RESUMEN
Cell-mediated immunity is critical for long-term protection against most viral infections, including coronaviruses. We studied 23 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected survivors over a 1-year post-symptom onset (PSO) interval by ex vivo cytokine enzyme-linked immunosorbent spot assay (ELISpot) assay. All subjects demonstrated SARS-CoV-2-specific gamma interferon (IFN-γ), interleukin 2 (IL-2), and granzyme B (GzmB) T cell responses at presentation, with greater frequencies in severe disease. Cytokines, mainly produced by CD4+ T cells, targeted all structural proteins (nucleocapsid, membrane, and spike) except envelope, with GzmB and IL-2 greater than IFN-γ. Mathematical modeling predicted that (i) cytokine responses peaked at 6 days for IFN-γ, 36 days for IL-2, and 7 days for GzmB, (ii) severe illness was associated with reduced IFN-γ and GzmB but increased IL-2 production rates, and (iii) males displayed greater production of IFN-γ, whereas females produced more GzmB. Ex vivo responses declined over time, with persistence of IL-2 in 86% and of IFN-γ and GzmB in 70% of subjects at a median of 336 days PSO. The average half-life of SARS-CoV-2-specific cytokine-producing cells was modeled to be 139 days (~4.6 months). Potent T cell proliferative responses persisted throughout observation, were CD4 dominant, and were capable of producing all 3 cytokines. Several immunodominant CD4 and CD8 epitopes identified in this study were shared by seasonal coronaviruses or SARS-CoV-1 in the nucleocapsid and membrane regions. Both SARS-CoV-2-specific CD4+ and CD8+ T cell clones were able to kill target cells, though CD8 tended to be more potent. IMPORTANCE Our findings highlight the relative importance of SARS-CoV-2-specific GzmB-producing T cell responses in SARS-CoV-2 control and shared CD4 and CD8 immunodominant epitopes in seasonal coronaviruses or SARS-CoV-1, and they indicate robust persistence of T cell memory at least 1 year after infection. Our findings should inform future strategies to induce T cell vaccines against SARS-CoV-2 and other coronaviruses.
Asunto(s)
COVID-19 , Citocinas , Inmunidad , SARS-CoV-2 , Linfocitos T CD4-Positivos , Linfocitos T CD8-positivos , COVID-19/inmunología , Vacunas contra la COVID-19 , Citocinas/inmunología , Femenino , Humanos , Memoria Inmunológica , Interferón gamma/metabolismo , Interleucina-2/inmunología , Masculino , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
BACKGROUND: The clinical significance of incidentally found RV abnormalities on low-risk SPECT studies is not well-defined. The objective of this study was to determine the predictive value of incidental right ventricular (RV) abnormalities identified on single photon emission computed tomography (SPECT) scans for mortality and pulmonary hypertension (PH). METHODS: We retrospectively analyzed all low-risk SPECT studies in patients without known coronary artery or pulmonary vascular disease, performed at our institution, from 2007-2020. Adjusted Cox proportional hazards models were used to evaluate the association between incidental RV abnormalities on low-risk SPECT studies and outcomes. RESULTS: Of the 4761 patients included in the analysis, mortality events were present in 494, and echocardiographic PH was present in 619. Incidental RV abnormalities on low-risk SPECT studies were significantly and independently associated with all-cause mortality (HR = 1.41, CI [1.07-1.86], P = 0.0152) and echocardiographic PH (HR = 2.06, CI [1.64-2.60], P < 0.0001). CONCLUSIONS: These data suggest incidental RV abnormalities found on low-risk SPECT imaging studies are significantly and independently associated with increased mortality and risk of developing echocardiographic PH, and could identify high-risk patients for closer monitoring and additional diagnostic testing.
Asunto(s)
Cardiopatías Congénitas , Hipertensión Pulmonar , Disfunción Ventricular Derecha , Ecocardiografía , Cardiopatías Congénitas/complicaciones , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/diagnóstico por imagen , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Tomografía Computarizada de Emisión de Fotón Único/métodos , Disfunción Ventricular Derecha/diagnóstico por imagen , Disfunción Ventricular Derecha/etiología , Función Ventricular DerechaRESUMEN
Multiple drug-resistant (MDR) Shigella isolates have been reported worldwide. Between May 2017 and September 2018, 55 Shigella flexneri 2a isolates were collected from 3322 stool samples of 0-10-year-old outpatients with diarrhea at the Children's Hospital of Urumqi, China. All isolates were characterized using serotyping, antimicrobial susceptibility testing, and whole-genome sequencing. A total of 54 of 55 (98.2%) isolates exhibited MDR phenotypes and had accumulated multiple resistance determinants, particularly of fluoroquinolones and cephalosporins preferred for shigellosis treatment: point mutations in quinolone resistance-determining regions (QRDRs) of topoisomerases (GyrA (S83L, D87N) and ParC (S80I) [n = 9]; GyrA (S83L) and ParC (S80I) [n = 45]) and acquisition of qnrS1 (n = 3) and blaCTX-M (n = 8). Over 70% of isolates acquired two point mutations of GyrA (S83L) and ParC (S80I) in QRDRs and 11 highly resistant isolates accumulated three point mutations in QRDRs or acquired qnrS1. Four S. flexneri 2a isolates from three single-nucleotide polymorphism clusters exhibited coresistance to ciprofloxacin, cefotaxime, or azithromycin (AZM), which are used as first- and second-line shigellosis treatment antimicrobials in clinics. Our data indicated that fluoroquinolones should be terminated in shigellosis treatment for outpatients in Urumqi. The transferable antimicrobial resistance determinants have been identified for third-generation cephalosporins and AZM. Novel strategies are urgently required for developing empirical medication to reduce the antimicrobial selective pressure and prevent dissemination of MDR S. flexneri 2a isolates.
Asunto(s)
Antiinfecciosos , Disentería Bacilar , Quinolonas , Shigella , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiinfecciosos/farmacología , Cefalosporinas/farmacología , Cefalosporinas/uso terapéutico , China/epidemiología , Farmacorresistencia Bacteriana/genética , Disentería Bacilar/tratamiento farmacológico , Disentería Bacilar/epidemiología , Fluoroquinolonas/farmacología , Fluoroquinolonas/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana , Pacientes Ambulatorios , Quinolonas/farmacología , Shigella/genética , Shigella flexneri/genéticaRESUMEN
Cocaine can cause a myriad of changes in the lung, which can range from bronchoconstriction to destruction of the alveolar-capillary membrane and acute lung injury. Cocaine-induced bronchospasm is a diagnosis of exclusion that should be considered when the clinical presentation of acute hypoxic and hypercapneic respiratory failure cannot be explained by chronic obstructive pulmonary disease or asthma exacerbation, anaphylaxis to food or medications, exercise, or infection. Here, we present two patients with acute hypoxic and hypercapneic respiratory failure that was ultimately attributed to cocaine use shortly prior to symptom onset.
Asunto(s)
Asma , Espasmo Bronquial , Cocaína/toxicidad , Enfermedad Aguda , Asma/inducido químicamente , Asma/diagnóstico , Asma/fisiopatología , Espasmo Bronquial/inducido químicamente , Espasmo Bronquial/diagnóstico , Espasmo Bronquial/fisiopatología , Trastornos Relacionados con Cocaína/complicaciones , Trastornos Relacionados con Cocaína/diagnóstico , Trastornos Relacionados con Cocaína/fisiopatología , Diagnóstico Diferencial , Femenino , Humanos , Persona de Mediana EdadRESUMEN
ABSTRACT: The next era of assessment in medical education promises new assessment systems, increased focus on ensuring high-quality equitable patient care, and precision education to drive learning and improvement. The potential benefits of using learning analytics and technology to augment medical training abound. To ensure that the ideals of this future for medical education are realized, educators should partner with trainees to build and implement new assessment systems. Coproduction of assessment systems by educators and trainees will help to ensure that new educational interventions are feasible and sustainable. In this paper, the authors provide a trainee perspective on 5 key areas that affect trainees in the next era of assessment: (1) precision education, (2) assessor education, (3) transparency in assessment development and implementation, (4) ongoing evaluation of the consequences of assessment, and (5) patient care data as sources of education outcomes.As precision education is developed, it is critical that trainees understand how their educational data are collected, stored, and ultimately utilized for educational outcomes. Since assessors play a key role in generating assessment data, it is important that they are prepared to give high-quality assessments and are continuously evaluated on their abilities. Transparency in the development and implementation of assessments requires communicating how assessments are created, the evidence behind them, and their intended uses. Furthermore, ongoing evaluation of the intended and unintended consequences that new assessments have on trainees should be conducted and communicated to trainees. Finally, trainees should participate in determining what patient care data are used to inform educational outcomes. The authors believe that trainee coproduction is critical to building stronger assessment systems that utilize evidence-based educational theories for improved learning and ultimately better patient care.
Asunto(s)
Competencia Clínica , Educación Médica , Humanos , Aprendizaje , Calidad de la Atención de Salud , Evaluación Educacional , Educación de Postgrado en MedicinaRESUMEN
Background: Pulmonary hypertension (PH) frequently complicates the course of patients with left heart disease (PH-LHD) and is associated with worse clinical outcomes. Mortality calculators for PH-LHD are lacking, and it is unclear whether any risk prediction tools originally derived from other forms of PH can accurately predict outcomes in patients with PH-LHD. Methods: We retrospectively analyzed data from 161 patients diagnosed with PH-LHD referred to our pulmonary hypertension center from 2016 to 2022. We calculated the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL 2.0) risk score and categorized patients as low, intermediate, or high-risk. We assessed survival at 1 and 3 years using Kaplan-Meier and Cox proportional hazards, as well as classification performance using a concordance index. Results: At the first outpatient visit, 15% of patients were stratified as low-risk, 27% as intermediate, and 57% as high-risk. Cumulative 1-year survival rates were 100%, 94%, and 91% for the low, intermediate, and high-risk strata, respectively. Cumulative 3-year survival rates were 96%, 89%, and 70% for the low, intermediate, and high-risk strata, respectively. We found no difference in outcomes at 1 year between risk groups. High-risk patients had an increased risk of death at 3 years using REVEAL 2.0 (HR 5.32, p < 0.001). However, while REVEAL 2.0 accurately discriminated high-risk patients, the hazard ratio was not statistically different between patients classified as intermediate-risk compared to low-risk. Conclusion: REVEAL 2.0 accurately predicted 3-year survival in PH-LHD patients with high-risk features. However, the mortality risk between patients classified as intermediate-risk was not different from the low-risk stratum, suggesting inaccurate classification for this group of patients.
RESUMEN
BACKGROUND: The goal of this study was to evaluate how the administration of concurrent tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) therapy with variable dosing for complicated parapneumonic effusions and empyema affects patient outcomes in an inner-city community hospital. METHODS: This retrospective analysis was performed at an inner-city hospital located in Raleigh, North Carolina. A list of all patients treated with tPA and DNase between July 1, 2015, and December 31, 2017, was generated and screened. Data were collected through a review of past medical records, including demographics, past medical history, and details about their hospital course. RESULTS: A total of 38 patients were found to have been treated with concurrent tPA and DNase for complicated parapneumonic effusion or empyema. Twenty (52.6%) patients received the full six doses of combined concurrent tPA/DNase. Of the 18 (47.4%) patients who did not receive the full six doses, 11 did not require the full six doses for effusion resolution, and seven had to discontinue therapy due to tube blockage or pain. Only seven (18.4%) patients had complications related to tPA/DNase administration, most commonly pain. Nineteen (50%) patients had complete radiological clearance of effusion, with 13 (34.2%) having partial clearance, and six (15.8%) having no change or worsening of their effusion. Eight (21.1%) patients needed further surgical management of their effusion. CONCLUSIONS: The current most common dosing pattern for combined tPA and DNase therapy of twice daily for three days may not be optimal for all patients. The dosing regimen should be individualized depending on clinical response. Concurrent dosing is safe.
RESUMEN
BACKGROUND: Patients suffering from pulmonary arterial hypertension (PAH) demand frequent assessment to keep pace with a dynamic and sometimes rapidly progressive disease course. To improve our understanding of patient monitoring, we conducted a survey of pulmonary hypertension (PH) providers to establish real-world practice patterns. OBJECTIVE: To evaluate the type and frequency of patient assessment methods employed by expert PH providers following PAH diagnosis METHODS: A descriptive cross-sectional survey of PH providers across the United States was utilized to assess provider practices. Between September 14, 2017 to October 17, 2017, a survey was distributed electronically to PH experts assessing follow-up frequency and testing evaluation of patients with PAH. RESULTS: 40 (11.4%) providers completed the survey, representing cardiologists, pulmonologists, and advanced practice providers at centers who cared for an average of 95 patients per year with PAH. Follow-up testing and clinic evaluation was influenced by severity of patient illness. Frequency of re-assessment of clinic follow-up, six-minute walk test, echocardiogram, brain natriuretic peptide, and right heart catheterization in various clinical scenarios all reflected disparate practice. CONCLUSIONS: Current clinical practice patterns in the monitoring of patients with PAH are variable and do not necessarily reflect guideline-based practices, suggesting the need for further research and improved guidelines on the frequency of follow up and repeat testing.
Asunto(s)
Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Humanos , Estudios Transversales , Hipertensión Pulmonar Primaria Familiar , EcocardiografíaRESUMEN
The coronavirus of 2019 (COVID-19) disrupted delivery of healthcare. Patients with pulmonary hypertension (PH), especially pulmonary arterial hypertension (PAH), require significant resources for both diagnosis and management and are at high risk for decompensation due to disruption in their care. A survey consisting of 47 questions related to the care of patients with PH was designed by the American College of Chest Physicians 2020-2021 Pulmonary Vascular Disease (PVD) NetWork Steering Committee and sent to all members of the PVD NetWork, as well as the multiple other professional networks for PH. Participation was voluntary and anonymous. Responses were collected from November 2020 through February 2021. Ninety-five providers responded to this survey. The majority (93%) believe that care of PH patients has been affected by the pandemic. Sixty-seven percent observed decreased referrals for PH evaluation. Prior to the pandemic, only 15% used telemedicine for management of PH patients compared to 84% during the pandemic. Telemedicine was used most for follow up of selected low-risk patients (49%). While 22% respondents were completely willing to prescribe new PAH therapy via telemedicine, 11% respondents were completely unwilling. Comfort levels differed based on type of medication being prescribed. Over 90% of providers experienced disruptions in obtaining testing and 31% experienced disruptions in renewal or approval of medications. Overall, providers perceived that the COVID-19 pandemic caused significant disruption of care for PH patients. Telemedicine utilization increased but was used mostly in low-risk patients. Some providers had a decreased level of comfort prescribing PAH therapy via telemedicine encounters.
Asunto(s)
COVID-19 , Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Telemedicina , Humanos , COVID-19/epidemiología , Pandemias , Hipertensión Pulmonar/epidemiología , Hipertensión Pulmonar/terapia , Atención a la Salud , Hipertensión Arterial Pulmonar/epidemiología , Hipertensión Arterial Pulmonar/terapia , Hipertensión Pulmonar Primaria FamiliarRESUMEN
ABSTRACT: Nurse practitioners (NPs) and physician assistants (PA) are increasingly providing care to the critically ill patients in the intensive care unit. We structured a 4-month training program for our existing NPs and PAs and assessed their knowledge and skill pre and post training. The program was composed of blended didactic in critical care medicine topics, critical care simulations in simulation laboratory, and supervised critical care procedures. Formal knowledge and skill assessments were performed before and after the program to assess success in meeting predefined learning objectives. The mean preintervention medical knowledge assessment score was 3.37 ± 0.56 SD, which significantly improved to 3.86 ± 0.46 SD (p < .00001). For clinical skills for critical care procedures, the mean preintervention score was 3.10 ± 0.86 SD, which improved to 3.61 ± 0.92 SD (p < .00001). The overall knowledge (including medical knowledge and clinical skills) improved from mean 3.30 ± 0.86 SD to 3.80 ± 0.42 SD. The improvement was seen regardless of the duration of experience in critical care medicine. We concluded that structured didactics with supervised procedural training along with dedicated training in simulation laboratories, even for a short period, improves the overall knowledge and clinical skills required to work in a critical care setting.
Asunto(s)
Enfermeras Practicantes , Asistentes Médicos , Competencia Clínica , Cuidados Críticos , Humanos , Unidades de Cuidados IntensivosRESUMEN
Nontuberculous mycobacterial infection, particularly Mycobacterium avium complex (MAC), which is also known as Lady Windermere syndrome usually presents with chronic cough, typically seen in elderly caucasian women who chronically suppress the normal cough reflex. Computerized tomography of the chest in patients with MAC infection can present as a tree in bud nodules, pulmonary nodules, cavity, or consolidation. However, other coexisting diseases such as lung cancer should be kept in mind while investigating these radiographic changes in patients with suspected MAC infection, more so if they have underlying risk factors for malignancy. We present a patient with suspected MAC infection who had co-existing lung adenocarcinoma.
RESUMEN
Inhaled bronchodilators and corticosteroids, when indicated, form the backbone of COPD therapy. However, over the last decade there has been an emergence of adjunct therapies in oral or inhaled form that are now part of the therapeutic approach to COPD. While these therapies have shown to be beneficial when used in the appropriate instances, there are particular considerations that need to be minded when using these therapies. This review article discussed the mechanism of roflumilast, macrolide antibiotics, other chronic antibiotic regimens, vitamin D supplementation, oral corticosteroids, n-acetylcysteine, and nebulized hypertonic saline, the clinical data behind each of these therapies, adverse events associated with therapy, and the expert recommendations for their utilization. Our goal is to provide a brief but informative and clinically useful review of commonly encountered therapies used in advanced COPD.
RESUMEN
Lung cancer is one of the most common malignancies globally with lung adenocarcinoma as the most common type of lung cancer. With new classification of lung cancers in 2011, it has become pertinent that adequate tissue is obtained for the diagnosis and subtyping of lung adenocarcinoma particularly for prognostication. Transbronchial cryobiopsy is a minimally invasive procedure which helps obtain adequate tissue and avoid surgical lung biopsy.
RESUMEN
Transbronchial lung biopsy using cryoadhesion is a diagnostic technique gaining in popularity. Several studies have been performed on its diagnostic yield and safety profile. However, definitive conclusions are limited due to the heterogeneity of results. The most common complications described in the current literature are pneumothorax and hemorrhage. This case describes a 60-year-old female who developed a cavitary lung lesion shortly after undergoing transbronchial lung cryobiopsy, highlighting the need for further research on the rarer complications that may be associated with this promising procedure.
RESUMEN
Mono-(2-ethylhexyl) phthalate (MEHP), the active metabolite of di-(2-ethylhexyl) phthalate (DEHP), is a plasticizer with endocrine disruptor activity that has been shown to stimulate basal steroid biosynthesis in Leydig cells. The mechanism by which it does so is unknown. Using MA-10 mouse tumor Leydig cells, we assessed the effects of MEHP on reactive oxygen species (ROS) levels, and on the signal transduction pathways that mobilize cholesterol. Exposure to 0-300 µM MEHP stimulated basal progesterone production in a dose-dependent manner. Progesterone stimulation was correlated with increases in the phosphorylation of hormone-sensitive lipase (HSL; aka cholesteryl ester hydrolase), which is involved in the production of free cholesterol, and of steroidogenic acute regulatory (STAR) protein expression. Co-treating MA-10 cells with MEHP and the ROS scavenger N-acetyl cysteine (NAC) blocked the activation of HSL, blunted MEHP-induced STAR, and reduced basal progesterone formation. These observations suggest that ROS generation by MEHP leads to activation of HSL and increase in STAR which, together, result in increased free-cholesterol bioavailability and progesterone formation.
Asunto(s)
Colesterol/metabolismo , Dietilhexil Ftalato/análogos & derivados , Disruptores Endocrinos/toxicidad , Células Intersticiales del Testículo/efectos de los fármacos , Plastificantes/toxicidad , Progesterona/metabolismo , Esterol Esterasa/metabolismo , Acetilcisteína/farmacología , Animales , Línea Celular Tumoral , Dietilhexil Ftalato/toxicidad , Células Intersticiales del Testículo/metabolismo , Masculino , Ratones , Oxidación-Reducción , Fosfoproteínas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Breast cancer relapse remains a common cause of morbidity and mortality in patients who undergo initial treatment with surgery and with or without concurrent chemotherapy or radiation. Relapse rates remain high within the first decade after initial treatment, after which the risk of relapse decreases. While common within the first year of breast cancer diagnosis, pleural metastasis with malignant pleural effusion (MPE) after 10-12 years of a disease-free period is rare. Here, we present two uncommon cases of delayed breast cancer relapses with pleural metastasis, which caused MPEs.
RESUMEN
Instillation of an autologous blood patch for prolonged air leak (PAL) in chest tube system has been studied and determined to be a safe and effective treatment plan for adults. The current recommended treatment guidelines for a PAL in adolescent secondary to a spontaneous pneumothorax are surgical intervention. This paper serves as documentation of two case reports with successful treatment of PALs with autologous blood patch in two adolescent patients.
RESUMEN
Previous studies suggest that genetic variants within genes affecting the circadian rhythm influence the development of posttraumatic stress symptoms (PTSS). In the present study, we used data from three emergency care-based cohorts to search genetic variants in circadian pathway genes previously associated with neuropsychiatric disorders for variants that influence PTSS severity. The three cohorts used included a discovery cohort of African American men and women enrolled following motor vehicle collision (n = 907) and two replication cohorts: one of multi-ethnic women enrolled following sexual assault (n = 274) and one of multi-ethnic men and women enrolled following major thermal burn injury (n = 68). DNA and RNA were collected from trauma survivors at the time of initial assessment. Validated questionnaires were used to assess peritraumatic distress severity and to assess PTSS severity 6 weeks, 6 months, and 1 year following trauma exposure. Thirty-one genetic variants from circadian rhythm genes were selected for analyses, and main effect and potential gene*stress and gene*sex interactions were evaluated. Secondary analyses assessed whether associated genetic variants affected mRNA expression levels. We found that six genetic variants across five circadian rhythm-associated genes predicted PTSS outcomes following motor vehicle collision (p < 0.05), but only two of these variants survived adjustment for multiple comparisons (False Discovery Rate < 5%). The strongest of these associations, an interaction between the PAR-zip transcription factor, thyrotroph embryonic factor (TEF) variant rs5758324 and peritraumatic distress, predicted PTSS development in all three cohorts. Further analysis of genetic variants in the genetic region surrounding TEFrs5758324 (±125,000 nucleotides) indicated that this allele showed the strongest association. Further, TEF RNA expression levels (determined via RNA-seq) were positively associated with PTSS severity in distressed individuals with at least one copy of the TEFrs5758324 minor allele. These results suggest that rs5758324 genetic variant in TEF, a regulator of clock-controlled genes and key mediator of the core circadian rhythm, influence PTSS severity in a stress-dependent manner.