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16 result(s) for "Siner, Jonathan"
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Circulating monocytes from systemic sclerosis patients with interstitial lung disease show an enhanced profibrotic phenotype
Profibrotic cells derived from circulating CD14+ monocytes include fibrocytes and alternatively activated macrophages. These cells are associated with interstitial lung disease (ILD) and are implicated in the pathogenesis of systemic sclerosis (SSc); however, the simultaneous presence of profibrotic cells and their associated mediators in the circulation of these patients has not been defined. We hypothesized that monocytes from patients with SSc-related ILD (SSc-ILD) would show profibrotic characteristics when compared with normal controls. We recruited patients with SSc-ILD (n=12) and normal controls (n=27) and quantified circulating collagen-producing cells by flow cytometry for CD45 and pro-collagen I. The in vitro activation potential of CD14+ monocytes in response to lipopolysaccharide was assessed using flow cytometry for CD163, and by ELISA for CCL18 and IL-10 secretion. Profibrotic mediators in plasma were quantified using Luminex-based assays. The concentration of circulating collagen-producing cells was increased in the SSc-ILD patients when compared with controls. These cells were composed of both CD34+ fibrocytes and a population of CD34+CD14+ cells. Cultured CD14+ monocytes from SSc-ILD patients revealed a profibrotic phenotype characterized by expression of CD163 and by enhanced secretion of CCL18 and IL-10 in response to proinflammatory activation. Plasma levels of IL-10, MCP-1, IL-1RA, and TNF levels were significantly elevated in the plasma of the SSc-ILD cohort. Subgroup analysis of the normal controls revealed that unlike the subjects ≤35 years, subjects ≥60 years old showed higher levels of circulating CD34+CD14+ cells, collagen-producing CD14+ monocytes, CD163+ monocytes, IL-4, IL-10, IL-13, MCP-1, and CCL18. These data indicate that the blood of patients with SSc-ILD and of healthy aged controls is enriched for fibrocytes, profibrotic monocytes, and fibrosis-associated mediators. Investigations defining the factors responsible for this peripheral blood profile may provide new insight into SSc-ILD as well as the pathophysiology of aging.
“Deterioration to Door Time”: An Exploratory Analysis of Delays in Escalation of Care for Hospitalized Patients
BACKGROUNDTimely escalation of care for patients experiencing clinical deterioration in the inpatient setting is challenging. Deterioration on a general floor has been associated with an increased risk of death, and the early period of deterioration may represent a time during which admission to the intensive care unit (ICU) improves survival. Previous studies examining the association between delay from onset of clinical deterioration to ICU transfer and mortality are few in number and were conducted more than 10 years ago.OBJECTIVEWe aimed to evaluate the impact of delays in the escalation of care among clinically deteriorating patients in the current era of inpatient medicine.DESIGN AND PARTICIPANTSThis was a retrospective cohort study that analyzed data from 793 patients transferred from non-intensive care unit (ICU) inpatient floors to the medical intensive care unit (MICU), from 2011 to 2013 at an urban, tertiary, academic medical center.MAIN MEASURES“Deterioration to door time (DTDT)” was defined as the time between onset of clinical deterioration (as evidenced by the presence of one or more vital sign indicators including respiratory rate, systolic blood pressure, and heart rate) and arrival in the MICU.KEY RESULTSIn our sample, 64.6 % had delays in care escalation, defined as greater than 4 h based on previous studies. Mortality was significantly increased beginning at a DTDT of 12.1 h after adjusting for age, gender, and severity of illness.CONCLUSIONSDelays in the escalation of care for clinically deteriorating hospitalized patients remain frequent in the current era of inpatient medicine, and are associated with increased in-hospital mortality. Development of performance measures for the care of clinically deteriorating inpatients remains essential, and timeliness of care escalation deserves further consideration.
Relationship Between Laryngeal Sensation, Length of Intubation, and Aspiration in Patients with Acute Respiratory Failure
Dysphagia is common in hospitalized patients post-extubation and associated with poor outcomes. Laryngeal sensation is critical for airway protection and safe swallowing. However, current understanding of the relationship between laryngeal sensation and aspiration in post-extubation populations is limited. Acute respiratory failure patients requiring intensive care unit admission and mechanical ventilation received a Flexible Endoscopic Evaluation of Swallowing (FEES) within 72 h of extubation. Univariate and multivariable analyses were performed to examine the relationship between laryngeal sensation, length of intubation, and aspiration. Secondary outcomes included pharyngolaryngeal secretions, pneumonia, and diet recommendations. One-hundred and three patients met inclusion criteria. Fifty-one patients demonstrated an absent laryngeal adductor reflex (LAR). Altered laryngeal sensation correlated with the presence of secretions (p = 0.004). There was a significant interaction between the LAR, aspiration, and duration of mechanical ventilation. Altered laryngeal sensation was significantly associated with aspiration on FEES only in patients with a shorter length of intubation (p = 0.008). Patients with altered laryngeal sensation were prescribed significantly more restricted liquid (p = 0.03) and solid (p = 0.001) diets. No relationship was found between laryngeal sensation and pneumonia. There is a high prevalence of laryngeal sensory deficits in mechanically ventilated patients post-extubation. Altered laryngeal sensation was associated with secretions, aspiration, and modified diet recommendations especially in those patients with a shorter length of mechanical ventilation. These results demonstrate that laryngeal sensory abnormalities impact the development of post-extubation dysphagia.
Oral Alimentation in Neonatal and Adult Populations Requiring High-Flow Oxygen via Nasal Cannula
Use of high-flow oxygen via nasal cannula (HFO 2 -NC) is increasingly common in intensive care unit (ICU) settings. Despite the critical interface between respiration and swallowing, and the high acuity of patients in ICUs, the impact of HFO 2 -NC on feeding and swallowing is unknown. The present prospective, single-center, cohort study investigated the impact of HFO 2 -NC use on oral alimentation in neonatal and adult ICU patients. Oral alimentation status was evaluated in 100 consecutive ICU inpatients (50 neonatal and 50 adult) requiring HFO 2 -NC. Participant characteristics, respiratory support, successful initiation of oral feeding in neonates, and successful resumption of oral feeding in adults were recorded. Seventeen of 50 (34 %) neonates requiring HFO 2 -NC were deemed developmentally and medically appropriate by the neonatologist and nursing to begin oral alimentation. All 17 (100 %) were successful with initiation of oral feedings. Thirty-three of 50 (66 %) continued nil per os due to prematurity or medical conditions precluding oral alimentation at time of data collection. Thirty-nine of 50 (78 %) adults requiring HFO 2 -NC were deemed medically appropriate by the intensivist and nursing to resume oral alimentation ( n  = 34) or with a functional swallow without aspiration on FEES ( n  = 5). All 39 (100 %) resumed oral alimentation successfully. Eleven of 50 (22 %) continued nil per os due to severe respiratory issues precluding both swallow testing and oral alimentation at time of data collection. All developmentally and medically appropriate neonatal and adult patients requiring HFO 2 -NC were successful with either the introduction or resumption of oral alimentation. Patients requiring HFO 2 -NC who are identified as having feeding or swallowing issues should be referred for swallowing evaluations using the same criteria as patients who do not require HFO 2 -NC, as it is not the use of HFO 2 -NC but rather patient-specific determinants of feeding and swallowing readiness and their underlying medical conditions that impact readiness for oral alimentation status.
Early Warning Scores With and Without Artificial Intelligence
Early warning decision support tools to identify clinical deterioration in the hospital are widely used, but there is little information on their comparative performance. To compare 3 proprietary artificial intelligence (AI) early warning scores and 3 publicly available simple aggregated weighted scores. This retrospective cohort study was performed at 7 hospitals in the Yale New Haven Health System. All consecutive adult medical-surgical ward hospital encounters between March 9, 2019, and November 9, 2023, were included. Simultaneous Epic Deterioration Index (EDI), Rothman Index (RI), eCARTv5 (eCART), Modified Early Warning Score (MEWS), National Early Warning Score (NEWS), and NEWS2 scores. Clinical deterioration, defined as a transfer from ward to intensive care unit or death within 24 hours of an observation. Of the 362 926 patient encounters (median patient age, 64 [IQR, 47-77] years; 200 642 [55.3%] female), 16 693 (4.6%) experienced a clinical deterioration event. eCART had the highest area under the receiver operating characteristic curve at 0.895 (95% CI, 0.891-0.900), followed by NEWS2 at 0.831 (95% CI, 0.826-0.836), NEWS at 0.829 (95% CI, 0.824-0.835), RI at 0.828 (95% CI, 0.823-0.834), EDI at 0.808 (95% CI, 0.802-0.812), and MEWS at 0.757 (95% CI, 0.750-0.764). After matching scores at the moderate-risk sensitivity level for a NEWS score of 5, overall positive predictive values (PPVs) ranged from a low of 6.3% (95% CI, 6.1%-6.4%) for an EDI score of 41 to a high of 17.3% (95% CI, 16.9%-17.8%) for an eCART score of 94. Matching scores at the high-risk specificity of a NEWS score of 7 yielded overall PPVs ranging from a low of 14.5% (95% CI, 14.0%-15.2%) for an EDI score of 54 to a high of 23.3% (95% CI, 22.7%-24.2%) for an eCART score of 97. The moderate-risk thresholds provided a median of at least 20 hours of lead time for all the scores. Median lead time at the high-risk threshold was 11 (IQR, 0-69) hours for eCART, 8 (IQR, 0-63) hours for NEWS, 6 (IQR, 0-62) hours for NEWS2, 5 (IQR, 0-56) hours for MEWS, 1 (IQR, 0-39) hour for EDI, and 0 (IQR, 0-42) hours for RI. In this cohort study of inpatient encounters, eCART outperformed the other AI and non-AI scores, identifying more deteriorating patients with fewer false alarms and sufficient time to intervene. NEWS, a non-AI, publicly available early warning score, significantly outperformed EDI. Given the wide variation in accuracy, additional transparency and oversight of early warning tools may be warranted.
Clinical characteristics and outcomes for 7,995 patients with SARS-CoV-2 infection
Severe acute respiratory syndrome virus (SARS-CoV-2) has infected millions of people worldwide. Our goal was to identify risk factors associated with admission and disease severity in patients with SARS-CoV-2. This was an observational, retrospective study based on real-world data for 7,995 patients with SARS-CoV-2 from a clinical data repository. Yale New Haven Health (YNHH) is a five-hospital academic health system serving a diverse patient population with community and teaching facilities in both urban and suburban areas. The study included adult patients who had SARS-CoV-2 testing at YNHH between March 1 and April 30, 2020. Primary outcomes were admission and in-hospital mortality for patients with SARS-CoV-2 infection as determined by RT-PCR testing. We also assessed features associated with the need for respiratory support. Of the 28605 patients tested for SARS-CoV-2, 7995 patients (27.9%) had an infection (median age 52.3 years) and 2154 (26.9%) of these had an associated admission (median age 66.2 years). Of admitted patients, 2152 (99.9%) had a discharge disposition at the end of the study period. Of these, 329 (15.3%) required invasive mechanical ventilation and 305 (14.2%) expired. Increased age and male sex were positively associated with admission and in-hospital mortality (median age 80.7 years), while comorbidities had a much weaker association with the risk of admission or mortality. Black race (OR 1.43, 95%CI 1.14-1.78) and Hispanic ethnicity (OR 1.81, 95%CI 1.50-2.18) were identified as risk factors for admission, but, among discharged patients, age-adjusted in-hospital mortality was not significantly different among racial and ethnic groups. This observational study identified, among people testing positive for SARS-CoV-2 infection, older age and male sex as the most strongly associated risks for admission and in-hospital mortality in patients with SARS-CoV-2 infection. While minority racial and ethnic groups had increased burden of disease and risk of admission, age-adjusted in-hospital mortality for discharged patients was not significantly different among racial and ethnic groups. Ongoing studies will be needed to continue to evaluate these risks, particularly in the setting of evolving treatment guidelines.
Abnormalities of Aspiration and Swallowing Function in Survivors of Acute Respiratory Failure
The mechanisms responsible for aspiration are relatively unknown in patients recovering from acute respiratory failure (ARF) who required mechanical ventilation. Though many conditions may contribute to swallowing dysfunction, alterations in laryngeal structure and swallowing function likely play a role in the development of aspiration. At four university-based tertiary medical centers, we conducted a prospective cohort study of ARF patients who required intensive care and mechanical ventilation for at least 48 h. Within 72 h after extubation, a Fiberoptic Flexible Endoscopic Evaluation of Swallowing (FEES) examination was performed. Univariate and multivariable analyses examined the relationship between laryngeal structure and swallowing function abnormalities. Aspiration was the primary outcome, defined as a Penetration- Aspiration Scale (PAS) score of 6 or greater. Two other salient signs of dysphagia—spillage and residue—were secondary outcomes. A total of 213 patients were included in the final analysis. Aspiration was detected in 70 patients (33%) on at least one bolus. The most commonly aspirated consistency was thin liquids (27%). In univariate analyses, several abnormalities in laryngeal anatomy and structural movement were significantly associated with aspiration, spillage, and residue. In a multivariable analysis, the only variables that remained significant with aspiration were pharyngeal weakness (Odds ratio = 2.57, 95%CI = 1.16–5.84, p = 0.019) and upper airway edema (Odds ratio = 3.24, 95%CI = 1.44–7.66, p = 0.004). These results demonstrated that dysphagia in ARF survivors is multifactorial and characterized by both anatomic and physiologic abnormalities. These findings may have important implications for the development of novel interventions to treat dysphagia in ARF survivors.Clinical Trials Registration ClinicalTrials.gov Identifier: NCT02363686, Aspiration in Acute Respiratory Failure Survivors
Correction to: Abnormalities of Aspiration and Swallowing Function in Survivors of Acute Respiratory Failure
Due to the errors occurred in the originally published version, this article is being reprinted in its entirety as Correction. All errors have been corrected. It is the correct version.
Prospective Validation of Central Line–Days Derived From an Electronic Medical Record System
Validation of the number of central line–days by hospitals is required by the National Healthcare Safety Network. A prospective study that compared a daily report of such days generated by an electronic medical record with observational audits by nurses revealed that the report was 100% sensitive and 99.9% specific. Infect. Control Hosp. Epidemiol. 2015;36(9):1098–1099