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1.
Eur J Radiol ; 177: 111595, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38970994

RESUMEN

PURPOSE: CT perfusion (CTP) is a valuable tool in suspected acute ischemic stroke. A substantial variability of the delay between contrast injection and bolus arrival in the brain is conceivable. We investigated the distribution of the peak positions of the concentration time curves measured in an artery (arterial input function, AIF) and - in cases with ischemia - also measured in the penumbra. METHODS: We report on 2624 perfusion scans (52 % female, mean age 72.2 ± 14.4 years) with stroke present in 1636 cases. From the attenuation time curves of the AIF and the penumbra, we calculated the respective bolus peak positions and investigated the distribution of the peak positions. Further, we analyzed the bolus peak positions for associations with age. RESULTS: The bolus peaked significantly later in older patients, both in the AIF and in the penumbra (all p < 0.001). In the whole cohort, we found a significant association of age with the bolus peak position of the AIF (ρ = 0.334; p < 0.001). In patients with stroke, age was also associated to the peak position of the AIF (ρ = 0.305; p < 0.001), and the penumbra (ρ = 0.246, p < 0.001). However, a substantial range of peak positions of the AIF and penumbra was noted across all age ranges. CONCLUSIONS: This study revealed a strong age-dependency of the contrast bolus arrival in both healthy and ischemic tissue. This variability makes non-uniform sampling schemes, which have been suggested to reduce radiation dose, problematic, as they might not always optimally capture the bolus in all cases.

3.
Ann Surg Oncol ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38990221

RESUMEN

BACKGROUND: Mastectomy skin flap necrosis (SFN) is common following nipple-sparing mastectomy (NSM), but studies on its quality-of-life (QOL) impact are limited. We examined patient-reported QOL and satisfaction after NSM with/without SFN utilizing the BREAST-Q patient-reported outcome measure (PROM) survey. PATIENTS AND METHODS: Patients undergoing NSM between April 2018 and July 2021 at our institution were examined; the BREAST-Q PROM was administered preoperatively, and at 6 months and 1 year postoperatively. SFN extent/severity was documented at 2-3 weeks postoperatively; QOL and satisfaction domains were compared between patients with/without SFN. RESULTS: A total of 573 NSMs in 333 patients were included, and 135 breasts in 82 patients developed SFN (24% superficial, 56% partial thickness, 16% full thickness). Patients with SFN reported significantly lower scores in the satisfaction with breasts (p = 0.032) and psychosocial QOL domains (p = 0.009) at 6 months versus those without SFN, with scores returning to baseline at 1 year in both domains. In the "physical well-being-of-the-chest" domain, there was an overall decline in scores among all patients; however, there were no significant differences at any time point between patients with or without SFN. Sexual well-being scores declined for patients with SFN compared with those without at 6 months and also at 1 year, but this did not reach significance (p = 0.13, p = 0.2, respectively). CONCLUSIONS: Patients undergoing NSM who developed SFN reported significantly lower satisfaction and psychosocial well-being scores at 6 months, which returned to baseline by 1 year. Physical well-being of the chest significantly declines after NSM regardless of SFN. Future studies with larger sample sizes and longer follow-up are needed to determine SFN's impact on long-term QOL.

5.
Plast Reconstr Surg ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38857436

RESUMEN

BACKGROUND: Autologous breast reconstruction (ABR) may confer higher patient reported outcomes than implant breast reconstruction, but an in-depth examination of factors associated with satisfaction after ABR is lacking. We aimed to determine independent predictors of 1-year Satisfaction with Breasts after ABR and assess the importance of elective procedures on satisfaction. METHODS: A retrospective analysis of patients who underwent abdominal-based ABR between 2010 and 2021 and completed the BREAST-Q Satisfaction with Breasts module at 1-year was performed. Elective procedures comprised of breast revision and nipple areolar complex (NAC) reconstruction. RESULTS: 959 patients were included. Satisfaction with Breasts score improved from 53 (IQR: 44 to 64) preoperatively to 64 (53 to 78) at 1-year postoperatively (p<0.001). Factors significantly associated with decreased postoperative score included lower preoperative scores (ß=0.19 [95% CI: 0.08, 0.31], p=0.001), older age (ß=-0.17 [-0.34, -0.01], p=0.042), Asian race (versus White, ß=-6.7 [-12, -1.7], p=0.008), and a history of psychiatric diagnoses (ß=-3.4 [-6.2, -0.66], p=0.015). Patients who received radiation (ß=-5.6 [-9.0, -2.3], p=0.001) or had mastectomy skin flap/nipple necrosis (ß=-3.8 [-7.6, -0.06], p=0.046) also had significantly decreased scores. Satisfaction with Breasts significantly improved after breast revision procedures (54 [42 to 65] to 65 [54 to 78], p<0.001) and NAC reconstruction (58 [47 to 71] to 67 [57 to 82], p<0.001). CONCLUSION: Multiple independent patient and treatment level factors are associated with lower 1-year Satisfaction with Breasts following ABR. Elective procedures have the potential to improve satisfaction. Understanding these findings is imperative for optimizing clinical decision making and managing expectations.

6.
Front Microbiol ; 15: 1389257, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38933034

RESUMEN

Microbial inhibition by high ammonia concentrations is a recurring problem that significantly restricts methane formation from intermediate acids, i.e., propionate and acetate, during anaerobic digestion of protein-rich waste material. Studying the syntrophic communities that perform acid conversion is challenging, due to their relatively low abundance within the microbial communities typically found in biogas processes and disruption of their cooperative behavior in pure cultures. To overcome these limitations, this study examined growth parameters and microbial community dynamics of highly enriched mesophilic and ammonia-tolerant syntrophic propionate and acetate-oxidizing communities and analyzed their metabolic activity and cooperative behavior using metagenomic and metatranscriptomic approaches. Cultivation in batch set-up demonstrated biphasic utilization of propionate, wherein acetate accumulated and underwent oxidation before complete degradation of propionate. Three key species for syntrophic acid degradation were inferred from genomic sequence information and gene expression: a syntrophic propionate-oxidizing bacterium (SPOB) "Candidatus Syntrophopropionicum ammoniitolerans", a syntrophic acetate-oxidizing bacterium (SAOB) Syntrophaceticus schinkii and a novel hydrogenotrophic methanogen, for which we propose the provisional name "Candidatus Methanoculleus ammoniitolerans". The results revealed consistent transcriptional profiles of the SAOB and the methanogen both during propionate and acetate oxidation, regardless of the presence of an active propionate oxidizer. Gene expression indicated versatile capabilities of the two syntrophic bacteria, utilizing both molecular hydrogen and formate as an outlet for reducing equivalents formed during acid oxidation, while conserving energy through build-up of sodium/proton motive force. The methanogen used hydrogen and formate as electron sources. Furthermore, results of the present study provided a framework for future research into ammonia tolerance, mobility, aggregate formation and interspecies cooperation.

7.
Ann Neurol ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38934493

RESUMEN

OBJECTIVE: To investigate whether choroid plexus volumes in subacute coronavirus disease 2019 (COVID-19) patients with neurological symptoms could indicate inflammatory activation or barrier dysfunction and assess their association with clinical data. METHODS: Choroid plexus volumes were measured in 28 subacute COVID-19 patients via cerebral magnetic resonance imaging (MRI), compared with those in infection-triggered non-COVID-19 encephalopathy patients (n = 25), asymptomatic individuals after COVID-19 (n = 21), and healthy controls (n = 21). Associations with inflammatory serum markers (peak counts of leukocytes, C-reactive protein [CRP], interleukin 6), an MRI-based marker of barrier dysfunction (CSF volume fraction [V-CSF]), and clinical parameters like olfactory performance and cognitive scores (Montreal Cognitive Assessment) were investigated. RESULTS: COVID-19 patients showed significantly larger choroid plexus volumes than control groups (p < 0.001, η2 = 0.172). These volumes correlated significantly with peak leukocyte levels (p = 0.001, Pearson's r = 0.621) and V-CSF (p = 0.009, Spearman's rho = 0.534), but neither with CRP nor interleukin 6. No significant correlations were found with clinical parameters. INTERPRETATION: In patients with subacute COVID-19, choroid plexus volume is a marker of central nervous system inflammation and barrier dysfunction in the presence of neurologic symptoms. The absence of plexus enlargement in infection-triggered non-COVID-19 encephalopathy suggests a specific severe acute respiratory syndrome coronavirus 2 effect. This study also documents an increase in choroid plexus volume for the first time as a parainfectious event. ANN NEUROL 2024.

8.
Clin Trials ; : 17407745241255087, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38895970

RESUMEN

BACKGROUND: Performing large randomized trials in anesthesiology is often challenging and costly. The clinically integrated randomized trial is characterized by simplified logistics embedded into routine clinical practice, enabling ease and efficiency of recruitment, offering an opportunity for clinicians to conduct large, high-quality randomized trials under low cost. Our aims were to (1) demonstrate the feasibility of the clinically integrated trial design in a high-volume anesthesiology practice and (2) assess whether trial quality improvement interventions led to more balanced accrual among study arms and improved trial compliance over time. METHODS: This is an interim analysis of recruitment to a cluster-randomized trial investigating three nerve block approaches for mastectomy with immediate implant-based reconstruction: paravertebral block (arm 1), paravertebral plus interpectoral plane blocks (arm 2), and serratus anterior plane plus interpectoral plane blocks (arm 3). We monitored accrual and consent rates, clinician compliance with the randomized treatment, and availability of outcome data. Assessment after the initial year of implementation showed a slight imbalance in study arms suggesting areas for improvement in trial compliance. Specific improvement interventions included increasing the frequency of communication with the consenting staff and providing direct feedback to clinician investigators about their individual recruitment patterns. We assessed overall accrual rates and tested for differences in accrual, consent, and compliance rates pre- and post-improvement interventions. RESULTS: Overall recruitment was extremely high, accruing close to 90% of the eligible population. In the pre-intervention period, there was evidence of bias in the proportion of patients being accrued and receiving the monthly block, with higher rates in arm 3 (90%) compared to arms 1 (81%) and 2 (79%, p = 0.021). In contrast, in the post-intervention period, there was no statistically significant difference between groups (p = 0.8). Eligible for randomization rate increased from 89% in the pre-intervention period to 95% in the post-intervention period (difference 5.7%; 95% confidence interval = 2.2%-9.4%, p = 0.002). Consent rate increased from 95% to 98% (difference of 3.7%; 95% confidence interval = 1.1%-6.3%; p = 0.004). Compliance with the randomized nerve block approach was maintained at close to 100% and availability of primary outcome data was 100%. CONCLUSION: The clinically integrated randomized trial design enables rapid trial accrual with a high participant compliance rate in a high-volume anesthesiology practice. Continuous monitoring of accrual, consent, and compliance rates is necessary to maintain and improve trial conduct and reduce potential biases. This trial methodology serves as a template for the implementation of other large, low-cost randomized trials in anesthesiology.

10.
Ann Plast Surg ; 92(6S Suppl 4): S453-S460, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38857013

RESUMEN

BACKGROUND: Individual outcomes may not accurately reflect the quality of perioperative care. Textbook outcomes (TOs) are composite metrics that provide a comprehensive evaluation of hospital performance and surgical quality. This study aimed to investigate the prevalence and predictors of TOs in a multi-institutional cohort of patients who underwent breast reconstruction with deep inferior epigastric artery perforator flaps. METHODS: For autologous reconstruction, a TO was previously defined as a procedure without intraoperative complications, reoperation, infection requiring intravenous antibiotics, readmission, mortality, systemic complications, operative duration ≤12 hours for bilateral and ≤10 hours for unilateral/stacked reconstruction, and length of stay (LOS) ≤5 days. We investigated associations between patient-level factors and achieving a TO using multivariable regression analysis. RESULTS: Of 1000 patients, most (73.2%) met a TO. The most common reasons for deviation from a TO were reoperation (9.6%), prolonged operative time (9.5%), and prolonged LOS (9.2%). On univariate analysis, tobacco use, obesity, widowed/divorced marital status, and contralateral prophylactic mastectomy or bilateral reconstruction were associated with a lower likelihood of TOs (P < 0.05). After adjustment, bilateral prophylactic mastectomy (odds ratio [OR], 5.71; P = 0.029) and hormonal therapy (OR, 1.53; P = 0.050) were associated with a higher likelihood of TOs; higher body mass index (OR, 0.91; P = <0.001) was associated with a lower likelihood. CONCLUSION: Approximately 30% of patients did not achieve a TO, and the likelihood of achieving a TO was influenced by patient and procedural factors. Future studies should investigate how this metric may be used to evaluate patient and hospital-level performance to improve the quality of care in reconstructive surgery.


Asunto(s)
Mamoplastia , Colgajo Perforante , Humanos , Femenino , Mamoplastia/métodos , Persona de Mediana Edad , Colgajo Perforante/irrigación sanguínea , Colgajo Perforante/trasplante , Adulto , Estudios Retrospectivos , Neoplasias de la Mama/cirugía , Arterias Epigástricas/trasplante , Microcirugia/métodos , Resultado del Tratamiento , Complicaciones Posoperatorias/epidemiología , Mastectomía/métodos , Tiempo de Internación/estadística & datos numéricos
11.
J Neurosurg Pediatr ; : 1-6, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38905707

RESUMEN

OBJECTIVE: Occurring once in every 2000 live births, craniosynostosis (CS) is the most frequent cranial birth defect. Although the genetic etiologies of syndromic CS cases are well defined, the genetic cause of most nonsyndromic cases remains unknown. METHODS: The authors analyzed exome or RNA sequencing data from 876 children with nonsyndromic CS, including 291 case-parent trios and 585 additional probands. The authors also utilized the GeneMatcher platform and the Gabriella Miller Kids First genome sequencing project to identify additional CS patients with AXIN1 mutations. RESULTS: The authors describe 11 patients with nonsyndromic CS harboring rare, damaging mutations in AXIN1, an inhibitor of Wnt signaling. AXIN1 regulates signaling upstream of key mediators of osteoblast differentiation. Three of the 6 mutations identified in trios occurred de novo in the proband, while 3 were transmitted from unaffected parents. Patients with nonsyndromic CS were highly enriched for mutations in AXIN1 compared to both expectation (p = 0.0008) and exome sequencing data from > 76,000 healthy controls (p = 2.3 × 10-6), surpassing the thresholds for genome-wide significance. CONCLUSIONS: These findings describe the first phenotype associated with mutations in AXIN1, with mutations identified in approximately 1% of nonsyndromic CS cases. The results strengthen the existing link between Wnt signaling and maintenance of cranial suture patency and have implications for genetic testing in families with CS.

12.
Ann Surg ; 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38747145

RESUMEN

OBJECTIVE: To establish globally applicable benchmark outcomes for pelvic exenteration (PE) in patients with locally advanced primary (LARC) and recurrent rectal cancer (LRRC), using outcomes achieved at highly specialised centres. BACKGROUND DATA: PE is established as the standard of care for selected patients with LARC and LRRC. There are currently no available benchmarks against which surgical performance in PE can be compared for audit and quality improvement. METHODS: This international multicentre retrospective cohort study included patients undergoing PE for LARC or LRRC at 16 highly experienced centres between 2018 and 2023. Ten outcome benchmarks were established in a lower-risk subgroup. Benchmarks were defined by the 75th percentile of the results achieved at the individual centres. RESULTS: 763 patients underwent PE, of which 464 patients (61%) had LARC and 299 (39%) had LRRC. 544 patients (71%) who met predefined lower risk criteria formed the benchmark cohort. For LARC patients, the calculated benchmark threshold for major complication rate was ≤44%; comprehensive complication index (CCI): ≤30.2; 30-day mortality rate: 0%; 90-day mortality rate: ≤4.3%; R0 resection rate: ≥79%. For LRRC patients, the calculated benchmark threshold for major complication rate was ≤53%; CCI: ≤34.1; 30-day mortality rate: 0%; 90-day mortality rate: ≤6%; R0 resection rate: ≥77%. CONCLUSIONS: The reported benchmarks for PE in patients with LARC and LRRC represent the best available care for this patient group globally and can be used for rigorous assessment of surgical quality and to facilitate quality improvement initiatives at international exenteration centres.

13.
Mol Ecol ; 33(13): e17424, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38813851

RESUMEN

Climate change and land use change are two main drivers of global biodiversity decline, decreasing the genetic diversity that populations harbour and altering patterns of local adaptation. Landscape genomics allows measuring the effect of these anthropogenic disturbances on the adaptation of populations. However, both factors have rarely been considered simultaneously. Based on a set of 3660 SNPs from which 130 were identified as outliers by a genome-environment association analysis (LFMM), we modelled the spatial turnover of allele frequencies in 19 localities of Pinus leiophylla across the Avocado Belt in Michoacán state, Mexico. Then, we evaluated the effect of climate change and land use change scenarios, in addition to evaluating assisted gene flow strategies and connectivity metrics across the landscape to identify priority conservation areas for the species. We found that localities in the centre-east of the Avocado Belt would be more vulnerable to climate change, while localities in the western area are more threatened by land conversion to avocado orchards. Assisted gene flow actions could aid in mitigating both threats. Connectivity patterns among forest patches will also be modified by future habitat loss, with central and eastern parts of the Avocado Belt maintaining the highest connectivity. These results suggest that areas with the highest priority for conservation are in the eastern part of the Avocado Belt, including the Monarch Butterfly Biosphere Reserve. This work is useful as a framework that incorporates distinct layers of information to provide a more robust representation of the response of tree populations to anthropogenic disturbances.


Asunto(s)
Cambio Climático , Flujo Génico , Persea , Pinus , Polimorfismo de Nucleótido Simple , Pinus/genética , Persea/genética , México , Frecuencia de los Genes , Adaptación Fisiológica/genética , Genética de Población , Conservación de los Recursos Naturales , Ecosistema , Variación Genética
14.
J Plast Reconstr Aesthet Surg ; 93: 173-182, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38703705

RESUMEN

PURPOSE: The BREAST-Q Breast Cancer module is a patient-reported outcome measure for women with breast cancer diagnosis. Our research team developed and validated a novel BREAST-Q scale for this module that measures quality of life outcomes specific to cancer worry. The aim of this study was to investigate patient related breast reconstruction factors that are associated with worse scores on the new BREAST-Q Cancer Worry Scale. METHODS: Women with a history of breast cancer treated with mastectomy and reconstruction, aged ≥18 years, and English-speaking were recruited through the Love Research Army between October and November 2019. Participants completed demographic and clinical questions alongside the BREAST-Q Cancer Worry Scale. Univariable and multivariable regression analyses were used to identify participant characteristics associated with cancer worry scores. RESULTS: Among the 554 potential respondents, 538 (97.1%) completed the Cancer Worry Scale. The average patient age was 58.4 (+9.8) years. Cancer Worry scores were normally distributed with a mean of 46.4 (+17.2). Cancer Worry scores were significantly associated (p < 0.01) with younger age, history of radiation therapy, complications associated with breast surgery since diagnosis, use of textured breast implants, and shorter duration since surgery. CONCLUSIONS: This exploratory analysis provides evidence of patient characteristics that may be associated with cancer worry following postmastectomy breast reconstruction.


Asunto(s)
Ansiedad , Neoplasias de la Mama , Mamoplastia , Mastectomía , Medición de Resultados Informados por el Paciente , Calidad de Vida , Humanos , Femenino , Persona de Mediana Edad , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/psicología , Mamoplastia/psicología , Estudios Transversales , Ansiedad/etiología , Ansiedad/psicología , Mastectomía/psicología , Anciano , Adulto , Implantes de Mama/psicología
15.
Nat Commun ; 15(1): 4430, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38789420

RESUMEN

Histone H2AX plays a key role in DNA damage signalling in the surrounding regions of DNA double-strand breaks (DSBs). In response to DNA damage, H2AX becomes phosphorylated on serine residue 139 (known as γH2AX), resulting in the recruitment of the DNA repair effectors 53BP1 and BRCA1. Here, by studying resistance to poly(ADP-ribose) polymerase (PARP) inhibitors in BRCA1/2-deficient mammary tumours, we identify a function for γH2AX in orchestrating drug-induced replication fork degradation. Mechanistically, γH2AX-driven replication fork degradation is elicited by suppressing CtIP-mediated fork protection. As a result, H2AX loss restores replication fork stability and increases chemoresistance in BRCA1/2-deficient tumour cells without restoring homology-directed DNA repair, as highlighted by the lack of DNA damage-induced RAD51 foci. Furthermore, in the attempt to discover acquired genetic vulnerabilities, we find that ATM but not ATR inhibition overcomes PARP inhibitor (PARPi) resistance in H2AX-deficient tumours by interfering with CtIP-mediated fork protection. In summary, our results demonstrate a role for H2AX in replication fork biology in BRCA-deficient tumours and establish a function of H2AX separable from its classical role in DNA damage signalling and DSB repair.


Asunto(s)
Proteína BRCA1 , Proteína BRCA2 , Replicación del ADN , Resistencia a Antineoplásicos , Histonas , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Animales , Femenino , Humanos , Ratones , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteína BRCA1/metabolismo , Proteína BRCA1/deficiencia , Proteína BRCA1/genética , Proteína BRCA2/metabolismo , Proteína BRCA2/genética , Proteína BRCA2/deficiencia , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Proteínas Portadoras/metabolismo , Proteínas Portadoras/genética , Línea Celular Tumoral , Roturas del ADN de Doble Cadena , Daño del ADN , Reparación del ADN , Replicación del ADN/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Histonas/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Recombinasa Rad51/metabolismo , Recombinasa Rad51/genética , Proteína 1 de Unión al Supresor Tumoral P53/metabolismo , Proteína 1 de Unión al Supresor Tumoral P53/genética , Ratones Desnudos
16.
Neurology ; 102(12): e209442, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38771998

RESUMEN

BACKGROUND AND OBJECTIVES: Few population-based studies have assessed associations between the use of antithrombotic (platelet antiaggregant or anticoagulant) drugs and location-specific risks of spontaneous intracerebral hemorrhage (s-ICH). In this study, we estimated associations between antithrombotic drug use and the risk of lobar vs nonlobar incident s-ICH. METHODS: Using Danish nationwide registries, we identified cases in the Southern Denmark Region of first-ever s-ICH in patients aged 50 years or older between 2009 and 2018. Each verified case was classified as lobar or nonlobar s-ICH and matched to controls in the general population by age, sex, and calendar year. Prior antithrombotic use was ascertained from a nationwide prescription registry. We calculated odds ratios (aORs) for associations between the use of clopidogrel, aspirin, direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA), and lobar and nonlobar ICH in conditional logistic regression analyses that were adjusted for potential confounders. RESULTS: A total of 1,040 cases of lobar (47.9% men, mean age [SD] 75.2 [10.7] years) and 1,263 cases of nonlobar s-ICH (54.2% men, mean age 73.6 [11.4] years) were matched to 41,651 and 50,574 controls, respectively. A stronger association with lobar s-ICH was found for clopidogrel (cases: 7.6%, controls: 3.5%; aOR 3.46 [95% CI 2.45-4.89]) vs aspirin (cases: 22.9%, controls: 20.4%; aOR 2.14 [1.74-2.63; p = 0.019). Corresponding estimates for nonlobar s-ICH were not different between clopidogrel (cases: 5.4%, controls: 3.4%; aOR 2.44 [1.71-3.49]) and aspirin (cases: 20.7%, controls: 19.2%; aOR 1.77 [1.47-2.15]; p = 0.12). VKA use was associated with higher odds of both lobar (cases: 14.3%, controls: 6.1%; aOR 3.66 [2.78-4.80]) and nonlobar (cases: 15.4%, controls: 5.5%; aOR 4.62 [3.67-5.82]) s-ICH. The association of DOAC use with lobar s-ICH (cases: 3.5%, controls: 2.7%; aOR 1.66 [1.02-2.70]) was weaker than that of VKA use (p = 0.006). Corresponding estimates for nonlobar s-ICH were not different between DOACs (cases: 5.1%, controls: 2.4%; aOR 3.44 [2.33-5.08]) and VKAs (p = 0.20). DISCUSSION: Antithrombotics were associated with higher risks of s-ICH, but the strength of the associations varied by s-ICH location and drug, which may reflect differences in the cerebral microangiopathies associated with lobar vs nonlobar hemorrhages and the mechanisms of drug action.


Asunto(s)
Hemorragia Cerebral , Fibrinolíticos , Sistema de Registros , Humanos , Masculino , Femenino , Anciano , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/inducido químicamente , Dinamarca/epidemiología , Persona de Mediana Edad , Fibrinolíticos/efectos adversos , Anciano de 80 o más Años , Inhibidores de Agregación Plaquetaria/efectos adversos , Anticoagulantes/efectos adversos , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Aspirina/efectos adversos , Incidencia
17.
Am J Cardiol ; 222: 131-140, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38703884

RESUMEN

Step-down oral antibiotic therapy is associated with a non-inferior long-term outcome compared with continued intravenous antibiotic therapy in the treatment of left-sided infective endocarditis. We aimed to analyze whether step-down oral therapy compared with continued intravenous antibiotic therapy is also associated with a non-inferior outcome in patients with large vegetations (vegetation length ≥ 10 mm) or among patients who underwent surgery before step-down oral therapy. We included patients without presence of aortic root abscess at diagnosis from the POET (Partial Oral Antibiotic Endocarditis Treatment) study. Multivariable Cox regression analyses were used to find associations between large vegetation, cardiac surgery, step-down oral therapy, and the primary end point (composite of all-cause mortality, unplanned cardiac surgery, embolic event, or relapse of positive blood cultures during follow-up). A total of 368 patients (age 68 ± 12, 77% men) were included. Patients with large vegetations (n = 124) were more likely to undergo surgery compared with patients with small vegetations (n = 244) (65% vs 20%, p <0.001). During a median 1,406 days of follow-up, 146 patients reached the primary end point. Large vegetations were not associated with the primary end point (hazard ratio 0.74, 95% confidence interval 0.47 to 1.18, p = 0.21). Step-down oral therapy was non-inferior to continued intravenous antibiotic in all subgroups when stratified by the presence of a large vegetation at baseline and early cardiac surgery. Step-down oral therapy is safe in the presence of a large vegetation at diagnosis and among patients who underwent early cardiac surgery.


Asunto(s)
Antibacterianos , Endocarditis Bacteriana , Humanos , Masculino , Femenino , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Anciano , Administración Oral , Endocarditis Bacteriana/tratamiento farmacológico , Resultado del Tratamiento , Persona de Mediana Edad , Estudios de Seguimiento , Procedimientos Quirúrgicos Cardíacos , Administración Intravenosa
19.
Nat Commun ; 15(1): 3720, 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697958

RESUMEN

Spin-orbit coupling in noncentrosymmetric crystals leads to spin-momentum locking - a directional relationship between an electron's spin angular momentum and its linear momentum. Isotropic orthogonal Rashba spin-momentum locking has been studied for decades, while its counterpart, isotropic parallel Weyl spin-momentum locking has remained elusive in experiments. Theory predicts that Weyl spin-momentum locking can only be realized in structurally chiral cubic crystals in the vicinity of Kramers-Weyl or multifold fermions. Here, we use spin- and angle-resolved photoemission spectroscopy to evidence Weyl spin-momentum locking of multifold fermions in the chiral topological semimetal PtGa. We find that the electron spin of the Fermi arc surface states is orthogonal to their Fermi surface contour for momenta close to the projection of the bulk multifold fermion at the Γ point, which is consistent with Weyl spin-momentum locking of the latter. The direct measurement of the bulk spin texture of the multifold fermion at the R point also displays Weyl spin-momentum locking. The discovery of Weyl spin-momentum locking may lead to energy-efficient memory devices and Josephson diodes based on chiral topological semimetals.

20.
Nat Commun ; 15(1): 4256, 2024 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-38762609

RESUMEN

After contracting COVID-19, a substantial number of individuals develop a Post-COVID-Condition, marked by neurologic symptoms such as cognitive deficits, olfactory dysfunction, and fatigue. Despite this, biomarkers and pathophysiological understandings of this condition remain limited. Employing magnetic resonance imaging, we conduct a comparative analysis of cerebral microstructure among patients with Post-COVID-Condition, healthy controls, and individuals that contracted COVID-19 without long-term symptoms. We reveal widespread alterations in cerebral microstructure, attributed to a shift in volume from neuronal compartments to free fluid, associated with the severity of the initial infection. Correlating these alterations with cognition, olfaction, and fatigue unveils distinct affected networks, which are in close anatomical-functional relationship with the respective symptoms.


Asunto(s)
COVID-19 , Disfunción Cognitiva , Fatiga , Imagen por Resonancia Magnética , Trastornos del Olfato , SARS-CoV-2 , Humanos , COVID-19/complicaciones , COVID-19/diagnóstico por imagen , COVID-19/fisiopatología , COVID-19/patología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/fisiopatología , Disfunción Cognitiva/virología , Masculino , Fatiga/fisiopatología , Femenino , Persona de Mediana Edad , Trastornos del Olfato/diagnóstico por imagen , Trastornos del Olfato/virología , Trastornos del Olfato/fisiopatología , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/fisiopatología , Síndrome Post Agudo de COVID-19 , Anciano
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