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1.
Artigo em Inglês | MEDLINE | ID: mdl-39018442

RESUMO

ABSTRACT: Many subspecialties of pathology have initiated novel methods and strategies to connect with medical students and residents, stimulate interest, and offer mentorship. Emerging concern about the future of forensic pathology has been highlighted in contemporary literature as recruitment of new fellows has stagnated and workforce shortage concerns have blossomed. Amidst these challenges, the potential role of social networking platforms like social media (SoMe) in enhancing autopsy pathology/forensics education has garnered attention, yet literature focusing specifically on its application in autopsy and forensic pathology remains limited. This review aims to provide a comprehensive narrative overview of the current literature on the established uses of SoMe in forensic pathology. It seeks to build upon existing recommendations, introducing a contemporary compilation of online resources designed to facilitate virtual engagement among pathologists, learners, patients, and families. The review supports the idea that strategic, ethical, and conscientious use of SoMe has a place in addressing the growing workforce shortages and closing educational gaps in forensic pathology by enhancing exposure to the field and dispelling antiquated stereotypes.

2.
Microbiol Spectr ; : e0087924, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012111

RESUMO

Most pneumococcal disease occurs among infants and older adults and is thought to be driven by the transmission of Streptococcus pneumoniae from young children to these vulnerable age groups. However, pneumococcal disease outbreaks also affect non-elderly adults living or working in congregate, close-contact settings. Little is known about pneumococcal carriage in such populations. From July to November 2020, we collected saliva from low-income adult farmworkers in Monterey County, California, and tested for pneumococcal carriage following culture enrichment via quantitative PCR assays targeting the pneumococcal lytA and piaB genes. Participants were considered to carry pneumococci if lytA and piaB cycle threshold values were both below 40. Among 1,283 participants enrolled in our study, 117 (9.1%) carried pneumococci. Carriers tended more often than non-carriers to be exposed to children aged <5 years [odds ratio (OR) = 1.45 (0.95-2.20)] and overcrowding [OR = 1.48 (0.96-2.30) and 2.84 (1.20-6.73), respectively, for participants in households with >2-4 and >4 persons per bedroom vs ≤2 persons per bedroom]. Household overcrowding remained associated with increased risk of carriage among participants not exposed to children aged <5 years [OR = 2.05 (1.18-3.59) for participants living in households with >2 vs ≤2 persons per bedroom]. Exposure to children aged <5 years and overcrowding were each associated with increased pneumococcal density among carriers [piaB cT difference of 2.04 (0.36-3.73) and 2.44 (0.80-4.11), respectively]. While exposure to young children was a predictor of pneumococcal carriage, associations of overcrowding with increased prevalence and density of carriage in households without young children suggest that transmission also occurs among adults in close-contact settings.IMPORTANCEAlthough infants and older adults are the groups most commonly affected by pneumococcal disease, outbreaks are known to occur among healthy, working-age populations exposed to overcrowding, including miners, shipyard workers, military recruits, and prisoners. Carriage of Streptococcus pneumoniae is the precursor to pneumococcal disease, and its relation to overcrowding in adult populations is poorly understood. We used molecular methods to characterize pneumococcal carriage in culture-enriched saliva samples from low-income adult farmworkers in Monterey County, CA. While exposure to children in the household was an important risk factor for pneumococcal carriage, living in an overcrowded household without young children was an independent predictor of carriage as well. Moreover, participants exposed to children or overcrowding carried pneumococci at higher density than those without such exposures, suggesting recent transmission. Our findings suggest that, in addition to transmission from young children, pneumococcal transmission may occur independently among adults in overcrowded settings.

3.
J Forensic Sci ; 69(3): 932-943, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38314613

RESUMO

An extreme, known potential outcome of intimate partner violence (IPV) is death, with national data revealing females are more likely to be killed by intimate partners than by others. In a novel pairing, the King County Medical Examiner's Office data management system and the Washington State Attorney General's Office's Homicide Information Tracking System were retrospectively analyzed (1978-2016) with information gathered pertaining to female homicide victims. Analyses show that female victims commonly knew their assailant(s) (79.3%) who were overwhelmingly male (92.8%) and commonly intimate partners (31.4%). Disproportionately represented were Black (20.17%) and Native American (4.25%) females; Asian/Pacific Islander (2.5 times that of Whites) and elderly (24%) females among homicide-suicide deaths; and Asian/Pacific Islander and Hispanic females in cases of IPV. "Domestic violence" was the most cited motive (34.3%) and most assaults occurred in a residence (58.73%). Females under 10 years of age were most commonly killed by a parent or caregiver (42.86%), while those over 70 were most likely to be killed by a child (23.08%) or spouse (21.80%). Serial murders, most commonly by the Green River Killer (80%) but including others, accounted for at least 7% of deaths, with victims notably young and commonly sex workers (68%). As compared to males, females were more likely to be killed by multiple modalities, asphyxia, and sharp force, though IPV-related deaths were more likely to be associated with firearms. This study reinforces the vulnerability of females to IPV, sexual assault, and serial murders as well as to caretakers at the extremities of age.


Assuntos
Homicídio , Violência por Parceiro Íntimo , Humanos , Homicídio/estatística & dados numéricos , Feminino , Washington/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Masculino , Adolescente , Distribuição por Sexo , Criança , Idoso , Adulto Jovem , Violência por Parceiro Íntimo/estatística & dados numéricos , Distribuição por Idade , Grupos Raciais/estatística & dados numéricos , Vítimas de Crime/estatística & dados numéricos , Pré-Escolar , Etnicidade/estatística & dados numéricos , Suicídio Consumado/estatística & dados numéricos , Lactente , Idoso de 80 Anos ou mais
4.
J Hosp Med ; 19(5): 356-367, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38243720

RESUMO

BACKGROUND: Sitting at the bedside may improve patient-clinician communication; however, many clinicians do not regularly sit during inpatient encounters. OBJECTIVE: To determine the impact of adding wall-mounted folding chairs inside patient rooms, beyond any impact from a resident education campaign, on the patient-reported frequency of sitting at the bedside by internal medicine resident physicians. DESIGN, SETTING, AND PARTICIPANTS: Prospective, controlled pre-post trial between 2019 and 2022 (data collection paused 2020-2021 due to COVID-19) at an academic hospital in Baltimore, Maryland. Folding chairs were installed in two of four internal medicine units and educational activities were delivered equally across all units. MAIN OUTCOME AND MEASURES: Patient-reported frequency of sitting at bedside, assessed as means on Likert-type items with 1 being "never" and 5 being "every single time." We also examined the frequency of other patient-reported communication behaviors. RESULTS: Two hundred fifty six and 206 patients enrolled in the pre and post-intervention periods, respectively. The mean frequency of patient-reported sitting by resident physicians increased from 1.8 (SD 1.2) to 2.3 (1.2) on education-only units (absolute difference 0.48 [95% CI: 0.21-0.75]) and from 2.0 (1.3) to 3.2 (1.4) on units receiving chairs (1.16, [0.87-1.45]). Comparing differences between groups using ordered logistic regression adjusting for clustering within residents, units with added chairs had greater increases in sitting (odds ratio 2.05 [1.10-3.82]), spending enough time at the bedside (2.43 [1.32-4.49]), and checking for understanding (3.04 [1.44-6.39]). Improvements in sitting and other behaviors were sustained on both types of units. CONCLUSIONS: Adding wall-mounted folding chairs may help promote effective patient-clinician communication.


Assuntos
COVID-19 , Internato e Residência , Humanos , Masculino , Feminino , Estudos Prospectivos , COVID-19/epidemiologia , Pessoa de Meia-Idade , Postura Sentada , Relações Médico-Paciente , Medicina Interna/educação , Decoração de Interiores e Mobiliário , Quartos de Pacientes , SARS-CoV-2 , Idoso , Baltimore , Comunicação , Adulto
6.
BMC Med Educ ; 23(1): 862, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957655

RESUMO

BACKGROUND AND OBJECTIVES: Because much of the work in academic medicine is done by committee, early career URiM faculty, are often asked to serve on multiple committees, including diversity work that may not be recognized as important. They may also be asked to serve on committees to satisfy a diversity "check box," and may be asked more often than their non-URiM peers to serve in this capacity. We sought to describe the committee experiences of early career URiM faculty, hypothesizing that they may see committee service as a minority tax. METHODS: Participants in the Leadership through Scholarship Fellowship (LTSF) were asked to share their experiences with committee service in their careers after participating in a faculty development discussion. Their responses were analyzed and reported using qualitative, open, axial, and abductive reasoning methods. RESULTS: Four themes, with eight sub-themes (in parenthesis), emerged from the content analysis of the LTSF fellows responses to the prompt: Time commitment (Timing of committee work and lack of protected time for research and scholarship), URiM Committee service (Expectation that URiM person will serve on committees and consequences for not serving), Mentoring issues (no mentoring regarding committee service, faculty involvement is lacking and the conflicting nature of committee work) and Voice (Lack of voice or acknowledgement). CONCLUSIONS: Early career URiM faculty reported an expectation of serving on committees and consequences for not serving related to their identity, but other areas of committee service they shared were not connected to their URiM identity. Because most of the experiences were not connected to the LTSF fellows' URiM identity, this group has identified areas of committee service that may affect all early career faculty. More research is necessary to determine how committee service affects URiM and non-URiM faculty in academic family medicine.


Assuntos
Medicina de Família e Comunidade , Tutoria , Humanos , Docentes de Medicina , Grupos Minoritários , Mentores
7.
Nat Commun ; 14(1): 5208, 2023 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-37626123

RESUMO

Aberrant enhancer activation is a key mechanism driving oncogene expression in many cancers. While much is known about the regulation of larger chromosome domains in eukaryotes, the details of enhancer-promoter interactions remain poorly understood. Recent work suggests co-activators like BRD4 and Mediator have little impact on enhancer-promoter interactions. In leukemias controlled by the MLL-AF4 fusion protein, we use the ultra-high resolution technique Micro-Capture-C (MCC) to show that MLL-AF4 binding promotes broad, high-density regions of enhancer-promoter interactions at a subset of key targets. These enhancers are enriched for transcription elongation factors like PAF1C and FACT, and the loss of these factors abolishes enhancer-promoter contact. This work not only provides an additional model for how MLL-AF4 is able to drive high levels of transcription at key genes in leukemia but also suggests a more general model linking enhancer-promoter crosstalk and transcription elongation.


Assuntos
Leucemia , Proteínas Nucleares , Humanos , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Sequências Reguladoras de Ácido Nucleico , Leucemia/genética , Regiões Promotoras Genéticas/genética , Proteínas de Ciclo Celular , Proteínas de Fusão Oncogênica/genética , Proteína de Leucina Linfoide-Mieloide/genética
8.
Artigo em Inglês | MEDLINE | ID: mdl-37093884

RESUMO

ABSTRACT: Intravascular large B-cell lymphoma is a rare subset of non-Hodgkin lymphoma composed of mature B lymphoma cells confined to the intravascular space. This disease remains elusive because it lacks a discrete tumor mass, can affect any part of the body, and has vague symptoms paired with heterogeneous clinical findings resulting in delayed or missed accurate diagnosis, even at postmortem examination. This is a case of a woman who died within hours of presenting to the emergency department with a diagnosis of intravascular large B-cell lymphoma made through autopsy examination, adding to the knowledge of this rare disease and bringing it to the attention of practicing autopsy and forensic pathologists.

10.
Clin Infect Dis ; 76(7): 1209-1217, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36401872

RESUMO

BACKGROUND: Streptococcus pneumoniae interacts with numerous viral respiratory pathogens in the upper airway. It is unclear whether similar interactions occur with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We collected saliva specimens from working-age adults undergoing SARS-CoV-2 molecular testing at outpatient clinics and via mobile community-outreach testing between July and November 2020 in Monterey County, California. After bacterial culture enrichment, we tested for pneumococci by means of quantitative polymerase chain reaction targeting the lytA and piaB genes, and we measured associations with SARS-CoV-2 infection using conditional logistic regression. RESULTS: Analyses included 1278 participants, with 564 enrolled in clinics and 714 enrolled through outreach-based testing. The prevalence of pneumococcal carriage was 9.2% (117 of 1278) among all participants (11.2% [63 of 564] in clinic-based testing and 7.6% [54 of 714] in outreach-based testing). The prevalence of SARS-CoV-2 infection was 27.4% (32 of 117) among pneumococcal carriers and 9.6% (112 of 1161) among noncarriers (adjusted odds ratio [aOR], 2.73 [95% confidence interval (CI): 1.58-4.69). Associations between SARS-CoV-2 infection and pneumococcal carriage were enhanced in the clinic-based sample (aOR, 4.01 [95% CI: 2.08-7.75]) and among symptomatic participants (3.38 [1.35-8.40]), compared with findings within the outreach-based sample and among asymptomatic participants. The adjusted odds of SARS-CoV-2 coinfection increased 1.24-fold (95% CI: 1.00-1.55-fold) for each 1-unit decrease in piaB quantitative polymerase chain reaction cycle threshold value among pneumococcal carriers. Finally, pneumococcal carriage modified the association of SARS-CoV-2 infection with recent exposure to a suspected coronavirus disease 2019 case (aOR, 7.64 [95% CI: 1.91-30.7] and 3.29 [1.94-5.59]) among pneumococcal carriers and noncarriers, respectively). CONCLUSIONS: Associations of pneumococcal carriage detection and density with SARS-CoV-2 suggest a synergistic relationship in the upper airway. Longitudinal studies are needed to determine interaction mechanisms between pneumococci and SARS-CoV-2.


Assuntos
COVID-19 , Infecções Pneumocócicas , Humanos , Adulto , Streptococcus pneumoniae/genética , COVID-19/epidemiologia , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/microbiologia , Nasofaringe/microbiologia , SARS-CoV-2
11.
mSphere ; 7(6): e0047122, 2022 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-36377882

RESUMO

Antimicrobial resistance in urinary tract infections (UTIs) is a major public health concern. This study aims to characterize the phenotypic and genetic basis of multidrug resistance (MDR) among expanded-spectrum cephalosporin-resistant (ESCR) uropathogenic Escherichia coli (UPEC) causing UTIs in California patient populations. Between February and October 2019, 577 ESCR UPEC isolates were collected from patients at 6 clinical laboratory sites across California. Lineage and antibiotic resistance genes were determined by analysis of whole-genome sequence data. The lineages ST131, ST1193, ST648, and ST69 were predominant, representing 46%, 5.5%, 4.5%, and 4.5% of the collection, respectively. Overall, 527 (91%) isolates had an expanded-spectrum ß-lactamase (ESBL) phenotype, with blaCTX-M-15, blaCTX-M-27, blaCTX-M-55, and blaCTX-M-14 being the most prevalent ESBL genes. In the 50 non-ESBL phenotype isolates, 40 (62%) contained blaCMY-2, which was the predominant plasmid-mediated AmpC (pAmpC) gene. Narrow-spectrum ß-lactamases, blaTEM-1B and blaOXA-1, were also found in 44.9% and 32.1% of isolates, respectively. Among ESCR UPEC isolates, isolates with an ESBL phenotype had a 1.7-times-greater likelihood of being MDR than non-ESBL phenotype isolates (P < 0.001). The cooccurrence of blaCTX-M-15, blaOXA-1, and aac(6')-Ib-cr within ESCR UPEC isolates was strongly correlated. Cooccurrence of blaCTX-M-15, blaOXA-1, and aac(6')-Ib-cr was associated with an increased risk of nonsusceptibility to piperacillin-tazobactam, cefepime, fluoroquinolones, and amikacin as well as MDR. Multivariate regression revealed the presence of blaCTX-M-55, blaTEM-1B, and the ST131 genotype as predictors of MDR. IMPORTANCE The rising incidence of resistance to expanded-spectrum cephalosporins among Escherichia coli strains, the most common cause of UTIs, is threatening our ability to successfully empirically treat these infections. ESCR E. coli strains are often MDR; therefore, UTI caused by these organisms often leads to treatment failure, increased length of hospital stay, and severe complications (D. G. Mark, Y.-Y. Hung, Z. Salim, N. J. Tarlton, et al., Ann Emerg Med 78:357-369, 2021, https://doi.org/10.1016/j.annemergmed.2021.01.003). Here, we performed an in-depth analysis of genetic factors of ESCR E. coli associated with coresistance and MDR. Such knowledge is critical to advance UTI diagnosis, treatment, and antibiotic stewardship.


Assuntos
Infecções por Escherichia coli , Escherichia coli Uropatogênica , Humanos , Cefalosporinas/farmacologia , Escherichia coli Uropatogênica/genética , Infecções por Escherichia coli/epidemiologia , beta-Lactamases/genética , Fenótipo , Monobactamas , Farmacorresistência Bacteriana Múltipla/genética
12.
Am Fam Physician ; 106(5): 513-522, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36379496

RESUMO

In the United States, 1 in 5 adults uses tobacco products. Cigarette smoking is the leading cause of preventable disease and death in the United States despite its known health effects. Although nearly one-half of people who smoke try to quit each year, only up to 1 in 20 who quit without support achieve abstinence for at least six months. All patients, including school-aged children and adolescents, should be asked if they smoke and offered evidence-based treatments for smoking cessation. Use of the 5 A's framework (ask, advise, assess, assist, arrange) can help clinicians promote smoking cessation. Clinical studies have demonstrated that combining pharmacotherapy with effective behavior strategies is significantly more effective than either approach alone. Pharmacotherapies approved by the U.S. Food and Drug Administration for smoking cessation include nicotine replacement therapy, bupropion, and varenicline. Extended use (greater than 12 weeks) of a controller therapy (varenicline, bupropion, or nicotine patch) is associated with significantly higher sustained quit rates and lower relapse rates than standard use (six to 12 weeks). e-Cigarettes are not approved by the U.S. Food and Drug Administration for smoking cessation, and evidence supporting their benefit is inconclusive. Lung cancer screening is recommended for adults 50 to 80 years of age who have a 20-pack-year smoking history and currently smoke or have quit within the past 15 years. Lung cancer screening should be combined with smoking cessation tools and treatment.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Neoplasias Pulmonares , Abandono do Hábito de Fumar , Adulto , Adolescente , Criança , Humanos , Adulto Jovem , Vareniclina/uso terapêutico , Dispositivos para o Abandono do Uso de Tabaco , Bupropiona/uso terapêutico , Detecção Precoce de Câncer , Recidiva Local de Neoplasia
13.
medRxiv ; 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36238718

RESUMO

Background: Streptococcus pneumoniae interacts with numerous viral respiratory pathogens in the upper airway. It is unclear whether similar interactions occur with SARS-CoV-2. Methods: We collected saliva specimens from working-age adults receiving SARS-CoV-2 molecular testing at outpatient clinics and via mobile community-outreach testing between July and November 2020 in Monterey County, California. Following bacterial culture enrichment, we tested for pneumococci by quantitative polymerase chain reaction (qPCR) targeting the lytA and piaB genes, and measured associations with SARS-CoV-2 infection via conditional logistic regression. Results: Analyses included 1,278 participants, with 564 enrolled in clinics and 714 enrolled through outreach-based testing. Prevalence of pneumococcal carriage was 9.2% (117/1,278) among all participants (11.2% [63/564] clinic-based testing; 7.6% [54/714] outreach testing). Prevalence of SARS-CoV-2 infection was 27.4% (32/117) among pneumococcal carriers and 9.6% (112/1,161) among non-carriers (adjusted odds ratio [aOR]: 2.73; 95% confidence interval: 1.58-4.69). Associations between SARS-CoV-2 infection and pneumococcal carriage were enhanced in the clinic-based sample (aOR=4.01 [2.08-7.75]) and among symptomatic participants (aOR=3.38 [1.35-8.40]), when compared to findings within the outreach-based sample and among asymptomatic participants. Adjusted odds of SARS-CoV-2 co-infection increased 1.24 (1.00-1.55)-fold for each 1-unit decrease in piaB qPCR C T value among pneumococcal carriers. Last, pneumococcal carriage modified the association of SARS-CoV-2 infection with recent exposure to a suspected COVID-19 case (aOR=7.64 [1.91-30.7] and 3.29 [1.94-5.59]) among pneumococcal carriers and non-carriers, respectively). Conclusions: Associations of pneumococcal carriage detection and density with SARS-CoV-2 suggest a synergistic relationship in the upper airway. Longitudinal studies are needed to determine interaction mechanisms between pneumococci and SARS-CoV-2. Key points: In an adult ambulatory and community sample, SARS-CoV-2 infection was more prevalent among pneumococcal carriers than non-carriers.Associations between pneumococcal carriage and SARS-CoV-2 infection were strongest among adults reporting acute symptoms and receiving SARS-CoV-2 testing in a clinical setting.

15.
J Natl Med Assoc ; 114(5): 534-550, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35963662

RESUMO

BACKGROUND: Informal estimates place the number of practicing Black forensic pathologists (BFPs) in the United States (US) at somewhere between 35 and 45 which is less than 10% the estimated total of 600. The legacy of medical and institutional racism means that BFPs in the US encounter particular challenges to training and career development that their White peers do not have to contend with. METHODS: A survey developed on SurveyMonkey in English, was distributed through social media networks and by direct email to known BFPs. Their responses to questions about the challenges they faced in training and as qualified specialists and factors that eased or facilitated their progress were collected and analyzed. FINDINGS: BFPs report challenges to recruitment and retention that are like those faced by Black peers in other medical specialties. INTERPRETATION: While personal determination is an essential ingredient to career success as a BFP, there are certain structural barriers that must be eliminated to increase the total number of BFPs. The pipeline that produces BFPs must be nurtured, reimagined, and reinvigorated.


Assuntos
Patologistas , Humanos , Inquéritos e Questionários , Estados Unidos
16.
Chem Commun (Camb) ; 58(19): 3166-3169, 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35170593

RESUMO

This article reports the synthesis and characterization of a novel self-immolative linker, based on thiocarbonates, which releases a free thiol upon activation via enzymes. We demonstrate that thiocarbonate self-immolative linkers can be used to detect the enzymes penicillin G amidase (PGA) and nitroreductase (NTR) with high sensitivity using absorption spectroscopy. Paired with modern thiol amplification technology, the detection of PGA and NTR were achieved at concentrations of 160 nM and 52 nM respectively. In addition, the PGA probe was shown to be compatible with both biological thiols and enzymes present in cell lysates.


Assuntos
Nitrorredutases/análise , Penicilina Amidase/análise , Compostos de Sulfidrila/química , Estrutura Molecular , Nitrorredutases/metabolismo , Penicilina Amidase/metabolismo , Espectrometria de Fluorescência
17.
Am J Forensic Med Pathol ; 42(3): 243-247, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33833195

RESUMO

ABSTRACT: The border wall between the United States and Mexico consists of stretches of metal fencing of varying heights alternating and overlapping with areas of electronic surveillance. Despite national conversations centered around the social, environmental, economic, and political implications of this wall, there is a paucity of studies on deaths occurring in this region. Herein are described 2 cases of fatal injuries sustained from scaling the fence and accidentally falling onto the United States' side in New Mexico. These injuries are compared with those typically incurred in falls from lower and higher heights, and implications of both lateral and vertical expansion of the wall are discussed.


Assuntos
Acidentes por Quedas , Emigração e Imigração , Ferimentos não Penetrantes/patologia , Adulto , Feminino , Fraturas Múltiplas/diagnóstico por imagem , Hemotórax/diagnóstico por imagem , Humanos , Masculino , Enfisema Mediastínico/diagnóstico por imagem , México , Pessoa de Meia-Idade , Pneumotórax/diagnóstico por imagem , Enfisema Subcutâneo/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Estados Unidos
18.
J Microbiol Methods ; 182: 106160, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33548393

RESUMO

The increasing prevalence of extended spectrum ß-lactamases (ESBLs) and plasmid-mediated AmpC (pAmpC) ß-lactamases among Enterobacterales threatens our ability to treat urinary tract infections (UTIs). These organisms are resistant to most ß-lactam antibiotics and are frequently multidrug-resistant (MDR). Consequently, they are often resistant to antibiotics used to empirically treat UTIs. The lack of rapid diagnostic and antibiotic susceptibility tests (AST) makes clinical management of UTIs caused by such organisms difficult, as standard culture and susceptibility assays require several days. We have adapted a biochemical detection assay, termed dual-enzyme trigger-enabled cascade technology (DETECT) for rapid detection of resistance (time-to-result of 3 h) to other antibiotics commonly used in treatment of UTIs. DETECT is activated by the presence of CTX-M and pAmpC ß-lactamases. In this proof-of-concept study, the adapted DETECT assay (AST-DETECT) has been performed on pure-cultures of Klebsiella pneumoniae and Escherichia coli (48 isolates) expressing ESBL or pAmpC ß-lactamases to perform AST for ciprofloxacin (sensitivity 96.9%, specificity 100%, accuracy 97.9%) nitrofurantoin (sensitivity 95.7%, specificity 91.7%, accuracy 94%) and trimethoprim/sulfamethoxazole (sensitivity 83.3%, specificity 100%, accuracy 89.4%). These results suggest that AST-DETECT may be adapted as a potential diagnostic platform to rapidly detect multidrug-resistant E. coli and K. pneumoniae that cause UTI.


Assuntos
Farmacorresistência Bacteriana Múltipla , Infecções por Escherichia coli/microbiologia , Escherichia coli , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae , Infecções Urinárias/microbiologia , Proteínas de Bactérias/metabolismo , Escherichia coli/isolamento & purificação , Escherichia coli/metabolismo , Humanos , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/metabolismo , Estudo de Prova de Conceito , beta-Lactamases/metabolismo
19.
Am J Forensic Med Pathol ; 42(1): 1-8, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33416234

RESUMO

ABSTRACT: The 2019 novel coronavirus disease (COVID-19) has spread worldwide, infiltrating, infecting, and devastating communities in all locations of varying demographics. An overwhelming majority of published literature on the pathologic findings associated with COVID-19 is either from living clinical cohorts or from autopsy findings of those who died in a medical care setting, which can confound pure disease pathology. A relatively low initial infection rate paired with a high biosafety level enabled the New Mexico Office of the Medical Investigator to conduct full autopsy examinations on suspected COVID-19-related deaths. Full autopsy examination on the first 20 severe acute respiratory syndrome coronavirus 2-positive decedents revealed that some extent of diffuse alveolar damage in every death due to COVID-19 played some role. The average decedent was middle-aged, male, American Indian, and overweight with comorbidities that included diabetes, ethanolism, and atherosclerotic and/or hypertensive cardiovascular disease. Macroscopic thrombotic events were seen in 35% of cases consisting of pulmonary thromboemboli and coronary artery thrombi. In 2 cases, severe bacterial coinfections were seen in the lungs. Those determined to die with but not of severe acute respiratory syndrome coronavirus 2 infection had unremarkable lung findings.


Assuntos
COVID-19/mortalidade , Pulmão/patologia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Autopsia , Índice de Massa Corporal , Edema Encefálico/patologia , Cardiomegalia/patologia , Comorbidade , Trombose Coronária/patologia , Bases de Dados Factuais , Fígado Gorduroso/patologia , Feminino , Patologia Legal , Glomerulosclerose Segmentar e Focal/patologia , Hepatomegalia/patologia , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Nefroesclerose/patologia , New Mexico/epidemiologia , Sobrepeso/epidemiologia , Pandemias , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/patologia , Edema Pulmonar/diagnóstico por imagem , Edema Pulmonar/patologia , Distribuição por Sexo , Streptococcus pneumoniae/isolamento & purificação , Tomografia Computadorizada por Raios X , Corpo Vítreo/química , Imagem Corporal Total
20.
Microb Drug Resist ; 27(4): 450-461, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32830997

RESUMO

Extended-spectrum ß-lactamase (ESBL)-producing Gram-negative bacteria (GNB) are increasingly identified as the cause of both community and healthcare-associated urinary tract infections (UTIs), with CTX-Ms being the most common ESBLs identified. CTX-M-producing GNB are resistant to most ß-lactam antibiotics and are frequently multidrug-resistant, which limits treatment options. Rapid diagnostic tests that can detect ESBL-producing GNB, particularly CTX-M producers, in the urine of patients with UTIs are needed. Results from such a test could direct the selection of appropriate antimicrobial therapy at the point-of-care (POC). In this study, we show that a chromogenic, dual enzyme-mediated amplification system (termed DETECT [dual-enzyme trigger-enabled cascade technology]) can identify CTX-M-producing GNB from unprocessed urine samples in 30 minutes. We first tested DETECT against a diverse set of recombinant ß-lactamases and ß-lactamase-producing clinical isolates to elucidate its selectivity. We then tested DETECT with 472 prospectively collected clinical urine samples submitted for urine culture to a hospital clinical microbiology laboratory. Of these, 118 (25%) were consistent with UTI, 13 (11%) of which contained ESBL-producing GNB. We compared DETECT results in urine against a standard phenotypic method to detect ESBLs, and polymerase chain reaction and sequencing for CTX-M genes. DETECT demonstrated 90.9% sensitivity and 97.6% specificity (AUC, 0.937; 95% confidence interval, 0.822-1.000), correctly identifying 10 of 11 urine samples containing a clinically significant concentration of CTX-M-producing GNB (including Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis). Our results demonstrate the clinical potential of DETECT to deliver diagnostic information at the POC, which could improve initial antibiotic selection.


Assuntos
Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Sistemas Automatizados de Assistência Junto ao Leito , Infecções Urinárias/microbiologia , Resistência beta-Lactâmica/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Urina/microbiologia , beta-Lactamases/farmacologia
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