of the current study is to provide the overall clinical outcomes and the impact of 30-day hypoattenuated leaflet thickening (HALT) on structural valve deterioration at 4 years. METHODS: The prospective, multicenter LRT trial was the first Food and Drug Administration-approved investigational device exemption study to evaluate feasibility and safety of TAVR in low-risk patients with symptomatic severe tricuspid aortic stenosis. Clinical outcomes and valve hemodynamics were documented annually through 4 years. RESULTS: A total of 200 patients were enrolled, and follow-up was available on 177 patients at 4 years. The rates of all-cause mortality and cardiovascular death were 11.9% and 3.3%, respectively. The stroke rate rose from 0.5% at 30 days to 7.5% at 4 years, and permanent pacemaker implantation rose from 6.5% at 30 days to 11.7% at 4 years. Endocarditis was detected in 2.5% of the cohort, with no new cases reported between 2 and 4 years. Transcatheter heart valve hemodynamics remained excellent post-procedure and were maintained (mean gradient 12.56±5.54 mm Hg and aortic valve area 1.69±0.52 cm2) at 4 years. At 30 days, HALT was observed in 14% of subjects who received a balloon-expandable transcatheter heart valve. There was no difference in valve hemodynamics between patients with and without HALT (mean gradient 14.94±5.01 mm Hg versus 12.3±5.57 mm Hg; P=0.23) at 4 years. The overall rate of structural valve deterioration was 5.8%, and there was no impact of HALT on valve hemodynamics, endocarditis, or stroke at 4 years. CONCLUSIONS: TAVR in low-risk patients with symptomatic severe tricuspid aortic stenosis was found to be safe and durable at 4 years. Structural valve deterioration rates were low irrespective of the type of valve, and the presence of HALT at 30 days did not affect structural valve deterioration, transcatheter valve hemodynamics, and stroke rate at 4 years. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02628899.
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Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Acidente Vascular Cerebral , Trombose , Substituição da Valva Aórtica Transcateter , Humanos , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Estudos Prospectivos , Fatores de Risco , Próteses Valvulares Cardíacas/efeitos adversos , Resultado do Tratamento , Hemodinâmica , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Trombose/etiologiaRESUMO
Surgical implantation of decellularized cadaveric arteries is routinely used to treat right-sided congenital cardiac lesions. These acellular conduits lack the capacity for somatic growth and are prone to stenosis and calcification, necessitating multiple operations throughout childhood. Islet-1+ cardiovascular progenitor cells (CPCs) have demonstrated the capacity for differentiation into all cell types of the heart and outflow tracts. We hypothesize that CPC seeding of decellularized pulmonary arteries and bioreactor culture under physiologic flow conditions will drive vascular differentiation of CPCs and result in a conduit more suitable for implantation and long-term growth. We began by decellularizing ovine pulmonary arteries and characterizing the composition of the extracellular matrix (ECM). Hemodynamic testing of decellularized vessels in a custom bioreactor was used to define the scaffold mechanical properties over a range of pressures and flow rates. Next, our expanded ovine CPCs were suspended in growth media and injected intramurally into decellularized pulmonary arteries that were subsequently cultured in either static or pulsatile cultures. A combination of immunohistochemistry, real-time polymerase chain reaction (PCR), and tissue bath contraction studies were used to evaluate the bioengineered arteries before transplantation. Pulmonary artery patches from the most favorable culture conditions were then implanted into juvenile sheep to provide proof of concept. Hematoxylin and eosin staining indicated complete removal of cell nuclei (n = 9), whereas double-stranded DNA isolation from tissue homogenates showed 99.1% DNA removal (p < 0.01, n = 4). Furthermore, trichrome and elastin staining verified maintenance of collagen and elastin. Immunohistochemistry and PCR analyses (n = 4 per group) confirmed contractile smooth muscle presence on only our 3-week pulsatile scaffolds via presence of calponin 1 and myosin heavy chain 11. Tissue bath studies demonstrated that smooth muscle contraction generated by our 3-week pulsatile scaffolds (2.23 ± 0.19 g, n = 4) is comparable with native tissue contraction strength (2.78 ± 0.06 g, n = 4). Ovine transplantation confirmed that our graft can be safely implanted, retains contractile smooth muscle cells, and recruits native endothelium. Longer duration of physiologic pulsatile culture drives differentiation of CPCs seeded on ECM conduits toward a mature, contractile phenotype that is maintained for several weeks in vivo. Longer term studies to assess somatic growth potential are needed. Impact statement The current field of vascular transplantation relies on cadaveric and synthetic grafts to treat right-sided congenital cardiac lesions. These grafts do not grow somatically with our patients. This results in multiple reoperations throughout childhood to increase the size of the graft. Our bioengineered alternative demonstrates successful implantation, contractile smooth muscle cells, and a native endothelial layer. This research demonstrates a pilot study confirming the viability of a bioengineered alternative to the current standard of care in the field of vascular transplantation.
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Elastina , Engenharia Tecidual , Ovinos , Animais , Engenharia Tecidual/métodos , Biomimética , Fluxo Pulsátil , Projetos Piloto , Células Cultivadas , Prótese Vascular , Contração Muscular , Cadáver , Alicerces TeciduaisRESUMO
BACKGROUND: Intermediate-risk pulmonary embolism is a common disease that is associated with significant morbidity and mortality; however, a standardized treatment protocol is not well-established. AREAS OF UNCERTAINTY: Treatments available for intermediate-risk pulmonary embolisms include anticoagulation, systemic thrombolytics, catheter-directed therapies, surgical embolectomy, and extracorporeal membrane oxygenation. Despite these options, there is no clear consensus on the optimal indication and timing of these interventions. THERAPEUTIC ADVANCES: Anticoagulation remains the cornerstone of treatment for pulmonary embolism; however, over the past 2 decades, there have been advances in the safety and efficacy of catheter-directed therapies. For massive pulmonary embolism, systemic thrombolytics and, sometimes, surgical thrombectomy are considered first-line treatments. Patients with intermediate-risk pulmonary embolism are at high risk of clinical deterioration; however, it is unclear whether anticoagulation alone is sufficient. The optimal treatment of intermediate-risk pulmonary embolism in the setting of hemodynamic stability with right heart strain present is not well-defined. Therapies such as catheter-directed thrombolysis and suction thrombectomy are being investigated given their potential to offload right ventricular strain. Several studies have recently evaluated catheter-directed thrombolysis and embolectomies and demonstrated the efficacy and safety of these interventions. Here, we review the literature on the management of intermediate-risk pulmonary embolisms and the evidence behind those interventions. CONCLUSIONS: There are many treatments available in the management of intermediate-risk pulmonary embolism. Although the current literature does not favor 1 treatment as superior, multiple studies have shown growing data to support catheter-directed therapies as potential options for these patients. Multidisciplinary pulmonary embolism response teams remain a key feature in improving the selection of advanced therapies and optimization of care.
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Embolia Pulmonar , Terapia Trombolítica , Humanos , Terapia Trombolítica/métodos , Resultado do Tratamento , Trombectomia/efeitos adversos , Fibrinolíticos/uso terapêutico , Embolectomia/efeitos adversos , Embolectomia/métodos , Embolia Pulmonar/terapia , Anticoagulantes/uso terapêuticoRESUMO
Mycobacteriophages are a diverse group of viruses infecting Mycobacterium with substantial therapeutic potential. However, as this potential becomes realized, the molecular details of phage infection and mechanisms of resistance remain ill-defined. Here we use live-cell fluorescence microscopy to visualize the spatiotemporal dynamics of mycobacteriophage infection in single cells and populations, showing that infection is dependent on the host nucleoid-associated Lsr2 protein. Mycobacteriophages preferentially adsorb at Mycobacterium smegmatis sites of new cell wall synthesis and following DNA injection, Lsr2 reorganizes away from host replication foci to establish zones of phage DNA replication (ZOPR). Cells lacking Lsr2 proceed through to cell lysis when infected but fail to generate consecutive phage bursts that trigger epidemic spread of phage particles to neighbouring cells. Many mycobacteriophages code for their own Lsr2-related proteins, and although their roles are unknown, they do not rescue the loss of host Lsr2.
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Bacteriófagos , Micobacteriófagos , Mycobacterium , Micobacteriófagos/genética , Mycobacterium smegmatis/genéticaRESUMO
BACKGROUND: Standard dose (≤ 1 g) tranexamic acid (TXA) has established mortality benefit in trauma patients. The role of high dose IV TXA (≥2 g or ≥30 mg/kg as a single bolus) has been evaluated in the surgical setting, however, it has not been studied in trauma. We reviewed the available evidence of high dose IV TXA in any setting with the goal of informing its use in the adult trauma population. METHODS: We searched MEDLINE, EMBASE and unpublished sources from inception until July 27, 2022 for studies that compared standard dose with high dose IV TXA in adults (≥ 16 years of age) with hemorrhage. Screening and data abstraction was done independently and in duplicate. We pooled trial data using a random effects model and considered randomized controlled trials (RCTs) and observational cohort studies separately. We assessed the individual study risk of bias using the Cochrane Risk of Bias for RCTs and the Newcastle-Ottawa Scale for observational cohort studies. The overall certainty of evidence was assessed using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). RESULTS: We included 20 studies with a combined total of 12,523 patients. Based on pooled RCT data, and as compared to standard dose TXA, high dose IV TXA probably decreases transfusion requirements (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.76 to 0.97, moderate certainty) but with possibly no effect on blood loss (mean difference [MD] 43.31 ml less, 95% CI 135.53 to 48.90 ml less, low certainty), and an uncertain effect on thromboembolic events (OR 1.33, 95% CI 0.86 to 2.04, very low certainty) and mortality (OR 0.70, 95% CI 0.37 to 1.32, very low certainty). CONCLUSION: When compared to standard dose, high dose IV TXA probably reduces transfusion requirements with an uncertain effect on thromboembolic events and mortality. LEVEL OF EVIDENCE: Systematic review and meta-analysis, level IV.
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Antifibrinolíticos , Ácido Tranexâmico , Adulto , Humanos , Hemorragia , Transfusão de Sangue , Perda Sanguínea Cirúrgica/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Leslie, Eric, Ann L. Gibson, Laura V. Gonzalez Bosc, Christine Mermier, Sean M. Wilson, and Michael R. Deyhle. Review: can maternal exercise prevent high-altitude pulmonary hypertension in children? High Alt Med Biol. 24:1-6, 2023.-Chronic high-altitude exposure reduces oxygen delivery to the fetus during pregnancy and causes pathologic pulmonary artery remodeling, This increases the risk of high-altitude pulmonary hypertension (PH), which is a particularly fatal disease that is difficult to treat. Therefore, finding ways to prevent high-altitude PH, including during the neonatal period, is preferable. Cardiorespiratory exercise can improve functional capacity and quality of life in patients with high-altitude PH. However, similar to other treatments and surgical procedures, the benefits are not enough to cure the disease after a diagnosis. Cardiorespiratory exercise by mothers during pregnancy (i.e., maternal exercise) has not been previously evaluated to prevent the development of high-altitude PH in children born and living at high altitude. This focused review describes the pathophysiology of high-altitude PH and the potential benefit of maternal exercise for preventing the disease caused by high-altitude pregnancies.
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Doença da Altitude , Hipertensão Pulmonar , Gravidez , Feminino , Recém-Nascido , Humanos , Criança , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/prevenção & controle , Hipertensão Pulmonar/diagnóstico , Altitude , Qualidade de Vida , Doença da Altitude/complicaçõesRESUMO
BACKGROUND: The prevalence of coronary artery disease (CAD) in patients undergoing TAVR varies and is associated with increased morbidity and mortality. We evaluated the outcomes of complex and high-risk percutaneous coronary interventions (CHIP-PCIs) and TAVR compared with standard PCI and TAVR. Between January 2014 and March 2021, a total of 276 consecutive patients with severe aortic stenosis (AS) who underwent TAVR and PCI at 3 centers within Northwell Health were retrospectively reviewed. CHIP-PCI was defined as PCI with one of the following: left ventricular ejection fraction (LVEF) <30%; left main coronary artery (LMCA)/chronic total occlusion (CTO) intervention; atherectomy; or need for left ventricular (LV) support. One hundred twenty- seven patients (46%) had CHIP-PCI prior to TAVR and 149 patients (54%) had standard PCI. Thirteen percent of CHIP-PCI and 22% of standard PCI cases were done concomitantly with TAVR. CHIP-PCI criteria were met for low EF (19%), LMCA (25%), CTO (3%), LV support (20%), and atherectomy (50%). The types of valves used were similarly divided (49% balloon expandable vs 51% self expanding. Major adverse cardiac or cerebrovascular event (MACCE) rate for CHIP-PCI/TAVR was 4.9% at 30 days vs 1.3% for standard PCI/TAVR (P=.09), driven by in-hospital stroke. At 1 year, the rates of MACCE for CHIP-PCI/TAVR remained higher than for standard PCI/TAVR, but was not statistically significant (8.7% vs 4%; P=.06), driven by revascularization. We found no differences between major and/or minor vascular complications. New York Heart Association classification at 1 month was similar (I/II 93% vs 95%; P=.87). Our study suggests that CHIP-PCI can be safely performed in patients with complex CAD and concomitant severe AS.
Assuntos
Estenose da Valva Aórtica , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/cirurgia , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Valva Aórtica/cirurgia , Fatores de RiscoRESUMO
AIMS: Usage of transcatheter aortic valve implantation (TAVI) for treatment of severe aortic stenosis is increasing across age groups. However, literature on age-specific TAVI outcomes is lacking. The purpose of this study is to assess the risks of procedural complications, mortality, and readmission in patients undergoing TAVI across different age groups. METHODS AND RESULTS: The Nationwide Readmissions Database was used to identify 84 017 patients undergoing TAVI from 2016 to 2018. Patients were stratified into four age groups: younger than 70, 70-79, 80-89, and older than 90. Complications, mortality, and readmission rates were compared between groups in a proportional hazards regression model. Risk of post-procedural stroke, acute kidney injury, and pacemaker or implantable cardioverter defibrillator implantation increased with incremental age grouping. Compared with patients younger than 70, patients aged 70-79 had no significant difference in mortality, whereas patients aged 80-89 and older than 90 had an increased mortality risk [odds ratio (OR) 1.39, confidence interval (CI) 1.14-1.70, P = 0.001 and OR 1.68, CI 1.33-2.12, P < 0.001, respectively]. Patients aged 80-89 and older than 90 had increased overall readmission compared with patients younger than 70 (HR 1.09, CI 1.03-1.14, P = 0.001 and HR 1.33, CI 1.25-1.41, P < 0.001, respectively). Cardiac readmissions followed the same trend. CONCLUSION: Patients aged 80-89 and older than 90 undergoing TAVI have increased risk of readmission, complications, and mortality compared with patients younger than 70.