The prevalence, risk factors, and outcomes of acute pulmonary embolism complicating sepsis and septic shock: a national inpatient sample analysis.

The study aimed to evaluate the prevalence, risk factors, and clinical outcomes of pulmonary embolism in patients diagnosed with sepsis with and without shock. The National Inpatient Sample was used to identify adults with sepsis with and without shock between 2017 and 2019. The prevalence of acute pulmonary embolism and the association of acute pulmonary embolism with in-hospital mortality, hospital length of stay for survivors, and overall costs of hospitalization were evaluated. Multivariable logistic and linear regression analyses, adjusted for various parameters, were used to explore these associations. Of the estimated 5,019,369 sepsis hospitalizations, 1.2% of patients with sepsis without shock and 2.3% of patients with septic shock developed pulmonary embolism. The odds ratio for in-hospital mortality was 1.94 (95% confidence interval (CI) 1.85-2.03, p < 0.001). The coefficient for hospital length of stay was 3.24 (95% CI 3.03-3.45, p < 0.001). The coefficient for total costs was 46,513 (95% CI 43,079-49,947, p < 0.001). The prevalence of pulmonary embolism in patients diagnosed with sepsis with and without shock was 1.2 and 2.3%, respectively. Acute pulmonary embolism was associated with higher in-hospital mortality, longer hospital length of stay for survivors, and higher overall costs of hospitalization.

Characteristics and Outcomes of Tracheostomized Patients With and Without COVID-19.

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.

Mortality of in-hospital cardiac arrest among patients with and without preceding sepsis: A national inpatient sample analysis.

INTRODUCTION: The impact of preceding sepsis on in-hospital cardiac arrest (IHCA)-related mortality has not been established. This study aimed to determine the association between IHCA-related mortality and sepsis. METHODS: This retrospective study used the National Inpatient Sample data from 01/2017 to 12/2019. The study included adults (≥18 years) who suffered from IHCA. The study classified cardiac arrest rhythms as ventricular tachycardia/ventricular fibrillation or pulseless electronic activity/asystole. We compared the IHCA-related in-hospital mortality between sepsis and non-sepsis groups in all patients and subgroups divided by cardiac arrest rhythm and age. Multivariable logistic regression analysis was performed to assess the independent association between sepsis and in-hospital mortality. RESULTS: A total of 357,850 hospitalizations who suffered from IHCA were identified, with sepsis present in 17.6% of patients. IHCA-related in-hospital mortality was 84.8% in sepsis and 68.4% in non-sepsis-related hospitalizations (p < 0.001). IHCA-related in-hospital mortality was higher in sepsis than in non-sepsis groups, regardless of age or cardiac arrest rhythms. In multivariable logistic regression analysis, sepsis was significantly associated with higher mortality with an odds ratio of 2.27 (95% confidence interval: 2.07-2.50, p < 0.001). CONCLUSION: Sepsis was associated with higher in-hospital cardiac arrest mortality compared to non-sepsis cases, regardless of age and cardiac rhythm.

Premorbid angiotensin converting enzyme inhibitors or angiotensin II receptor blockers in patients with sepsis.

OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analysis to investigate the effect of the premorbid use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (ACEI/ARB) on short-term mortality in patients with sepsis. DATA SOURCES: Embase, the Cochrane Central Register of Controlled Trials, and MEDLINE were searched for studies based on the below eligibility criteria. The protocol was registered at the PROSPERO (CRD42022309129). STUDY SELECTION: Eligibility criteria were as follows: (1) randomized controlled trials, cohort studies, cross-sectional studies, (2) patients with sepsis aged ≥16 years, and (3) received premorbid ACEI/ARB, or not. DATA EXTRACTION: The patient and study characteristics and outcomes were extracted. All analyses were presented with the use of random-effects models. The primary outcome was short-term mortality defined as ≤30-day, in-hospital, or intensive care unit (ICU)- mortality. The secondary outcome was acute kidney injury (AKI). DATA SYNTHESIS: Fifteen studies (N = 96,159) met the eligibility criteria. Of these, eleven studies (N = 40,360) reported unadjusted short-term mortalities. The pooled odds ratio (OR) of short-term mortality with the premorbid use of ACEI/ARB was as follows: OR, 0.86; 95% confidence interval (CI), 0.67 to 1.11; P = 0.24, I2 = 88%. Five studies reported an adjusted OR of short-term mortality with the premorbid use of ACEI/ARB as follows: OR, 0.74; 95%CI, 0.59 to 0.93; P < 0.01, I2 = 93%. Seven studies reported the pooled adjusted OR of AKI with the premorbid use of ACEI/ARB as follows: OR: 1.57, 95%CI: 1.26-1.96, p < 0.01, I2 = 69%. CONCLUSION: In this meta-analysis, the premorbid ACEI/ARB was associated with significantly lower short-term mortality in patients with sepsis despite the significantly higher risk of AKI.

Abnormal Pulmonary Function Testing as an Independent Risk Factor for Procedural Complications During Transthoracic Needle Biopsies.

BACKGROUND: Computed tomography (CT)-guided transthoracic needle biopsy is an important diagnostic tool for pulmonary nodules, offering a less invasive alternative to surgical procedures. This study aims to better risk stratify patients undergoing this procedure by analyzing the pulmonary function testing (PFT), imaging characteristics, and patient demographics most associated with complications. PATIENTS AND METHODS: This retrospective study involved 254 patients undergoing transthoracic needle biopsies at 3 hospitals between October 2016 and December 2019. Demographic data, extent of emphysema, and target lesion characteristics were recorded. Complications were defined as minor (small pneumothorax, mild hemoptysis, or pulmonary hemorrhage) and major (pneumothorax requiring chest tube, hemothorax, rapid atrial fibrillation, or postprocedure hypotension or hypoxia). RESULTS: There were 50 minor (20%) and 18 major complications (7%). As seen with prior studies, older age, increased distance to pleura, and smaller nodule size correlated with an increased risk of complications. Uniquely to our study, emphysema severity, seen on CT (P=0.008) and with decreased forced expiratory volume/forced vital capacity ratio, conferred an increased risk (62.94 vs. 68.74, P=0.05) of complications. Decreased Hounsfield unit of surrounding lung (a surrogate measure of emphysema) and decreased diffusion capacity (11.81 vs. 14.93, P=0.05) were associated with increased risk of major complications. Interestingly, body mass index and comorbidities had no correlation with complications. CONCLUSION: In addition to previous well-described characteristics, we described physiological data (abnormal PFTs), imaging findings, and nodule location as risk factors of procedural complications. Obtaining preprocedural PFT, in addition to reviewing CT imaging and demographic data, may aid clinicians in better risk stratifying patients undergoing transthoracic needle biopsies.

Risk Factors for Positive Follow-Up Blood Cultures in Gram-Negative Bacilli Bacteremia: Implications for Selecting Who Needs Follow-Up Blood Cultures.

BACKGROUND: The value of follow-up blood cultures (FUBCs) to document clearance of bacteremia due to Gram-negative bacilli (GNB) has not been well established. Although previous studies suggested that the yield of FUBCs for GNB bacteremia is low, it remains to be elucidated for whom FUBC may be beneficial and for whom it is unnecessary. METHODS: A retrospective cohort study was performed at 4 acute care hospitals to identify risk factors for positive FUBCs with GNB bacteremia and to better guide clinicians' decisions as to which patients may or may not benefit from FUBCs. Participants included adult patients with GNB bacteremia who had FUBCs and were admitted between January 2017 and December 2018. The primary outcomes were the factors associated with positive FUBCs and the yield of FUBCs with and without the factors. RESULTS: Of 306 patients with GNB bacteremia who had FUBCs, 9.2% (95% confidence interval, 6.2%-13.0%) had the same GNB in FUBCs. In the multivariate logistic regression analysis, end-stage renal disease on hemodialysis, intravascular device, and bacteremia due to extended-spectrum ß-lactamase or carbapenemase-producing organism were identified as independent predictors of positive FUBCs with GNB bacteremia. Approximately 7 FUBCs and 30 FUBCs were needed for patients with ≥1 or no risk factors, respectively, to yield 1 positive result.SummaryThis multi-site retrospective cohort study found that among patients with gram-negative bacilli (GNB) bacteremia, having ESRD on hemodialysis, intravascular devices, or bacteremia due to multi-drug resistant GNB were each independently associated with having a positive follow-up blood culture. CONCLUSIONS: Follow-up blood culture may not be necessary for all patients with GNB bacteremia and has the highest yield in patients with 1 or more risk factors.

Diaphragm Muscle Thinning in Subjects Receiving Mechanical Ventilation and Its Effect on Extubation.

BACKGROUND: Diaphragm muscle weakness and atrophy are consequences of prolonged mechanical ventilation. Our purpose was to determine whether thickness of the diaphragm (TDI) changes over time after intubation and whether the degree of change affects clinical outcome. METHODS: For this prospective, longitudinal observational study, we identified subjects who required mechanical ventilation and measured their TDI by ultrasonography. TDI was measured at baseline and repeated 72 h later and then weekly until the subject was either liberated from mechanical ventilation, was referred for tracheostomy, or died. The analysis was designed to determine whether baseline TDI and change in TDI affect extubation outcome. RESULTS: Of the 57 subjects who underwent both diaphragm measurements at 72 h, 16 died, 33 were extubated, and 8 underwent tracheostomy. Only 14 subjects received mechanical ventilation for 1 week, and 2 subjects received mechanical ventilation for 2 and 3 weeks. Females had significantly thinner baseline TDI (P = .008). At 72 h, TDI had decreased in 84% of subjects. We found no significant association between the rate of thinning and sex (P = .68), diagnosis of COPD (P = .36), current smoking (P = .85), or pleural effusion (P = .83). Lower baseline TDI was associated with higher likelihood of extubation: 12.5% higher for every 0.01-cm decrease in TDI (hazard ratio 0.875, 95% CI 0.80-0.96, P = .003). For every 0.01-cm decrease in TDI at 72 h, the likelihood of extubation increased by 17% (hazard ratio 0.83, 95% CI 0.70-0.99, P = .041). CONCLUSIONS: Although most of the subjects showed evidence of diaphragm thinning, we were unable to find a correlation with outcome of extubation failure. In fact, the thinner the diaphragm at baseline and the greater the extent of diaphragm thinning at 72 h, the greater the likelihood of extubation. Thickening ratio or other measurement may be a more reliable indicator of diaphragm dysfunction and should be explored.

Predictors of Acute Hemodynamic Decompensation in Early Sepsis: An Observational Study.

BACKGROUND: The study of sepsis is hindered by its heterogeneous time course and evolution. A subgroup of patients with severe sepsis develops shock soon after the initiation of treatment while others present hypotensive. We sought to determine the incidence of hypotension after the initiation of treatment for sepsis, and characterize their clinical features and course. METHODS: A retrospective review of electronic medical record of all septic patients (n = 542) that met the definition of septic shock within 24 hours of admission (2011 - 2012) at an urban Veteran Affairs Hospital was performed. Subjects either had 1) initial normotension (INT) with hypotension developing within 24 hours or 2) initial hypotension (IH). Logistic regression was used to model associated factors of INT/IH. RESULTS: INT occurred in 62 patients (11%) with average initial blood pressure of 120/71 mm Hg and developed hypotension to 79/48 mm Hg. IH was identified in 52 patients (10%) with average presenting blood pressure of 81/46 mm Hg. INT showed evidence of increased sympathetic tone with significantly higher heart rate, blood pressure and temperature. INT patients were younger, more frequently on alpha-blockers, and more likely septic from pneumonia compared to IH patients. INT and IH patients had similar timing of antibiotic initiation, amount of 24-hour fluid resuscitation, vasopressor use, organ dysfunction and mortality at 28 days. Using alpha-blockers, being Caucasian, and having higher temperatures were independent predictors of INT. CONCLUSION: INT is a distinctive presentation of septic shock characterized by rapid deterioration during early treatment. By further studying this subgroup, mediators of septic shock may be identified that clarify pathophysiology and provide timely targeted treatment.

The medical emergency team call: a sentinel event that triggers goals of care discussion.

OBJECTIVE: Several studies have questioned the effectiveness of rapid-response systems when measured by outcomes such as decreased overall hospital mortality or cardiac arrest rates. We studied an alternative outcome of rapid-response system implementation, namely, its effect on goals of care and designation of do not resuscitate. DESIGN: Retrospective chart review. SETTING: Veterans Administration Hospital in New York City. SUBJECTS: All patients requiring a medical emergency team call. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: : Monthly hospital census and discharge data, death occurrences, and do-not-resuscitate order placements were collected over an 8-year pre-medical emergency team and 5-year post-medical emergency team period. All medical emergency team calls and subsequent transfers to a critical care unit were reviewed and correlated to the placement and timing of do-not-resuscitate orders. Interrupted time-series analysis was used to evaluate the impact of the medical emergency team implementation on the change in trend of do-not-resuscitate orders and the hospital mortality. A total of 390 medical emergency team calls were associated with 109 do-not-resuscitate orders (28%). Of the 209 medical emergency team calls (54%) resulting in transfer to a critical care unit, 66 were associated with do-not-resuscitate orders, 73% of which were obtained after transfer. The odds of becoming do not resuscitate for a patient going to the ICU after the medical emergency team call were 2.9 (95% CI, 1.6-5.5; p = 0.001) times greater than for patients staying on the floors after the medical emergency team call. The medical emergency team implementation significantly changed the trend of do-not-resuscitate orders (p < 0.001) but had no impact on hospital mortality rate (p = 0.638). CONCLUSION: Implementation of a rapid-response system was associated with an increase in do-not-resuscitate order placement. As a sentinel event, medical emergency team activation and transfer to a critical care unit foster consideration of goals of care and frequently results in a transition to a palliative care strategy.

YKL-40 is a Protective Biomarker for Fatty Liver in World Trade Center Particulate Matter-Exposed Firefighters.

BACKGROUND: Serum biomarkers of metabolic syndrome predict abnormal lung function in World Trade Center particulate matter (WTC-PM)-exposed Fire Department of New York (FDNY) rescue workers. In animal models, exposure to ambient PM induces non-alcoholic fatty liver disease (NAFLD), a well-known comorbidity of metabolic syndrome. YKL-40 is an inflammatory biomarker for both liver and lung disease. We tested if YKL-40 is a biomarker for NAFLD in this dust-exposed cohort. METHODS: Using a nested case-control design, we studied 131 FDNY personnel who had Computer Tomography performed within 5 years post 9/11. NAFLD was defined by a liver/spleen attenuation ratio of ≤1. Serum biomarkers, lipid panel and liver function were measured in serum that had been drawn within 6 months of September 11, 2001. YKL-40 and chitotriosidase were assayed by ELISA. We tested biomarker and NAFLD association using logistic regression adjusted for age, BMI, and post-911 lung function. RESULTS: NAFLD was present in 29/131 (22%) of the cohort. In a multivariable model increasing YKL-40 was protective while increasing triglyceride and alkaline phosphatase were risk factors for NAFLD. CONCLUSIONS: Increased YKL-40 is a protective biomarker in non-alcoholic fatty liver disease. Further studies may reveal a link between PM-induced lung and liver diseases.

A novel surface-attached carvedilol solid dispersion with enhanced solubility and dissolution.

A novel surface-attached, spray-dried solid dispersion containing poorly water-soluble carvedilol (CV) without any change in the crystallinity was prepared using water, polyvinylpyrrolidone (PVP K30) and Tween 80. The solid dispersion was optimized by investigating the effects of the weight ratios of Tween 80/PVP K30 and carrier/drug on the aqueous solubility of CV. The optimum solid dispersion consisted of a relatively low carrier to drug weight ratio: the weight ratio of CV/PVP K30/Tween 80 was 12/4/2. Unlike conventional methods of solid dispersion preparation, this method yielded CV-loaded solid dispersion with no change in the crystallinity of the drug as was evident from SEM, DSC and XRD. It was demonstrated that the solid dispersions prepared had hydrophilic carriers attached to the surface of the drug, thus changing it from a hydrophobic to a hydrophilic form without changing the crystalline form. The optimized solid dispersion improved the drug solubility and dissolution rate by about 11,500-fold and twofold, respectively. It was further suggested that this method of solid dispersion preparation is better than conventional methods in terms of environmental and industrial standpoints. Thus, it was concluded that CV-loaded solid dispersion prepared using this method would be of use for delivering poorly water-soluble CV with enhanced solubility and dissolution, but without crystalline changes.

Diaphragm muscle thinning in patients who are mechanically ventilated.

BACKGROUND: Approximately 40% of patients in medical ICUs require mechanical ventilation (MV). Approximately 20% to 25% of these patients will encounter difficulties in discontinuing MV. Multiple studies have suggested that MV has an unloading effect on the respiratory muscles that leads to diaphragmatic atrophy and dysfunction, a process called ventilator-induced diaphragmatic dysfunction (VIDD). VIDD may be an important factor affecting when and if MV can be discontinued. A sensitive and specific diagnostic test for VIDD could provide the physician with valuable information that might influence decisions regarding extubation or tracheostomy. The purpose of this study was to quantify, using daily sonographic assessments, the rate and degree of diaphragm thinning during MV. METHODS: Seven intubated patients receiving MV during acute care were included. Using sonography, diaphragm muscle thickness was measured daily from the day of intubation until the patient underwent extubation or tracheostomy or died. We analyzed our data using standard descriptive statistics, linear regression, and mixed-model effects. RESULTS: The overall rate of decrease in the diaphragm thickness of all seven patients over time averaged 6% per day of MV, which differed significantly from zero. Similarly, the diaphragm thickness decreased for each patient over time. CONCLUSION: Sonographic assessment of the diaphragm provides noninvasive measurement of diaphragmatic thickness and the degree of diaphragm thinning in patients receiving MV. Our data show that diaphragm muscle thinning starts within 48 h after initiation of MV. However, it is unclear if diaphragmatic thinning correlates with diaphragmatic atrophy or pulmonary function. The relationship between diaphragm thinning and diaphragm strength remains to be elucidated.

Physicochemical characterization of tacrolimus-loaded solid dispersion with sodium carboxylmethyl cellulose and sodium lauryl sulfate.

To develop a novel tacrolimus-loaded solid dispersion with improved solubility, various solid dispersions were prepared with various ratios of water, sodium lauryl sulfate, citric acid and carboxylmethylcellulose-Na using spray drying technique. The physicochemical properties of solid dispersions were investigated using scanning electron microscopy, differential scanning calorimetery and powder X-ray diffraction. Furthermore, their solubility and dissolution were evaluated compared to drug powder. The solid dispersion at the tacrolimus/CMC-Na/sodium lauryl sulfate/citric acid ratio of 3/24/3/0.2 significantly improved the drug solubility and dissolution compared to powder. The scanning electron microscopy result suggested that carriers might be attached to the surface of drug in this solid dispersion. Unlike traditional solid dispersion systems, the crystal form of drug in this solid dispersion could not be converted to amorphous form, which was confirmed by the analysis of DSC and powder X-ray diffraction. Thus, the solid dispersion system with water, sodium lauryl sulfate, citric acid and CMC-Na should be a potential candidate for delivering a poorly water-soluble tacrolimus with enhanced solubility and no convertible crystalline.

Enhanced oral bioavailability of Coenzyme Q10 by self-emulsifying drug delivery systems.

To enhance the solubility and bioavailability of poorly water-soluble Coenzyme Q(10) (CoQ(10)), self-emulsifying drug delivery system (SEDDS) composed of oil, surfactant and cosurfactant for oral administration of CoQ(10) was formulated. The solubility of CoQ(10) was determined in various oils and surfactants. The formulations were prepared using two oils (Labrafil M 1944 and Labrafil M 2125), surfactant (Labrasol) and cosurfactant (Lauroglycol FCC and Capryol 90). In all the formulations, the level of CoQ(10) was fixed at 6% (w/v) of the vehicle. These formulations were characterized by solubility of the drug in the vehicle, particle size of the dispersed emulsion, zeta potential and drug release profile. Ternary phase diagrams were used to evaluate the emulsification domain. The self-emulsification time following introduction into an aqueous medium under gentle agitation was evaluated. The optimized SEDDS formulation consist of 65% (v/v) Labrasol, 25% (v/v) Labrafil M 1944 CS and 10% (v/v) Capryol 90 of each excipient showed minimum mean droplet size (about 240 nm) and optimal drug release profile in water. The pharmacokinetic study in rats for the optimized formulation was performed and compared to powder formulation. SEDDS have significantly increased the C(max) and area under the curve (AUC) of CoQ(10) compared to powder (P<0.05). Thus, this self-micro emulsifying drug delivery system should be an effective oral dosage form for improving oral bioavailability of lipophilic drug, CoQ(10).