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1.
N Engl J Med ; 388(24): 2219-2229, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37092792

RESUMO

BACKGROUND: Traumatic acute subdural hematomas frequently warrant surgical evacuation by means of a craniotomy (bone flap replaced) or decompressive craniectomy (bone flap not replaced). Craniectomy may prevent intracranial hypertension, but whether it is associated with better outcomes is unclear. METHODS: We conducted a trial in which patients undergoing surgery for traumatic acute subdural hematoma were randomly assigned to undergo craniotomy or decompressive craniectomy. An inclusion criterion was a bone flap with an anteroposterior diameter of 11 cm or more. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOSE) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 12 months. Secondary outcomes included the GOSE rating at 6 months and quality of life as assessed by the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L). RESULTS: A total of 228 patients were assigned to the craniotomy group and 222 to the decompressive craniectomy group. The median diameter of the bone flap was 13 cm (interquartile range, 12 to 14) in both groups. The common odds ratio for the differences across GOSE ratings at 12 months was 0.85 (95% confidence interval, 0.60 to 1.18; P = 0.32). Results were similar at 6 months. At 12 months, death had occurred in 30.2% of the patients in the craniotomy group and in 32.2% of those in the craniectomy group; a vegetative state occurred in 2.3% and 2.8%, respectively, and a lower or upper good recovery occurred in 25.6% and 19.9%. EQ-5D-5L scores were similar in the two groups at 12 months. Additional cranial surgery within 2 weeks after randomization was performed in 14.6% of the craniotomy group and in 6.9% of the craniectomy group. Wound complications occurred in 3.9% of the craniotomy group and in 12.2% of the craniectomy group. CONCLUSIONS: Among patients with traumatic acute subdural hematoma who underwent craniotomy or decompressive craniectomy, disability and quality-of-life outcomes were similar with the two approaches. Additional surgery was performed in a higher proportion of the craniotomy group, but more wound complications occurred in the craniectomy group. (Funded by the National Institute for Health and Care Research; RESCUE-ASDH ISRCTN Registry number, ISRCTN87370545.).


Assuntos
Craniotomia , Craniectomia Descompressiva , Hematoma Subdural Agudo , Humanos , Craniotomia/efeitos adversos , Craniotomia/métodos , Craniectomia Descompressiva/efeitos adversos , Craniectomia Descompressiva/métodos , Escala de Resultado de Glasgow , Hematoma Subdural Agudo/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Crânio/cirurgia , Resultado do Tratamento , Retalhos Cirúrgicos/cirurgia
2.
Circ Res ; 133(11): 885-898, 2023 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-37929582

RESUMO

BACKGROUND: Pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a common and highly morbid syndrome, but mechanisms driving PH-HFpEF are poorly understood. We sought to determine whether a well-accepted murine model of HFpEF also displays features of PH, and we sought to identify pathways that might drive early remodeling of the pulmonary vasculature in HFpEF. METHODS: Eight-week-old male and female C57BL/6J mice received either Nγ-nitro-L-arginine methyl ester and high-fat diet or control water and diet for 2, 5, and 12 weeks. The db/db mice were studied as a second model of HFpEF. Early pathways regulating PH were identified by bulk and single-cell RNA sequencing. Findings were confirmed by immunostain in lungs of mice or lung slides from clinically performed autopsies of patients with PH-HFpEF. ELISA was used to verify IL-1ß (interleukin-1 beta) in mouse lung, mouse plasma, and also human plasma from patients with PH-HFpEF obtained at the time of right heart catheterization. Clodronate liposomes and an anti-IL-1ß antibody were utilized to deplete macrophages and IL-1ß, respectively, to assess their impact on pulmonary vascular remodeling in HFpEF in mouse models. RESULTS: Nγ-nitro-L-arginine methyl ester/high-fat diet-treated mice developed PH, small vessel muscularization, and right heart dysfunction. Inflammation-related gene ontologies were overrepresented in bulk RNA sequencing analysis of whole lungs, with an increase in CD68+ cells in both murine and human PH-HFpEF lungs. Cytokine profiling showed an increase in IL-1ß in mouse and human plasma. Finally, clodronate liposome treatment in mice prevented PH in Nγ-nitro-L-arginine methyl ester/high-fat diet-treated mice, and IL-1ß depletion also attenuated PH in Nγ-nitro-L-arginine methyl ester/high-fat diet-treated mice. CONCLUSIONS: We report a novel model for the study of PH and right heart remodeling in HFpEF, and we identify myeloid cell-derived IL-1ß as an important contributor to PH in HFpEF.


Assuntos
Insuficiência Cardíaca , Hipertensão Pulmonar , Animais , Feminino , Humanos , Masculino , Camundongos , Ácido Clodrônico , Insuficiência Cardíaca/metabolismo , Hipertensão Pulmonar/etiologia , Interleucina-1beta , Camundongos Endogâmicos C57BL , Células Mieloides/metabolismo , Volume Sistólico/fisiologia
3.
Adv Funct Mater ; 34(21)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38952568

RESUMO

Embedded bioprinting overcomes the barriers associated with the conventional extrusion-based bioprinting process as it enables the direct deposition of bioinks in 3D inside a support bath by providing in situ self-support for deposited bioinks during bioprinting to prevent their collapse and deformation. Embedded bioprinting improves the shape quality of bioprinted constructs made up of soft materials and low-viscosity bioinks, leading to a promising strategy for better anatomical mimicry of tissues or organs. Herein, the interplay mechanism among the printing process parameters toward improved shape quality is critically reviewed. The impact of material properties of the support bath and bioink, printing conditions, cross-linking mechanisms, and post-printing treatment methods, on the printing fidelity, stability, and resolution of the structures is meticulously dissected and thoroughly discussed. Further, the potential scope and applications of this technology in the fields of bioprinting and regenerative medicine are presented. Finally, outstanding challenges and opportunities of embedded bioprinting as well as its promise for fabricating functional solid organs in the future are discussed.

4.
BMC Med ; 22(1): 249, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38886716

RESUMO

BACKGROUND: Residing in a disadvantaged neighborhood has been linked to increased mortality. However, the impact of residential segregation and social vulnerability on cause-specific mortality is understudied. Additionally, the circulating metabolic correlates of neighborhood sociodemographic environment remain unexplored. Therefore, we examined multiple neighborhood sociodemographic metrics, i.e., neighborhood deprivation index (NDI), residential segregation index (RSI), and social vulnerability index (SVI), with all-cause and cardiovascular disease (CVD) and cancer-specific mortality and circulating metabolites in the Southern Community Cohort Study (SCCS). METHODS: The SCCS is a prospective cohort of primarily low-income adults aged 40-79, enrolled from the southeastern United States during 2002-2009. This analysis included self-reported Black/African American or non-Hispanic White participants and excluded those who died or were lost to follow-up ≤ 1 year. Untargeted metabolite profiling was performed using baseline plasma samples in a subset of SCCS participants. RESULTS: Among 79,631 participants, 23,356 deaths (7214 from CVD and 5394 from cancer) were documented over a median 15-year follow-up. Higher NDI, RSI, and SVI were associated with increased all-cause, CVD, and cancer mortality, independent of standard clinical and sociodemographic risk factors and consistent between racial groups (standardized HRs among all participants were 1.07 to 1.20 in age/sex/race-adjusted model and 1.04 to 1.08 after comprehensive adjustment; all P < 0.05/3 except for cancer mortality after comprehensive adjustment). The standard risk factors explained < 40% of the variations in NDI/RSI/SVI and mediated < 70% of their associations with mortality. Among 1110 circulating metabolites measured in 1688 participants, 134 and 27 metabolites were associated with NDI and RSI (all FDR < 0.05) and mediated 61.7% and 21.2% of the NDI/RSI-mortality association, respectively. Adding those metabolites to standard risk factors increased the mediation proportion from 38.4 to 87.9% and 25.8 to 42.6% for the NDI/RSI-mortality association, respectively. CONCLUSIONS: Among low-income Black/African American adults and non-Hispanic White adults living in the southeastern United States, a disadvantaged neighborhood sociodemographic environment was associated with increased all-cause and CVD and cancer-specific mortality beyond standard risk factors. Circulating metabolites may unveil biological pathways underlying the health effect of neighborhood sociodemographic environment. More public health efforts should be devoted to reducing neighborhood environment-related health disparities, especially for low-income individuals.


Assuntos
População Branca , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Negro ou Afro-Americano/estatística & dados numéricos , Doenças Cardiovasculares/mortalidade , Mortalidade/tendências , Características da Vizinhança , Neoplasias/mortalidade , Neoplasias/sangue , Pobreza , Estudos Prospectivos , Características de Residência , Fatores Socioeconômicos , Sudeste dos Estados Unidos/epidemiologia , População Branca/estatística & dados numéricos , Brancos
5.
Liver Transpl ; 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39185907

RESUMO

Cardiac dysfunction in patients with liver disease has been recognized since the 1950s. Initially attributed to shared risk factors, it is now evident that cardiac dysfunction in patients with cirrhosis can occur in the absence of known cardiac, i.e., coronary artery and valvular heart disease, and across all etiologies for cirrhosis. In 1996 this myocardial dysfunction was termed cirrhotic cardiomyopathy (CCM). The pathophysiologic mechanisms underlying CCM include impaired beta-adrenergic membrane function and circulating proinflammatory and cardiotoxic substances. In 2005, the first diagnostic criteria for CCM were introduced enabling greater sensitivity and accuracy of diagnosis. Since 2005, advancements in echocardiographic methods and better understanding of the pathophysiology of cardiac dysfunction in patients with cirrhosis necessitated revision of CCM criteria. Changes in CCM criteria included removal of blunted contractile or heart rate response on stress testing and addition of global longitudinal systolic strain. Refinement of criteria for diastolic dysfunction were also incorporated into the new diagnostic approach. Since 2020, the prevalence of the disorder and clinical considerations for pre-transplant, peritransplant, and post-transplant patients with cirrhosis have been further evaluated and CCM was found to adversely impact clinical outcomes during all three phases of care. Future research considerations should address the timing of universal echocardiographic screening for patients with cirrhosis, utility of biomarkers in aiding CCM diagnosis, impact of CCM on right heart function, and role of anti-remodeling agents post-liver transplant (post-LT).

6.
J Biomed Inform ; 157: 104707, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39142598

RESUMO

OBJECTIVE: Traditional knowledge-based and machine learning diagnostic decision support systems have benefited from integrating the medical domain knowledge encoded in the Unified Medical Language System (UMLS). The emergence of Large Language Models (LLMs) to supplant traditional systems poses questions of the quality and extent of the medical knowledge in the models' internal knowledge representations and the need for external knowledge sources. The objective of this study is three-fold: to probe the diagnosis-related medical knowledge of popular LLMs, to examine the benefit of providing the UMLS knowledge to LLMs (grounding the diagnosis predictions), and to evaluate the correlations between human judgments and the UMLS-based metrics for generations by LLMs. METHODS: We evaluated diagnoses generated by LLMs from consumer health questions and daily care notes in the electronic health records using the ConsumerQA and Problem Summarization datasets. Probing LLMs for the UMLS knowledge was performed by prompting the LLM to complete the diagnosis-related UMLS knowledge paths. Grounding the predictions was examined in an approach that integrated the UMLS graph paths and clinical notes in prompting the LLMs. The results were compared to prompting without the UMLS paths. The final experiments examined the alignment of different evaluation metrics, UMLS-based and non-UMLS, with human expert evaluation. RESULTS: In probing the UMLS knowledge, GPT-3.5 significantly outperformed Llama2 and a simple baseline yielding an F1 score of 10.9% in completing one-hop UMLS paths for a given concept. Grounding diagnosis predictions with the UMLS paths improved the results for both models on both tasks, with the highest improvement (4%) in SapBERT score. There was a weak correlation between the widely used evaluation metrics (ROUGE and SapBERT) and human judgments. CONCLUSION: We found that while popular LLMs contain some medical knowledge in their internal representations, augmentation with the UMLS knowledge provides performance gains around diagnosis generation. The UMLS needs to be tailored for the task to improve the LLMs predictions. Finding evaluation metrics that are aligned with human judgments better than the traditional ROUGE and BERT-based scores remains an open research question.


Assuntos
Registros Eletrônicos de Saúde , Unified Medical Language System , Humanos , Aprendizado de Máquina , Processamento de Linguagem Natural , Sistemas de Apoio a Decisões Clínicas , Diagnóstico por Computador/métodos
7.
Mycoses ; 67(9): e13790, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39278818

RESUMO

BACKGROUND AND OBJECTIVES: Candidaemia is a potentially life-threatening emergency in the intensive care units (ICUs). Surveillance using common protocols in a large network of hospitals would give meaningful estimates of the burden of candidaemia and central line associated candidaemia in low resource settings. We undertook this study to understand the burden and epidemiology of candidaemia in multiple ICUs of India, leveraging the previously established healthcare-associated infections (HAI) surveillance network. Our aim was also to assess the impact that the pandemic of COVID-19 had on the rates and associated mortality of candidaemia. METHODS: This study included adult patients from 67 Indian ICUs in the AIIMS-HAI surveillance network that conducted BSI surveillance in COVID-19 and non-COVID-19 ICUs during and before the COVID-19 pandemic periods. Hospitals identified healthcare-associated candidaemia and central line associated candidaemia and reported clinical and microbiological data to the network as per established and previously published protocols. RESULTS: A total of 401,601 patient days and 126,051 central line days were reported during the study period. A total of 377 events of candidaemia were recorded. The overall rate of candidaemia in our network was 0.93/1000 patient days. The rate of candidaemia in COVID-19 ICUs (2.52/1000 patient days) was significantly higher than in non-COVID-19 ICUs (1.05/patient days) during the pandemic period. The rate of central line associated candidaemia in COVID-19 ICUs (4.53/1000 central line days) was also significantly higher than in non-COVID-19 ICUs (1.73/1000 central line days) during the pandemic period. Mortality in COVID-19 ICUs associated with candidaemia (61%) was higher than that in non-COVID-19 ICUs (41%). A total of 435 Candida spp. were isolated. C. tropicalis (26.7%) was the most common species. C. auris accounted for 17.5% of all isolates and had a high mortality. CONCLUSION: Patients in ICUs with COVID-19 infections have a much higher risk of candidaemia, CLAC and its associated mortality. Network level data helps in understanding the true burden of candidaemia and will help in framing infection control policies for the country.


Assuntos
COVID-19 , Candidemia , Infecção Hospitalar , Unidades de Terapia Intensiva , Humanos , COVID-19/epidemiologia , Candidemia/epidemiologia , Índia/epidemiologia , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Infecção Hospitalar/epidemiologia , SARS-CoV-2 , Idoso , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/microbiologia , Pandemias
8.
Childs Nerv Syst ; 40(3): 919-924, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37930424

RESUMO

A 13-year-old female patient presented with painless vision loss and proptosis for 18 months. Imaging findings were highly suggestive of a supraorbital aneurysmal bone cyst (ABC) for which she underwent complete surgical excision. Postoperatively, she developed left hemiparesis. Computed tomography angiography (CTA) revealed right complete internal carotid arterial (ICA) thrombosis. This was managed conservatively, and she improved in hemiparesis over the next 3 weeks. Histopathology report revealed osteosarcoma with secondary ABC, for which she was referred for radiotherapy. At 1.5 months follow-up, the patient's left lower limb power improved to 4 + /5. She was walking without support, and her left upper limb power was 4/5.


Assuntos
Cistos Ósseos Aneurismáticos , Neoplasias Ósseas , Osteossarcoma , Adolescente , Feminino , Humanos , Cistos Ósseos Aneurismáticos/complicações , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Cistos Ósseos Aneurismáticos/cirurgia , Neoplasias Ósseas/complicações , Angiografia por Tomografia Computadorizada , Paresia
9.
Pediatr Cardiol ; 45(5): 1015-1022, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38565667

RESUMO

Prenatal diagnosis of critical congenital heart disease (CCHD) has improved over time, and previous studies have identified CCHD subtype and socioeconomic status as factors influencing rates of prenatal diagnosis. Our objective of this single-center study was to compare prenatal diagnosis rates of newborns with CCHD admitted for cardiac intervention from the COVID-19 pandemic period (March 2020 to March 2021) to the pre-pandemic period and identify factors associated with the lack of CCHD prenatal diagnosis. The overall rate of CCHD and rates of the various CCHD diagnoses were calculated and compared with historical data collection periods (2009-2012 and 2013-2016). Compared with the 2009-2012 pre-pandemic period, patients had 2.17 times higher odds of having a prenatal diagnosis of CCHD during the pandemic period controlling for lesion type (aOR = 2.17, 95% CI 1.36-3.48, p = 0.001). Single ventricle lesions (aOR 6.74 [4.64-9.80], p < 0.001) and outflow tract anomalies (aOR 2.20 [1.56-3.12], p < 0.001) had the highest odds of prenatal diagnosis compared with the remaining lesions. Patients with outflow tract anomalies had higher odds for prenatal detection in the pandemic period compared with during the 2009-2012 pre-pandemic period (aOR 2.01 [1.06-3.78], p = 0.031). In conclusion, prenatal detection of CCHD among newborns presenting for cardiac intervention appeared to have improved during the pandemic period.


Assuntos
COVID-19 , Cardiopatias Congênitas , Diagnóstico Pré-Natal , Humanos , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/diagnóstico , COVID-19/epidemiologia , COVID-19/diagnóstico , Feminino , Recém-Nascido , Gravidez , Diagnóstico Pré-Natal/estatística & dados numéricos , Diagnóstico Pré-Natal/métodos , Masculino , SARS-CoV-2 , Estudos Retrospectivos , Pandemias
10.
BMC Biol ; 21(1): 79, 2023 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-37041515

RESUMO

BACKGROUND: Baleen whales are a clade of gigantic and highly specialized marine mammals. Their genomes have been used to investigate their complex evolutionary history and to decipher the molecular mechanisms that allowed them to reach these dimensions. However, many unanswered questions remain, especially about the early radiation of rorquals and how cancer resistance interplays with their huge number of cells. The pygmy right whale is the smallest and most elusive among the baleen whales. It reaches only a fraction of the body length compared to its relatives and it is the only living member of an otherwise extinct family. This placement makes the pygmy right whale genome an interesting target to update the complex phylogenetic past of baleen whales, because it splits up an otherwise long branch that leads to the radiation of rorquals. Apart from that, genomic data of this species might help to investigate cancer resistance in large whales, since these mechanisms are not as important for the pygmy right whale as in other giant rorquals and right whales. RESULTS: Here, we present a first de novo genome of the species and test its potential in phylogenomics and cancer research. To do so, we constructed a multi-species coalescent tree from fragments of a whole-genome alignment and quantified the amount of introgression in the early evolution of rorquals. Furthermore, a genome-wide comparison of selection rates between large and small-bodied baleen whales revealed a small set of conserved candidate genes with potential connections to cancer resistance. CONCLUSIONS: Our results suggest that the evolution of rorquals is best described as a hard polytomy with a rapid radiation and high levels of introgression. The lack of shared positive selected genes between different large-bodied whale species supports a previously proposed convergent evolution of gigantism and hence cancer resistance in baleen whales.


Assuntos
Neoplasias , Baleias , Animais , Filogenia , Genoma , Genômica , Neoplasias/genética
11.
BMC Biol ; 21(1): 229, 2023 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-37867198

RESUMO

BACKGROUND: Venoms, which have evolved numerous times in animals, are ideal models of convergent trait evolution. However, detailed genomic studies of toxin-encoding genes exist for only a few animal groups. The hyper-diverse hymenopteran insects are the most speciose venomous clade, but investigation of the origin of their venom genes has been largely neglected. RESULTS: Utilizing a combination of genomic and proteo-transcriptomic data, we investigated the origin of 11 toxin genes in 29 published and 3 new hymenopteran genomes and compiled an up-to-date list of prevalent bee venom proteins. Observed patterns indicate that bee venom genes predominantly originate through single gene co-option with gene duplication contributing to subsequent diversification. CONCLUSIONS: Most Hymenoptera venom genes are shared by all members of the clade and only melittin and the new venom protein family anthophilin1 appear unique to the bee lineage. Most venom proteins thus predate the mega-radiation of hymenopterans and the evolution of the aculeate stinger.


Assuntos
Venenos de Abelha , Abelhas/genética , Animais , Perfilação da Expressão Gênica , Transcriptoma , Genômica , Duplicação Gênica
12.
Sensors (Basel) ; 24(7)2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38610544

RESUMO

The growth in linked and autonomous vehicles has led to the emergence of vehicular ad hoc networks (VANETs) as a means to enhance road safety, traffic efficiency, and passenger comfort. However, VANETs face challenges in facilitating trustworthiness and high-quality services due to communication delays caused by traffic, dynamic topology changes, variable speeds, and other influencing factors. Hence, there is a need for a reliable data dissemination scheme capable of reducing communication delays among hops by identifying effective forwarder nodes. In this paper, we propose a novel, weighted, estimated, spider monkey-based, nature-inspired optimization (w-SMNO) method to generate a set of efficient relays. Additionally, we introduce a dynamic weight assignment and configuration model to enhance system accuracy using a neural network based on backpropagation with gradient descent optimization techniques to minimize errors in the machine learning model. The w-SMNO also incorporates a distinct algorithm for effective relay selection among multiple monkey spider groups. The simulation results demonstrate substantial improvements in w-SMNO, with a 35.7% increase in coverage, a 41.2% reduction in the end-to-end delay, a 36.4% improvement in the message delivery rate, and a 38.4% decrease in the collision rate compared to the state-of-the-art approaches.

13.
Environ Monit Assess ; 196(7): 666, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38935201

RESUMO

The metal intoxication and its associated adverse effects to humans have led to the research for development of water treatment technologies from pollution hazards. Therefore, development of cheaper water remediation technologies is more urgent than ever. Clays and clay minerals are naturally occurring, inexpensive, non-toxic materials possessing interesting chemical and physical properties. As a result of interesting surface properties, these have been developed as efficient absorbent in water remediation. Recently, clay-polymer nanocomposites have provided a cost-effective technological platform for removing contaminants from water. Covering research advancements from past 25 years, this review highlights the developments in clay-polymer nanocomposites and their advanced technical applications are evaluated with respect to the background and issues in remediation of toxic metals and organic compounds from water. The extensive analysis of literature survey of more than two decades suggests that future work need to highlight on advancement of green and cost-effective technologies. The development of understanding of the interaction and exchange between toxin and clay-polymer composites would provide new assembly methods of nanocomposites with functional molecules or nanomaterials need to be extended to increase the detection and extraction limit to parts per trillion.


Assuntos
Argila , Nanocompostos , Polímeros , Poluentes Químicos da Água , Purificação da Água , Nanocompostos/química , Argila/química , Polímeros/química , Purificação da Água/métodos , Poluentes Químicos da Água/análise , Silicatos de Alumínio/química
14.
Am Heart J ; 265: 1-10, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37343812

RESUMO

BACKGROUND: Some patients with heart failure (HF) have low natriuretic peptide (NP) levels. It is unclear whether specific populations are disproportionately excluded from participation in randomized clinical trials (RCT) with inclusion requirements for elevated NPs. We investigated factors associated with unexpectedly low NP levels in a cohort of patients hospitalized with HF, and the implications on racial diversity in a prototype HF RCT. METHODS: We created a retrospective cohort of 31,704 patients (age 72 ± 16 years, 49% female, 52% Black) hospitalized with HF from 2010 to 2020 with B-type natriuretic peptide (BNP) measurements. Factors associated with unexpectedly low BNP levels (<50 pg/mL) were identified using multivariable logistic regression models. We simulated patient eligibility for a prototype HF trial using specific inclusion and exclusion criteria, and varying BNP cut-offs. RESULTS: Unexpectedly low BNP levels were observed in 8.9% of the cohort. Factors associated with unexpectedly low BNP levels included HFpEF (aOR 3.76, 95% CI: 3.36, 4.20), obesity (aOR 1.96, 95% CI: 1.73, 2.21), self-identification as Black (aOR 1.53, 95% CI: 1.36, 1.71), and male gender (aOR 1.45, 95% CI: 1.31, 1.60). Applying limited clinical inclusion and exclusion criteria from PARAGLIDE-HF disproportionately excluded Black patients, with impairment in renal function having the greatest impact. Adding thresholds for BNP of ≥35, ≥50, ≥67, ≥100, and ≥150 pg/mL demonstrated the risk of exclusion was higher for Black compared to non-Black patients (RR = 2.03 [95% CI: 1.73, 2.39], 1.90 [95% CI: 1.68, 2.15], 1.63 [95% CI: 1.48, 1.81], 1.38 [95% CI: 1.28, 1.50], and 1.23 [95% CI: 1.15, 1.31], respectively). CONCLUSIONS: Nearly 10% of patients hospitalized with HF have unexpectedly low BNP levels. Simulating inclusion into a prototype HFpEF RCT demonstrated that requiring increasingly elevated NP levels disproportionately excludes Black patients.

15.
Crit Care ; 27(1): 228, 2023 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-37296432

RESUMO

OBJECTIVE: To evaluate the safety, feasibility, and efficacy of combined adrenergic blockade with propranolol and clonidine in patients with severe traumatic brain injury (TBI). BACKGROUND: Administration of adrenergic blockade after severe TBI is common. To date, no prospective trial has rigorously evaluated this common therapy for benefit. METHODS: This phase II, single-center, double-blinded, pilot randomized placebo-controlled trial included patients aged 16-64 years with severe TBI (intracranial hemorrhage and Glasgow Coma Scale score ≤ 8) within 24 h of ICU admission. Patients received propranolol and clonidine or double placebo for 7 days. The primary outcome was ventilator-free days (VFDs) at 28 days. Secondary outcomes included catecholamine levels, hospital length of stay, mortality, and long-term functional status. A planned futility assessment was performed mid-study. RESULTS: Dose compliance was 99%, blinding was intact, and no open-label agents were used. No treatment patient experienced dysrhythmia, myocardial infarction, or cardiac arrest. The study was stopped for futility after enrolling 47 patients (26 placebo, 21 treatment), per a priori stopping rules. There was no significant difference in VFDs between treatment and control groups [0.3 days, 95% CI (- 5.4, 5.8), p = 1.0]. Other than improvement of features related to sympathetic hyperactivity (mean difference in Clinical Features Scale (CFS) 1.7 points, CI (0.4, 2.9), p = 0.012), there were no between-group differences in the secondary outcomes. CONCLUSION: Despite the safety and feasibility of adrenergic blockade with propranolol and clonidine after severe TBI, the intervention did not alter the VFD outcome. Given the widespread use of these agents in TBI care, a multi-center investigation is warranted to determine whether adrenergic blockade is of therapeutic benefit in patients with severe TBI. Trial Registration Number NCT01322048.


Assuntos
Lesões Encefálicas Traumáticas , Propranolol , Humanos , Propranolol/farmacologia , Propranolol/uso terapêutico , Clonidina/farmacologia , Clonidina/uso terapêutico , Projetos Piloto , Resultado do Tratamento , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/tratamento farmacológico , Adrenérgicos
16.
Childs Nerv Syst ; 39(9): 2391-2397, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37486437

RESUMO

INTRODUCTION: Dorsal spurs in Type I split cord malformations (SCM-I) are infrequent findings. The pathogenesis of the same is debatable. The objective of this study is to analyze our experience with SCM-I patients having dorsal bony spurs. METHODOLOGY: Retrospective analysis of SCM patients operated from 2010 to 2017 was performed. Their demographic profile, clinic-radiological features, operative findings, and outcome following surgery were recorded. RESULTS: Twenty-four cases of Type I SCM harboring dorsal bony spurs were identified with mean age of 4.96 years. The commonest split site was lumbar, documented in 62.5%. Scoliosis was observed in 58.3%. Pre-operative neurological deficits were seen in 66.6% cases with asymmetric weakness of limbs seen in 16.6%. There was no new neurological deficit observed post-operatively. CONCLUSIONS: This is the largest series of dorsal spurs occurring in SCM, reported in literature so far. Meticulous pre-operative evaluation and imaging are important to identify dorsal spurs for appropriate management and good clinical outcome. Differentiating dorsal spur from ventral spur is important as it has a bearing on surgical approach.


Assuntos
Defeitos do Tubo Neural , Escoliose , Humanos , Criança , Pré-Escolar , Estudos Retrospectivos , Centros de Atenção Terciária , Defeitos do Tubo Neural/complicações , Defeitos do Tubo Neural/diagnóstico por imagem , Defeitos do Tubo Neural/cirurgia , Radiografia , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Medula Espinal/cirurgia , Imageamento por Ressonância Magnética
17.
JAMA ; 330(23): 2258-2266, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-37950918

RESUMO

Importance: Dietary sodium recommendations are debated partly due to variable blood pressure (BP) response to sodium intake. Furthermore, the BP effect of dietary sodium among individuals taking antihypertensive medications is understudied. Objectives: To examine the distribution of within-individual BP response to dietary sodium, the difference in BP between individuals allocated to consume a high- or low-sodium diet first, and whether these varied according to baseline BP and antihypertensive medication use. Design, Setting, and Participants: Prospectively allocated diet order with crossover in community-based participants enrolled between April 2021 and February 2023 in 2 US cities. A total of 213 individuals aged 50 to 75 years, including those with normotension (25%), controlled hypertension (20%), uncontrolled hypertension (31%), and untreated hypertension (25%), attended a baseline visit while consuming their usual diet, then completed 1-week high- and low-sodium diets. Intervention: High-sodium (approximately 2200 mg sodium added daily to usual diet) and low-sodium (approximately 500 mg daily total) diets. Main Outcomes and Measures: Average 24-hour ambulatory systolic and diastolic BP, mean arterial pressure, and pulse pressure. Results: Among the 213 participants who completed both high- and low-sodium diet visits, the median age was 61 years, 65% were female and 64% were Black. While consuming usual, high-sodium, and low-sodium diets, participants' median systolic BP measures were 125, 126, and 119 mm Hg, respectively. The median within-individual change in mean arterial pressure between high- and low-sodium diets was 4 mm Hg (IQR, 0-8 mm Hg; P < .001), which did not significantly differ by hypertension status. Compared with the high-sodium diet, the low-sodium diet induced a decline in mean arterial pressure in 73.4% of individuals. The commonly used threshold of a 5 mm Hg or greater decline in mean arterial pressure between a high-sodium and a low-sodium diet classified 46% of individuals as "salt sensitive." At the end of the first dietary intervention week, the mean systolic BP difference between individuals allocated to a high-sodium vs a low-sodium diet was 8 mm Hg (95% CI, 4-11 mm Hg; P < .001), which was mostly similar across subgroups of age, sex, race, hypertension, baseline BP, diabetes, and body mass index. Adverse events were mild, reported by 9.9% and 8.0% of individuals while consuming the high- and low-sodium diets, respectively. Conclusions and Relevance: Dietary sodium reduction significantly lowered BP in the majority of middle-aged to elderly adults. The decline in BP from a high- to low-sodium diet was independent of hypertension status and antihypertensive medication use, was generally consistent across subgroups, and did not result in excess adverse events. Trial Registration: ClinicalTrials.gov Identifier: NCT04258332.


Assuntos
Pressão Sanguínea , Hipertensão , Sódio na Dieta , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Estudos Cross-Over , Dieta Hipossódica , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Hipertensão/fisiopatologia , Sódio/farmacologia , Cloreto de Sódio na Dieta/efeitos adversos , Cloreto de Sódio na Dieta/farmacologia , Sódio na Dieta/efeitos adversos , Sódio na Dieta/farmacologia
18.
Knowl Based Syst ; 2782023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37780058

RESUMO

Nearest neighbor search, also known as NNS, is a technique used to locate the points in a high-dimensional space closest to a given query point. This technique has multiple applications in medicine, such as searching large medical imaging databases, disease classification, and diagnosis. However, when the number of points is significantly large, the brute-force approach for finding the nearest neighbor becomes computationally infeasible. Therefore, various approaches have been developed to make the search faster and more efficient to support the applications. With a focus on medical imaging, this paper proposes DenseLinkSearch (DLS), an effective and efficient algorithm that searches and retrieves the relevant images from heterogeneous sources of medical images. Towards this, given a medical database, the proposed algorithm builds an index that consists of pre-computed links of each point in the database. The search algorithm utilizes the index to efficiently traverse the database in search of the nearest neighbor. We also explore the role of medical image feature representation in content-based medical image retrieval tasks. We propose a Transformer-based feature representation technique that outperformed the existing pre-trained Transformer-based approaches on benchmark medical image retrieval datasets. We extensively tested the proposed NNS approach and compared the performance with state-of-the-art NNS approaches on benchmark datasets and our created medical image datasets. The proposed approach outperformed the existing approaches in terms of retrieving accurate neighbors and retrieval speed. In comparison to the existing approximate NNS approaches, our proposed DLS approach outperformed them in terms of lower average time per query and ≥ 99% R@10 on 11 out of 13 benchmark datasets. We also found that the proposed medical feature representation approach is better for representing medical images compared to the existing pre-trained image models. The proposed feature extraction strategy obtained an improvement of 9.37%, 7.0%, and 13.33% in terms of P@5, P@10, and P@20, respectively, in comparison to the best-performing pre-trained image model. The source code and datasets of our experiments are available at https://github.com/deepaknlp/DLS.

19.
Cluster Comput ; 26(1): 575-586, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35602318

RESUMO

In recent times, energy related issues have become challenging with the increasing size of data centers. Energy related issues problems are becoming more and more serious with the growing size of data centers. Green cloud computing (GCC) becomes a recent computing platform which aimed to handle energy utilization in cloud data centers. Load balancing is generally employed to optimize resource usage, throughput, and delay. Aiming at the reduction of energy utilization at the data centers of GCC, this paper designs an energy efficient resource scheduling using Cultural emperor penguin optimizer (CEPO) algorithm, called EERS-CEPO in GCC environment. The proposed model is aimed to distribute work load amongst several data centers or other resources and thereby avoiding overload of individual resources. The CEPO algorithm is designed based on the fusion of cultural algorithm (CA) and emperor penguin optimizer (EPO), which boosts the exploitation capabilities of EPO algorithm using the CA, shows the novelty of the work. The EERS-CEPO algorithm has derived a fitness function to optimally schedule the resources in data centers, minimize the operational and maintenance cost of the GCC, and thereby decrease the energy utilization and heat generation. To ensure the improvised performance of the EERS-CEPO algorithm, a wide range of experiments is performed and the experimental outcomes highlighted the better performance over the recent state of art techniques.

20.
Indian J Urol ; 39(4): 303-310, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38077208

RESUMO

Introduction: Stereotactic body radiotherapy (SBRT) has been found to be an effective and safe modality with excellent oncological outcome in medically inoperable primary renal cell carcinoma (RCC) and oligometastases. There is scarcity of data on the synchronous delivery of SBRT to primary and oligometastatic RCC in patients unfit for nephrectomy. Here, we report the findings of a retrospective study of prospectively collected data on "total ablative SBRT." Methods: Oligometastatic RCC patients with intact primary tumors were enrolled between May 2021 and June 2022. SBRT was synchronously delivered to the primary tumor and metastases. Demographics, treatment, oncologic outcomes, and toxicity were assessed. Kaplan-Meier estimates were generated for oncologic outcomes. The primary endpoint of this study was feasibility and tolerability. Results: Eleven patients were enrolled between May 2021 and June 2022. One patient died at 2 months after SBRT due to viral pneumonitis (possibly COVID pneumonia). Nine patients (82%) had metastatic disease, while 2 (18%) were stage II. The average maximal diameter of primary was 68.7 mm (range, 23-128 mm). The SBRT doses for primary and metastasis ranged from 40 to 55 Gray (Gy) in 5 to 7 fractions and 22 to 40Gy in 2 to 5 fractions, respectively. The median follow-up period was 10.5 months (Range: 4-15 months). Response assessment was available for ten patients. Local control, marginal control, regional control and initial oligometastatic control (OMC) rates were 100%. OMC declined to 87.5% as one patient had recurrence in irradiated subcarinal lymphnode at 7 months. The metastatic control rate was 80% and loco-regional progression-free survival was 8 months (range, 4-15 months). Toxicities were minimal and manageable. At the last follow-up, 7 of 11 patients were alive with an overall survival of 63.5%. Six patients received systemic therapy after SBRT. Conclusions: Synchronous delivery of SBRT to primary and oligometastatic sites in patients unfit for nephrectomy was feasible and tolerable with good locoregional control. The total ablative SBRT strategy needs to be explored in similar cohorts.

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