RESUMEN
Outcomes of tracheostomized patients with COVID-19 are seldomly investigated with conflicting evidence from the existing literature. OBJECTIVES: To create a study evaluating the impact of COVID-19 on tracheostomized patients by comparing clinical outcomes and weaning parameters in COVID-19 positive and negative cohorts. DESIGN SETTING AND PARTICIPANTS: A retrospective observational cohort study of 604 tracheostomized patients hospitalized in 16 ICUs in New York City between March 9, 2020, and September 8, 2021. MAIN OUTCOMES AND MEASURES: Patients were stratified into two cohorts: 398 COVID-19 negative (COVID-ve) and 206 COVID-19 positive (COVID+ve) patients. Clinical characteristics, outcomes, and weaning parameters (first pressure support [PS], tracheostomy collar [TC], speech valve placement, and decannulation) were analyzed. RESULTS: COVID+ve had fewer comorbidities including coronary artery disease, congestive heart failure, malignancy, chronic kidney disease, liver disease, and HIV (p < 0.05). Higher Fio2 (53% vs 44%), positive end-expiratory pressure (PEEP) (7.15 vs 5.69), Pco2 (45.8 vs 38.2), and lower pH (7.41 vs 7.43) were observed at the time of tracheostomy in COVID+ve (p < 0.005). There was no statistical difference in post-tracheostomy complication rates. Longer time from intubation to tracheostomy (15.90 vs 13.60 d; p = 0.002), tracheostomy to first PS (2.87 vs 1.80 d; p = 0.005), and TC placement (11.07 vs 4.46 d; p < 0.001) were seen in COVID+ve. However, similar time to speech valve placement, decannulation, and significantly lower 1-year mortality (23.3% vs 36.7%; p = 0.001) with higher number of discharges to long-term acute care hospital (LTACH) (23.8% vs 13.6%; p = 0.015) were seen in COVID+ve. CONCLUSIONS AND RELEVANCE: Patients with COVID-19 required higher Fio2 and PEEP ventilatory support at the time of tracheostomy, with no observed change in complication rates. Despite longer initial weaning period with PS or TC, similar time to speech valve placement or decannulation with significantly lower mortality and higher LTACH discharges suggest favorable outcome in COVID-19 positive patients. Higher ventilatory support requirements and prolonged weaning should not be a deterrent to pursuing a tracheostomy.
RESUMEN
OBJECTIVES: The COVID-19 pandemic in the USA has been accompanied by high rates of mortality and an unprecedented need for palliative care delivery. Little is known about the use of palliative care services in intensive care unit (ICU) settings during the COVID-19 pandemic. METHODS: This is a retrospective cohort study of critically ill COVID-19 patients requiring ICU admission, between 7 March and 14 April 2020 to two academic teaching hospitals in New York City. Palliative care consultation included a one-time telemedicine consultation or continued telemedicine consultation and follow-up with multidisciplinary team involvement. Patient information was collected from the electronic health record and analyses were conducted with Stata V.15.1 (StataCorp) statistical software. RESULTS: A total of 151 critically ill patients with COVID-19 pneumonia requiring ICU admission were identified, of whom 59 (39.07%) received an inpatient palliative care consultation. More than half of patients died (n=85/151, 56.29%), with 57.65% (n=49/85) of these patients receiving palliative care services during their hospitalisation. Patients who received palliative care consultation were more likely to be older, sicker and receive mechanical ventilation than their counterparts. Patients who died and did not receive palliative care were younger and required non-invasive ventilation support. CONCLUSION: There is a lack of utilisation of palliative care in COVID-19 patients admitted to the ICU. Further research into predictors of poor outcomes in critically ill COVID-19 patients may help identify patients that would benefit from early palliative care involvement going forward.
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COVID-19 , Humanos , COVID-19/terapia , Cuidados Paliativos , Ciudad de Nueva York/epidemiología , SARS-CoV-2 , Enfermedad Crítica/terapia , Pandemias , Estudios Retrospectivos , Respiración Artificial , Unidades de Cuidados IntensivosRESUMEN
Data are conflicting regarding the impact of tobacco smoking in people with pneumonia due to SARS-CoV-2 infection (COVID-19). We performed a retrospective multicentre cohort study of 9991 consecutive patients hospitalized in a major New York academic center between March 7th and June 5th, 2020 with laboratory-confirmed COVID-19. The clinical outcomes assessed included risk of hospitalization, in-hospital mortality, risk of intensive care unit (ICU) admission, and need for mechanical ventilation among smokers (current and former). Multivariable logistic regression and propensity score models were built to adjust for potential confounders. Among 9991 consecutive patients diagnosed with COVID-19, 2212 (22.1%) patients were self-reported smokers (406 current and 1806 former). Current smoking was not associated with an increased risk of hospitalization (propensity score [PS]-adjusted OR 0.91; p = .46), in-hospital mortality (PS-OR 0.77; p = .12), ICU admission (PS-OR 1.18; p = .37), or intubation (PS-OR 1.04; p = .85). Similarly, former smoking was not associated with an increased risk of hospitalization (PS-OR 0.88; p = .11), in-hospital mortality (PS-OR 1.03; p = .78), ICU admission (PS-OR 1.03; p = .95), or intubation (PS-OR 0.93; p = .57). Furthermore, smoking (current or former) was not associated with an increased risk of hospitalization (PS-OR 0.85; p = .05), in-hospital mortality (PS-OR 0.94; p = .49), ICU admission (PS-OR 0.86; p = .17), or intubation (PS-OR 0.79; p = .06). Smoking is a well-known risk factor associated with greater susceptibility and subsequent increased severity of respiratory infections. In the current COVID-19 pandemic, smokers may have increased risk and severe pneumonia. In the current COVID-19 pandemic, smokers are believed to have an increased risk of mortality as well as severe pneumonia. However, in our analysis of real-world clinical data, smoking was not associated with increased in-patient mortality in COVID-19 pneumonia, in accordance with prior reports.
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COVID-19/mortalidad , Cuidados Críticos/estadística & datos numéricos , Fumar/mortalidad , COVID-19/patología , Síndrome de Liberación de Citoquinas/patología , Femenino , Mortalidad Hospitalaria , Hospitalización/estadística & datos numéricos , Humanos , Inflamación/patología , Masculino , Persona de Mediana Edad , Ciudad de Nueva York , Respiración Artificial/estadística & datos numéricos , Estudios Retrospectivos , SARS-CoV-2RESUMEN
A 56-year-old man presented to the ED of an outside hospital with 2 days of bleeding gums and easy bruising. He denied episodes of melena, hematemesis, or hematuria and had no epistaxis. Routine blood work showed pancytopenia and evidence of diffuse intravascular coagulation. A bone marrow biopsy confirmed the diagnosis of acute promyelocytic leukemia. He was transferred to our hospital for treatment.
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Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/patología , Infiltración Leucémica/diagnóstico , Infiltración Leucémica/patología , Pulmón/patología , Biopsia , Médula Ósea/patología , Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Humanos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Infiltración Leucémica/tratamiento farmacológico , Recuento de Leucocitos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Radiografía Torácica , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Pregnancy physiology may predispose women to the development of airflow limitations during sleep. The goal of this study was to evaluate whether pregnant women suspected of sleep-disordered breathing (SDB) are more likely to have airflow limitations compared to non-pregnant controls. METHODS: We recruited pregnant women referred for polysomnography for a diagnosis of SDB. Non-pregnant female controls matched for age, body mass index (BMI), and apnoea-hypopnoea index (AHI) were identified from a database. We examined airflow tracings for changes in amplitude and shape. We classified airflow limitation by (a) amplitude criteria defined as decreased airflow of > or =10 s without desaturation or arousal (FL 10), or decreased airflow of any duration combined with either 1-2% desaturation or arousal, (FL 1-2%); and (b) shape criteria defined as the presence of flattening or oscillations of the inspiratory flow curve. RESULTS: We identified 25 case-control pairs. Mean BMI was 44.0±6.9 in cases and 44.1±7.3 in controls. Using shape criteria, pregnant women had significantly more flow-limited breaths throughout total sleep time (32.4±35.8 vs. 9.4±17.9, p<0.0001) and in each stage of sleep (p<0.0001) than non-pregnant controls. In a subgroup analysis, pregnant women without a diagnosis of obstructive sleep apnoea (OSA) who had an AHI <5 had similar findings (p<0.0001). There was no difference in airflow limitation by amplitude criteria between pregnant women and controls (p=0.22). CONCLUSIONS: Pregnant women suspected of OSA have more frequent shape-defined airflow limitations than non-pregnant controls, even when they do not meet polysomnographic OSA criteria.
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Complicaciones del Embarazo/fisiopatología , Fenómenos Fisiológicos Respiratorios , Síndromes de la Apnea del Sueño/complicaciones , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Polisomnografía , Embarazo , Síndromes de la Apnea del Sueño/fisiopatología , Fases del Sueño/fisiologíaRESUMEN
Particulate matter (PM) has been associated with serious health effects within but also outside of the pulmonary system. Therefore, there is great interest in studying the biodistribution of PM after delivery to the lung to correlate sites of extrapulmonary particle accumulation and abnormal conditions known to be associated with PM exposure. Traditional PM tracking studies have introduced nanoparticles to animal models or humans and have determined the biodistribution with gamma counting, gamma camera, and inductively coupled plasma mass spectrometry (ICP-MS). The authors here demonstrate that positron emission tomography (PET) is a powerful tool that can be employed to visualize the deposition and track the fate of nanoparticles in the mouse model. In these studies, approximately 100-nm polystyrene nanoparticles were labeled with the positron emitter 64Cu bound by the chelator (S)-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (p-SCN-Bn-DOTA). The labeled nanoparticles were instilled intratracheally into C57BL/6 mice; the initial deposition and biodistribution through 48 h was determined by PET imaging. In addition to static imaging, dynamic imaging was performed in the Sprague-Dawley rat model to demonstrate that PET can capture particle movement in pseudo-time-lapse videos. Particle deposition and clearance was clearly identified by PET, and the same animals could be imaged repeatedly without any adverse effects from anesthesia. PET has the potential to require many fewer animals than traditional methods while still providing quantitative results. In addition, the initial deposition pattern in each animal can be accurately determined and the same animal monitored over time so that data interpretation is not clouded by variations in initial deposition profiles.
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Contaminantes Atmosféricos/farmacocinética , Nanopartículas , Material Particulado/farmacocinética , Tomografía de Emisión de Positrones/métodos , Contaminantes Atmosféricos/química , Contaminantes Atmosféricos/toxicidad , Alternativas al Uso de Animales/métodos , Animales , Quelantes/química , Radioisótopos de Cobre/química , Radioisótopos de Cobre/farmacocinética , Vías de Administración de Medicamentos , Femenino , Compuestos Heterocíclicos/química , Imagenología Tridimensional/métodos , Isotiocianatos/química , Límite de Detección , Masculino , Ratones , Ratones Endogámicos C57BL , Nanopartículas/administración & dosificación , Nanopartículas/química , Nanopartículas/toxicidad , Material Particulado/administración & dosificación , Material Particulado/química , Material Particulado/toxicidad , Poliestirenos/química , Ratas , Ratas Sprague-Dawley , Distribución Tisular , Imagen de Cuerpo EnteroRESUMEN
The hedgehog signaling network regulates pattern formation, proliferation, cell fate and stem/progenitor cell self-renewal in many organs. Altered hedgehog signaling is implicated in 20-25% of all cancers, including breast cancer. We demonstrated previously that heterozygous disruption of the gene encoding the patched-1 (PTCH1) hedgehog receptor, a negative regulator of smoothened (Smo) in the absence of ligand, led to mammary ductal dysplasia in virgin mice. We now show that expression of activated human SMO (SmoM2) under the mouse mammary tumor virus (MMTV) promoter in transgenic mice leads to increased proliferation, altered differentiation, and ductal dysplasias distinct from those caused by Ptch1 heterozygosity. SMO activation also increased the mammosphere-forming efficiency of primary mammary epithelial cells. However, limiting-dilution transplantation showed a decrease in the frequency of regenerative stem cells in MMTV-SmoM2 epithelium relative to wild type, suggesting enhanced mammosphere-forming efficiency was due to increased survival or activity of division-competent cell types under anchorage-independent growth conditions, rather than an increase in the proportion of regenerative stem cells per se. In human clinical samples, altered hedgehog signaling occurs early in breast cancer development, with PTCH1 expression reduced in approximately 50% of ductal carcinoma in situ (DCIS) and invasive breast cancers (IBC). Conversely, SMO is ectopically expressed in 70% of DCIS and 30% of IBC. Surprisingly, in both human tumors and MMTV-SmoM2 mice, SMO rarely colocalized with the Ki67 proliferation marker. Our data suggest that altered hedgehog signaling may contribute to breast cancer development by stimulating proliferation, and by increasing the pool of division-competent cells capable of anchorage-independent growth.
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Transformación Celular Neoplásica/metabolismo , Enfermedad Fibroquística de la Mama/etiología , Proteínas Hedgehog/metabolismo , Glándulas Mamarias Animales/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animales , Apoptosis , Caspasa 3/metabolismo , Diferenciación Celular , Proliferación Celular , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Enfermedad Fibroquística de la Mama/genética , Enfermedad Fibroquística de la Mama/patología , Humanos , Antígeno Ki-67/análisis , Antígeno Ki-67/metabolismo , Glándulas Mamarias Animales/química , Glándulas Mamarias Animales/patología , Virus del Tumor Mamario del Ratón/genética , Ratones , Ratones Transgénicos , Receptores Patched , Receptor Patched-1 , Regiones Promotoras Genéticas , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Receptores Acoplados a Proteínas G/análisis , Receptores Acoplados a Proteínas G/genética , Receptor Smoothened , TransgenesRESUMEN
Synthesis of a radiolabeled diglyceride, 3-[(18)F]fluoro-1,2-dipalmitoylglycerol [[(18)F]fluorodipalmitin ([(18)F]FDP)], and its potential as a reagent for radiolabeling long-circulating liposomes were investigated. The incorporation of (18)F into the lipid molecule was accomplished by nucleophilic substitution of the p-toluenesulfonyl moiety with a decay-corrected yield of 43+/-10% (n=12). Radiolabeled, long-circulating polyethylene-glycol-coated liposomes were prepared using a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] ammonium salt (61:30:9) and [(18)F]FDP with a decay-corrected yield of 70+/-8% (n=4). PET imaging and biodistribution studies were performed with free [(18)F]FDP and liposome-incorporated [(18)F]FDP. Freely injected [(18)F]FDP had the highest uptake in the liver, spleen and lungs. Liposomal [(18)F]FDP remained in blood circulation at near-constant levels for at least 90 min, with a peak concentration near 2.5%ID/cc. Since [(18)F]FDP was incorporated into the phospholipid bilayer, it could potentially be used for radiolabeling a variety of lipid-based drug carriers.