Patient Controlled Subcutaneous Analgesia of Hydromorphone Versus Morphine to Treat Moderate and Severe Cancer Pain: A Randomized Double-Blind Controlled Trial.

CONTEXT: Hydromorphone and morphine are the common drugs used for the treatment of moderate to severe cancer pain. Patient controlled subcutaneous analgesia (PCSA) is an effective technique to manage cancer pain. However, few studies have been conducted to show the efficacy and safety of PCSA of hydromorphone for the relief of cancer pain. OBJECTIVES: To explore the short-term efficacy and safety of PCSA elicited by hydromorphone for moderate to severe cancer pain. METHODS: This was a single-center, randomized, active-controlled, double-blind trial (from April 2019 to August 2021). Sixty patients with moderate to severe cancer pain were randomized (1:1) to hydromorphone or morphine groups according to drug delivery by PCSA. The primary outcome was the pain intensity measured by a numerical rating scale (NRS) at 72 hours. Secondary outcomes included pain intensity measured by NRS at baseline, 15 minutes, 30 minutes, two hours, eight hours, 24 hours and 48 hours. The daily occurrence of breakthrough pain (BTP), impact of pain on quality of life measured by the brief pain inventory (BPI), the daily additional consumption of opioids and the incidence of adverse events were also recorded. Adverse events included nausea, vomiting, dizziness, constipation and respiratory depression. RESULTS: A total of 57 patients (28 patients in the hydromorphone group and 29 patients in the morphine group) in the West China Hospital of Sichuan University were investigated. The mean (standard deviation [SD]) NRS in the two groups at baseline was 7.8 (1.7) in the hydromorphone group and 7.6 (1.7) in the morphine group, and at 72 hours were 3.4 (1.8) and 3.2 (1.5), respectively. The postoperative NRS in both groups was decreased significantly compared to baseline. The mean (SD) NRS at 30 minutes in the hydromorphone group was significantly lower than in the morphine group (3.9 [2.6] vs. 5.3 [2.1], P = 0.035). The daily occurrence of BTP in both groups at 48 hours and 72 hours decreased significantly compared to the corresponding baseline (P < 0.05), and there was no significant difference between the two groups. The total scores and sub-item scores of BPI at 24 hours and 72 hours after PCSA in both groups decreased significantly from baseline. A comparison of daily additional consumption of opioids between the two groups revealed no statistically significant difference. There were no significant differences in the incidences of nausea, vomiting, dizziness or constipation between the two groups (P > 0.05). CONCLUSION: This study found that the PCSA of both hydromorphone and morphine could effectively and safely relieve short-term moderate to severe cancer pain. Of note, the PCSA of hydromorphone took effect more quickly than that of morphine.

LncRNA modulates Hippo-YAP signaling to reprogram iron metabolism.

Iron metabolism dysregulation is tightly associated with cancer development. But the underlying mechanisms remain poorly understood. Increasing evidence has shown that long noncoding RNAs (lncRNAs) participate in various metabolic processes via integrating signaling pathway. In this study, we revealed one iron-triggered lncRNA, one target of YAP, LncRIM (LncRNA Related to Iron Metabolism, also named ZBED5-AS1 and Loc729013), which effectively links the Hippo pathway to iron metabolism and is largely independent on IRP2. Mechanically, LncRIM directly binds NF2 to inhibit NF2-LATS1 interaction, which causes YAP activation and increases intracellular iron level via DMT1 and TFR1. Additionally, LncRIM-NF2 axis mediates cellular iron metabolism dependent on the Hippo pathway. Clinically, high expression of LncRIM correlates with poor patient survival, suggesting its potential use as a biomarker and therapeutic target. Taken together, our study demonstrated a novel mechanism in which LncRIM-NF2 axis facilitates iron-mediated feedback loop to hyperactivate YAP and promote breast cancer development.

Changes of blood gas analysis in moderate-to-severe acute respiratory distress syndrome patients during long-term prone position ventilation: a retrospective cohort study.

Background: Prone position ventilation (PPV) has been recommended for patients with acute respiratory distress syndrome (ARDS) to improve oxygenation. However, whether prolonged prone ventilation will aggravate hyperoxia and whether abdominal compression will aggravate permissive hypercapnia acidosis are topics of concern. We carried out a retrospective analysis to investigate the issues above. Methods: Clinical data were collected from 97 moderate-to-severe ARDS patients who received PPV as part of their treatment in the intensive care unit (ICU) of the First Affiliated Hospital of Guangzhou Medical University from November 2015 to May 2021. We collected arterial blood gas of patients according to the 3 periods: supine position ventilation (SPV), PPV early stage (within 4 hours), and PPV middle and late stage (6 hours or later). We established a linear mixed-effects models with "body position changes, times of PPV, gender, age, baseline SOFA, and baseline APACHE II" as fixed effects, and individual and the number of prone positions as random intercept and random slope to investigate the effect of body position changes on blood gas analysis. Results: Among the 97 patients received PPV included, 51 were ICU survivors. Arterial partial pressure of oxygen (PaO2) and PaO2/fraction of inspired oxygen (FiO2) ratio were significantly higher at the early, middle and late stages of PPV than those in SPV [PFR (mmHg): 158 (118.00, 203.00) vs. 161 (129.00, 202.75) vs. 123 (91.75, 163.00), P<0.05]. Despite the synchronized reduction of FiO2, the incidence of hyperoxia in the prone position was still significantly higher than that in the supine position [hyperoxia (%):33.33 vs. 33.56 vs. 12.42, P<0.05]; there was no significant change in arterial carbon dioxide partial pressure (PaCO2) at each stage of PPV, but there was a significant increase in PH at PPV middle and late stages than those at early stage [PH: 7.39 (7.34, 7.42) vs. 7.37 (7.31, 7.41), P<0.05]. Conclusions: Although PPV improves the patients' oxygenation, the associated incidence of hyperoxia exceeds 33%. Down-regulate FiO2 more sharply after PPV is necessary, if oxygenation conditions permit. PPV may alleviate the acidosis associated with permissive hypercapnia in ARDS patients treated with lung protective ventilation strategy (LPVS).

A feasibility study of reduced full-of-view synthetic high-b-value diffusion-weighted imaging in uterine tumors.

OBJECTIVES: This study aimed to evaluate the feasibility of reduced full-of-view synthetic high-b value diffusion-weighted images (rFOV-syDWIs) in the clinical application of cervical cancer based on image quality and diagnostic efficacy. METHODS: We retrospectively evaluated the data of 35 patients with cervical cancer and 35 healthy volunteers from May to November 2021. All patients and volunteers underwent rFOV-DWI scans, including a 13b-protocol: b = 0, 25, 50, 75, 100, 150, 200, 400, 600, 800, 1000, 1200, and 1500 s/mm2 and a 5b-protocol: b = 0, 100, 400, 800,1500 s/mm2. rFOV-syDWIs with b values of 1200 (rFOV-syDWIb=1200) and 1500 (rFOV-syDWIb=1500) were generated from two different multiple-b-value image datasets using a mono-exponential fitting algorithm. According to homoscedasticity and normality assessed by the Levene's test and Shapiro-Wilk test, the inter-modality differences of quantitative measurements were, respectively, examined by Wilcoxon signed-rank test or paired t test and the inter-group differences of ADC values were examined by independent t test or Mann-Whitney U test. RESULTS: A higher inter-reader agreement between SNRs and CNRs was found in 13b-protocol and 5b-protocol rFOV-syDWIb=1200/1500 compared to 13b-protocol rFOV-sDWIb=1200/1500 (p < 0.05). AUC of 5b-protocol syADCmean,b=1200/1500 and syADCminimum,b=1200/1500 was equal or higher than that of 13b-protocol sADCmean,b=1200/1500 and sADCminimum,b=1200/1500. CONCLUSIONS: rFOV-syDWIs provide better lesion clarity and higher image quality than rFOV-sDWIs. 5b-protocol rFOV-syDWIs shorten scan time, and synthetic ADCs offer reliable diagnosis value as scanned 13b-protocol DWIs.

Electrical impedance tomography for titration of positive end-expiratory pressure in acute respiratory distress syndrome patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is one of most common comorbidities in acute respiratory distress syndrome (ARDS). There are few specific studies on the appropriate ventilation strategy for patients with ARDS comorbid with COPD, especially regarding on positive end-expiratory pressure (PEEP) titration. METHODS: To compare the respiratory mechanics in mechanical ventilated ARDS patients with or without COPD and to determine whether titration of PEEP based on electrical impedance tomography (EIT) is superior to the ARDSnet protocol. This is a single center, perspective, repeated measure study. ARDS patients requiring mechanical ventilation who were admitted to the intensive care unit between August 2017 and December 2020 were included. ARDS patients were divided according to whether they had COPD into a COPD group and a non-COPD group. Respiratory mechanics, gas exchange, and hemodynamics during ventilation were compared between the groups according to whether the PEEP level was titrated by EIT or the ARDSnet protocol. RESULTS: A total of twenty-seven ARDS patients including 14 comorbid with and 13 without COPD who met the study eligibility criteria were recruited. The PEEP levels titrated by EIT and the ARDSnet protocol were lower in the COPD group than in the non-COPD group (6.93 ± 1.69 cm H2O vs. 12.15 ± 2.40 cm H2O, P < 0.001 and 10.43 ± 1.20 cm H2O vs. 14.0 ± 3.0 cm H2O, P < 0.001, respectively). In the COPD group, the PEEP level titrated by EIT was lower than that titrated by the ARDSnet protocol (6.93 ± 1.69 cm H2O vs. 10.43 ± 1.20 cm H2O, P < 0.001), as was the global inhomogeneity (GI) index (0.397 ± 0.040 vs. 0.446 ± 0.052, P = 0.001), plateau airway pressure (16.50 ± 4.35 cm H2O vs. 20.93 ± 5.37 cm H2O, P = 0.001), dead space ventilation ratio (48.29 ± 6.78% vs. 55.14 ± 8.85%, P < 0.001), ventilation ratio (1.63 ± 0.33 vs. 1.87 ± 0.33, P < 0.001), and mechanical power (13.92 ± 2.18 J/min vs. 15.87 ± 2.53 J/min, P < 0.001). The cardiac index was higher when PEEP was treated by EIT than when it was titrated by the ARDSnet protocol (3.41 ± 0.50 L/min/m2 vs. 3.02 ± 0.43 L/min/m2, P < 0.001), as was oxygen delivery (466.40 ± 71.08 mL/min/m2 vs. 411.10 ± 69.71 mL/min/m2, P = 0.001). CONCLUSION: Titrated PEEP levels were lower in patients with ARDS with COPD than in ARDS patients without COPD. In ARDS patient comorbid with COPD, application of PEEP titrated by EIT was lower than those titrated by the ARDSnet protocol, which contributed to improvements in the ventilation ratio, mechanical energy, cardiac index, and oxygen delivery with less of an adverse impact on hemodynamics.

Current Status of Cell-Based Therapies for COVID-19: Evidence From Mesenchymal Stromal Cells in Sepsis and ARDS.

The severe respiratory consequences of the coronavirus disease 2019 (COVID-19) pandemic have prompted the urgent need for novel therapies. Cell-based therapies, primarily using mesenchymal stromal cells (MSCs), have demonstrated safety and potential efficacy in the treatment of critical illness, particularly sepsis and acute respiratory distress syndrome (ARDS). However, there are limited preclinical data for MSCs in COVID-19. Recent studies have shown that MSCs could decrease inflammation, improve lung permeability, enhance microbe and alveolar fluid clearance, and promote lung epithelial and endothelial repair. In addition, MSC-based therapy has shown promising effects in preclinical studies and phase 1 clinical trials in sepsis and ARDS. Here, we review recent advances related to MSC-based therapy in the context of sepsis and ARDS and evaluate the potential value of MSCs as a therapeutic strategy for COVID-19.

Earlier diagnosis improves COVID-19 prognosis: a nationwide retrospective cohort analysis.

BACKGROUND: Risk of adverse outcomes in COVID-19 patients by stratifying by the time from symptom onset to confirmed diagnosis status is still uncertain. METHODS: We included 1,590 hospitalized COVID-19 patients confirmed by real-time RT-PCR assay or high-throughput sequencing of pharyngeal and nasal swab specimens from 575 hospitals across China between 11 December 2019 and 31 January 2020. Times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit and from first medical visit to confirmed diagnosis were described and turned into binary variables by the maximally selected rank statistics method. Then, survival analysis, including a log-rank test, Cox regression, and conditional inference tree (CTREE) was conducted, regarding whether patients progressed to a severe disease level during the observational period (assessed as severe pneumonia according to the Chinese Expert Consensus on Clinical Practice for Emergency Severe Pneumonia, admission to an intensive care unit, administration of invasive ventilation, or death) as the prognosis outcome, the dependent variable. Independent factors included whether the time from symptom onset to confirmed diagnosis was longer than 5 days (the exposure) and other demographic and clinical factors as multivariate adjustments. The clinical characteristics of the patients with different times from symptom onset to confirmed diagnosis were also compared. RESULTS: The medians of the times from symptom onset to confirmed diagnosis, from symptom onset to first medical visit, and from first medical visit to confirmed diagnosis were 6, 3, and 2 days. After adjusting for age, sex, smoking status, and comorbidity status, age [hazard ratio (HR): 1.03; 95% CI: 1.01-1.04], comorbidity (HR: 1.84; 95% CI: 1.23-2.73), and a duration from symptom onset to confirmed diagnosis of >5 days (HR: 1.69; 95% CI: 1.10-2.60) were independent predictors of COVID-19 prognosis, which echoed the CTREE models, with significant nodes such as time from symptom onset to confirmed diagnosis, age, and comorbidities. Males, older patients with symptoms such as dry cough/productive cough/shortness of breath, and prior COPD were observed more often in the patients who procrastinated before initiating the first medical consultation. CONCLUSIONS: A longer time from symptom onset to confirmed diagnosis yielded a worse COVID-19 prognosis.

A phosphatidic acid-binding lncRNA SNHG9 facilitates LATS1 liquid-liquid phase separation to promote oncogenic YAP signaling.

Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid-liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 (SNHG9) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).

Independent risk factors of hypoxemia in patients after surgery with acute type A aortic dissection.

BACKGROUND: This study aimed to investigate independent risk factors of postoperative hypoxemia in patients with acute type A aortic dissection (ATAAD). METHODS: A single-center retrospective study was conducted with enrolled 75 ATAAD patients following surgery, which were stratified into three groups on the basis of the postoperative PaO2/FiO2 ratio: severe hypoxemia group (PaO2/FiO2 ratio ≤100 mmHg); moderate hypoxemia group (100 mmHg < PaO2/FiO2 ratio ≤200 mmHg); and non-hypoxemia group (PaO2/FiO2 ratio >200 mmHg). The patient's demography, perioperative laboratory results, operative details, clinical outcomes were collected and analyzed. Univariable and multivariable analyses were performed and logistic regression model was established. RESULTS: The incidence of postoperative severe hypoxemia and hypoxemia was 32% and 52%, respectively. Among the three groups, severe hypoxemia group exhibited a high significance of body mass index (BMI) and preoperative white blood cell (WBC) and main distribution of hypertension; meanwhile, Marfan syndrome was mainly distributed in non-hypoxemia group. On intensive care unit (ICU) admission, severe hypoxemia group exhibited a high significance of Acute Physiology and Chronic Health Evaluation (APACHE II) score of postoperative patients, and more patients would present shock. Moreover, severe hypoxemia group patients had a higher incidence of postoperative acute kidney injury (AKI) and usage of renal replacement therapy, longer length of stay (LOS) of ICU, and shorter 28 days ventilator-free days (VFDs). CONCLUSIONS: The incidence of postoperative hypoxemia was high in ATAAD patients owing to comprehensive high-risk factors. Besides, postoperative complications negatively impacted their clinical outcomes.

MiR-1179 is downregulated in cervical cancer and its overexpression suppresses cancer cells invasion by targeting CHAF1A/ZEB1.

The anticancer effect of miR-1179 has been extensively studied in many tumors. The mechanism of miR-1179 action in cervical cancer, however, remains largely unknown. In the present study, miR-1179 was downregulated in both cervical cancer cell lines and cancer tissues. In addition, miR-1179 mimic suppressed cancer cells invasion and epithelial-mesenchymal transition (EMT) in cervical cancer SiHa and Caski cells. We found that chromatin assembly factor 1 subunit A (CHAF1A) might be a direct target of miR-1179 and could be regulated by miR-1179. Furthermore, CHAF1A shRNA suppressed the cervical cancer cells invasion and the expression of EMT-promoted proteins. Reversely, CHAF1A overexpression not only promoted cervical cancer cells invasion but also upregulated the level of Zinc finger E-box binding protein 1 (ZEB1), an EMT-related protein. The induction of ZEB1 could be counteracted by miR-1179 overexpression. It was observed that in cervical cancer patients' tissues, miR-1179 was downregulated while the pathway of CHAF1A/ZEB1 was upregulated. In summary, our research indicated that the miR-1179 might regulate CHAF1A/ZEB1 axis and inhibit the invasion of cervical cancer cells.

COVID-19-associated coagulopathy: thromboembolism prophylaxis and poor prognosis in ICU.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with coagulation abnormalities which are indicators of higher mortality especially in severe cases. METHODS: We studied patients with proven COVID-19 disease in the intensive care unit of Jinyintan Hospital, Wuhan, China from 30 to 2019 to 31 March 2020. RESULTS: Of 180 patients, 89 (49.44 %) had died, 85 (47.22 %) had been discharged alive, and 6 (3.33 %) were still hospitalised by the end of data collection. A D-dimer concentration of > 0.5 mg/L on admission was significantly associated with 30 day mortality, and a D-dimer concentration of > 5 mg/L was found in a much higher proportion of non-survivors than survivors. Sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC) scoring systems were dichotomised as < 4 or ≥ 4 and < 5 or ≥ 5, respectively, and the mortality rate was significantly different between the two stratifications in both scoring systems. Enoxaparin was administered to 68 (37.78 %) patients for thromboembolic prophylaxis, and stratification by the D-dimer concentration and DIC score confirmed lower mortality in patients who received enoxaparin when the D-dimer concentration was > 2 than < 2 mg/L or DIC score was ≥ 5 than < 5. A low platelet count and low serum calcium concentration were also related to mortality. CONCLUSIONS: A D-dimer concentration of > 0.5 mg/L on admission is a risk factor for severe disease. A SIC score of > 4 and DIC score of > 5 may be used to predict mortality. Thromboembolic prophylaxis can reduce mortality only in patients with a D-dimer concentration of > 2 mg/L or DIC score of ≥ 5.

Qualitative and quantitative assessment of pendelluft: a simple method based on electrical impedance tomography.

BACKGROUND: Pendelluft, defined as asynchronous alveolar ventilation, is caused by different regional time constants or dynamic pleural pressure variations. The aim of the present study was to propose a simple method to evaluate pendelluft based on electrical impedance tomography (EIT). The efficacy of this method was demonstrated in well-known pendelluft scenarios in 6 patients. METHODS: Two patients with flail chest after accidents, two patients with acute respiratory distress syndrome (ARDS) and two patients with acutely exacerbated obstructive lung disease were prospectively included. EIT measurements were performed before and after surgery (in patients with flail chest, who had video-assisted thoracoscopic surgery with ribs fixation), or at two different levels of positive end-expiratory pressure (PEEP; ARDS patients), or two different time points (obstructive lung disease). Pendelluft was assessed by regional phase shift (defined as time difference between global and regional impedance-time curves) and amplitude differences (defined as the impedance difference between sum of all regional tidal variation and the global tidal variation). RESULTS: In patients with flail chest, pendelluft diminished several days after surgery (pendelluft amplitude normalized to tidal impedance variation reduced from 88% to 2% in one patient, 12% to 2% in the other). Increased PEEP reduced the amplitude of pendelluft (from 3% to 0% in one patient, 20% to 2% in the other) but not necessarily the phase shifts (average time differences were <0.1 second for both patients for both ins- and expiration) in ARDS patients. Pendelluft assessment in obstructive lung diseases reflected the change in airway resistance (from 5% to 1% in one patient after broncholytic medication administration, as airway resistance fell from 15 to 11 cmH2O/L/s; from 9% to 35% in the other patient with acute exacerbation, the corresponding airway resistance increased from 15 to 22 cmH2O/L/s). CONCLUSIONS: The proposed EIT-based method can be used to evaluate the degree of pendelluft in dimension of phase shift and amplitude difference.

Clinical characteristics and outcomes of critically ill patients with novel coronavirus infectious disease (COVID-19) in China: a retrospective multicenter study.

PURPOSE: An ongoing outbreak of coronavirus disease 2019 (COVID-19) emerged in Wuhan since December 2019 and spread globally. However, information about critically ill patients with COVID-19 is still limited. We aimed to describe the clinical characteristics and outcomes of critically ill patients with COVID-19 and figure out the risk factors of mortality. METHODS: We extracted data retrospectively regarding 733 critically ill adult patients with laboratory-confirmed COVID-19 from 19 hospitals in China through January 1 to February 29, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were collected. The primary outcome was 28-day mortality. Data were compared between survivors and non-survivors. RESULTS: Of the 733 patients included in the study, the median (IQR) age was 65 (56-73) years and 256 (34.9%) were female. Among these patients, the median (IQR) APACHE II score was 10 (7 to 14) and 28-day mortality was 53.8%. Respiratory failure was the most common organ failure (597 [81.5%]), followed by shock (20%), thrombocytopenia (18.8%), central nervous system (8.6%) and renal dysfunction (8%). Multivariate Cox regression analysis showed that older age, malignancies, high APACHE II score, high D-dimer level, low PaO2/FiO2 level, high creatinine level, high hscTnI level and low albumin level were independent risk factors of 28-day mortality in critically ill patients with COVID-19. CONCLUSION: In this case series of critically ill patients with COVID-19 who were admitted into the ICU, more than half patients died at day 28. The higher percentage of organ failure in these patients indicated a significant demand for critical care resources.

Clinical Features of Coronavirus Disease 2019 Patients With Mechanical Ventilation: A Nationwide Study in China.

OBJECTIVES: The outbreak of coronavirus disease 2019 is becoming a worldwide pandemic. Mechanical ventilation is lifesaving for respiratory distress, this study was designed to delineate the clinical features of the coronavirus disease 2019 patients with mechanical ventilation from a national cohort in China. DESIGN: Prospective observational study. SETTING: The rapid spread of severe acute respiratory syndrome coronavirus 2 has infected more than 7.7 million people and caused more than 423,000 deaths. PATIENTS: Adult hospitalized coronavirus disease 2019 patients with mechanical ventilation from 557 hospitals from China. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: From a nationwide cohort, 141 coronavirus disease 2019 cases with mechanical ventilation were extracted from 1,590 cases. Cigarette smoke, advanced age, coexisting chronic illness, elevated systolic blood pressure, high body temperature, and abnormal laboratory findings are common in these ventilated cases. Multivariate regression analysis showed that higher odds of in-hospital death was associated with invasive mechanical ventilation requirement (hazard ratio: 2.95; 95% CI, 1.40-6.23; p = 0.005), and coexisting chronic obstructive pulmonary disease (hazard ratio, 4.57; 95% CI, 1.65-12.69; p = 0.004) and chronic renal disease (hazard ratio, 5.45; 95% CI, 1.85-16.12; p = 0.002). Compared with patients with noninvasive mechanical ventilation, patients who needs invasive mechanical ventilation showed higher rate of elevated D-dimer (> 1.5 mg/L) at admission (hazard ratio, 3.28, 95% CI, 1.07-10.10; p = 0.039). CONCLUSIONS: The potential risk factors of elevated D-dimer level could help clinicians to identify invasive mechanical ventilation requirement at an early stage, and coexisting chronic obstructive pulmonary disease or chronic renal disease are independent risk factors associated with fatal outcome in coronavirus disease 2019 patients with mechanical ventilation.

Development and Validation of a Clinical Risk Score to Predict the Occurrence of Critical Illness in Hospitalized Patients With COVID-19.

Importance: Early identification of patients with novel coronavirus disease 2019 (COVID-19) who may develop critical illness is of great importance and may aid in delivering proper treatment and optimizing use of resources. Objective: To develop and validate a clinical score at hospital admission for predicting which patients with COVID-19 will develop critical illness based on a nationwide cohort in China. Design, Setting, and Participants: Collaborating with the National Health Commission of China, we established a retrospective cohort of patients with COVID-19 from 575 hospitals in 31 provincial administrative regions as of January 31, 2020. Epidemiological, clinical, laboratory, and imaging variables ascertained at hospital admission were screened using Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to construct a predictive risk score (COVID-GRAM). The score provides an estimate of the risk that a hospitalized patient with COVID-19 will develop critical illness. Accuracy of the score was measured by the area under the receiver operating characteristic curve (AUC). Data from 4 additional cohorts in China hospitalized with COVID-19 were used to validate the score. Data were analyzed between February 20, 2020 and March 17, 2020. Main Outcomes and Measures: Among patients with COVID-19 admitted to the hospital, critical illness was defined as the composite measure of admission to the intensive care unit, invasive ventilation, or death. Results: The development cohort included 1590 patients. the mean (SD) age of patients in the cohort was 48.9 (15.7) years; 904 (57.3%) were men. The validation cohort included 710 patients with a mean (SD) age of 48.2 (15.2) years, and 382 (53.8%) were men and 172 (24.2%). From 72 potential predictors, 10 variables were independent predictive factors and were included in the risk score: chest radiographic abnormality (OR, 3.39; 95% CI, 2.14-5.38), age (OR, 1.03; 95% CI, 1.01-1.05), hemoptysis (OR, 4.53; 95% CI, 1.36-15.15), dyspnea (OR, 1.88; 95% CI, 1.18-3.01), unconsciousness (OR, 4.71; 95% CI, 1.39-15.98), number of comorbidities (OR, 1.60; 95% CI, 1.27-2.00), cancer history (OR, 4.07; 95% CI, 1.23-13.43), neutrophil-to-lymphocyte ratio (OR, 1.06; 95% CI, 1.02-1.10), lactate dehydrogenase (OR, 1.002; 95% CI, 1.001-1.004) and direct bilirubin (OR, 1.15; 95% CI, 1.06-1.24). The mean AUC in the development cohort was 0.88 (95% CI, 0.85-0.91) and the AUC in the validation cohort was 0.88 (95% CI, 0.84-0.93). The score has been translated into an online risk calculator that is freely available to the public (http://118.126.104.170/). Conclusions and Relevance: In this study, a risk score based on characteristics of COVID-19 patients at the time of admission to the hospital was developed that may help predict a patient's risk of developing critical illness.

Risk Factors of Fatal Outcome in Hospitalized Subjects With Coronavirus Disease 2019 From a Nationwide Analysis in China.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has become a global health emergency. The cumulative number of new confirmed cases and deaths are still increasing out of China. Independent predicted factors associated with fatal outcomes remain uncertain. RESEARCH QUESTION: The goal of the current study was to investigate the potential risk factors associated with fatal outcomes from COVID-19 through a multivariate Cox regression analysis and a nomogram model. STUDY DESIGN AND METHODS: A retrospective cohort of 1,590 hospitalized patients with COVID-19 throughout China was established. The prognostic effects of variables, including clinical features and laboratory findings, were analyzed by using Kaplan-Meier methods and a Cox proportional hazards model. A prognostic nomogram was formulated to predict the survival of patients with COVID-19. RESULTS: In this nationwide cohort, nonsurvivors included a higher incidence of elderly people and subjects with coexisting chronic illness, dyspnea, and laboratory abnormalities on admission compared with survivors. Multivariate Cox regression analysis showed that age ≥ 75 years (hazard ratio [HR], 7.86; 95% CI, 2.44-25.35), age between 65 and 74 years (HR, 3.43; 95% CI, 1.24-9.5), coronary heart disease (HR, 4.28; 95% CI, 1.14-16.13), cerebrovascular disease (HR, 3.1; 95% CI, 1.07-8.94), dyspnea (HR, 3.96; 95% CI, 1.42-11), procalcitonin level > 0.5 ng/mL (HR, 8.72; 95% CI, 3.42-22.28), and aspartate aminotransferase level > 40 U/L (HR, 2.2; 95% CI, 1.1-6.73) were independent risk factors associated with fatal outcome. A nomogram was established based on the results of multivariate analysis. The internal bootstrap resampling approach suggested the nomogram has sufficient discriminatory power with a C-index of 0.91 (95% CI, 0.85-0.97). The calibration plots also showed good consistency between the prediction and the observation. INTERPRETATION: The proposed nomogram accurately predicted clinical outcomes of patients with COVID-19 based on individual characteristics. Earlier identification, more intensive surveillance, and appropriate therapy should be considered in patients at high risk.

Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis.

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. OBJECTIVE: To evaluate the risk of serious adverse outcomes in patients with COVID-19 by stratifying the comorbidity status. METHODS: We analysed data from 1590 laboratory confirmed hospitalised patients from 575 hospitals in 31 provinces/autonomous regions/provincial municipalities across mainland China between 11 December 2019 and 31 January 2020. We analysed the composite end-points, which consisted of admission to an intensive care unit, invasive ventilation or death. The risk of reaching the composite end-points was compared according to the presence and number of comorbidities. RESULTS: The mean age was 48.9 years and 686 (42.7%) patients were female. Severe cases accounted for 16.0% of the study population. 131 (8.2%) patients reached the composite end-points. 399 (25.1%) reported having at least one comorbidity. The most prevalent comorbidity was hypertension (16.9%), followed by diabetes (8.2%). 130 (8.2%) patients reported having two or more comorbidities. After adjusting for age and smoking status, COPD (HR (95% CI) 2.681 (1.424-5.048)), diabetes (1.59 (1.03-2.45)), hypertension (1.58 (1.07-2.32)) and malignancy (3.50 (1.60-7.64)) were risk factors of reaching the composite end-points. The hazard ratio (95% CI) was 1.79 (1.16-2.77) among patients with at least one comorbidity and 2.59 (1.61-4.17) among patients with two or more comorbidities. CONCLUSION: Among laboratory confirmed cases of COVID-19, patients with any comorbidity yielded poorer clinical outcomes than those without. A greater number of comorbidities also correlated with poorer clinical outcomes.

Pharmacokinetics of and maintenance dose recommendations for vancomycin in severe pneumonia patients undergoing continuous venovenous hemofiltration with the combination of predilution and postdilution.

PURPOSE: Therapeutic vancomycin levels are difficult to maintain in severe pneumonia patients who are receiving IV vancomycin therapy while on continuous venovenous hemofiltration (CVVH). The objective of this study was to determine the pharmacokinetics and maintenance dose recommendations of vancomycin in severe pneumonia patients receiving CVVH. METHODS: A prospective study was conducted in the intensive care unit of a university hospital. Ten severe pneumonia patients receiving vancomycin and CVVH treatment were determined the initial and steady-state pharmacokinetics of vancomycin. CVVH was performed in mixed predilution and postdilution mode with a blood flow rate of 180 mL/min and an ultrafiltrate flow rate of 30-40 mL/kg/h. Group A received an initial dose of 500 mg only, whereas group B received 500 mg every 12 h until steady state is achieved. Serum and ultrafiltrate were collected over 12 h after infusion of vancomycin. RESULTS: After initial dosing, the mean sieving coefficient (SC) was 0.72 ± 0.02, and CVVH clearance (CLCVVH, 1.35 ± 0.03 L/h) constituted 60.55% ± 13.69% of total vancomycin clearance (CLtot, 2.36 ± 0.72 L/h). When steady state was reached, the SC of the patients was 0.71 ± 0.03, and the CLCVVH (1.34 ± 0.06 L/h) accounted for 66.96% ± 6.05% of the CLtot (2.03 ± 0.27 L/h). The recommended maintenance dose for vancomycin in severe pneumonia patients was 400-650 mg every 12 h, which was calculated based on CLtot, to achieve a trough concentration of 15-20 mg/L at steady state. CONCLUSIONS: Single administration or multiple administration does not affect SC and CLCVVH. Owing to therapeutic vancomycin levels is difficult to maintain in severe pneumonia patients who are receiving IV vancomycin therapy while on CVVH, close monitoring of serum trough concentrations is required.

A narrative review of electrical impedance tomography in lung diseases with flow limitation and hyperinflation: methodologies and applications.

Electrical impedance tomography (EIT) is a functional radiation-free imaging technique that measures regional lung ventilation distribution by calculating the impedance changes in the corresponding regions. The aim of the present review was to summarize the current literature concerning the methodologies and applications of EIT in lung diseases with flow limitation and hyperinflation. PubMed was searched up to May 2020 to identify studies investigating the use of EIT in patients with asthma, bronchiectasis, bronchitis, bronchiolitis, chronic obstructive pulmonary disease, and cystic fibrosis. The extracted data included study design, EIT methodologies, interventions, validation and comparators, population characteristics, and key findings. Of the 44 included studies, seven were related to simulation, animal experimentation, or reconstruction algorithm development with evaluation on patients; 27 studies had the primary objective of validating EIT technique and measures including regional ventilation distribution, regional EIT-spirometry parameters, end-expiratory lung impedance, and regional time constants; and 10 studies had the primary objective of applying EIT to monitor the response to therapeutic interventions, including various ventilation supports, patient repositioning, and airway suctioning. In pediatric and adult patients, EIT has been successfully validated for assessing spatial and temporal ventilation distribution, measuring changes in lung volume and flow, and studying regional respiratory mechanics. EIT has also demonstrated potential as an alternative or supplement to well-established measurement modalities (e.g., conventional pulmonary function testing) to monitor the progression of obstructive lung diseases, although the existing literature lacks prediction values as references and lacks clinical outcome evidence.