RESUMO
CASE PRESENTATION: A 63-year-old Japanese woman with no medical history presented as an outside hospital transfer for further management of acute hypoxemic respiratory failure. Per her family, the patient had developed a rash and intermittent shortness of breath 2 months prior to hospital presentation. The rash was described as an erythematous maculopapular rash located on her proximal arms, chest, and upper eyelids. She saw her primary care physician, who prescribed a course of oral and topical corticosteroids. Despite these symptoms, the patient had an excellent functional status and exercised several times per week without muscle weakness. Two months following the initial presentation, the patient progressively became lethargic, prompting her son to bring her to the hospital for admission and evaluation. While in the hospital, the patient had progressive shortness of breath and developed worsening hypoxemic respiratory failure. Despite broad-spectrum antibiotics, her hypoxemia worsened, requiring intubation. She was subsequently started on 80 mg of IV methylprednisolone three times daily and transferred to our institution for further management. The patient arrived from the outside hospital receiving deep sedation and paralysis. Despite maximal ventilator settings, the patient remained hypoxemic and developed shock requiring multiple vasopressors.
Assuntos
Exantema , Doenças Pulmonares Intersticiais , Insuficiência Respiratória , Dispneia , Feminino , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/diagnóstico , Metilprednisolona , Pessoa de Meia-Idade , Insuficiência Respiratória/diagnóstico , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapiaRESUMO
Background Clustering key clinical characteristics of participants in the Severe Asthma Research Program (SARP), a large, multicenter prospective observational study of patients with asthma and healthy controls, has led to the identification of novel asthma phenotypes. Purpose To determine whether quantitative CT (qCT) could help distinguish between clinical asthma phenotypes. Materials and Methods A retrospective cross-sectional analysis was conducted with the use of qCT images (maximal bronchodilation at total lung capacity [TLC], or inspiration, and functional residual capacity [FRC], or expiration) from the cluster phenotypes of SARP participants (cluster 1: minimal disease; cluster 2: mild, reversible; cluster 3: obese asthma; cluster 4: severe, reversible; cluster 5: severe, irreversible) enrolled between September 2001 and December 2015. Airway morphometry was performed along standard paths (RB1, RB4, RB10, LB1, and LB10). Corresponding voxels from TLC and FRC images were mapped with use of deformable image registration to characterize disease probability maps (DPMs) of functional small airway disease (fSAD), voxel-level volume changes (Jacobian), and isotropy (anisotropic deformation index [ADI]). The association between cluster assignment and qCT measures was evaluated using linear mixed models. Results A total of 455 participants were evaluated with cluster assignments and CT (mean age ± SD, 42.1 years ± 14.7; 270 women). Airway morphometry had limited ability to help discern between clusters. DPM fSAD was highest in cluster 5 (cluster 1 in SARP III: 19.0% ± 20.6; cluster 2: 18.9% ± 13.3; cluster 3: 24.9% ± 13.1; cluster 4: 24.1% ± 8.4; cluster 5: 38.8% ± 14.4; P < .001). Lower whole-lung Jacobian and ADI values were associated with greater cluster severity. Compared to cluster 1, cluster 5 lung expansion was 31% smaller (Jacobian in SARP III cohort: 2.31 ± 0.6 vs 1.61 ± 0.3, respectively, P < .001) and 34% more isotropic (ADI in SARP III cohort: 0.40 ± 0.1 vs 0.61 ± 0.2, P < .001). Within-lung Jacobian and ADI SDs decreased as severity worsened (Jacobian SD in SARP III cohort: 0.90 ± 0.4 for cluster 1; 0.79 ± 0.3 for cluster 2; 0.62 ± 0.2 for cluster 3; 0.63 ± 0.2 for cluster 4; and 0.41 ± 0.2 for cluster 5; P < .001). Conclusion Quantitative CT assessments of the degree and intraindividual regional variability of lung expansion distinguished between well-established clinical phenotypes among participants with asthma from the Severe Asthma Research Program study. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Verschakelen in this issue.
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Asma , Asma/diagnóstico por imagem , Estudos Transversais , Feminino , Humanos , Pulmão/diagnóstico por imagem , Fenótipo , Doença Pulmonar Obstrutiva Crônica , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodosRESUMO
CASE PRESENTATION: A 47-year-old Hispanic woman presented to a pulmonology clinic with 2 weeks of cough productive of white sputum and worsening dyspnea on exertion, requiring increasing supplemental oxygen. In addition, she reported fatigue, night sweats, diffuse myalgias, and extremity weakness. She denied hemoptysis, fevers, chills, weight loss, or rash. Her medical history is significant for undifferentiated rapidly progressive hypoxemic respiratory failure 2 years before her current presentation. At that time, she presented to the ED with 3 weeks of progressive shortness of breath and cough. Chest CT imaging showed bilateral infiltrates concerning for infection, and she was treated empirically for community-acquired pneumonia. She developed worsening hypoxemic respiratory failure despite broadening of her antibiotics and subsequently required intubation. Her course was further complicated by pulseless electrical activity arrest with return of spontaneous circulation and development of shock requiring multiple vasopressors. Because of difficulty with oxygenation, she was referred to our center for extracorporeal membrane oxygenation evaluation and was ultimately started on venous-arterial extracorporeal membrane oxygenation. Bronchoscopy with BAL was negative for bacterial, viral, and fungal origins, and initial autoimmune evaluation (antinuclear antibody and rheumatoid factor) was negative, except an elevated creatine kinase (CK) to 3,000. Her course was complicated by heparin-induced thrombocytopenia, and as a result she suffered limb ischemia requiring amputation of her left lower extremity. Elevated CK at that time was attributed to compartment syndrome before amputation. The patient recovered clinically with supportive care and was ultimately discharged on 2 L supplemental oxygen, with a diagnosis of acute respiratory failure of unclear origin. The patient had stability in her clinical symptoms until this current presentation.
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Miosite/complicações , Miosite/diagnóstico , Insuficiência Respiratória/etiologia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Pessoa de Meia-Idade , Miosite/terapia , Insuficiência Respiratória/terapiaRESUMO
Background: The optimal resuscitative fluid remains controversial. Objective: To assess the association between crystalloid fluid and outcomes in critically ill adults. Methods: Cumulative Index to Nursing and Allied Health Literature, Scopus, PubMed, and Cochrane Central Register for Controlled Trials were searched from inception through July 2019. Cohort studies and randomized trials of critically ill adults provided predominantly nonperioperative fluid resuscitation with balanced crystalloids or 0.9% sodium chloride (saline) were included. Results: Thirteen studies (n = 30 950) were included. Balanced crystalloids demonstrated lower hospital or 28-/30-day mortality (risk ratio [RR] = 0.86; 95% CI = 0.75-0.99; I2 = 82%) overall, in observational studies (RR = 0.64; 95% CI = 0.41-0.99; I2 = 63%), and approached significance in randomized trials (RR = 0.94; 95% CI = 0.88-1.02; I2 = 0%). New acute kidney injury occurred less frequently with balanced crystalloids (RR = 0.91; 95% CI = 0.85-0.98; I2 = 0%), though progression to renal replacement therapy was similar (RR = 0.91; 95% CI = 0.79-1.04; I2 = 38%). In the sepsis cohort, odds of hospital or 28-/30-day mortality were similar, but the odds of major adverse kidney events occurring in the first 30 days were less with balanced crystalloids than saline (OR = 0.78; 95% CI = 0.66-0.91; I2 = 42%). Conclusion and Relevance: Resuscitation with balanced crystalloids demonstrated lower hospital or 28-/30-day mortality compared with saline in critically ill adults but not specifically those with sepsis. Balanced crystalloids should be provided preferentially to saline in most critically ill adult patients.
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Soluções Cristaloides/administração & dosagem , Hidratação/métodos , Soluções para Reidratação/administração & dosagem , Sepse/terapia , Cloreto de Sódio/administração & dosagem , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapia , Adulto , Estado Terminal , Soluções Cristaloides/efeitos adversos , Humanos , Tempo de Internação , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Soluções para Reidratação/efeitos adversos , Terapia de Substituição Renal , Sepse/mortalidade , Cloreto de Sódio/efeitos adversosRESUMO
PURPOSE: To evaluate the effects of midodrine in addition to intravenous vasopressor therapy on outcomes in adults recovering from shock. MATERIALS AND METHODS: PubMed, Scopus, Clinicaltrials.gov, and published abstracts were searched from inception to November 2018 for studies comparing outcomes in shock after midodrine initiation versus no midodrine. RESULTS: Three studies with 2533 patients were included. Patients in whom midodrine was added to intravenous vasopressor therapy compared to intravenous vasopressor therapy alone experienced similar intensive care unit (ICU; mean difference [MD]: 1.38 days, 95% confidence interval [CI]: -3.48 to 6.23, I2 = 93%) and hospital lengths of stay (MD: 4.37 days, 95% CI: -3.45 to 12.19, I2 = 93%) and intravenous vasopressor duration after midodrine initiation (MD: 7.28 days, 95% CI: -0.86 to 15.41, I2 = 97%). Mortality was similar between groups (odds ratio: 0.74, 95% CI: 0.44-1.27, I2 = 65%). Qualitative assessment of reporting biases revealed minimal location bias, moderate selective outcome reporting bias, no selective analysis reporting bias, and no conflict of interest bias. CONCLUSIONS: Midodrine had no effect on ICU or hospital length of stay. These results were highly susceptible to the study heterogeneity and availability. Future investigation into standardized initiation of midodrine at an adequate dosage with an expedited titration strategy is needed in order to assess the utility of this strategy in shock management.
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Midodrina , Choque , Administração Intravenosa , Adulto , Humanos , Unidades de Terapia Intensiva , Choque/tratamento farmacológico , Vasoconstritores/uso terapêuticoRESUMO
There have been significant advancements in the various imaging techniques being used for the evaluation of asthmatic patients, both from a clinical and research perspective. Imaging characteristics can be used to identify specific asthmatic phenotypes and provide a more detailed understanding of endotypes contributing to the pathophysiology of the disease. Computed tomography, magnetic resonance imaging, and positron emission tomography can be used to assess pulmonary structure and function. It has been shown that specific airway and lung density measurements using computed tomography correlate with clinical parameters, including severity of disease and pathology, but also provide unique phenotypes. Hyperpolarized 129Xe and 3He are gases used as contrast media for magnetic resonance imaging that provide measurement of distal lung ventilation reflecting small-airway disease. Positron emission tomography can be useful to identify and target lung inflammation in asthmatic patients. Furthermore, imaging techniques can serve as a potential biomarker and be used to assess response to therapies, including newer biological treatments and bronchial thermoplasty.
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Asma/diagnóstico por imagem , Asma/patologia , Biomarcadores , Humanos , Pulmão/patologia , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios XRESUMO
Although a small proportion of patients with asthma have severe disease, it accounts for the majority of morbidity related to the illness. Severe asthma comprises a heterogeneous group of phenotypes. Targeted treatments for these phenotypes represent a major advancement in the management of severe asthma. Omalizumab, a monoclonal antibody to IgE, improves asthma control in patients with a predominant allergic phenotype. Monoclonal antibodies targeted to interleukin 4α and interleukin 5 have shown substantial benefit in patients with the eosinophilic asthma phenotype; so too have monoclonal antibodies targeted to interleukin 13 in patients with a type 2 allergic phenotype. Bronchial thermoplasty, a new technique to reduce airway smooth muscle mass, improves symptoms and reduces exacerbations in patients with severe uncontrolled asthma and the chronic airflow obstruction phenotype. While awaiting comparative trials, we can now use a targeted approach with these phenotypes, guiding our treatment selection with the best evidence. This Review will focus on the latest developments in these new treatments and inform the clinician on how to select the appropriate patient for these treatments.
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Antiasmáticos/uso terapêutico , Asma/terapia , Terapia Biológica/métodos , Termoplastia Brônquica/métodos , Índice de Gravidade de Doença , Asma/patologia , Progressão da Doença , Humanos , Omalizumab/uso terapêutico , Fenótipo , Eosinofilia Pulmonar/terapia , Resultado do TratamentoRESUMO
In 2013, a before-and-after intervention study was conducted to evaluate the effect 24-hour intensivist coverage on length of stay and rates of catheter-associated urinary tract infection, central-line associated blood stream infection, and ventilator-associated events. Intensivist coverage for 24 hours did not decrease length of stay or result in a decrease in any specific infection rate.
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Infecções Relacionadas a Cateter/epidemiologia , Unidades de Terapia Intensiva , Tempo de Internação/estatística & dados numéricos , Admissão e Escalonamento de Pessoal/organização & administração , Pneumonia Associada à Ventilação Mecânica/epidemiologia , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva/organização & administração , Melhoria de Qualidade , Estudos Retrospectivos , Recursos HumanosRESUMO
Cisplatin is effective against solid tumors including ovarian cancer. However, inherent or acquired cisplatin resistance limits clinical success. We recently demonstrated that a combination of sodium arsenite (NaAsO2) and hyperthermia sensitizes p53-expressing ovarian cancer cells to cisplatin by modulating DNA repair pathway and enhancing platinum accumulation. However, it is not understood how this combination therapy modulates cell cycle following platinum-DNA damage. The goal of the present study was to determine if NaAsO2 and hyperthermia alter cisplatin-induced G2 arrest and cause mitotic arrest and mitotic catastrophe. Human epithelial ovarian cancer cells (A2780 and A2780/CP70) were treated with cisplatin ± 20 µM NaAsO2 at 37 or 39°C for 1 h. Cisplatin ± NaAsO2 at 37 or 39°C caused cells to accumulate in G2/M compartment at 36 h after treatment. Western blot analysis of cyclin A and cyclin B suggested that combined NaAsO2, hyperthermia, and cisplatin induced mitotic arrest. However, we observed < 3% mitotic index and phosphorylation of histone H3 on serine 10 was undetectable. These results did not confirm mitotic arrest. BUBR1 (BUB1B) also was not phosphorylated, suggesting disrupted mitotic checkpoint. Postmitotic cells accumulated in pseudo-G1 as demonstrated by cyclin E stabilization, CDKN1A induction, and hypophosphorylation of retinoblastoma protein. These cells also were positive for Annexin V binding indicating they were apoptotic. In summary, cisplatin plus NaAsO2 and hyperthermia induced pseudo-G1 associated apoptosis in ovarian cancer cells.