Physical discomforts, feeling of the high work intensity and the related risk factors of the frontline medical staff during COVID-19 epidemic: an early-outbreak, national survey in China.

Background: Facing the unknown virus, COVID-19 medical staff kept wearing thick personal protective equipment during their work in the early stage of the outbreak. The survey was designed to investigate the physical discomforts, the feeling of the work intensity and the related risk factors of the frontline medical staff during COVID-19 epidemic in the early outbreak. Methods: An national survey was carried out in China from March 17th 2020 to March 20th 2020 by applying a standardized WeChat questionnaire survey. The doctors or nurses working in the wards for the confirmed COVID-19 patients on front-line were eligible to participate in the survey. Descriptive analysis and multivariate logistic regression analysis were used. Results: A total number of 515 COVID-19 medical staff, including 190 physicians and 325 nurses participated in this survey. 375 medical staff (72.8%) experienced physical discomforts at work, mostly consist of dyspnea (45.8%), pain (41.0%), chest distress (24.1%), dizziness (18.8%), and weakness (17.5%), while wearing thick isolation clothes at work. The mean onset time and peak time of these symptoms were 2.4 h and 3.5 h after working, respectively. 337 medical staff (65.4%) suffered from sleep disorders. 51 medical staff (10%) were highly worried about being infected by COVID-19 even during their work breaks. 246 medical staffs (47.8%) felt high work intensity and the independent influential factors were the effective daily sleep time and anxiety levels at break time (p = 0.04). Conclusion: The frontline medical staff during COVID-19 epidemic felt different physical discomforts when they wear thick isolation clothes at work in the early outbreak and they felt high work intensity. These precious data will help optimize the work management strategy to ensure the physical and mental health of medical staff in the face of similar outbreaks in future.

Identification of risk factors for iatrogenic hypophosphatemia: A retrospective case-control study.

BACKGROUND AND OBJECTIVES: To investigate the iatrogenic risk factors for hypophosphatemia in intensive care unit (ICU) patients. METHODS AND STUDY DESIGN: A total of 120 patients were enrolled and further divided into 4 groups, namely normal, mild, moderate or severe, according to the degree of hypophosphatemia. A number of related factors were analyzed and compared among the 4 groups, including the treatment method and outcomes. Univariate and multivariate regression analyses were employed to identify and confirm the risk factors associated with the occurrence of hypophosphatemia. RESULTS: The results revealed that the acute physiology and chronic health evaluation II (APACHEII), Sequential Organ Failure Assessment (SOFA), modified NUTrition Risk in Critically ill (NUTRIC) scores as well as the length of patient stays in ICUs exhibited a gradually increasing trend of aggravation of hypophosphatemia. Univariate regression analysis identified the use of dehydrating drugs to be closely associated with the occurrence of hypophosphatemia, which was further confirmed by a multivariate regression analysis. CONCLUSIONS: The use of dehydrating drugs led to hypophosphatemia; therefore blood phosphorus concentrations should be closely monitored during treatment of ICU patients.

Cytokine levels in sputum, not serum, may be more helpful for indicating the damage in the lung and the prognosis of severe COVID-19 - A case series.

PURPOSE: To describe the relationship between the severity of lung damage and cytokine levels in sputum, bronchoalveolar lavage fluid (BALF), serum. METHOD: Eight severe patients infected with coronavirus disease 2019 (COVID-19) were admitted and their cytokines and chest computed tomography (CT) were analyzed. RESULTS: Compared with in serum, IL-6 and TNF-α in sputum and in BALF show more directly reflect the severity of COVID-19 critical patients. The gradient ratio of IL-6 levels may predict the prognosis of severe patients. CONCLUSION: Cytokine levels in the sputum may be more helpful for indicating lung damage. Local intervention through the respiratory tract is expected to benefit patients with severe COVID-19.

Risk factors and predictors of QTc prolongation in critically ill Chinese patients.

BACKGROUND: To recognize and validate the predictor of risk factors for ICU patients with QTc intervals ≥500 ms. METHODS: We retrospectively reviewed 160 ICU patients with their medical electronic records including all demographic data, diagnosis measurements, ECGs and medication from March 1, 2018 to December 1, 2018. All information of patients' baseline, comorbidities, electrolytes and Long QT syndrome (LQTS)-inducing medications of patients with QT interval corrected (QTc) ≥ 500 ms (n = 80) and <500 ms (n = 80) were collected and analyzed using univariate and multivariate analyses to find predictors. RESULTS: Comparing to patients with QTc < 500 ms, patients with QTc ≥ 500 ms had increased SOFA (P = 0.010) and APACHE II scores (P = 0.002), longer lengths of ICU stays (P < 0.001), greater incidence of congestive heart failure (P = 0.005) and more preset risk factors (P < 0.001). The frequency of administration of mosapride (P = 0.015), amiodarone (P = 0.027) and number of combined LQTS-inducing medications (P = 0.012) were greater in patients with QTc ≥ 500 ms than in those with QTc < 500 ms. But after multivariate analysis, we found that risk factors related to a QTc ≥ 500 ms were only congestive heart failure (OR: 5.28), number of combined LQTS-inducing medications (OR: 1.60) and APACHE II score (OR: 1.08). CONCLUSIONS: For critically ill patients, congestive heart failure, number of combined LQTS-inducing medications and APACHE II score are proved as risk factors associated with QTc > 500 ms.

Acute right ventricular dysfunction in severe COVID-19 pneumonia.

To investigate the right heart function in coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome (ARDS), a retrospective analysis of 49 COVID-19 patients with ARDS was performed. Patients were divided into severe group and critically-severe group according to the severity of illness. Age-matched healthy volunteers were recruited as a control group. The cardiac cavity diameters, tricuspid annular plane systolic excursion (TAPSE), tricuspid valve regurgitation pressure gradient biggest (TRPG), pulmonary arterial systolic pressure (PASP), maximum inferior vena cava diameter (IVCmax) and minimum diameter (IVCmin), and inferior vena cava collapse index (ICV-CI) were measured using echocardiography. We found that the TAPSE was significantly decreased in pneumonia patients compared to healthy subjects (P < 0.0001), and it was significantly lower in critically-severe patients (P = 0.0068). The TAPSE was less than 17 mm in three (8.6%) severe and five (35.7%) critically-severe patients. In addition, the TAPSE was significantly decreased in severe ARDS patients than in mild ARDS patients. The IVCmax and IVCmin were significantly increased in critically-severe patients compared to healthy subjects and severe patients (P < 0.01), whereas the ICV-CI was significantly decreased (P < 0.05). COVID-19 patients had significantly larger right atrium and ventricle than healthy controls (P < 0.01). The left ventricular ejection fraction (LVEF) in critically-severe patients was significantly lower than that in severe patients and healthy controls (P < 0.05). Right ventricular function was impaired in critically-severe COVID-19 patients. The assessment and protection of the right heart function in COVID-19 patients should be strengthened.

Protective effect of nimesulide on acute lung injury in mice with severe acute pancreatitis.

The study was designed to investigate the effect of Nimesulide (NIM) on acute lung injury (ALI) in mice with severe acute pancreatitis (SAP). In our study, caerulein and LPS were employed to establish the ALI mice model induced by SAP. All animals were divided into four groups randomly: control, model (SAP), NIM low and high dosages groups. Following treatment with NIM, histopathology observation of pancreatic tissues and lung tissues were detected by hematoxylin and eosin (H&E) staining. The levels of serum amylase, lipase, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and IL-6 were measured by ELISA. The ratio of wet lung to dry lung (W/D) was calculated. In addition, the expression levels of TNF-α, IL-1ß and IL-6 were measured by Western blotting. Moreover, the expression of cyclooxygenase-2 (COX-2) was detected using Immunohistochemistry analysis. The results revealed that NIM markedly improved pancreatic histological injury and decreased the levels of serum amylase, lipase, TNF-α, IL-1ß and IL-6 in a dose-dependent after NIM treatment. For ALI induced by SAP, pulmonary edema were significantly alleviated compared with the mice in SAP group. In addition, the decreased ratio of W/D were observed after NIM intervene. The expression levels of TNF-α, IL-1ß and IL-6 proteins were downregulated following NIM treatment. More, NIM inhibited the expression of COX2 in lung tissues. Taken together, our study demonstrated that NIM was able to protect against ALI induced by SAP via inhibiting inflammation, which will be of novel therapeutic strategies for the clinical treatment of ALI.

Autophagy is essential for flavopiridol­induced cytotoxicity against MCF­7 breast cancer cells.

Flavopiridol (FP) exerts antitumoral effects by triggering tumor cell cycle arrest and cytotoxicity in human breast cancer cell lines. The potent antitumor activity of FP is through its inhibition of cyclin­dependent kinases; however, this may not be the only mechanism of action. The present study aimed to investigate whether FP is able to induce autophagy and to examine the effects of autophagy on cell death in FP­treated MCF­7 human breast cancer cells. MCF­7 cells were treated with either FP alone or FP in combination with chloroquine (CQ). Expression levels of autophagy­related protein LC3B­II and p62/sequestosome 1 (SQSTM1) were used to monitor autophagic flux. MCF­7 cells were transfected with autophagy­related 5 (ATG5) small interfering (si)RNA to block autophagy. Cell viability and cell cycle status were determined. Following incubation with FP, MCF­7 cells exhibited significantly higher autophagy compared with untreated control cells, and the level of autophagy is comparable with cells under rapamycin induction, which was verified by immunodetection of LC3B­II and p62/SQSTM1 expression and inhibition by CQ. The addition of CQ treatment or ATG5­siRNA transfection against autophagy components attenuated the cytotoxic effects of FP treatment of MCF­7 cells. Furthermore, this autophagy inhibition did not impair the FP­induced cell cycle arrest. These results revealed that autophagy may be involved in FP­induced MCF­7 cell death and autophagy inhibition enhanced the tumor cell pro­survival ability. It is possibly that potential autophagy regulatory drugs may be used as a chemotherapy adjuvant.

Clinical application of intra-aortic balloon pump in patients with cardiogenic shock during the perioperative period of cardiac surgery.

Intra-aortic balloon pumps (IABP) have saved many patients with cardiogenic shock during the perioperative period of cardiac surgery. However, the ideal insertion timing is controversial. In the present study, we aimed to optimize the insertion timing, in order to increase the survival rate of the patients. A total of 197 patients with cardiogenic shock during the perioperative period of cardiac surgery and implemented IABP from January 2011 to October 2015 were selected for the study. Patients were divided into five groups on the basis of application timing of IABP: 0-60, 61-120, 121-180, 181-240 and >240 min. The 30-day mortality, application rate of continuous renal replacement therapy (CRRT), duration of mechanical ventilation, duration of hospital stay and hospitalization charges were analyzed in the above groups. The risk factors related to mortality and the occurrence of IABP complications were also analyzed. The mortality in the 0-60, 61-120, 121-180, 181-240 and >240 min groups were 42.17, 36.6, 77.3, 72.7 and 79.3%, respectively. Earlier IABP insertion resulted in less patients receiving CRRT from acute renal failure and less daily hospitalization charges. However, the IABP application timing had no effect on indexes such as hospitalization duration, duration of mechanical ventilation and total hospitalization charges. Multifactor logistic regression analysis indicated that the independent risk factors of death in patients with cardiogenic shock during cardiac surgery were related to IABP support timing and vasoactive-inotropic score (VIS) before balloon insertion. In the first 120 min of cardiogenic shock during the perioperative period of cardiac surgery, IABP application decreased 30-day mortality. Mortality was related with VIS score of patients, which can be used to predict the prognosis of patients with cardiogenic shock.

Anti­migratory effect of rapamycin impairs allograft imaging by 18F­fluorodeoxyglucose­labeled splenocytes.

Tracking lymphocyte migration is an emerging strategy for non­invasive nuclear imaging of allografts; however, its clinical application remains to be fully demonstrated. In the present study, the feasibility of using rapamycin­treated 18F­fluorodeoxyglucose (18F­FDG)­labeled splenocytes for the in vivo imaging of allografts was evaluated. C57BL/6 skin was heterotopically transplanted onto non­obese diabetic/severe combined immunodeficient recipient mice. BALB/c 18F­FDG­labeled splenocytes with or without rapamycin pretreatment (designated as FR and FC cells, respectively) were transferred into recipient mice 30 days later. Imaging of radiolabeled cells in the skin grafts was conducted through in vivo dynamic whole­body phosphor­autoradiography and histological analysis. Notably, rapamycin impaired the migration of 18F­FDG­labeled splenocytes to the graft. At all time points, the radioactivity of allografts (digital light units/mm2) was significantly lower in the group that received FR cells, compared with the group that received FC cells (P<0.01). Furthermore, the peak allograft to native skin ratio was 1.29±0.02 at 60 min for the FR group and 3.29±0.17 at 30 min for the FC group (P<0.001). In addition, the in vivo radioactivity of the allografts was observed to be correlated with the transferred cells, which were observed histologically (r2=0.887; P<0.0001). Although 18F­FDG­labeled splenocytes migrated to the allograft, imaging of these cells may not be possible in the presence of rapamycin.

Autophagy in allografts rejection: A new direction?

Despite the introduction of new and effective immunosuppressive drugs, acute cellular graft rejection is still a major risk for graft survival. Modulating the dosage of immunosuppressive drugs is not a good choice for all patients, new rejection mechanisms discovery are crucial to limit the inflammatory process and preserve the function of the transplant. Autophagy, a fundamental cellular process, can be detected in all subsets of lymphocytes and freshly isolated naive T lymphocytes. It is required for the homeostasis and function of T lymphocytes, which lead to cell survival or cell death depending on the context. T cell receptor (TCR) stimulation and costimulator signals induce strong autophagy, and autophagy deficient T cells leads to rampant apoptosis upon TCR stimulation. Autophagy has been proved to be activated during ischemia-reperfusion (I/R) injury and associated with grafts dysfunction. Furthermore, Autophagy has also emerged as a key mechanism in orchestrating innate and adaptive immune response to self-antigens, which relates with negative selection and Foxp3(+) Treg induction. Although, the role of autophagy in allograft rejection is unknown, current data suggest that autophagy indeed sweeps across both in the graft organs and recipients lymphocytes after transplantation. This review presents the rationale for the hypothesis that targeting the autophagy pathway could be beneficial in promoting graft survival after transplantation.

[Effect of airway humidification on lung injury induced by mechanical ventilation].

OBJECTIVE: To explore the effect of airway humidification on lung injury as a result of mechanical ventilation with different tidal volume (VT). METHODS: Twenty-four male Japanese white rabbits were randomly divided into four groups: low VT with airway humidification group, high VT with airway humidification group, low VT and high VT group without humidification, with 6 rabbits in each group. Mechanical ventilation was started after intubation and lasted for 6 hours. Low VT denoted 8 mL/kg, while high VT was 16 mL/kg, fraction of inspired oxygen (FiO2) denoted 0.40, positive end-expiratory pressure (PEEP) was 0. Temperature at Y piece of circuit in airway humidification groups was monitored and controlled at 40 centigrade. Arterial blood gas analysis, including pH value, arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), lung mechanics indexes, including peak airway pressure (P(peak)) and airway resistance (Raw), and lung compliance was measured at 0, 2, 4, 6 hours of mechanical ventilation. The levels of tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in plasma and bronchoalveolar lavage fluid (BALF) were determined by enzyme linked immunosorbent assay (ELISA). The animals were sacrificed at the end of mechanical ventilation. The wet to dry (W/D) ratio of lung tissues was calculated. Histopathologic changes in the lung tissueies were observed with microscope, and lung injury score was calculated. Scanning and transmission electron microscopies were used to examine the integrity of the airway cilia and the tracheal epithelium. RESULTS: Compared with low V(T) group, pH value in high V(T) group was significantly increased, PaCO2was significantly lowered, and no difference in PaO2was found. P(peak), Raw, and lung compliance were significantly increased during mechanical ventilation. There were no significant differences in blood gas analysis and lung mechanics indexes between low V(T) with airway humidification group and low V(T) group. Compared with high V(T) group, PaCO2in high V(T) with airway humidification group was significantly decreased, Ppeak raised obviously, and no difference in pH value, PaO2, Raw and pulmonary compliance was found. Compared with low V(T) with airway humidification group, no difference in blood gas analysis (PaCO2, mmHg, 1 mmHg=0.133 kPa) was found, but Ppeak (cmH2O, 1 cmH2O=0.098 kPa), Raw (cmH2O), and lung compliance (mL/cmH2O) were increased significantly in high V(T) with airway humidification group (PaCO2at 2 hours: 27.96 ± 4.64 vs. 36.08 ± 2.11, 4 hours: 28.62 ± 2.93 vs. 34.55 ± 5.50, 6 hours: 29.33 ± 2.14 vs. 35.01 ± 5.53; Ppeak at 0 hour: 14.34 ± 1.97 vs. 8.84 ± 1.32, 2 hours: 17.33 ± 0.52 vs. 11.17 ± 2.14, 4 hours: 17.83 ± 0.98 vs. 12.67 ± 2.06, 6 hours: 18.67 ± 1.22 vs. 13.50 ± 2.16; Raw at 0 hour: 37.36 ± 5.14 vs. 27.0 5 ± 2.93, 2 hours: 43.94 ± 6.58 vs. 31.95 ± 3.56, 4 hours: 48.04 ± 6.07 vs. 35.24 ± 3.50, 6 hours: 50.33 ± 6.34 vs. 36.66 ± 3.64; pulmonary compliance at 6 hours: 2.28 ± 0.18 vs. 1.86 ± 0.37, all P<0.05). The lung W/D ratio in high VT group was significantly higher than that of the low V(T) group (6.17 ± 2.14 vs. 3.50 ± 1.52, P<0.05). W/D in high V(T) with airway humidification group was higher than that of low V(T) with airway humidification group but without statistically significant difference (5.17 ± 2.14 vs. 3.00 ± 1.10, P>0.05). Microscopic observation showed that cilia were partially detached, adhered and sparse in low V(T) group, while cilia in high V(T) group showed serious detachment and lodging. Remaining cilia were sparse, with lodging, and cellular structure was damaged. Lung tissue pathological injury score in the high V(T) group was significantly higher than that of low V(T) group (6.17 ± 2.14 vs. 3.50 ± 1.52, P<0.05). Cilia density and cellularity were normal in low V(T) with airway humidification group, and no difference in lung tissue pathological injury score was found compared with low V(T) group (3.00 ± 1.10 vs. 3.50 ± 1.52, P>0.05). Cilia were severely detached, adhered and lodging, and cellularity were not obvious in high V(T) with airway humidification group, and lung tissue pathological injury score was elevated significantly than that of the low V(T) with airway humidification group but without statistically significant difference (5.17 ± 2.14 vs. 3.00 ± 1.10, P>0.05). TNF-α and IL-8 concentrations showed no change in plasma and BALF in all groups during ventilation, and no significant difference was found among the groups. CONCLUSIONS: Airway humidification can alleviate pathological lung injury, damage of cilia and cellular structure in trachea caused by mechanical ventilation with low and high V(T). High V(T) with humidification can result in serious pulmonary edema.

The significance of post-operative creatinine in predicting prognosis in cardiac surgery patients.

The purpose of the study is to investigate the effectiveness of serum creatinine, the most common indicator of acute kidney injury (AKI), in predicting the prognosis of critically ill patients after cardiac surgery. Also, we sought to validate the use of this biomarker in assessing the direct outcome of a clinical setting. We selected 592 patients from our hospital; the relevant information including name, disease, gender, age, EuroSCORE, length of stay (LOS), days of mechanical ventilation, days of noninvasive positive pressure ventilation, days of continuous renal replacement treatment, and mortality was recorded. Creatinine of pre-operative, 24, and 48 h post-operation specimens were analyzed. The difference in serum creatinine levels at various time points was compared using t test. Spearman correlation was used to analyze the correlation of serum creatinine to AKI and hard outcomes. Receiver-operating characteristic curves were generated, and the areas under the curves (AUCs) were compared to validate the adequacy of creatinine in predicting the post-operative AKI. The 48 h post-operative and pre-operative serum creatinine were found to be informative in predicting the outcome of patients as indicated by the t test and Spearman correlation analysis. The 48 h creatinine with AUC of 0.811 was indicated to be significantly associated with the hard outcome. However, the 24 h and pre-operative creatinine with AUCs of 0.701 and 0.658, respectively, were not adequately related to the outcomes. In conclusion, contrary to the existing belief that creatinine is not an informative parameter for the diagnosis and prognosis of AKI, we found that when measured at 48 h of cardiac surgery, serum creatinine is reflective of the outcome.

[Effects of cardiac sympathetic blockade on left ventricular diastolic function in patients with dilated cardiomyopathy and severe heart failure].

OBJECTIVE: To investigate the effects of cardiac sympathetic blockade on left ventricular diastolic function in patients with dilated cardiomyopathy and severe heart failure (HF). METHODS: Thirty-nine consecutive patients with dilated cardiomyopathy and severe HF with a left ventricular ejection fraction < 35% were randomly divided into 2 groups: control group (n = 16, 12 males and 4 females, aged 56 +/- 16, undergoing routine anti-HF treatment), and cardiac sympathetic blockade (TEB) group (n = 23, 18 males and 5 females, aged 51 +/- 13, undergoing sympathectomy at the interspinal space T3 - 4 or T4 - 5 in addition to the routine anti-HF treatment). Transthoracic echocardiography was conducted before the treatment and 1 month after the treatment to measure the left atrial diameter (Lad), left ventricular diastolic end diameter (LVDEd), ejection fraction (EF), peak early and late diastolic mitral inflow velocity (Em and Am) at 6 mitral annular sites, and the mean values of Em and Am (MEm and MAm). RESULTS: The Lad of the TEB group was 40.4 +/- 5.3 mm, significantly shorter than that of the control group (45.2 mm +/- 7.3 mm. P < 0.05). The LEDEd of the TEB group was 66 mm +/- 6 mm, significantly shorter than that of the control group (71 mm +/- 6 mm, P < 0.05). The EF of the TEB group was 35% +/- 7%, significantly higher than that of the control group (23% +/- 6%, P < 0.05). The MEm of the TEB group was 5.7 cm/s +/- 1.5 cm/s, significantly faster than that of the control group (7.1 cm/s +/- 1.7 cm/s, P < 0.05); and the MAm of the TEB group was 7.1 cm/s +/- 2.1 cm/s, significantly faster than that of the control group (5.4 cm/s +/- 1.8 cm/s, P < 0.05). In the control group the values of Lad, LVDEd, EF, Am, MEm, and MAm did not change significantly, and the Em values significantly increased only at 2 mitral annular sites after the treatment. CONCLUSION: Sympathetic blockade reduces the left ventricular cavity and boosts up the ejection performance, thus improving the left ventricular diastolic function.