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1.
Proc Natl Acad Sci U S A ; 121(10): e2310852121, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38416678

RESUMEN

Enterococci are gut microbes of most land animals. Likely appearing first in the guts of arthropods as they moved onto land, they diversified over hundreds of millions of years adapting to evolving hosts and host diets. Over 60 enterococcal species are now known. Two species, Enterococcus faecalis and Enterococcus faecium, are common constituents of the human microbiome. They are also now leading causes of multidrug-resistant hospital-associated infection. The basis for host association of enterococcal species is unknown. To begin identifying traits that drive host association, we collected 886 enterococcal strains from widely diverse hosts, ecologies, and geographies. This identified 18 previously undescribed species expanding genus diversity by >25%. These species harbor diverse genes including toxins and systems for detoxification and resource acquisition. Enterococcus faecalis and E. faecium were isolated from diverse hosts highlighting their generalist properties. Most other species showed a more restricted distribution indicative of specialized host association. The expanded species diversity permitted the Enterococcus genus phylogeny to be viewed with unprecedented resolution, allowing features to be identified that distinguish its four deeply rooted clades, and the entry of genes associated with range expansion such as B-vitamin biosynthesis and flagellar motility to be mapped to the phylogeny. This work provides an unprecedentedly broad and deep view of the genus Enterococcus, including insights into its evolution, potential new threats to human health, and where substantial additional enterococcal diversity is likely to be found.


Asunto(s)
Enterococcus faecium , Infecciones por Bacterias Grampositivas , Animales , Humanos , Enterococcus/genética , Antibacterianos/farmacología , Enterococcus faecium/genética , Enterococcus faecalis/genética , Filogenia , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Bacteriana
2.
Antimicrob Agents Chemother ; : e0109024, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39302119

RESUMEN

Genomic surveillance detected clonal Escherichia coli sequence type-361 isolates carrying blaNDM-5, blaKPC-3, blaCTX-M-15, and rmtB1 from a patient in Ukraine and four wounded foreign soldiers evacuated to Germany. Isolates were non-susceptible to carbapenems, aminoglycosides, and cefiderocol and aztreonam/avibactam due to a PBP3 YRIN insertion and the blaCMY-145 AmpC ß-lactamase. Coordinated surveillance efforts across civilian, military, and veteran healthcare systems are essential to prevent further spread as international volunteers return home after medical evacuation from Ukraine.

3.
J Transl Med ; 22(1): 256, 2024 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-38461265

RESUMEN

BACKGROUND: Children with cancer receiving chemotherapy commonly report a cluster of psychoneurological symptoms (PNS), including pain, fatigue, anxiety, depression, and cognitive dysfunction. The role of the gut microbiome and its functional metabolites in PNS is rarely studied among children with cancer. This study investigated the associations between the gut microbiome-metabolome pathways and PNS in children with cancer across chemotherapy as compared to healthy children. METHODS: A case-control study was conducted. Cancer cases were recruited from Children's Healthcare of Atlanta and healthy controls were recruited via flyers. Participants reported PNS using the Pediatric Patient-Reported Outcomes Measurement Information System. Data for cases were collected pre-cycle two chemotherapy (T0) and post-chemotherapy (T1), whereas data for healthy controls were collected once. Gut microbiome and its metabolites were measured using fecal specimens. Gut microbiome profiling was performed using 16S rRNA V4 sequencing, and metabolome was performed using an untargeted liquid chromatography-mass spectrometry approach. A multi-omics network integration program analyzed microbiome-metabolome pathways of PNS. RESULTS: Cases (n = 21) and controls (n = 14) had mean ages of 13.2 and 13.1 years. For cases at T0, PNS were significantly associated with microbial genera (e.g., Ruminococcus, Megasphaera, and Prevotella), which were linked with carnitine shuttle (p = 0.0003), fatty acid metabolism (p = 0.001) and activation (p = 0.001), and tryptophan metabolism (p = 0.008). Megasphaera, clustered with aspartate and asparagine metabolism (p = 0.034), carnitine shuttle (p = 0.002), and tryptophan (p = 0.019), was associated with PNS for cases at T1. Gut bacteria with potential probiotic functions, along with fatty acid metabolism, tryptophan, and carnitine shuttle, were more clustered in cancer cases than the control network and this linkage with PNS needs further studies. CONCLUSIONS: Using multi-omics approaches, this study indicated specific microbiome-metabolome pathways linked with PNS in children with cancer across chemotherapy. Due to limitations such as antibiotic use in cancer cases, these findings need to be further confirmed in a larger cohort.


Asunto(s)
Microbioma Gastrointestinal , Neoplasias , Humanos , Niño , Microbioma Gastrointestinal/genética , Metabolómica/métodos , Síndrome , Multiómica , Triptófano , ARN Ribosómico 16S/genética , Estudios de Casos y Controles , Metaboloma , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Ácidos Grasos , Carnitina/análisis , Heces/microbiología
4.
Mult Scler ; 30(10): 1268-1277, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39234802

RESUMEN

BACKGROUND: Cerebrospinal fluid (CSF) oligoclonal bands (OCB) are a diagnostic biomarker in multiple sclerosis (MS). The central vein sign (CVS) is an imaging biomarker for MS that may improve diagnostic accuracy. OBJECTIVES: The objective of the study is to examine the diagnostic performance of simplified CVS methods in comparison to OCB in participants with clinical or radiological suspicion for MS. METHODS: Participants from the CentrAl Vein Sign in MS (CAVS-MS) pilot study with CSF testing were included. Select-3 and Select-6 (counting up to three or six CVS+ lesions per scan) were rated on post-gadolinium FLAIR* images. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value for Select-3, Select-6, OCB, and combinations thereof were calculated for MS diagnosis at baseline and at 12 months. RESULTS: Of 53 participants, 25 were OCB+. At baseline, sensitivity for MS diagnosis was 0.75 for OCB, 0.83 for Select-3, and 0.71 for Select-6. Specificity for MS diagnosis was 0.76 for OCB, 0.48 for Select-3, and 0.86 for Select-6. At 12 months, PPV for MS diagnosis was 0.95 for Select-6 and 1.00 for Select-6 with OCB+ status. DISCUSSION: Results suggest similar diagnostic performance of simplified CVS methods and OCB. Ongoing studies will refine whether CVS could be used in replacement or in conjunction with OCB.


Asunto(s)
Imagen por Resonancia Magnética , Esclerosis Múltiple , Bandas Oligoclonales , Humanos , Bandas Oligoclonales/líquido cefalorraquídeo , Adulto , Femenino , Masculino , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/líquido cefalorraquídeo , Persona de Mediana Edad , Proyectos Piloto , Sensibilidad y Especificidad , Biomarcadores/líquido cefalorraquídeo , Venas Cerebrales/diagnóstico por imagen , Valor Predictivo de las Pruebas
5.
Proc Natl Acad Sci U S A ; 118(48)2021 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-34819373

RESUMEN

A protracted outbreak of New Delhi metallo-ß-lactamase (NDM)-producing carbapenem-resistant Klebsiella pneumoniae started in Tuscany, Italy, in November 2018 and continued in 2020 and through 2021. To understand the regional emergence and transmission dynamics over time, we collected and sequenced the genomes of 117 extensively drug-resistant, NDM-producing K. pneumoniae isolates cultured over a 20-mo period from 76 patients at several healthcare facilities in southeast Tuscany. All isolates belonged to high-risk clone ST-147 and were typically nonsusceptible to all first-line antibiotics. Albeit sporadic, resistances to colistin, tigecycline, and fosfomycin were also observed as a result of repeated, independent mutations. Genomic analysis revealed that ST-147 isolates circulating in Tuscany were monophyletic and highly genetically related (including a network of 42 patients from the same hospital and sharing nearly identical isolates), and shared a recent ancestor with clinical isolates from the Middle East. While the blaNDM-1 gene was carried by an IncFIB-type plasmid, our investigations revealed that the ST-147 lineage from Italy also acquired a hybrid IncFIB/IncHIB-type plasmid carrying the 16S methyltransferase armA gene as well as key virulence biomarkers often found in hypervirulent isolates. This plasmid shared extensive homologies with mosaic plasmids circulating globally including from ST-11 and ST-307 convergent lineages. Phenotypically, the carriage of this hybrid plasmid resulted in increased siderophore production but did not confer virulence to the level of an archetypical, hypervirulent K. pneumoniae in a subcutaneous model of infection with immunocompetent CD1 mice. Our findings highlight the importance of performing genomic surveillance to identify emerging threats.


Asunto(s)
Brotes de Enfermedades , Farmacorresistencia Bacteriana Múltiple/genética , Infecciones por Klebsiella/epidemiología , Klebsiella pneumoniae/genética , Animales , Antibacterianos , Proteínas Bacterianas/genética , Biomarcadores , Carbapenémicos , Colistina , Biología Computacional/métodos , Infección Hospitalaria/epidemiología , Humanos , Italia/epidemiología , Estimación de Kaplan-Meier , Funciones de Verosimilitud , Ratones , Pruebas de Sensibilidad Microbiana , Preparaciones Farmacéuticas , Plásmidos , Polimorfismo de Nucleótido Simple , beta-Lactamasas/genética
6.
Euro Surveill ; 29(24)2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38873796

RESUMEN

In 2003-2023, amid 5,436 Acinetobacter baumannii isolates collected globally through the Multidrug-Resistant Organism Repository and Surveillance Network, 97 were ST19PAS, 34 of which carbapenem-resistant. Strains (n = 32) sampled after 2019 harboured either bla OXA-23, bla OXA-72, and/or bla NDM-5. Phylogenetic analysis of the 97 isolates and 11 publicly available ST19 genomes revealed three sub-lineages of carbapenemase-producing isolates from mainly Ukraine and Georgia, including an epidemic clone carrying all three carbapenemase genes. Infection control and global surveillance of carbapenem-resistant A. baumannii remain important.


Asunto(s)
Infecciones por Acinetobacter , Acinetobacter baumannii , Proteínas Bacterianas , beta-Lactamasas , Humanos , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/enzimología , Acinetobacter baumannii/genética , Infecciones por Acinetobacter/microbiología , Antibacterianos/farmacología , Proteínas Bacterianas/genética , beta-Lactamasas/genética , Carbapenémicos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Georgia (República) , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Filogenia , Ucrania
7.
Emerg Infect Dis ; 29(8): 1692-1695, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37406356

RESUMEN

Blood and surveillance cultures from an injured service member from Ukraine grew Acinetobacter baumannii, Klebsiella pneumoniae, Enterococcus faecium, and 3 distinct Pseudomonas aeruginosa strains. Isolates were nonsusceptible to most antibiotics and carried an array of antibiotic resistant genes, including carbapenemases (blaIMP-1, blaNDM-1, blaOXA-23, blaOXA-48, blaOXA-72) and 16S methyltransferases (armA and rmtB4).


Asunto(s)
Acinetobacter baumannii , Personal Militar , Humanos , Ucrania/epidemiología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Bacterias/genética , beta-Lactamasas/genética , Farmacorresistencia Bacteriana Múltiple/genética
8.
Am Heart J ; 253: 76-85, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35841944

RESUMEN

BACKGROUND: Despite guideline recommendations to optimize low-density lipoprotein cholesterol (LDL-C) reduction with intensification of lipid-lowering therapy (LLT) in patients with atherosclerotic cardiovascular disease (ASCVD), few of these patients achieve LDL-C < 70 mg/dL in practice. PURPOSE: We developed a real-time, targeted electronic health record (EHR) alert with embedded ordering capability to promote intensification of evidence based LLT in outpatients with very high risk ASCVD. METHODS: We designed a pragmatic, multicenter, single-blind, cluster randomized trial to test the effectiveness of an EHR-based LLT intensification alert. The study will enroll about 100 providers who will be randomized to either receive the alert or undergo usual care for outpatients with high risk ASCVD with LDL-C > 70 mg/dL. Total enrollment will include 2,500 patients. The primary outcome will be the proportion of patients with LLT intensification at 90 days. Secondary outcomes include achieved LDL-C at 6 months and the proportion of patients with LDL-C < 70 mg/dL or < 55 mg/dL at 6 months. RESULTS: Enrollment of 1,250 patients (50% of goal) was reached within 47 days (50% women, mean age 72, median LDL-C 91). At baseline, 71%, 9%, and 3% were on statins, ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors, respectively. CONCLUSIONS: PRagmatic Trial of Messaging to Providers about Treatment of HyperLIPIDemia has rapidly reached 50% enrollment of patients with very high risk ASCVD, demonstrating low baseline LLT utilization. This pragmatic, EHR-based trial will determine the effectiveness of a real-time, targeted EHR alert with embedded ordering capability to promote LLT intensification. Findings from this low-cost, widely scalable intervention to improve LDL-C may have important public health implications. TRIAL REGISTRATION: clinicaltrials.gov NCT04394715.


Asunto(s)
Aterosclerosis , Enfermedades Cardiovasculares , Hiperlipidemias , Anciano , Anticolesterolemiantes/uso terapéutico , Aterosclerosis/complicaciones , Enfermedades Cardiovasculares/complicaciones , LDL-Colesterol , Femenino , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Hiperlipidemias/complicaciones , Hiperlipidemias/tratamiento farmacológico , Masculino , Estudios Multicéntricos como Asunto , Pacientes Ambulatorios , Ensayos Clínicos Pragmáticos como Asunto , Método Simple Ciego
9.
Magn Reson Med ; 85(2): 802-817, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32820572

RESUMEN

PURPOSE: Two-dimensional creatine CEST (2D-CrCEST), with a slice thickness of 10-20 mm and temporal resolution (τRes ) of about 30 seconds, has previously been shown to capture the creatine-recovery kinetics in healthy controls and in patients with abnormal creatine-kinase kinetics following the mild plantar flexion exercise. Since the distribution of disease burden may vary across the muscle length for many musculoskeletal disorders, there is a need to increase coverage in the slice-encoding direction. Here, we demonstrate the feasibility of 3D-CrCEST with τRes of about 30 seconds, and propose an improved voxel-wise B1+ -calibration approach for CrCEST. METHODS: The current 7T study with enrollment of 5 volunteers involved collecting the baseline CrCEST imaging for the first 2 minutes, followed by 2 minutes of plantar flexion exercise and then 8 minutes of postexercise CrCEST imaging, to detect the temporal evolution of creatine concentration following exercise. RESULTS: Very good repeatability of 3D-CrCEST findings for activated muscle groups on an intraday and interday basis was established, with coefficient of variance of creatine recovery constants (τCr ) being 7%-15.7%, 7.5%, and 5.8% for lateral gastrocnemius, medial gastrocnemius, and peroneus longus, respectively. We also established a good intraday and interday scan repeatability for 3D-CrCEST and also showed good correspondence between τCr measurements using 2D-CrCEST and 3D-CrCEST acquisitions. CONCLUSION: In this study, we demonstrated for the first time the feasibility and the repeatability of the 3D-CrCEST method in calf muscle with improved B1+ correction to measure creatine-recovery kinetics within a large 3D volume of calf muscle.


Asunto(s)
Creatina , Imagen por Resonancia Magnética , Ejercicio Físico , Humanos , Cinética , Músculo Esquelético/diagnóstico por imagen
10.
Am J Kidney Dis ; 77(4): 490-499.e1, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33422598

RESUMEN

RATIONALE & OBJECTIVE: Although coronavirus disease 2019 (COVID-19) has been associated with acute kidney injury (AKI), it is unclear whether this association is independent of traditional risk factors such as hypotension, nephrotoxin exposure, and inflammation. We tested the independent association of COVID-19 with AKI. STUDY DESIGN: Multicenter, observational, cohort study. SETTING & PARTICIPANTS: Patients admitted to 1 of 6 hospitals within the Yale New Haven Health System between March 10, 2020, and August 31, 2020, with results for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing via polymerase chain reaction of a nasopharyngeal sample. EXPOSURE: Positive test for SARS-CoV-2. OUTCOME: AKI by KDIGO (Kidney Disease: Improving Global Outcomes) criteria. ANALYTICAL APPROACH: Evaluated the association of COVID-19 with AKI after controlling for time-invariant factors at admission (eg, demographic characteristics, comorbidities) and time-varying factors updated continuously during hospitalization (eg, vital signs, medications, laboratory results, respiratory failure) using time-updated Cox proportional hazard models. RESULTS: Of the 22,122 patients hospitalized, 2,600 tested positive and 19,522 tested negative for SARS-CoV-2. Compared with patients who tested negative, patients with COVID-19 had more AKI (30.6% vs 18.2%; absolute risk difference, 12.5% [95% CI, 10.6%-14.3%]) and dialysis-requiring AKI (8.5% vs 3.6%) and lower rates of recovery from AKI (58% vs 69.8%). Compared with patients without COVID-19, patients with COVID-19 had higher inflammatory marker levels (C-reactive protein, ferritin) and greater use of vasopressors and diuretic agents. Compared with patients without COVID-19, patients with COVID-19 had a higher rate of AKI in univariable analysis (hazard ratio, 1.84 [95% CI, 1.73-1.95]). In a fully adjusted model controlling for demographic variables, comorbidities, vital signs, medications, and laboratory results, COVID-19 remained associated with a high rate of AKI (adjusted hazard ratio, 1.40 [95% CI, 1.29-1.53]). LIMITATIONS: Possibility of residual confounding. CONCLUSIONS: COVID-19 is associated with high rates of AKI not fully explained by adjustment for known risk factors. This suggests the presence of mechanisms of AKI not accounted for in this analysis, which may include a direct effect of COVID-19 on the kidney or other unmeasured mediators. Future studies should evaluate the possible unique pathways by which COVID-19 may cause AKI.


Asunto(s)
Lesión Renal Aguda/epidemiología , COVID-19/epidemiología , Lesión Renal Aguda/sangre , Lesión Renal Aguda/terapia , Anciano , Proteína C-Reactiva/metabolismo , COVID-19/metabolismo , COVID-19/terapia , Estudios de Cohortes , Creatinina/sangre , Diuréticos/uso terapéutico , Femenino , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Diálisis Renal , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/epidemiología , Respiración Artificial , Factores de Riesgo , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Estados Unidos/epidemiología , Vasoconstrictores/uso terapéutico
11.
Cereb Cortex ; 30(3): 1830-1842, 2020 03 14.
Artículo en Inglés | MEDLINE | ID: mdl-31599922

RESUMEN

Cigarette smoking during pregnancy is a major public health concern, resulting in detrimental health effects in the mother and her offspring. The adverse behavioral consequences for children include increased risk for attention deficit hyperactivity disorder, working memory deficits, epilepsy, novelty-seeking, and risk-taking behaviors. Some of these behavioral conditions are consistent with an imbalance in frontal cortical excitatory (glutamate) and inhibitory (GABA) neurotransmitter signaling. We used a GAD67-GFP knock-in mouse model to examine if developmental nicotine exposure alters frontal cortical GABA neuron numbers, GABA-to-non-GABA neuron ratio and behavioral phenotypes. Female mice were exposed to nicotine (100 or 200 µg/mL) in drinking water beginning 3 weeks prior to breeding and until 3 weeks postpartum. Male and female offspring were examined beginning at 60 days of age. The nicotine exposure produced dose-dependent decreases in GABA-to-non-GABA neuron ratios in the prefrontal and medial prefrontal cortices without perturbing the intrinsic differences in cortical thickness and laminar distribution of GABA or non-GABA neurons between these regions. A significant increase in exploratory behavior and a shift toward "approach" in the approach-avoidance paradigm were also observed. Thus, developmental nicotine exposure shifts the cortical excitation-inhibition balance toward excitation and produces behavioral changes consistent with novelty-seeking behavior.


Asunto(s)
Conducta Exploratoria/efectos de los fármacos , Neuronas GABAérgicas/efectos de los fármacos , Nicotina/farmacología , Agonistas Nicotínicos/farmacología , Animales , Conducta Animal/efectos de los fármacos , Modelos Animales de Enfermedad , Femenino , Lóbulo Frontal/efectos de los fármacos , Trastornos de la Memoria/complicaciones , Memoria a Corto Plazo/efectos de los fármacos , Ratones , Corteza Prefrontal/efectos de los fármacos , Embarazo , Efectos Tardíos de la Exposición Prenatal
12.
Dig Dis Sci ; 66(7): 2240-2249, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-32797346

RESUMEN

BACKGROUND: Adult liver-related hospitalizations have recently increased in the USA, but data are limited for the pediatric population. AIMS: Utilizing the Office of Statewide Health Planning and Development hospital claims database (covering > 98% of all California hospitalizations), we aimed to characterize the demographic, clinical, and socioeconomic factors of liver disease-associated admissions among children between 2005 and 2015. METHODS: We used ICD-9 codes to identify admissions associated with liver disease in patients up to 21 years of age. Patient characteristics were described as percentages and evaluated using the χ2 test. We used linear regression to examine changes over time. RESULTS: We analyzed 37,372 eligible admissions. Overall, close to one-third (28%) and one-half (48.0%) of admissions occurred in the age group 0-5 years and 16-21 years, respectively, with the remaining 23.1% occurring in the age group between 5 and 15 years. Over half (54.9%) were in males. By race, blacks made up half of the admission (49.7%), while by ethnicity, Hispanic also accounted for half of the admission (49.7%). Medicaid and Medicare payors were also disproportionately represented (54.6%). The most common liver disease was Alagille syndrome (29.2%) in 2005. Between 2005 and 2015, both the number of pediatric liver-associated admissions and the proportion of pediatric liver admissions over total admissions increased from 3130 to 3429 and 1.2% to 1.6%, respectively (both p = 0.001). By 2015, while Alagille syndrome admissions decreased to 26.4% (p = 0.004), NAFLD admission increased to 19.7% (p < 0.001). CONCLUSION: Major disparities exist in inpatient liver disease burden for blacks and Hispanics with liver disease, while NAFLD emerged as a rapidly rising liver disease in pediatrics.


Asunto(s)
Hospitalización/tendencias , Hepatopatías/epidemiología , Grupos Raciales , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Medicaid , Medicare , Factores Socioeconómicos , Estados Unidos , Adulto Joven
13.
J Am Soc Nephrol ; 31(6): 1348-1357, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32381598

RESUMEN

BACKGROUND: Timely prediction of AKI in children can allow for targeted interventions, but the wealth of data in the electronic health record poses unique modeling challenges. METHODS: We retrospectively reviewed the electronic medical records of all children younger than 18 years old who had at least two creatinine values measured during a hospital admission from January 2014 through January 2018. We divided the study population into derivation, and internal and external validation cohorts, and used five feature selection techniques to select 10 of 720 potentially predictive variables from the electronic health records. Model performance was assessed by the area under the receiver operating characteristic curve in the validation cohorts. The primary outcome was development of AKI (per the Kidney Disease Improving Global Outcomes creatinine definition) within a moving 48-hour window. Secondary outcomes included severe AKI (stage 2 or 3), inpatient mortality, and length of stay. RESULTS: Among 8473 encounters studied, AKI occurred in 516 (10.2%), 207 (9%), and 27 (2.5%) encounters in the derivation, and internal and external validation cohorts, respectively. The highest-performing model used a machine learning-based genetic algorithm, with an overall receiver operating characteristic curve in the internal validation cohort of 0.76 [95% confidence interval (CI), 0.72 to 0.79] for AKI, 0.79 (95% CI, 0.74 to 0.83) for severe AKI, and 0.81 (95% CI, 0.77 to 0.86) for neonatal AKI. To translate this prediction model into a clinical risk-stratification tool, we identified high- and low-risk threshold points. CONCLUSIONS: Using various machine learning algorithms, we identified and validated a time-updated prediction model of ten readily available electronic health record variables to accurately predict imminent AKI in hospitalized children.


Asunto(s)
Lesión Renal Aguda/etiología , Adolescente , Niño , Niño Hospitalizado , Preescolar , Registros Electrónicos de Salud , Femenino , Humanos , Lactante , Aprendizaje Automático , Masculino , Estudios Retrospectivos
14.
J Appl Clin Med Phys ; 22(6): 11-15, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34018313

RESUMEN

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: (1) Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. (2) Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances.


Asunto(s)
Física Sanitaria , Oncología por Radiación , Humanos , Sociedades , Estados Unidos
15.
Am J Kidney Dis ; 76(6): 806-814.e1, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32505812

RESUMEN

RATIONALE & OBJECTIVE: Acute kidney injury (AKI) is diagnosed based on changes in serum creatinine concentration, a late marker of this syndrome. Algorithms that predict elevated risk for AKI are of great interest, but no studies have incorporated such an algorithm into the electronic health record to assist with clinical care. We describe the experience of implementing such an algorithm. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 2,856 hospitalized adults in a single urban tertiary-care hospital with an algorithm-predicted risk for AKI in the next 24 hours>15%. Alerts were also used to target a convenience sample of 100 patients for measurement of 16 urine and 6 blood biomarkers. EXPOSURE: Clinical characteristics at the time of pre-AKI alert. OUTCOME: AKI within 24 hours of pre-AKI alert (AKI24). ANALYTICAL APPROACH: Descriptive statistics and univariable associations. RESULTS: At enrollment, mean predicted probability of AKI24 was 19.1%; 18.9% of patients went on to develop AKI24. Outcomes were generally poor among this population, with 29% inpatient mortality among those who developed AKI24 and 14% among those who did not (P<0.001). Systolic blood pressure<100mm Hg (28% of patients with AKI24 vs 18% without), heart rate>100 beats/min (32% of patients with AKI24 vs 24% without), and oxygen saturation<92% (15% of patients with AKI24 vs 6% without) were all more common among those who developed AKI24. Of all biomarkers measured, only hyaline casts on urine microscopy (72% of patients with AKI24 vs 25% without) and fractional excretion of urea nitrogen (20% [IQR, 12%-36%] among patients with AKI24 vs 34% [IQR, 25%-44%] without) differed between those who did and did not develop AKI24. LIMITATIONS: Single-center study, reliance on serum creatinine level for AKI diagnosis, small number of patients undergoing biomarker evaluation. CONCLUSIONS: A real-time AKI risk model was successfully integrated into the EHR.


Asunto(s)
Lesión Renal Aguda/diagnóstico , Creatinina/sangre , Pacientes Internos , Medición de Riesgo/métodos , Lesión Renal Aguda/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Nitrógeno de la Urea Sanguínea , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Curva ROC , Índice de Severidad de la Enfermedad
16.
Biometrics ; 76(1): 257-269, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31350904

RESUMEN

The field of neuroimaging dedicated to mapping connections in the brain is increasingly being recognized as key for understanding neurodevelopment and pathology. Networks of these connections are quantitatively represented using complex structures, including matrices, functions, and graphs, which require specialized statistical techniques for estimation and inference about developmental and disorder-related changes. Unfortunately, classical statistical testing procedures are not well suited to high-dimensional testing problems. In the context of global or regional tests for differences in neuroimaging data, traditional analysis of variance (ANOVA) is not directly applicable without first summarizing the data into univariate or low-dimensional features, a process that might mask the salient features of high-dimensional distributions. In this work, we consider a general framework for two-sample testing of complex structures by studying generalized within-group and between-group variances based on distances between complex and potentially high-dimensional observations. We derive an asymptotic approximation to the null distribution of the ANOVA test statistic, and conduct simulation studies with scalar and graph outcomes to study finite sample properties of the test. Finally, we apply our test to our motivating study of structural connectivity in autism spectrum disorder.


Asunto(s)
Biometría/métodos , Conectoma/estadística & datos numéricos , Adolescente , Análisis de Varianza , Trastorno del Espectro Autista/diagnóstico por imagen , Niño , Simulación por Computador , Interpretación Estadística de Datos , Imagen de Difusión Tensora/estadística & datos numéricos , Humanos
17.
J Appl Clin Med Phys ; 21(7): 11-15, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31800151

RESUMEN

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances. Approved by AAPM's Executive Committee May 28, 2019.


Asunto(s)
Física Sanitaria , Oncología por Radiación , Humanos , Sociedades , Estados Unidos
18.
PLoS Med ; 16(7): e1002861, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31306408

RESUMEN

BACKGROUND: Acute kidney injury (AKI) is an adverse event that carries significant morbidity. Given that interventions after AKI occurrence have poor performance, there is substantial interest in prediction of AKI prior to its diagnosis. However, integration of real-time prognostic modeling into the electronic health record (EHR) has been challenging, as complex models increase the risk of error and complicate deployment. Our goal in this study was to create an implementable predictive model to accurately predict AKI in hospitalized patients and could be easily integrated within an existing EHR system. METHODS AND FINDINGS: We performed a retrospective analysis looking at data of 169,859 hospitalized adults admitted to one of three study hospitals in the United States (in New Haven and Bridgeport, Connecticut) from December 2012 to February 2016. Demographics, medical comorbidities, hospital procedures, medications, and laboratory data were used to develop a model to predict AKI within 24 hours of a given observation. Outcomes of AKI severity, requirement for renal replacement therapy, and mortality were also measured and predicted. Models were trained using discrete-time logistic regression in a subset of Hospital 1, internally validated in the remainder of Hospital 1, and externally validated in Hospital 2 and Hospital 3. Model performance was assessed via the area under the receiver-operator characteristic (ROC) curve (AUC). The training set cohort contained 60,701 patients, and the internal validation set contained 30,599 patients. External validation data sets contained 43,534 and 35,025 patients. Patients in the overall cohort were generally older (median age ranging from 61 to 68 across hospitals); 44%-49% were male, 16%-20% were black, and 23%-29% were admitted to surgical wards. In the training set and external validation set, 19.1% and 18.9% of patients, respectively, developed AKI. The full model, including all covariates, had good ability to predict imminent AKI for the validation set, sustained AKI, dialysis, and death with AUCs of 0.74 (95% CI 0.73-0.74), 0.77 (95% CI 0.76-0.78), 0.79 (95% CI 0.73-0.85), and 0.69 (95% CI 0.67-0.72), respectively. A simple model using only readily available, time-updated laboratory values had very similar predictive performance to the complete model. The main limitation of this study is that it is observational in nature; thus, we are unable to conclude a causal relationship between covariates and AKI and do not provide an optimal treatment strategy for those predicted to develop AKI. CONCLUSIONS: In this study, we observed that a simple model using readily available laboratory data could be developed to predict imminent AKI with good discrimination. This model may lend itself well to integration into the EHR without sacrificing the performance seen in more complex models.


Asunto(s)
Lesión Renal Aguda/epidemiología , Técnicas de Apoyo para la Decisión , Pacientes Internos , Admisión del Paciente/tendencias , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/terapia , Anciano , Anciano de 80 o más Años , Connecticut/epidemiología , Registros Electrónicos de Salud , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Diálisis Renal , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo
19.
Artículo en Inglés | MEDLINE | ID: mdl-30397055

RESUMEN

Lipopeptide daptomycin is a last-line cell-membrane-targeting antibiotic to treat multidrug-resistant Staphylococcus aureus Alarmingly, daptomycin-resistant S. aureus isolates have emerged. The mechanisms underlying daptomycin resistance are diverse and share similarities with resistances to cationic antimicrobial peptides and other lipopeptides, but they remain to be fully elucidated. We selected mutants with increased resistance to daptomycin from a library of transposon insertions in sequent type 8 (ST8) S. aureus HG003. Insertions conferring increased daptomycin resistance were localized to two genes, one coding for a hypothetical lipoprotein (SAOUHSC_00362, Dsp1), and the other for an alkaline shock protein (SAOUHSC_02441, Asp23). Markerless loss-of-function mutants were then generated for comparison. All transposon mutants and knockout strains exhibited increased daptomycin resistance compared to those of wild-type and complemented strains. Null and transposon insertion mutants also exhibited increased resistance to cationic antimicrobial peptides. Interestingly, the Δdsp1 mutant also showed increased resistance to vancomycin, a cell-wall-targeting drug with a different mode of action. Null mutations in both dsp1 and asp23 resulted in increased tolerance as reflected by reduced killing to both daptomycin and vancomycin, as well as an increased tolerance to surfactant (Triton X-100). Neither mutant exhibited increased resistance to lysostaphin, a cell-wall-targeting endopeptidase. These findings identified two genes core to the S. aureus species that make previously uncharacterized contributions to antimicrobial resistance and tolerance in S. aureus.


Asunto(s)
Antibacterianos/farmacología , Proteínas Bacterianas/genética , Daptomicina/farmacología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/genética , Membrana Celular/efectos de los fármacos , Elementos Transponibles de ADN/genética , Farmacorresistencia Bacteriana Múltiple/genética , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/tratamiento farmacológico , Vancomicina/farmacología
20.
J Environ Manage ; 232: 1012-1020, 2019 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-33395753

RESUMEN

Carcinoscorpius rotundicauda and Tachypleus gigas may co-exist and share common spawning grounds elsewhere but at Balok (East Coast of Peninsular Malaysia), C. rotundicauda is an understudied species. Neglected as research candidate because of inaccessible spawning grounds, smaller size and less commercial value than T. gigas and also, difficulty to attain from the wild has made C. rotundicauda population status remaining unidentified at Balok. This standpoint drove the present attempt because anthropic activities like structure placement and mining are point-source for runoffs that load sediments into Balok River. While erosion-accretion events have altered Balok River width, the shore sediments in Balok Beach were transitioned between medium-fine and fine sand between years 2012 and 2016. Eventually by year 2016, the C. rotundicauda were depositing 5117 eggs in 91 nests from 200 to 1000 m range along this corridor facing South China Sea. From this yield, C. rotundicauda released 2880 eggs in 56 nests during the Southwest monsoon, 1254 eggs in 19 nests during the Northeast monsoon and 983 eggs in 16 nests during the Inter-monsoon seasons. Though female C. rotundicauda opted to lay their eggs in shallow burrows at lower shorelines, the absence of erosion and substantial silt and clay (>20%) deposition facilitates C. rotundicauda embryogenesis with brief periods of temperature and salinity shocks during day-time falling tides. This encourages C. rotundicauda to emerge with increasing abundance and carry out bi-monthly spawning at Balok Beach. In short, shore restoration initiatives like systematic boat docking, proper disposal of nets and waste and, periodic fish-catching operations were effectively led by the Balok fisher citizen scientist. This successful community joint-cooperation proves that citizen-led caretaking of degraded beaches offers marine life protection and are practical for coastal area management especially at areas where other oviparous animals such as turtles and crocodiles are harboured.

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