Preparation and Characterization of Methyl Jasmonate Microcapsules and Their Preserving Effects on Postharvest Potato Tuber.

Potato tubers tend to sprout during long-term storage, resulting in quality deterioration and shortened shelf life. Restrictions on the use of chlorpropham, the major potato sprout suppressant, have led to a need to seek alternative methods. In this study, the effects of methyl jasmonate (MeJA) solutions and MeJA microcapsules on sprouting and other key quality attributes of the potato tuber were investigated. The results showed that the MeJA solution was most effective at 300 µmol L-1 according to TOPSIS analysis. To prepare MeJA microcapsules, the optimal formulation is with 0.04% emulsifier, 2.5% sodium alginate, 0.5% chitosan and 3% CaCl2. Compared to 300 µmol L-1 MeJA solution, MeJA microcapsules consumed a lower dose of MeJA but demonstrated a better retaining effect on the overall quality attributes of potato tubers. MeJA microcapsules are promising agents for the preservation of postharvest potato tubers.

Multicenter Study of Temporal Changes and Prognostic Value of a CT Visual Severity Score in Hospitalized Patients With Coronavirus Disease (COVID-19).

BACKGROUND. Chest CT findings have the potential to guide treatment of hospitalized patients with coronavirus disease (COVID-19). OBJECTIVE. The purpose of this study was to assess a CT visual severity score in hospitalized patients with COVID-19, with attention to temporal changes in the score and the role of the score in a model for predicting in-hospital complications. METHODS. This retrospective study included 161 inpatients with COVID-19 from three hospitals in China who underwent serial chest CT scans during hospitalization. CT examinations were evaluated using a visual severity scoring system. The temporal pattern of the CT visual severity score across serial CT examinations during hospitalization was characterized using a generalized spline regression model. A prognostic model to predict major complications, including in-hospital mortality, was created using the CT visual severity score and clinical variables. External model validation was evaluated by two independent radiologists in a cohort of 135 patients from a different hospital. RESULTS. The cohort included 91 survivors with nonsevere disease, 55 survivors with severe disease, and 15 patients who died during hospitalization. Median CT visual lung severity score in the first week of hospitalization was 2.0 in survivors with non-severe disease, 4.0 in survivors with severe disease, and 11.0 in nonsurvivors. CT visual severity score peaked approximately 9 and 12 days after symptom onset in survivors with nonsevere and severe disease, respectively, and progressively decreased in subsequent hospitalization weeks in both groups. In the prognostic model, in-hospital complications were independently associated with a severe CT score (odds ratio [OR], 31.28), moderate CT score (OR, 5.86), age (OR, 1.09 per 1-year increase), and lymphocyte count (OR, 0.03 per 1 × 109/L increase). In the validation cohort, the two readers achieved C-index values of 0.92-0.95, accuracy of 85.2-86.7%, sensitivity of 70.7-75.6%, and specificity of 91.4-91.5% for predicting in-hospital complications. CONCLUSION. A CT visual severity score is associated with clinical disease severity and evolves in a characteristic fashion during hospitalization for COVID-19. A prognostic model based on the CT visual severity score and clinical variables shows strong performance in predicting in-hospital complications. CLINICAL IMPACT. The prognostic model using the CT visual severity score may help identify patients at highest risk of poor outcomes and guide early intervention.

Adherence to blood product transfusion guidelines-An observational study of the current transfusion practice in a medical intensive care unit.

BACKGROUND: Blood transfusions though life-saving are not entirely benign. They are the most overused procedure in the hospital and have been under scrutiny by the 'Choosing Wisely campaign'. The strict adoption of restrictive transfusion guidelines could improve patient outcomes while reducing cost. OBJECTIVES: In this study, we evaluate adherence to restrictive transfusion guidelines, along with hospital mortality and length of stay (LOS) in transfusion events with a pre-transfusion haemoglobin (Hb) ≥7 g/dl. Additionally, we evaluated associated costs accrued due to unnecessary transfusions. METHODS: We conducted a retrospective observational study in a 64-bed medical intensive care unit (MICU) of an academic medical centre involving all adult patients (N = 957) requiring packed red blood cell transfusion between January 2015 and December 2015. RESULTS: In total, 3140 units were transfused with a mean pre-transfusion Hb of 6.75 ± 0.86 g/dl. Nine hundred forty-four (30%) transfusion events occurred with a pre-transfusion Hb ≥7 g/dl, and 385 (12.3%) of these occurred in patients without hypotension, tachycardia, use of vasopressors, or coronary artery disease. Forgoing them could have led to a savings of approximately 0.3 million dollars. Transfusion events with pre-transfusion Hb ≥7 g/dl were associated with an increased mortality in patients with acute blood loss (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.11-3.88; p = 0.02) and LOS in patients with chronic blood loss (ß1 .8.26, 95% CI 4.09-12.43; p < 0.01). CONCLUSION: A subset of anaemic patients in the MICU still receive red blood cell transfusions against restrictive guidelines offering hospitals the potential for effective intervention that has both economic and clinical implications.

Pulmonary cryptococcosis characteristics in immunocompetent patients-A 20-year clinical retrospective analysis in China.

BACKGROUND: Pulmonary cryptococcosis (PC) is not considered an rare, opportunistic infection anymore. The immunocompetent population accounts for an increasing proportion of the morbidity. OBJECTIVE: This study investigated the clinical characteristics of PC patients spanning 20 years, in a referral centre of China. PATIENTS/METHODS: We retrospectively investigated the clinical data of 99 patients with PC who were diagnosed at Peking Union Medical College Hospital (PUMCH) from January 1998 to December 2017. RESULTS: Pulmonary cryptococcosis incidence in PUMCH has seen sharp increase in two decades. There were 40.4% (40/99), 17.2% (17/99) and 42.4% (42/99) immunocompetent, mildly immunocompromised and severe immunocompromised patients, respectively. Significantly higher (P = .035) male predominance in immunocompetent and mildly immunocompromised groups (68.4%, 39/57) compared with severe immunocompromised group (45.2%, 19/42) was found. Overall, 27.5% (11/40) immunocompetent patients reported a significant difference (P = .02) in history of more than weekly drinking, higher than mildly or severe immunocompromised. No significant difference occurred in symptoms and radiographic characteristics among the groups. In pulmonary computerised tomography findings, the non-air pathway feature was the dominant distribution characteristics in all patients with PC (P = .002). The gap in body dissemination frequency between immunocompetent combined with mildly immunocompromised (5.26%, 3/57) and severe immunocompromised (19.0%, 8/42) was marginally significant (P = .05). CONCLUSIONS: Gender and alcohol drinking could be PC risk factors of concern in patients without severe immunodeficiency. No significant difference occurred in symptoms or radiographic characteristics between patients with different levels of immune status. The unique radiographic non-air pathway distribution in the lung may be the feature of Cryptococcus invasion that may enhance accurate diagnosis.

Mechanistic Investigations of Photoinduced Oxygenation of Ru(II) Bis-bipyridyl Flavonolate Complexes.

We previously reported that a Ru-bound flavonolate model of flavonol dioxygenases, [RuII(bpy)2(3-hydroxyfla)][PF6], photochemically reacts with dioxygen in two different manners. Broad-band excitation generates mixtures of products characteristic of 1,3-addition of dioxygen across the central pyrone ring, as is observed in enzymatic reactions. However, low temperature excitation at wavelengths longer than 400 nm generates a unique Ru-bound 2-benzoatophenylglyoxylate product resulting from a 1,2-dioxetane intermediate. Herein, we investigate this reactivity in a series of Ru(II)bis-bipyridyl flavonolate complexes [RuII(bpy)2(3-hydroxyflaR)][PF6] (bpy = 2,2'-bipyridine; fla = flavonolate; R = p-OMe (1), p-Me (2), p-H (3), p-Cl (4)), and [RuII(bpy)2(5-hydroxyfla)][PF6] (5). The complexes' structures, photophysical and electrochemical properties, and photochemical reactivity with oxygen were investigated in detail. Two different reaction product mixtures, from 1,2- and 1,3-additions of dioxygen, are observed by illumination into distinct excitation/emission manifolds. By analogy to previous reports of excited state intramolecular proton transfer, the two manifolds are attributed to tautomeric diradicals that predict the observed reactivity patterns.

Efficacy and safety of oral compared with intravenous tranexamic acid in reducing blood loss after primary total knee and hip arthroplasty: a meta-analysis.

BACKGROUND: Tranexamic acid (TXA) is an anti-fibrinolytic agent successfully preventing blood loss when using intravenously (IV) in total hip arthroplasty (THA) and total knee arthroplasty (TKA). An oral administration, which is available on blood sparing, has been reported exhibit profound cost-saving benefits. The aim of this meta-analysis is to investigate whether the administration of oral and intravenous tranexamic acid postoperatively has equivalent blood-sparing properties in these patients. METHODS: The online electronic databases were searched for eligible literatures updated on September 2018. Studies assessing the effect between oral TXA and intravenous TXA (IV-TXA) in those undergoing TKA or THA were included. All the data were pooled with the corresponding 95% confidence interval (CI) using RevMan software. Based on the heterogeneity, we performed a systematic analysis to explore the overall results across the included studies. RESULTS: Nine studies met our inclusion criteria. No significant differences were identified with regard to the Hb drop (SMD = - 0.03,95%CI = - 0.18-0.12, P = 0.67), total Hb loss (SMD = 0.10,95%CI = - 0.06-0.26, P = 0.24), total blood loss (SMD = - 0.00,95%CI = - 0.20-0.20, P = 1.00), transfusion rate (OR = 0.77,95%CI = 0.54-1.10, P = 0.14), DVT rate (OR = 0.58,95%CI = 0.19-1.75, P = 0.33), and length of hospital stay (SMD = - 0.05,95%CI = - 0.28-0.17, P = 0.63) between the oral groups and intravenous group. CONCLUSION: The blood-sparing efficacy of oral TXA is similar to that of the intravenous forms in the setting of THA and TKA. Considering the cost-benefit superiority and ease of administration of oral TXA, further studies and clinical trials are required to further identify the optimal administration for THA and TKA.

A needle-like reusable surface-enhanced Raman scattering substrate, and its application to the determination of acetamiprid by combining SERS and thin-layer chromatography.

A micro surface-enhanced Raman scattering (SERS) substrate has been fabricated by electrochemical deposition of dendrite-like gold on carbon fiber needles (Au-CFNs). Scanning electron microscopy and energy dispersive spectroscopy were used to confirm the presence of the gold nanostructure on the CFNs. This substrate has a Raman scattering enhancement factor as high as 3.3 × 10^7 when using rhodamine 6G as the reporter molecule. The high SERS sensitivity is attributed to the massive hotspots on gold bulges that enhance the local surface plasmon resonance. The Au-CFN substrate was reproduced 10 times after electrochemically wiping off the analytes from the needle-like electrode. The substrate has attractive features such as convenient sampling, low sample dosage, and minimal invasion. It was applied, in combination with thin-layer chromatography, for the determination of acetamiprid on vegetables. The result was more accurate because the sample information of both the surface and the bulk can be obtained at the same time after inserting the tip of this needle substrate into the TLC plate. The limit of detection for acetamiprid is 0.05 µg⋅mL-1 and the linear range is 0.1-10 µg⋅mL-1. Graphical abstract A reusable micro needle-like SERS substrate was fabricated and applied for pesticide residue analysis. The SERS signal of acetamiprid can be acquired on the tip of this micro needle-like Au-CFN substrate. This substrate can be reused for 10 times.

The Breast and Cervical Cancer Early Detection Program, Medicaid, and breast cancer outcomes among Ohio's underserved women.

BACKGROUND: As an organized screening program, the national Breast and Cervical Cancer Early Detection Program (BCCEDP) was launched in the early 1990s to improve breast cancer outcomes among underserved women. To analyze the impact of the BCCEDP on breast cancer outcomes in Ohio, this study compared cancer stages and mortality across BCCEDP participants, Medicaid beneficiaries, and "all others." METHODS: This study linked data across the Ohio Cancer Incidence Surveillance System, Medicaid, the BCCEDP database, death certificates, and the US Census and identified 26,426 women aged 40 to 64 years who had been diagnosed with incident invasive breast cancer during the years 2002-2008 (deaths through 2010). The study groups were as follows: BCCEDP participants (1-time or repeat users), Medicaid beneficiaries (women enrolled in Medicaid before their cancer diagnosis [Medicaid/prediagnosis] or around the time of their cancer diagnosis [Medicaid/peridiagnosis]), and all others (women identified as neither BCCEDP participants nor Medicaid beneficiaries). The outcomes included advanced-stage cancer at diagnosis and mortality. A multivariable logistic and survival analysis was conducted to examine the independent association between the BCCEDP and Medicaid status and the outcomes. RESULTS: The percentage of women presenting with advanced-stage disease was highest among women in the Medicaid/peridiagnosis group (63.4%) and lowest among BCCEDP repeat users (38.6%). With adjustments for potential confounders and even in comparison with Medicaid/prediagnosis beneficiaries, those in the Medicaid/peridiagnosis group were twice as likely to be diagnosed with advanced-stage disease (adjusted odds ratio, 2.20; 95% confidence interval, 1.83-2.66). CONCLUSIONS: Medicaid/peridiagnosis women are at particularly high risk to be diagnosed with advanced-stage disease. Efforts to reduce breast cancer disparities must target this group of women before they present to Medicaid. Cancer 2017;123:3097-106. © 2017 American Cancer Society.

Trends in Survival of Patients With Uterine Serous Carcinoma From 1988 to 2011: A Population-Based Study.

OBJECTIVE: Our study used the Surveillance, Epidemiology, and End Result database to determine if the changes in treatment paradigm observed over the last 2 decades have improved outcomes in patients with uterine serous carcinoma (USC). METHODS: Women with USC were identified using the Surveillance, Epidemiology, and End Result database from 1988 to 2011 (n = 8230) and grouped into 3 cohorts (1988-1997, 1998-2004, and 2005-2011). Disease-specific survival and overall survival were estimated. Kaplan-Meier survival curves and Cox regression models were used. RESULTS: Disease-specific survival (59 vs 94 months vs not reached; P < 0.001) and overall survival (31 vs 37 vs 45 months; P < 0.001) improved over time. In univariable analyses, only those with stage I-III and those who reside in the Western or Central regions were noted to have improvement over time. In multivariable analyses when adjusting for age, race, marital status, stage, geographic location, cancer-related surgery, extent of lymphadenectomy, and adjuvant radiation, patients who received the diagnosis during 2005 to 2011 were 22% less likely to die of uterine cancer (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.70-0.87; P < 0.001) and 17% less likely to die of any cause (HR, 0.83; 95% CI, 0.76-0.90; P < 0.0001) compared with patients who received a diagnosis during 1988-1997. Similarly, patients who received a diagnosis during 1998-2004 were 15% less likely to die of uterine cancer (HR, 0.85; 95% CI, 0.77-0.94; P = 0.0015) and 10% less likely to die of any cause (HR, 0.90; 95% CI, 0.83-0.97; P = 0.0048) compared with patients who received a diagnosis during 1988-1997. CONCLUSIONS: Changes in treatment trends for USC over the last 2 decades have resulted in an improvement in outcome especially those with stage I-III disease.

Six-Minute Walk Test as a Predictor of Diagnosis, Disease Severity, and Clinical Outcomes in Scleroderma-Associated Pulmonary Hypertension: The DIBOSA Study.

BACKGROUND: Pulmonary hypertension (PH) is a common complication of scleroderma (SSc) and is a leading cause of morbidity and mortality. OBJECTIVES: To explore the utility of the 6MWT in the prediction of SSc-PH and to assess its prognostic implications. METHODS: A retrospective review of SSc patients from 2003 to 2013, with 6MWT and echocardiogram (n = 286), was conducted. Presence of PH was defined by right heart catheterization. Patients were randomized into development and validation cohorts. Using regression techniques, we developed a scoring system to predict the presence of SSc-PH and tested it in our validation cohort. Trends of mortality and disease severity were studied for incremental scores. RESULTS: The DIBOSA scoring system includes DIstance walked in 6 min, BOrg dyspnea index, and SAturation of oxygen at 6 min. The DIBOSA score in the development cohort ranged from 0 to 3, resulting in an area of 0.858 (P < 0.0001) under the ROC curve. A score of 0 had a NPV of 100% and a score of 3 had a PPV of 86.58%. The validation cohort had an area under the ROC curve of 0.842. The DIBOSA score correlated with both pulmonary artery pressures and mortality. The 3-year survival rates for DIBOSA scores of 0, 1, 2, and 3 were 100, 100, 87.67, and 66.67%, respectively (HR = 3.92, P < 0.0001). CONCLUSIONS: DIBOSA score is a sensitive tool for the prediction of SSc-PH. The DIBOSA score is a direct predictor of mortality in SSc-PH and strongly correlates with pulmonary pressures. 6MWT can be used to predict clinical outcomes in SSc-PH.

Racial disparity in survival of patients with uterine serous carcinoma: Changes in clinical characteristics, patterns of care and outcomes over time from 1988 to 2011.

OBJECTIVES: To determine if the disparities in the outcome between white (W) and African American (AA) patients with uterine serous carcinoma (USC) have changed over time. METHODS: Women with USC were identified using the SEER database from 1988 to 2011 (N=7667). Years of the study were divided into three periods (1988-1997, 1998-2004 and 2005-2011). Overall (OS) and disease-specific survivals (DSS) was estimated. RESULTS: Over the three time periods, African American patients continued to be younger and less likely to have cancer directed surgery and extensive lymphadenectomy when compared to white patients. In multivariable analysis adjusting for age, race, marital status, stage, cancer-directed surgery, extent of lymphadenectomy, adjuvant radiation, and geographic location, AA was significantly associated with worse DSS and OS in the three time periods compared to white race. African American patients were 29% (95% CI 1.03-1.62, p=0.027) in 1988-1997, 40% in 1998-2004 (95% CI 1.21-1.63, p<0.0001) and 34% in 2005-2011 (95% CI 1.13-1.59, p=0.0008) more likely to die from uterine cancer compared to their white counterparts. A slight improvement in the difference in OS over time was noted comparing African American and white patients. African American patients were 46% (95% CI 1.23-1.73, p<0.0001) in 1988-1997, 39% in 1998-2004 (95% CI 1.23-1.56, p<0.0001) and 26% in 2005-2011 (95% CI 1.10-1.45, p<0.0001) more likely to die from any cause compared to their white counterparts. CONCLUSIONS: Significant improvement in outcome was noted in both racial groups over time. However, African American patients continued to have worse outcome than white patients over time.

Characterization of the Initial Intermediate Formed during Photoinduced Oxygenation of the Ruthenium(II) Bis(bipyridyl)flavonolate Complex.

A ruthenium(II) flavonolate complex, [Ru(II)(bpy)2fla][BF4], was synthesized to model the reactivity of the flavonol dioxygenases. The treatment of dry CH3CN solutions of [Ru(II)(bpy)2fla][BF4] with dioxygen under light leads to the oxidative O-heterocyclic ring opening of the coordinated substrate flavonolate, resulting in the formation of [Ru(II)(bpy)2(carboxylate)][BF4] (carboxylate = O-benzoylsalicylate or benzoate) species, as determined by electrospray ionization mass spectrometry. Moderation of the excitation and temperature allowed isolation and characterization of an intermediate, [Ru(II)(bpy)2bpg][BF4] (bpg = 2-benzoyloxyphenylglyoxylate), generated by the 1,2-addition of dioxygen to the central flavonolate ring.

Lasting Effects of the Breast and Cervical Cancer Early Detection Program on Breast Cancer Detection and Outcomes, Ohio, 2000-2009.

INTRODUCTION: The National Breast and Cervical Cancer Early Detection Program (BCCP) in Ohio provides screening and treatment services for uninsured low-income women aged 40 to 64. Because participation in the BCCP might engender greater self-efficacy for cancer screening, we hypothesized that breast cancer and survival outcomes would be better in BCCP participants who become age-eligible to transition to Medicare than in their low-income non-BCCP counterparts. METHODS: Linking data from the 2000 through 2009 Ohio Cancer Incidence Surveillance System with the BCCP database, Medicare files, Ohio death certificates (through 2010), and the US Census, we identified Medicare beneficiaries who were aged 66 to 74 and diagnosed with incident invasive breast cancer. We compared the following outcomes between BCCP women (n = 93) and low-income non-BCCP women (n = 420): receipt of screening mammography in previous year, advanced-stage disease at diagnosis, timely and standard care, all-cause survival, and cancer survival. We conducted multivariable logistic regression and survival analysis to examine the association between BCCP status and each of the outcomes, adjusting for patient covariates. RESULTS: Women who participated in the BCCP were nearly twice as likely as low-income non-BCCP women to have undergone screening mammography in the previous year (adjusted odds ratio, 1.77; 95% confidence interval, 1.01-3.09). No significant differences were detected in any other outcomes. CONCLUSION: With the exception of screening mammography, the differences in outcomes were not significant, possibly because of the small size of the study population. Future analysis should be directed toward identifying the factors that explain these findings.

Critical Care Among Disadvantaged Minority Groups Made Equitable: Trends Throughout the COVID-19 Pandemic.

BACKGROUND: US racial and ethnic minorities have well-established elevated rates of comorbidities, which, compounded with healthcare access inequity, often lead to worse health outcomes. In the current COVID-19 pandemic, it is important to understand existing disparities in minority groups' critical care outcomes and mechanisms behind these-topics that have yet to be well-explored. OBJECTIVE: Assess for disparities in racial and ethnic minority groups' COVID-19 critical care outcomes. DESIGN: Retrospective cohort study. PARTICIPANTS: A total of 2125 adult patients who tested positive for COVID-19 via RT-PCR between March and December 2020 and required ICU admission at the Cleveland Clinic Hospital Systems were included. MAIN MEASURES: Primary outcomes were mortality and hospital length of stay. Cohort-wide analysis and subgroup analyses by pandemic wave were performed. Multivariable logistic regression models were built to study the associations between mortality and covariates. KEY RESULTS: While crude mortality was increased in White as compared to Black patients (37.5% vs. 30.5%, respectively; p = 0.002), no significant differences were appraised after adjustment or across pandemic waves. Although median hospital length of stay was comparable between these groups, ICU stay was significantly different (4.4 vs. 3.4, p = 0.003). Mortality and median hospital and ICU length of stay did not differ significantly between Hispanic and non-Hispanic patients. Neither race nor ethnicity was associated with mortality due to COVID-19, although APACHE score, CKD, malignant neoplasms, antibiotic use, vasopressor requirement, and age were. CONCLUSIONS: We found no significant differences in mortality or hospital length of stay between different races and ethnicities. In a pandemic-influenced critical care setting that operated outside conditions of ICU strain and implemented standardized protocol enabling equitable resource distribution, disparities in outcomes often seen among racial and ethnic minority groups were successfully mitigated.

A thermodynamic and kinetic study of hydride transfer of a caffeine derivative.

One representative type of heterocyclic compound that can release a hydride ion is 7,8-dihydro-9-methylcaffeine (CAFH). The one-electron oxidation potential of CAFH [-0.294 (V vs Fc(+/0))] and the one-electron reduction potential of CAF(+) [-2.120 (V vs Fc(+/0))] were obtained using two different methods, CV and OSWV. Applying titration calorimetry data in thermodynamic cycles, the enthalpies of CAFH releasing a hydride ion [57.6 kcal/mol] and releasing a hydrogen atom [80.3 kcal/mol] and of its radical cation CAFH(•+) releasing a proton [33.0 kcal/mol] and releasing a hydrogen atom [38.4 kcal/mol] have been determined. Several conclusions can be drawn from the thermodynamic results: (1) CAFH is a very good single-electron donor whose single-electron oxidation potential is much less positive than that of NAD(P)H model compound BNAH [E(ox) = 0.219 V vs Fc(+/0)]. (2) The single-electron reduction potential of CAF(+) is much more negative than that of BNA(+) [E(red) = -1.419 V], which means that CAF(+) is not a good electron acceptor. Furthermore, CAFH is a very good hydride donor compared to BNAH. The results of non-steady-state kinetic studies, for the reaction of CAFH and AcrH(+)ClO(4)(-), show that the ratio of t(0.50)/t(0.05) is larger than 13.5 and the ratio of k(init)/k(pfo) is larger than 1. The pseudo-first-order rate constants obtained at different reaction stages decrease with the time, and the kinetic isotope was observed to be small at a short reaction time and slowly increases to 3.72 with the progress of the reaction. These kinetic results clearly display that the hydride transfer of CAFH to AcrH(+) in acetonitrile is not a one-step mechanism, while the thermodynamic results show that CAFH is a very good electron donor. The combination of the kinetic results with the thermodynamics analysis shows that the hydride transfer of the caffeine derivative CAFH takes place by a two-step reversible mechanism and there is an intermediate in the reaction.

Risk factors associated with development of coinfection in critically Ill patients with COVID-19.

BACKGROUND: At outset of the coronavirus disease 2019 (COVID-19) pandemic, the significance of bacterial and fungal coinfections in individuals with COVID-19 was unknown. Initial reports indicated that the prevalence of coinfection in the general population was low, but there was uncertainty regarding the risk of coinfection in critically ill patients. METHODS: Nine hundred critically ill adult patients with COVID-19 infection were enrolled in this observational case-control study. Patients with a coinfection (case) and patients without a coinfection (control) were compared using univariate and multivariable analyses. A subgroup analysis was performed on patients with coinfection, dividing them into early (infection within 7 days) and late (infection after 7 days) infection groups. RESULTS: Two hundred and thirty-three patients (25.9%) had a bacterial or fungal coinfection. Vasopressor use (P<0.001) and severity of illness (higher Acute Physiology and Chronic Health Evaluation III score, P=0.009) were risk factors for the development of a coinfection. Patients with coinfection had higher mortality and length of stay. Vasopressor and corticosteroid use and central line and foley catheter placement were risk factors for late infection (>7 days). There were high rates of drug-resistant infections. CONCLUSIONS: Critically ill patients with COVID-19 are at risk for both community-acquired and hospital-acquired infections throughout their hospitalization for COVID-19. It is important to consider the development of a coinfection in clinically worsening critically ill patients with COVID-19 and consider the likelihood of drug-resistance when choosing an empiric regimen.

TIME FROM HOSPITAL ADMISSION TO ONSET OF SEPTIC SHOCK IS ASSOCIATED WITH HIGHER IN-HOSPITAL MORTALITY.

ABSTRACT: Objective: Several studies have shown septic shock developing later during the hospital stay is associated with higher mortality. However, the precise point at which time from hospital admission to the onset of septic shock (admission-shock-onset-time) becomes an independent prognostic marker of mortality remains unknown. This study evaluated the association between admission-shock-onset-time and in-hospital mortality among patients with septic shock and the optimal cutoff period to categorize early- and late-onset septic shock. Method: We conducted a single-center retrospective, observational cohort study at a quaternary academic hospital comprising adult patients with septic shock admitted to a medical intensive care unit (ICU) from January 2011 to December 2020. A multivariable additive logistic regression model was developed to assess if log-transformed admission-shock-onset-time was associated with in-hospital mortality. The thin plate spline function was used to describe the nonlinear relationship between the log-transformed admission-shock-onset-time and in-hospital mortality. The primary outcome was in-hospital mortality, and the secondary outcome was ICU mortality. Results: Two thousand five hundred twenty patients met the inclusion criteria with an overall in-hospital mortality of 37.3%. The log-transformed admission-shock-onset-time was associated with higher in-hospital and ICU mortality even after adjusting for clinical variables. The odds ratio for in-hospital mortality continued to increase throughout the observation period. The adjusted odds ratio exceeded 2 in between 20.1 and 54.6 h, and it surpassed 3 in between 54.6 and 148.4 h of the time from the hospital admission to shock onset. Conclusion: In-hospital mortality continued to rise as admission-shock-onset-time increased in patients with septic shock. No clear dichotomization between early and late septic shock could be ascertained, and this categorization may limit our understanding of the temporal relationship of shock onset to mortality.

COPD Overdiagnosis and Its Effect on 30-Day Hospital Readmission Rates.

BACKGROUND: Although specific guidelines exist for diagnosing COPD on the basis of spirometry testing data (FEV1/FVC < 0.70 or above the lower limit of normal), the literature suggests that overdiagnosis is common. Whether overdiagnosis increases 30-d readmission rates has not yet been explored. The objective of this study was to determine the prevalence of COPD overdiagnosis and its effect on 30-d hospital readmission rates in our institution. METHODS: We retrospectively identified all subjects who were coded with a COPD hospital discharge in 2018 at Cleveland Clinic main campus and had spirometry data available, including FEV1 and FVC. FEV1/FVC was calculated and compared with the predicted lower limit of normal values. Hospital discharge diagnosis and 30-d hospital readmission data were captured along with comorbidities and other demographics. RESULTS: In 2018, there were 424 hospital discharges with a COPD diagnosis with spirometry testing available. Of these subjects, 124 (29%) were overdiagnosed in the lower limit of normal group and 99 (23.3%) were in the ≥ 0.70 group. One hundred subjects (23.6%) had a 30-d hospital readmission. Of these subjects, 35 had FEV1/FVC that was greater than their predicted lower limit of normal on spirometry. Of the 324 subjects who were not readmitted within 30 d, 89 (27.5%) had FEV1/FVC greater than the lower limit of normal. If the 35 readmitted subjects had not been coded with COPD, the 30-d readmission rate would have decreased significantly from 23.6% to 16.7% (100 of 424 vs 65 of 389, P = .01). Even if all of the 124 subjects who had pulmonary function test data greater than the lower limit of normal had not been counted, the readmission rate would still have decreased from 23.6% to 21.7%, but this was not significant (from 100 of 424 to 65 of 300, P = .3). CONCLUSIONS: COPD was overdiagnosed in our cohort of subjects; this was true whether the FEV1/FVC < 0.70 standard or the lower limit of normal standard was used. Furthermore, this overdiagnosis artificially inflated the 30-d readmission rate. These results illustrate the caution providers should use when making a COPD diagnosis.

Tocilizumab in Coronavirus Disease 2019-Related Critical Illness: A Propensity Matched Analysis.

The primary objective was to evaluate ICU mortality at 28 days in patients with severe hypoxemic respiratory failure due to coronavirus disease 2019 infection who received tocilizumab. The secondary objectives were to evaluate ICU-, hospital-, mechanical ventilation-, and vasopressor-free days at day 28 and development of secondary infections. DESIGN: Retrospective, observational, multicenter, cohort study between March 15, 2020, and May 31, 2020. Using propensity score matching based on ICU admission source, C-reactive protein, Sequential Organ Failure Assessment score, vasopressor use, age, race, weight, and mechanical ventilation, patients who received tocilizumab were matched to patients who did not receive tocilizumab. SETTING: Ten hospitals within the Cleveland Clinic Enterprise. PATIENTS: Adult patients admitted to a medical, surgical, neurosciences, or mixed ICU with severe acute respiratory syndrome coronavirus 2 infection. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four-hundred forty-four patients were included: 342 patients (77%) did not receive tocilizumab and 102 patients (23%) received tocilizumab. Of those, 82 patients in each arm were matched. Before matching, patients who received tocilizumab had higher Sequential Organ Failure Assessment scores (6.1 ± 3.4 vs 4.7 ± 3.6), higher C-reactive protein (21.0 ± 10.2 vs 13.7 ± 9.6 mg/dL), higher frequency of intubation, vasopressor requirement, and paralytics. After matching, characteristics were more balanced and over 85% of patients required mechanical ventilation. ICU mortality was lower in tocilizumab group (23.2% vs 37.8%; risk difference, -15%; 95% CI, -29% to -1%), with more ICU-, hospital-, and vasoactive-free days at day 28 compared with those who did not receive tocilizumab. There was no difference in mechanical ventilation-free days at day 28 or development of secondary infections. CONCLUSIONS: Tocilizumab use was associated with a significant decrease in ICU mortality in critically ill coronavirus disease 2019 patients with severe hypoxemic respiratory failure. Future randomized controlled trials limited to tocilizumab administration in critically ill coronavirus disease 2019 patients, with severe hypoxemic respiratory failure, are needed to support these findings.

Single-Center Experience of Outcomes and Prescribing Patterns of IV Immunoglobulin Use in Critically Ill Patients.

Previous literature has not compared prescribing practices of IV immunoglobulin in medical ICU survivors and nonsurvivors. The objective of this study was to study IV immunoglobulin use in patients admitted to a medical ICU evaluating differences between hospital survivors and nonsurvivors in regards to level of evidence supporting use, prescribing patterns, and cost. DESIGN: Retrospective, observational study. SETTING: Single, academic medical center medical ICU. PATIENTS: Adults who received greater than or equal to 1 dose of IV immunoglobulin during their medical ICU admission from 2011 to 2018. INTERVENTIONS: Prescribing patterns, level of evidence supporting use, and cost. MEASUREMENTS AND MAIN RESULTS: A total of 389 patients received greater than or equal to 1 dose of IV immunoglobulin for 46 discrete indications and 36.5% of indications had low-quality data supporting use of IV immunoglobulin. The primary indication for IV immunoglobulin was hypogammaglobulinemia (35.5%) followed by antibody-mediated lung transplant rejection (15.4%). Nonsurvivors received lower median dosing (g/kg) and number of doses compared with survivors (0.4 g/kg [0.4-1 g/kg] vs 0.5 g/kg [0.4-1 g/kg] [p = 0.0003] and 1.0 [1-2] vs 2 [1-3] doses [p = 0.0001], respectively). Dosing was based on ideal body weight in 258 patients (66%). High-quality data supported IV immunoglobulin use in 15 patients (4%). The median cost per dose of IV immunoglobulin in nonsurvivors was $4,893 ($4,078-$8,155) versus $5,709 ($4,078-$10,602) in survivors (p = 0.04). CONCLUSIONS: IV immunoglobulin is prescribed for many indications in the medical ICU with low-quality evidence supporting its use and dosing regimens are variable. Hospital survivors received a higher dose and greater number of doses of IV immunoglobulin compared with nonsurvivors. National guidelines are needed to help inform IV immunoglobulin utilization and reduce healthcare costs.