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1.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-39395599

RESUMO

INTRODUCTION AND OBJECTIVES: Myval technology represents the first balloon-expandable alternative since the Edwards system became commercially available. Despite certain controversies, its use has rapidly expanded. We aimed to gather all the available literature regarding its indications and outcomes. METHODS: A comprehensive search of articles published between December 2016 and May 2024 was conducted using BioMedCentral, Google Scholar, and PubMed to evaluate the main outcomes of Myval for native aortic stenosis (AS) (meta-analysis) and off-label uses (systematic review). RESULTS: A total of 151 studies were identified, and 74 were included in the analysis, covering aortic (n = 51), mitral (n = 9), tricuspid (n = 6), and pulmonary (n = 8) valve positions. A meta-analysis of studies on native AS demonstrated that Myval is safe and effective, with a 30-day mortality rate of 1.3%, good hemodynamic performance, low rates of pacemaker implantation (8.8%), and ≥ moderate paravalvular regurgitation (1.3%). Compared with other contemporary devices, Myval was competitive and associated with lower rates of pacemaker implantation. In a systematic review of off-label indications, Myval was also found to be safe and effective. In bicuspid AS, pure regurgitation, and aortic valve-in-valve procedures, success rates were 100%, 92%, and 100%, respectively, with pacemaker rates of 9.9%, 22.2%, and 3%, respectively. For mitral valve-in-valve/in-ring procedures, the success rate was 96.9%, while in tricuspid and pulmonary positions, small case series reported 100% success rates for both, with minimal procedural complications. CONCLUSIONS: Myval technology is safe and effective for the treatment of native valvular disease and dysfunctional prostheses or rings in all heart valve positions, although larger scale studies are warranted.

2.
RSC Chem Biol ; 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39398890

RESUMO

Tryptophan plays a critical role in proteins by contributing to stability, allostery, and catalysis. Using fluorine (19F) nuclear magnetic resonance (NMR), protein conformational dynamics and structure-activity relationships (SARs) can be studied via fluorotryptophan reporters. Tryptophan analogs such as 4-, 5-, 6-, or 7-fluorotryptophan can be routinely incorporated into proteins during heterologous expression by arresting endogenous tryptophan biosynthesis. Building upon the large 19F chemical shift dispersion associated with 5-fluorotryptophan, we introduce an approach to the incorporation of 13C-enriched 5-fluorotryptophan using a direct biosynthetic precursor, 5-fluoroanthranilic acid-(phenyl-13C6). The homodimeric enzyme fluoroacetate dehalogenase (FAcD), a thermophilic alpha/beta hydrolase responsible for the hydrolysis of a C-F bond in fluoroacetate, was expressed and biosynthetically labeled with (phenyl-13C6) 5-fluorotryptophan. The resulting two-dimensional 19F-13C (transverse relaxation optimized spectroscopy) TROSY heteronuclear correlation spectra provide complete resolution of all 9 tryptophan residues in the apo enzyme and FAcD saturated with the substrate analog bromoacetate. The (19F,13C) correlation spectra also reveal a multitude of minor resonances in the apo sample. The role of each tryptophan residue in allosteric communication was validated with computational rigidity transmission allostery analysis, which in this case explores the relative interprotomer communication between all possible tryptophan pairs.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39252591

RESUMO

BACKGROUND: Hemodynamic impact of commissural alignment (CA) with self-expandable transcatheter aortic valves (TAVR) has not been investigated yet. AIMS: To determine hemodynamic impact of CA with self-expandable TAVR. METHODS: Multicentric ambispective study comparing patients who underwent self-expandable TAVR in seven centers with the Evolut Pro/Pro+ (EP) (Medtronic) and Acurate neo2 (AN2) (Boston Scientific) with and without CA strategies. The degree of commissural misalignment (CMA) was assessed by computed tomography/angiography and 1-year transvalvular gradients/regurgitation evaluated by echocardiography. A matched comparison according to annular dimensions/eccentricity, prosthesis size/type, and baseline left ventricular function and gradients was performed. RESULTS: A total of 557 patients, mean age 80.7 ± 6.6 years, 61.4% men, and STS score of 4.3 ± 3.1% were analyzed. A CA technique was attempted in 215 patients (38.6%), including 113 patients with AN2 and 102 patients with EP. None/mild CMA was found in 158 (73.5% vs. 43.6% if no CA attempted, p < 0.001) with no differences between devices (AN2:75.2%; EP:71.6%, p = 0.545). Patients with moderate/severe CMA had a greater aortic peak gradient (22.3 ± 8.7 vs. 19.7 ± 8.5, p = 0.001), significantly greater progression of both peak (p = 0.002) and mean gradients (p = 0.001) after matching, and higher rate of central aortic regurgitation (1.2% vs. 0.4%, p = 0.005) at 1-year, but not a greater proportion of patients with mean gradient ≥ 10 mmHg. CONCLUSIONS: The use of CA strategies significantly reduced the rate of CMA for the self-expandable TAVR devices ACN2 and EP which was associated to lower transvalvular gradients and intra-prosthetic regurgitation progression at 1-year although no criteria of structural deterioration were met at this follow up. CLINICALTRIALS: org: NCT05097183.

4.
Clin Neuroradiol ; 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39316116

RESUMO

PURPOSE: To evaluate a novel flow-independent sequence (Relaxation-Enhanced Angiography without Contrast and Triggering (REACT)) for imaging of the extracranial arteries in acute ischemic stroke (AIS) at 1.5 T. METHODS: This retrospective single-center study included 47 AIS patients who received REACT (scan time: 3:01 min) and contrast-enhanced MRA (CE-MRA) of the extracranial arteries at 1.5 T in clinical routine. Two radiologists assessed scans for proximal internal carotid artery (ICA) stenosis, stated their diagnostic confidence and rated the image quality of cervical arteries, impact of artifacts and image noise. Apparent signal- and contrast-to-noise ratios (aSNR/aCNR) were measured for the common carotid artery and ICA. RESULTS: REACT achieved a sensitivity of 95.0% and a specificity of 97.3% for ICA stenoses in high agreement with CE-MRA (κ = 0.83) with equal diagnostic confidence (p = 0.22). Image quality was rated higher for CE-MRA at the aortic arch (p = 0.002) and vertebral arteries (p < 0.001), whereas REACT provided superior results for the extracranial ICA (p = 0.008). Both sequences were only slightly affected by artifacts (p = 0.60), while image noise was more pronounced in CE-MRA (p < 0.001) in line with higher aSNR (p < 0.001) and aCNR (p < 0.001) values in REACT for all vessels. CONCLUSION: Given its good diagnostic performance while yielding comparable image quality and scan time to CE-MRA, REACT may be suitable for the imaging of the extracranial arteries in acute ischemic stroke at 1.5 T.

5.
Postepy Dermatol Alergol ; 41(4): 388-394, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39290900

RESUMO

Introduction: Allergic reactions caused by external factors are treated with medicinal products containing antihistamines, therefore their action is delayed in time. Combination of antihistamines and fast-acting analgesics may help to reduce discomfort associated with cutaneous reactions. Aim: To evaluate efficacy and safety of the combination topical gel containing diphenhydramine hydrochloride 20 mg/g and lidocaine hydrochloride 10 mg/g over placebo in the treatment of local skin inflammatory and allergic reactions. Material and methods: A study was a single-centre, single-dose, randomized, double-blind, two-treatment, two-period, two-sequence cross-over clinical trial (n = 44) in healthy subjects. Local skin inflammatory and allergic lesions were induced by the provocative test with histamine in healthy subjects. For all parameters recorded with the Visual Analogue Scale (VAS), the area under the curve (AUC) was calculated and the peak itch intensity was noted for every subject in response to the skin prick test. The primary endpoint of the study was the difference in AUC calculated from the intensity of itch for test product A (diphenhydramine hydrochloride 20 mg/g and lidocaine hydrochloride 10 mg/g, gel) and placebo product B. Results: The results revealed that itching intensity AUC was significantly greater for product B than for product A, on average by 2.05 points. A decrease in itching intensity was observed from the second minute after application of the test product. Conclusions: The study provided evidence for differences in efficacy between the product tested and placebo.

6.
Postepy Dermatol Alergol ; 41(4): 415-422, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39290904

RESUMO

Introduction: The pathogenesis of atopic dermatitis (AD) involves complex interactions between environmental factors, the skin microbiome, epidermal barrier defects, and altered immune responses that develop on a not fully understood specific genetic background. Aim: We aimed to evaluate the contribution of single nucleotide polymorphisms (SNPs) in the IL-35 genes (IL-12A and EBI3) towards AD susceptibility and clinical characteristics of AD in the Polish population. Two SNPs (rs568408, rs582054) in IL-12A and one SNP (rs428253) in EBI3 were selected. Material and methods: Blood samples were collected from 202 AD patients and 178 healthy individuals. SNPs in IL-35 genes were analysed by the polymerase chain reaction with sequence-specific primers (SSP-PCR) method. Results: For IL-12A rs568408, the AA genotype was significantly linked to increased odds of AD (OR = 34.61; 95% CI: 2.06-579.97, p = 0.0137) and marginally associated with normal total serum IgE levels (OR = 2.82; 95% CI: 0.97-8.16; p = 0.05), while the GA genotype showed significantly reduced odds of AD (OR = 0.53; 95% CI: 0.34-0.81; p = 0.0035). In the context of IL-12A rs582054, TT genotype carriers had increased odds of AD (OR = 2.05; 95% CI: 1.08-3.85; p = 0.03). Patients with the GG genotype of EBI3 rs428253 had decreased odds of high total serum IgE levels (OR = 0.42; 95% CI: 0.20-0.86; p = 0.02) and milder pruritus severity compared to CC genotype carriers (4.12 vs. 7.50; p = 0.02). Conclusions: IL-35 genetic variations appear to play a role in AD pathogenesis.

7.
Sci Rep ; 14(1): 21753, 2024 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-39294225

RESUMO

The aim of presented study was to test nutritional properties of potato tubers and silver ions accumulation pattern after foliar application of silver nanoparticles (AgNPs) during potato vegetation. Potato plants were sprayed with different concentration of Ag nanoparticles (0.1, 1.0 and 10 mg·dm-3) synthesized with incorporation with sodium dodecyl sulphate (SDS) and sodium citrate as stabilizing agent. The lowest amounts of silver ions were transported to the tubers after spraying with AgNPs synthesized with SDS, rather than with citrate. Nevertheless silver ions accumulation in tubers was negligible. SDS method of synthesis was more favourable in terms of nutritional properties of potato tubers. The highest tested concentration of AgNPs_SDS had a favourable effect on a variety of macro- and micronutrients, ascorbic acid and soluble sugars. In turn, lower concentrations of AgNPs_SDS increased the content of phenolic compounds and free radical scavenging efficiency of tubers. These correlations were also confirmed by Principal Component Analysis.


Assuntos
Nanopartículas Metálicas , Tubérculos , Prata , Solanum tuberosum , Solanum tuberosum/metabolismo , Solanum tuberosum/química , Nanopartículas Metálicas/química , Prata/química , Tubérculos/química , Tubérculos/metabolismo , Ácido Ascórbico/metabolismo , Ácido Ascórbico/análise , Antioxidantes , Dodecilsulfato de Sódio/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Fenóis/análise
8.
J Am Heart Assoc ; 13(19): e035460, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39291483

RESUMO

BACKGROUND: Patients with aortic stenosis may continue to have an increased risk of heart failure, arrhythmias, and death after successful transcatheter aortic valve implantation. Renin-angiotensin system inhibitors may be beneficial in this setting. We aimed to explore whether ramipril improves the outcomes of patients with aortic stenosis after transcatheter aortic valve implantation. METHODS AND RESULTS: PROBE (Prospective Randomized Open, Blinded Endpoint) was a multicenter trial comparing ramipril with standard care (control) following successful transcatheter aortic valve implantation in patients with left ventricular ejection fraction >40%. The primary end point was the composite of cardiac mortality, heart failure readmission, and stroke at 1-year follow-up. Secondary end points included left ventricular remodeling and fibrosis. A total of 186 patients with median age 83 years (range 79-86), 58.1% women, and EuroSCORE-II 3.75% (range 3.08-4.97) were randomized to receive either ramipril (n=94) or standard treatment (n=92). There were no significant baseline, procedural, or in-hospital differences. The primary end point occurred in 10.6% in the ramipril group versus 12% in the control group (P=0.776), with no differences in cardiac mortality (ramipril 1.1% versus control group 2.2%, P=0.619) but lower rate of heart failure readmissions in the ramipril group (3.2% versus 10.9%, P=0.040). Cardiac magnetic resonance analysis demonstrated better remodeling in the ramipril compared with the control group, with greater reduction in end-systolic and end-diastolic left ventricular volumes, but nonsignificant differences were found in the percentage of myocardial fibrosis. CONCLUSIONS: Ramipril administration after transcatheter aortic valve implantation in patients with preserved left ventricular function did not meet the primary end point but was associated with a reduction in heart failure re-admissions at 1-year follow-up. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03201185.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Estenose da Valva Aórtica , Insuficiência Cardíaca , Ramipril , Volume Sistólico , Substituição da Valva Aórtica Transcateter , Função Ventricular Esquerda , Remodelação Ventricular , Humanos , Ramipril/uso terapêutico , Substituição da Valva Aórtica Transcateter/efeitos adversos , Feminino , Masculino , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/mortalidade , Idoso , Idoso de 80 Anos ou mais , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Remodelação Ventricular/efeitos dos fármacos , Estudos Prospectivos , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/mortalidade , Readmissão do Paciente/estatística & dados numéricos , Fatores de Tempo
9.
Life (Basel) ; 14(9)2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39337978

RESUMO

The presence of Demodex spp. mites on the skin is a common phenomenon in the human population. In most people, it is an asymptomatic infestation, but in some patients, it can contribute to the occurrence of diseases such as demodicosis, rosacea, or blepharitis, as well as non-specific symptoms. In this study, the results of tests assessing the presence of Demodex spp. by direct microscopic examination (DME) in 2508 patients from northern Poland with the suspicion of demodicosis were retrospectively analyzed. A total of 3684 tests were performed. Among them, only 1585 (43.02%) revealed the presence of Demodex spp., while 2099 (56.98%) were negative. It was shown that in the analyzed population of patients with clinical suspicion of demodicosis, the degree of confirmation of the presence of Demodex spp. positively correlated with the patient's age (p = 0.001) and the mite was mainly found on the edges of eyelids and on the facial skin. Additionally, in men, the presence of Demodex was more often confirmed than in women (p = 0.004). In conclusion, the proper diagnosis of demodicosis still constitutes an important clinical problem due to the non-specificity of symptoms and the low confirmation of clinical suspicions of infestation by DME, especially in lower age groups.

10.
Plast Reconstr Surg ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39213030

RESUMO

BACKGROUND: Reconstruction of the midface after maxillectomy is extremely challenging due to the need to reestablish the contour of the midface, maintain oronasal separation, support the orbit, and to restore the dentition. In this study, we present our specific technique, surgical and functional outcomes, and pitfalls to avoid for reconstruction of the midface with the fibula osteocutaneous free flap. METHODS: A retrospective review of patients who underwent maxillary reconstruction with a fibula osteocutaneous free flap was performed. RESULTS: Eighty-five flaps were performed in 73 patients (61 patients received a fibula flap only; 12 patients received an additional soft tissue free flap). Reconstructions were performed for 82.2% Cordeiro type 2 and 18.8 % Cordeiro type 3a defects. Osseointegrated dental implants were placed in 95.9% of patients, 13.7% of whom underwent immediate implant placement. Concurrent orbital floor reconstruction was performed in 16.2% of patients. The rate of operative takeback was 18.9%, and total flap loss occurred in 2.7%. Hardware exposure occurred in 11.0% at a mean of 4.4 years postoperatively and palatal fistulae occurred in 5.5%, usually within the first 3 weeks following reconstruction. Functionally, 79.5% demonstrated excellent speech and 80.9% had unrestricted diet postoperatively. The mean follow-up period was 3.4 years. CONCLUSIONS: The present study shows that maxillary reconstruction with free fibula flap provides reliable reconstruction that restores dental, orbital, and midfacial support. Modifications and nuances to the reconstructive technique learned over time to avoid complications and improve outcomes are described herein.

11.
Eur Radiol ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39214894

RESUMO

OBJECTIVES: To evaluate the prognostic value of transit time (TT) assessment in the systemic circulation and organ perfusion in patients with ventricular dysfunction (VD). The primary endpoint was defined as death, heart failure admission, or ventricular arrhythmias, and the secondary endpoint was worsening renal function. METHODS: A retrospective study on 139 patients who underwent cardiac magnetic resonance for VD evaluation and 50 controls. TT was measured as peak-to-peak time in signal intensity over time curves obtained at different stages of circulation (right cavities, left cavities, aorta, and peripheral organs) from first-pass perfusion images. Outcomes were monitored over a median follow-up of 15 months. RESULTS: A total of 139 patients were included (84% male, age 63 [57-70] years). Patients exhibited significantly prolonged TT compared to controls, with in-patients showing longer times than outpatients. Among the 29 patients reaching the primary endpoint, both PTT and STT were significantly prolonged (PTT: 9.75 s vs 13.4 s, p < 0.01; STT: 4.77 s vs 7.00 s, p < 0.01). Concurrent prolongation of PTT (> 10 s) and STT (> 5 s) was associated with a higher event probability (42.3%), compared to isolated abnormalities (6.3% for PTT, 6.7% for STT). Multivariate analysis revealed that combined PTT and STT alteration independently predicted the combined endpoint (HR IC 95%: 8.685 (2.415-31.236), p = 0.001). Prolonged RPT was independently associated with renal function deterioration (OR IC 95%: 1.129 (1.015-1.256), p = 0.024). CONCLUSIONS: Evaluation of TT beyond pulmonary circulation provides prognostic insights into VD. Simultaneous assessment of PTT and STT enhances specificity compared to isolated PTT evaluation, predicting combined adverse events. RPT is independently associated with renal impairment. CLINICAL RELEVANCE STATEMENT: For the first time, it is described that transit time can be evaluated in systemic circulation and in peripheral organs and that this assessment can be easily made from conventional CMR perfusion images and holds significant prognostic value. KEY POINTS: Pulmonary transit time is a valuable hemodynamic parameter; systemic transit time may also be valuable. Transit time can be measured in the systemic circulation, and is longer in patients with ventricular dysfunction. Systemic transit time assessed by magnetic resonance imaging identifies patients with ventricular dysfunction who will experience events during follow-up.

12.
J Fungi (Basel) ; 10(8)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39194860

RESUMO

Onychomycosis is a common fungal nail infection that is difficult to diagnose due to its similarity to other nail conditions. Accurate identification is essential for effective treatment. The current gold standard methods include microscopic examination with potassium hydroxide, fungal cultures, and Periodic acid-Schiff biopsy staining. These conventional techniques, however, suffer from high turnover times, variable sensitivity, reliance on human interpretation, and costs. This study examines the potential of integrating AI (artificial intelligence) with visualization tools like dermoscopy and microscopy to improve the accuracy and efficiency of onychomycosis diagnosis. AI algorithms can further improve the interpretation of these images. The review includes 14 studies from PubMed and IEEE databases published between 2010 and 2024, involving clinical and dermoscopic pictures, histopathology slides, and KOH microscopic images. Data extracted include study type, sample size, image assessment model, AI algorithms, test performance, and comparison with clinical diagnostics. Most studies show that AI models achieve an accuracy comparable to or better than clinicians, suggesting a promising role for AI in diagnosing onychomycosis. Nevertheless, the niche nature of the topic indicates a need for further research.

13.
J Biomol NMR ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39172315

RESUMO

Side chain isotope labelling is a powerful tool to study protein structure and interactions by NMR spectroscopy. 1H,13C labelling of side-chain methyl groups in a deuterated background allows studying large molecules, while side-chain aromatic groups are highly sensitive to the interaction with ligands, drugs, and other proteins. In E. coli, side chain labelling is performed by substituting amino acids with isotope-labelled precursors. However, proteins that can only be produced in mammalian cells require expensive isotope-labelled amino acids. Here we provide a simple and cost-effective method to label side chains in mammalian cells, which exploits the reversible reaction catalyzed by endogenous transaminases to convert isotope-labelled α-ketoacid precursors. We show by in-cell and in-lysate NMR spectroscopy that replacing an amino acid in the medium with its cognate precursor is sufficient to achieve selective labelling without scrambling, and how this approach allows monitoring conformational changes such as those arising from ligand binding.

14.
Front Pharmacol ; 15: 1445685, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39193329

RESUMO

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet they can induce immune-related adverse events (irAEs), including cutaneous toxicities such as lichenoid eruptions. Pembrolizumab, a PD-1 inhibitor, is known for its association with lichen-planus-like reactions, while the side effect profile of combining immunotherapy with MK-4830, a novel fully human IgG4 monoclonal antibody that targets ILT-4, remains limited. Case report: We present a case of a 47-year-old female with metastatic breast cancer who developed a grade 2 Common Terminology Criteria for Adverse Events (CTCAE) lichenoid reaction after 9 months of MK-4830 and pembrolizumab use. Confluent, erythematous papules with Wickham's striae appeared predominantly on the extremities. Initial therapy with high-potency topical corticosteroids proved insufficient, however prednisone 40 mg daily resulted in satisfactory remission of lichen-planus-like reaction, permitting continued immunotherapy without dosage adjustment. Conclusion: This case highlights the novel occurrence of lichenoid eruption induced by MK-4830 and pembrolizumab in breast cancer treatment. The patient was successfully treated with oral prednisone, which controlled the skin symptoms without interrupting ICI therapy. We emphasize that early diagnosis and treatment of low-grade lichenoid eruption can prevent the cessation of ICIs, thereby combining the benefits of managing irAEs and avoiding cancer progression, leading to a better long-term prognosis.

16.
Int J Cardiol ; 413: 132340, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-38992809

RESUMO

BACKGROUND: The current incidence and outcomes of structural transcatheter procedures in heart transplant (HTx) recipients and left-ventricular assist devices (LVAD) carriers is unknown. AIMS: To provide insights on structural transcatheter procedures performed across HTx and LVAD patients in Spain. METHODS: Multicenter, ambispective, observational nationwide registry. RESULTS: Until May/2023, 36 percutaneous structural interventions were performed (78% for HTx and 22% for LVAD) widely varying among centers (0%-1.4% and 0%-25%, respectively). Percutaneous mitral transcatheter edge-to-edge (TEER) was the most common (n = 12, 33.3%), followed by trancatheter aortic valve replacement (n = 11, 30.5%), and tricuspid procedures (n = 9, 25%). Mitral TEER resulted in mild residual mitral regurgitation in all but one case, mean gradient was <5 mmHg in 75% of them at 1-year, with no mortality and 8.3% re-admission rate. Tricuspid TEER resulted in 100% none/mild residual regurgitation with a 1-year mortality and readmission rates of 22% and 28.5%, respectively. Finally, trancatheter aortic valve replacement procedures (n = 8 in LVADs due to aortic regurgitation and n = 3 in HTx), were successful in all cases with one prosthesis degeneration leading to severe aortic regurgitation at 1-year, 18.2% mortality rate and no re-admissions. Globally, major bleeding rates were 7.9% and 12.5%, thromboembolic events 3.7% and 12.5%, readmissions 37% and 25%, and mortality 22% and 25%, in HTx and LVADs respectively. No death was related to the implanted transcatheter device. CONCLUSIONS: Most centers with HTx/LVAD programs perform structural percutaneous procedures but with very inconsistent incidence. They were associated with good safety and efficacy, but larger studies are required to provide formal recommendations.


Assuntos
Transplante de Coração , Coração Auxiliar , Sistema de Registros , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Espanha/epidemiologia , Idoso , Cateterismo Cardíaco/métodos , Adulto , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/epidemiologia
17.
J Med Chem ; 67(15): 13187-13196, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39069741

RESUMO

Fragment-based drug design is heavily dependent on the optimization of initial low-affinity binders. Herein we introduce an approach that uses selective labeling of methyl groups in leucine and isoleucine side chains to directly probe methyl-π contacts, one of the most prominent forms of interaction between proteins and small molecules. Using simple NMR chemical shift perturbation experiments with selected BRD4-BD1 binders, we find good agreement with a commonly used model of the ring-current effect as well as the overall interaction geometries extracted from the Protein Data Bank. By combining both interaction geometries and chemical shift calculations as fit quality criteria, we can position dummy aromatic rings into an AlphaFold model of the protein of interest. The proposed method can therefore provide medicinal chemists with important information about binding geometries of small molecules in fast and iterative matter, even in the absence of high-resolution experimental structures.


Assuntos
Modelos Moleculares , Ligantes , Humanos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/química , Ligação Proteica , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/metabolismo , Proteínas/química , Proteínas/metabolismo , Desenho de Fármacos , Espectroscopia de Ressonância Magnética , Proteínas que Contêm Bromodomínio
18.
J Cardiovasc Magn Reson ; 26(2): 101068, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39079602

RESUMO

BACKGROUND: Diagnosing myocarditis relies on multimodal data, including cardiovascular magnetic resonance (CMR), clinical symptoms, and blood values. The correct interpretation and integration of CMR findings require radiological expertise and knowledge. We aimed to investigate the performance of Generative Pre-trained Transformer 4 (GPT-4), a large language model, for report-based medical decision-making in the context of cardiac MRI for suspected myocarditis. METHODS: This retrospective study includes CMR reports from 396 patients with suspected myocarditis and eight centers, respectively. CMR reports and patient data including blood values, age, and further clinical information were provided to GPT-4 and radiologists with 1 (resident 1), 2 (resident 2), and 4 years (resident 3) of experience in CMR and knowledge of the 2018 Lake Louise Criteria. The final impression of the report regarding the radiological assessment of whether myocarditis is present or not was not provided. The performance of Generative pre-trained transformer 4 (GPT-4) and the human readers were compared to a consensus reading (two board-certified radiologists with 8 and 10 years of experience in CMR). Sensitivity, specificity, and accuracy were calculated. RESULTS: GPT-4 yielded an accuracy of 83%, sensitivity of 90%, and specificity of 78%, which was comparable to the physician with 1 year of experience (R1: 86%, 90%, 84%, p = 0.14) and lower than that of more experienced physicians (R2: 89%, 86%, 91%, p = 0.007 and R3: 91%, 85%, 96%, p < 0.001). GPT-4 and human readers showed a higher diagnostic performance when results from T1- and T2-mapping sequences were part of the reports, for residents 1 and 3 with statistical significance (p = 0.004 and p = 0.02, respectively). CONCLUSION: GPT-4 yielded good accuracy for diagnosing myocarditis based on CMR reports in a large dataset from multiple centers and therefore holds the potential to serve as a diagnostic decision-supporting tool in this capacity, particularly for less experienced physicians. Further studies are required to explore the full potential and elucidate educational aspects of the integration of large language models in medical decision-making.

19.
Rev Esp Quimioter ; 37(5): 401-408, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38934492

RESUMO

OBJECTIVE: Our aim was to analyse the relation between serial values of the indocyanine green plasma disappearance rate (ICG-PDR) with hospital mortality in the first 48 hours of ICU admission in patients with septic shock. METHODS: A prospective observational study was carried out over 12 months of patients admitted to the ICU with septic shock. Each patient underwent noninvasive determination of ICG-PDR at 24 and 48 hours with the LiMON® module. Follow-up was performed until hospital discharge or exitus. RESULTS: 63 patients. Age 61.1±12.3 years. 60.3% men. SOFA score on admission 8.7±3.3, APACHE II score was 27.9±10.7 points. A total of 44.4% of patients died. The ICG-PDR values in the first 24 hours of ICU admission were lower in nonsurvivors: 10.5 (5.7-13.0)%/min vs. 15.9 (11.4-28.0)%/min, p <0.001. Furthermore, in nonsurvivors, there was no improvement in ICG-PDR between 24 h and 48 h, while in survivors, there was an increase of 25%: 15.9 (11.4-28.0)%/min and 20.9 (18.0-27.0)%/min, p=0.020. The silhouette measure of ICG-PDR cohesion and separation for the clusters analysed (nonsurvivors and survivors) was satisfactory (0.6). ICG-PDR<11.7%/min was related to in-hospital mortality, ICG-PDR> 18%/min to survival, and the interval between 11.7% and 18%/min covered a range of uncertainty. In the two-stage cluster, ICG-PDR, SOFA and APACHE II present satisfactory predictive scores 24 hours after patient admission. CONCLUSIONS: ICG-PDR in our setting is a useful clinical prognostic tool and could optimise the decision tree in patients with septic shock.


Assuntos
Mortalidade Hospitalar , Verde de Indocianina , Unidades de Terapia Intensiva , Choque Séptico , Humanos , Choque Séptico/mortalidade , Choque Séptico/sangue , Masculino , Verde de Indocianina/farmacocinética , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Idoso , Corantes , APACHE , Prognóstico
20.
J Phys Chem A ; 128(25): 4976-4983, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38850250

RESUMO

Nonadiabatic interaction of adsorbate nuclear motion with the continuum of electronic states is known to affect the dynamics of chemical reactions at metal surfaces. A large body of work has probed the fundamental mechanisms of such interactions for atomic and diatomic molecules at surfaces. In polyatomic molecules, the possibility of mode-specific damping of vibrational motion due to the effects of electronic friction raises the question of whether such interactions could profoundly affect the outcome of chemistry at surfaces by selectively removing energy from a particular intramolecular adsorbate mode. However, to date, there have not been any fundamental experiments demonstrating nonadiabatic electron-vibration coupling in a polyatomic molecule at a surface. In this work, we scatter excited metastable formaldehyde and formaldehyde-d2 from a low work function surface and detect ejected exoelectrons that accompany molecular relaxation. The exoelectron ejection efficiency exhibits a strong dependence on the vibrational mode that is excited: out-of-plane bending excitation (ν4) leads to significantly more exoelectrons than does CO stretching excitation (ν2). The results provide clear evidence for mode-specific energy transfer from vibration to surface electrons.

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