The dual effects of dexmedetomidine on intestinal barrier and intestinal motility during sepsis.

BACKGROUND: Sepsis, characterized by dysregulated host responses to infection, remains a critical global health concern, with high morbidity and mortality rates. The gastrointestinal tract assumes a pivotal role in sepsis due to its dual functionality as a protective barrier against injurious agents and as a regulator of motility. Dexmedetomidine, an α2-adrenergic agonist commonly employed in critical care settings, exhibits promise in influencing the maintenance of intestinal barrier integrity during sepsis. However, its impact on intestinal motility, a crucial component of intestinal function, remains incompletely understood. METHODS: In this study, we investigated dexmedetomidine's multifaceted effects on intestinal barrier function and motility during sepsis using both in vitro and in vivo models. Sepsis was induced in Sprague-Dawley rats via cecal ligation and puncture. Rats were treated with dexmedetomidine post-cecal ligation and puncture, and various parameters were assessed to elucidate dexmedetomidine's impact. RESULTS: Our findings revealed a dichotomous influence of dexmedetomidine on intestinal physiology. In septic rats, dexmedetomidine administration resulted in improved intestinal barrier integrity, as evidenced by reduced mucosal hyper-permeability and morphological alterations. However, a contrasting effect was observed on intestinal motility, as dexmedetomidine treatment inhibited both the frequency and amplitude of contractions in isolated intestinal strips and decreased the distance of ink migration in vivo. Additionally, dexmedetomidine suppressed the secretion of pro-motility hormones while having no influence on hormones that inhibit intestinal peristalsis. CONCLUSION: The study revealed that during sepsis, dexmedetomidine exhibited protective effects on barrier integrity, although concurrently it hindered intestinal motility, partly attributed to its modulation of pro-motility hormone secretion. These findings underscore the necessity of a comprehensive understanding of dexmedetomidine's impact on multiple facets of gastrointestinal physiology in sepsis management, offering potential implications for therapeutic strategies and patient care.

Observation of the validity of the upper lip bite test in predicting difficult intubation.

The upper lip bite test (ULBT) is considered an effective method for predicting difficult airways, but data on the ULBT for predicting difficult tracheal intubation are lacking. This study aimed to examine the clinical utility of the ULBT in predicting difficult endotracheal intubation. We conducted an observational case-cohort study of adult patients undergoing elective surgery and requiring endotracheal intubation for general anesthesia. Difficult airway assessment was performed on the recruited patients before the operation, including the ULBT, mouth opening, thyromental distance, modified Mallampati test, and body mass index. The primary outcome was the incidence of difficult tracheal intubation. The receiver operating characteristic curve analysis was used to compare the performance of variables in predicting difficult tracheal intubation. We successfully recruited 2522 patients for analysis and observed 64 patients with difficult tracheal intubation. When predicting difficult tracheal intubation, grade 2 ULBT had a sensitivity of 0.75 and a specificity of 0.54, and grade 3 had a sensitivity of 0.28 and a specificity of 0.75. Compared with mouth opening, the area under the receiver operating characteristic curve of the ULBT was lower in predicting difficult tracheal intubation (0.69 [95% confidence interval: 0.67-0.71] vs. 0.84 [95% confidence interval: 0.82-0.87], P < 0.05).Clinical Trials Registry: ChiCTR-ROC-16009050, principal investigator: Weidong Yao.

Development and validation of a screening method for difficult tracheal intubation based on geometric simulation and computer technology.

BACKGROUND: The anatomical characteristics of difficult airways can be analysed geometrically. This study aims to develop and validate a geometry-assisted difficult airway screening method (GADAS method) for difficult tracheal intubation. METHODS: In the GADAS method, a geometric simulated model was established based on computer graphics. According to the law of deformation of the upper airway on laryngoscopy, the expected visibility of the glottis was calculated to simulate the real visibility on laryngoscopy. Validation of the new method: Approved by the Ethics Committee of Yijishan Hospital of Wannan Medical College. Adult patients who needed tracheal intubation under general anaesthesia for elective surgery were enrolled. The data of patients were input into the computer software to calculate the expected visibility of the glottis. The results of tracheal intubation were recorded by anaesthesiologists. The primary observation outcome was the screening performance of the expected visibility of the glottis for difficult tracheal intubation. RESULTS: The geometric model and software of the GADAS method were successfully developed and are available for use. We successfully observed 2068 patients, of whom 56 patients had difficult intubation. The area under the receiver operating characteristic curve of low expected glottis visibility for predicting difficult laryngoscopy was 0.96 (95% confidence interval [CI]: 0.95-0.96). The sensitivity and specificity were 89.3% (95% CI: 78.1-96.0%) and 94.3% (95% CI: 93.2%-95.3), respectively. CONCLUSIONS: It is feasible to screen difficult-airway patients by applying computer techniques to simulate geometric changes in the upper airway.

[Application effect analysis of lateral prone position ventilation in patients with acute respiratory distress syndrome].

OBJECTIVE: To investigate the effect of lateral prone position ventilation in patients with acute respiratory distress syndrome (ARDS). METHODS: A prospective control study was conducted. A total of 75 patients with moderate to severe ARDS admitted to the department of critical care medicine of Jingxian Hospital in Anhui province from January 2020 to December 2022 were selected as the research objects. According to the envelope method, the patients were divided into the lateral prone position ventilation group (38 cases) and the traditional prone position ventilation (PPV) group (37 cases), using lateral prone position ventilation and traditional PPV, respectively. The mechanical ventilation parameters were set according to the ARDS treatment guidelines and lung protective ventilation requirements in both groups, and the time of prone position for the first 3 times was not less than 16 hours per day. General data of patients were recorded, including heart rate (HR), mean arterial pressure (MAP), airway resistance and lung static compliance (Cst) before prone position (T0), 1 hour (T1), 4 hours (T2), 8 hours (T3), and before the end of prone position (T4), oxygenation index (PaO2/FiO2) before the first prone position (t0) and 12 hours (t1), 24 hours (t2), 48 hours (t3), and 72 hours (t4) after the intensive care unit (ICU) admission, as well as the incidence of pressure injury (PI) and vomiting, tracheal intubation time, and mechanical ventilation time. Repeated measures analysis of variance was used to compare the effects of different prone positions on patients before and after the prone position. RESULTS: There were no significant differences in age, gender, body mass index (BMI), acute physiology and chronic health evaluation II (APACHE II), underlying diseases, HR, MAP, pH value, PaO2/FiO2, blood lactic acid (Lac), arterial blood pressure of carbon dioxide (PaCO2) and other general information between the two groups. The HR (intergroup effect: F = 0.845, P = 0.361; time effect: F = 1.373, P = 0.247; interaction: F = 0.245, P = 0.894), MAP (intergroup effect: F = 1.519, P = 0.222; time effect: F = 0.169, P = 0.954; interaction: F = 0.449, P = 0.773) and airway resistance (intergroup effect: F = 0.252, P = 0.617; time effect: F = 0.578, P = 0.679; interaction: F = 1.467, P = 0.212) of T0-T4 between two groups showed no significant difference. The Cst of T0-T4 between the two groups showed no significant difference in the intergroup effect (F = 0.311, P = 0.579) and the interaction (F = 0.364, P = 0.834), while the difference in the time effect was statistically significant (F = 120.546, P < 0.001). The PaO2/FiO2 of t0-t4 between the two groups showed no significant difference in the intergroup effect (F = 0.104, P = 0.748) and the interaction (F = 0.147, P = 0.964), while the difference in the time effect was statistically significant (F = 17.638, P < 0.001). The group factors and time factors were tested separately, and there were no significant differences in the HR, MAP, airway resistance, Cst, PaO2/FiO2 between the two groups at different time points (all P > 0.05). The Cst at T1-T4 and PaO2/FiO2 at t1-t4 in the two groups were significantly higher than those at T0/t0 (all P < 0.05). There were no significant differences in the tracheal intubation time [days: 6.75 (5.78, 8.33) vs. 7.00 (6.30, 8.45)] and mechanical ventilation time [days: 8.30 (6.70, 9.20) vs. 7.40 (6.80, 8.75)] between the lateral prone position ventilation group and the traditional PPV group (both P > 0.05). However, the incidences of PI [7.9% (3/38) vs. 27.0% (10/37)] and vomiting [10.5% (4/38) vs. 29.7% (11/37)] in the lateral prone position ventilation group were significantly lower than those in the traditional PPV group (both P < 0.05). CONCLUSIONS: Both lateral prone position ventilation and traditional PPV can improve Cst and oxygenation in patients with moderate to severe ARDS. The two types of prone position have little influence on HR, MAP and airway resistance of patients, and there is no difference in the influence on tracheal intubation time and mechanical ventilation time of patients. However, the lateral prone position ventilation mode can reduce the incidence of PI and vomiting, and is worthy of clinical promotion and application.

[Analysis of the incidence and related factors of hypothermia in patients with continuous renal replacement therapy].

OBJECTIVE: To investigate the incidence and risk factors of hypothermia in patients with acute renal injury (AKI) receiving continuous renal replacement therapy (CRRT), and to compare the effects of different heating methods on the incidence of hypothermia in patients with CRRT. METHODS: A prospective study was conducted. AKI patients with CRRT who were admitted to the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from January 2020 to December 2022 were enrolled as the study subjects. Patients were divided into dialysate heating group and reverse-piped heating group according to randomized numerical table method. Both groups were provided with reasonable treatment mode and parameter setting by the bedside physician according to the patient's specific condition. The dialysis heating group used the AsahiKASEI dialysis machine heating panel to heat the dialysis solution at 37 centigrade. The reverse-piped heating group used the Barkey blood heater from the Prismaflex CRRT system to heat the dialysis solution, and the heating line temperature was set at 41 centigrade. The patient's temperature was then continuously monitored. Hypothermia was defined as a temperature lower than 36 centigrade or a drop of more than 1 centigrade from the basal body temperature. The incidence and duration of hypothermia were compared between the two groups. Binary multivariate Logistic regression analysis was used to explore the influencing factors of hypothermia during CRRT in AKI patients. RESULTS: A total of 73 patients with AKI treated with CRRT were eventually enrolled, including 37 in the dialysate heating group and 36 in the reverse-piped heating group. The incidence of hypothermia in the dialysis heating group was significantly lower than that in the reverse-piped heating group [40.5% (15/37) vs. 69.4% (25/36), P < 0.05], and the hypothermia occurred later than that in the reverse-piped heating group (hours: 5.40±0.92 vs. 3.35±0.92, P < 0.01). Patients were divided into hypothermic and non-hypothermic groups based on the presence or absence of hypothermia, and a univariate analysis of all indicators showed a significant decrease in mean arterial pressure (MAP) in hypothermic patients (n = 40) compared with the non-hypothermic patients [n = 33; mmHg (1 mmHg ≈ 0.133 kPa): 77.45±12.47 vs. 94.42±14.51, P < 0.01], shock, administration of medium and high doses of vasoactive drug (medium dose: 0.2-0.5 µg×kg-1×min-1, high dose: > 0.5 µg×kg-1×min-1) and CRRT treatment were significantly increased [shock: 45.0% (18/40) vs. 6.1% (2/33), administration of medium and high doses of vasoactive drugs: 82.5% (33/40) vs. 18.2% (6/33), administration of CRRT (mL×kg-1×h-1): 51.50±9.38 vs. 38.42±10.97, all P < 0.05], there were also significant differences in CRRT heating types between the two groups [in the hypothermia group, the main heating method was the infusion line heating, which was 62.5% (25/40), while in the non-hypothermia group, the main heating method was the dialysate heating, which was 66.7% (22/33), P < 0.05]. Including the above indicators in a binary multivariate Logistic regression analysis, it was found that shock [odds ratio (OR) = 17.633, 95% confidence interval (95%CI) was 1.487-209.064], mid-to-high-dose vasoactive drug (OR = 24.320, 95%CI was 3.076-192.294), CRRT heating type (reverse-piped heating; OR = 13.316, 95%CI was 1.485-119.377), and CRRT treatment dose (OR = 1.130, 95%CI was 1.020-1.251) were risk factors for hypothermia during CRRT in AKI patients (all P < 0.05), while MAP was protective factor (OR = 0.922, 95%CI was 0.861-0.987, P < 0.05). CONCLUSIONS: AKI patients have a high incidence of hypothermia during CRRT treatment, and the incidence of hypothermia can be effectively reduced by heating CRRT treatment fluids. Shock, use of medium and high doses of vasoactive drug, CRRT heating type, and CRRT treatment dose are risk factors for hypothermia during CRRT in AKI patients, with MAP is a protective factor.

SOV sensitizes gastric cancer cells to radiation by suppressing radiation-induced autophagy in vitro and in vivo.

Vanadium is a transition metal that naturally occurs in the environment and has a variety of biological and physiological impacts on humans. Sodium orthovanadate (SOV), a well-known chemical compound of vanadium, has shown notable anti-cancer activity in various types of human malignancies. However, the effect of SOV on stomach cancer is yet undetermined. Furthermore, only a few studies have investigated the association of SOV and radiosensitivity with stomach cancer. Our study has investigated the ability of SOV to increase the sensitivity of gastric cancer cells to radiation. To detect autophagy triggered by ionizing radiation and the influence of SOV on cell radiosensitivity, the Cell Counting Kit-8 (CCK8) test, EDU staining experiment, colony formation assay, and immunofluorescence were performed. The possible synergistic effects of SOV and irradiation were examined in vivo using a xenograft mouse model of stomach cancer cells. Both in vitro and in vivo studies showed that SOV markedly reduced the growth of stomach cancer cells and improved their radiosensitivity. Our results showed that SOV increased gastric cancer cells' radiosensitivity, thereby blocking the radiation-induced autophagy-related protein, ATG10. Thus, SOV can be considered a potential agent for radiosensitizing gastric cancer.

[Emergency treatment of centrifugal pump dysfunction in extracorporeal membrane oxygenation].

OBJECTIVE: To summarize the treatment process of rapid decrease in blood flow due to centrifugal pump dysfunction during extracorporeal membrane oxygenation (ECMO) and its related thinking. METHODS: On September 25, 2021, the ECMO treatment of a 14-year-old boy with severe mycoplasma pneumonia, severe viral pneumonia and acute respiratory distress syndrome (ARDS) admitted to the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College was analyzed. RESULTS: Oxygenation of the child was difficult to maintain under invasive mechanical ventilation, and lung consolidation progressed seriously. After evaluation, venous-venous ECMO (VV-ECMO) was implemented, then oxygenation was improved. In the 120th hour after VV-ECMO establishment, the blood flow sudden decreased, the speed was 3 822 r/min, while the flow was only 0.2 L/min, more over there was no change in the flow when the speed was increased. Before that, the ECMO speed was 3 530 r/min, and the flow was up to 3.4 L/min and stable. After rapid screening, it was determined that the centrifugal pump was dysfunction. ECMO was successfully replaced and the flow was satisfactory. CONCLUSIONS: At present, most ECMO centers do not routinely monitor the pressure before and after the pump. There is a lack of visual and quantitative techniques or indicators to judge the pump's function, and there is also a lack of corresponding clinical experience in treatment. This paper summarizes the investigation and treatment process of ECMO pump dysfunction of this case to provide reference.

[Effect of different connection schemes of continuous renal replacement therapy and extracorporeal membrane oxygenation on arterial and venous pressure: an in vitro and in vivo study].

OBJECTIVE: To investigate the effects of different connection schemes of continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation (ECMO) on arterial pressure (PA), venous pressure (PV), and transmembrane pressure (TMP), and to provide a theoretical basis for choosing a suitable connection scheme. METHODS: (1) In vitro study: the different connection schemes of CRRT and ECMO were simulated and divided into 6 schemes according to the connection between CRRT and ECMO circuits at different positions. Scheme A: connected to the front and back points of the oxygenator; scheme B: connected to the points behind and in front of the oxygenator; scheme C: connected to the points in front of the oxygenator and in front of the centrifugal pump; scheme D: connected to the points behind the oxygenator and in front of the centrifugal pump; scheme E: connected to the points in front of the oxygenator and the return catheter; scheme F: connected to the points after the oxygenator and the return catheter. Each set of ECMO circuits was measured 5 times under each connection scheme and different flow rates (2, 3, 4, 5, 5.5 L/min). Six ECMO circuits for a total of 30 measurements, and the PA, PV, and TMP of the 6 schemes were compared. (2) In vivo study: the patients who were treated with ECMO combined with CRRT in the department of critical care medicine of the First Affiliated Hospital of Wannan Medical College from August 2017 to August 2021 changed the connection scheme due to high PA or PV (from scheme A or B to scheme E or F) were retrospectively analyzed. The changes of PA and PV before and after changing the scheme were compared. RESULTS: (1) In vitro study results: there was no significant difference in PA between schemes A and B, C and D, E and F under different ECMO blood flow (2-5.5 L/min). The PA of schemes C and D was the lowest, followed by schemes E and F. PV of scheme B was higher than that of scheme A under different ECMO blood flow (2-5.5 L/min). There was no significant difference in PV between schemes C and D, E and F under high ECMO blood flow (3-5.5 L/min), and the absolute value of PV was lowest in schemes E and F. Compared with schemes A and B [partial PA > 300 mmHg (1 mmHg ≈ 0.133 kPa) at high flow rate], C and D (partial PV > 350 mmHg at high flow rate), schemes E and F were more reasonable connection schemes. TMP was negative in schemes C and D at ECMO blood flow of 5 L/min and 5.5 L/min (mmHg; 5 L/min: scheme C was -29.14±11.42, scheme D was -42.45±15.70; 5.5 L/min: scheme C was -35.75±13.21, scheme D was -41.58±15.42), which indicated the presence of dialysate reverse filtration. Most of the differences in TMP among schemes A, B, E, and F under different ECMO blood flow (2-5.5 L/min) were statistically significant, and the absolute value of mean fluctuation was 9.89-49.55 mmHg, all within the normal range. (2) In vivo study results: a total of 10 patients who changed the connection scheme (from scheme A or B to E or F) due to high PA or PV were enrolled, including 8 males and 2 females; 7 cases of venous-arterial ECMO (VA-ECMO) and 3 cases of venous-venous ECMO (VV-ECMO), all used continuous veno-venous hemodiafiltration (CVVHDF) mode. After changing the scheme, both PA and PV decreased significantly as compared with those before changing [PA (mmHg): 244.00±22.58 vs. 257.20±21.92, PV (mmHg): 257.20±18.43 vs. 326.40±15.41, both P < 0.01], and PV decreased more significantly than PA [difference (mmHg): 69.20±6.55 vs. 13.20±5.45, P < 0.01]. CONCLUSION: For patients treated with ECMO in combination with CRRT, the scheme of connecting the access line of CRRT to the pre-oxygenator or post-oxygenator and connecting the return line to the point of the return catheter can significantly reduce PA and PV and maintains normal CRRT operation even running high-flow ECMO.

The expression landscape of JAK1 and its potential as a biomarker for prognosis and immune infiltrates in NSCLC.

BACKGROUND: Janus-activated kinase-1 (JAK1) plays a crucial role in many aspects of cell proliferation, differentiation, apoptosis and immune regulation. However, correlations of JAK1 with prognosis and immune infiltration in NSCLC have not been documented. METHODS: We analyzed the relationship between JAK1 expression and NSCLC prognosis and immune infiltration using multiple public databases. RESULTS: JAK1 expression was significantly decreased in NSCLC compared with that in paired normal tissues. JAK1 overexpression indicated a favourable prognosis in NSCLC. In subgroup analysis, high JAK1 expression was associated with a preferable prognosis in lung adenocarcinoma (OS: HR, 0.74, 95% CI from 0.58 to 0.95, log-rank P = 0.017), not squamous cell carcinoma. In addition, data from Kaplan-Meier plotter revealed that JAK1 overexpression was associated with a preferable prognosis in male and stage N2 patients and patients without distant metastasis. Notably, increased levels of JAK1 expression were associated with an undesirable prognosis in patients with stage 1 (OS: HR, 1.46, 95% CI from 1.06 to 2.00, P = 0.02) and without lymph node metastasis (PFS: HR, 2.18, 95% CI from 1.06 to 4.46, P = 0.029), which suggests that early-stage NSCLC patients with JAK1 overexpression may have a bleak prognosis. Moreover, multiple immune infiltration cells, including NK cells, CD8 + T and CD4 + T cells, B cells, macrophages, neutrophils, and dendritic cells (DCs), in NSCLC were positively correlated with JAK1 expression. Furthermore, diverse immune markers are associated with JAK1 expression. CONCLUSIONS: JAK1 overexpression exhibited superior prognosis and immune infiltration in NSCLC.

[Analysis of the effect of sequential high-flow nasal canula oxygen therapy in post-extubation mechanically ventilated patients in intensive care unit].

OBJECTIVE: To observe the application effect of high-flow nasal canula oxygen therapy (HFNC) after extubation in patients with mechanical ventilation (MV) in the intensive care unit (ICU). METHODS: A prospective study was conducted. From January 2018 to June 2020, 163 MV patients admitted to Yijishan Hospital of Wannan Medical College were enrolled, and they were divided into HFNC group (82 cases) and traditional oxygen therapy group (81 cases) according to the oxygen therapy model. The patients included in the study were given conventional treatment according to their condition. In the HFNC group, oxygen was inhaled by a nasal high-flow humidification therapy instrument. The gas flow was gradually increased from 35 L/min to 60 L/min according to the patient's tolerance, and the temperature was set at 34-37 centigrade. The fraction of inspiration oxygen (FiO2) was set according to the patient's pulse oxygen saturation (SpO2) and SpO2 was maintained at 0.95-0.98. A disposable oxygen mask or nasal cannula was used to inhale oxygen in the traditional oxygen therapy group, and the oxygen flow was 5-8 L/min, maintaining the patient's SpO2 at 0.95-0.98. The differences in MV duration before extubation, total MV duration, intubation time, reintubation time, extubation failure rate, ICU mortality, ICU stay, and in-hospital stay were compared between the two groups, and weaning failure were analyzed. RESULTS: There was no significant differences in MV duration before extubation (days: 4.33±3.83 vs. 4.15±3.03), tracheal intubation duration (days: 4.34±1.87 vs. 4.20±3.35), ICU mortality [4.9% (4/82) vs. 3.7% (3/81)] and in-hospital stay [days: 28.93 (15.00, 32.00) vs. 27.69 (15.00, 38.00)] between HFNC group and traditional oxygen therapy group (all P > 0.05). The total MV duration in the HFNC group (days: 4.48±2.43 vs. 5.67±3.84) and ICU stay [days: 6.57 (4.00, 7.00) vs. 7.74 (5.00, 9.00)] were significantly shorter than those in the traditional oxygen therapy group, the reintubation duration of the HFNC group was significantly longer than that of the traditional oxygen therapy group (hours: 35.75±10.15 vs. 19.92±13.12), and the weaning failure rate was significantly lower than that of the traditional oxygen therapy group [4.9% (4/82) vs. 16.0% (13/81), all P < 0.05]. Among the reasons for weaning failure traditional oxygen therapy group had lower ability of airway secretion clearance than that of the HFNC group [8.64% (7/81) vs. 0% (0/82), P < 0.05], there was no statistically differences in the morbidity of heart failure, respiratory muscle weakness, hypoxemia, and change of consciousness between the two groups. CONCLUSIONS: For MV patients in the ICU, the sequential application of HFNC after extubation can reduce the rate of weaning failure and the incidence of adverse events, shorten the length of ICU stay.

Successful extracorporeal membrane oxygenation resuscitation of patient with cardiogenic shock induced by phaeochromocytoma crisis mimicking hyperthyroidism: A case report.

A 29-year-old woman presented to the emergency department with the acute onset of palpitations, shortness of breath, and haemoptysis. She reported having an abortion (56 days of pregnancy) 1 week before admission because of hyperthyroidism diagnosis during pregnancy. The first diagnoses considered were cardiomyopathy associated with hyperthyroidism, acute left ventricular failure, and hyperthyroidism crisis. The young woman's cardiocirculatory system collapsed within several hours. Hence, venoarterial extracorporeal membrane oxygenation (VA ECMO) was performed for this patient. Over the next 3 days after ECMO was established, repeat transthoracic echocardiography showed gradual improvements in biventricular function, and later the patient recovered almost completely. The patient's blood pressure increased to 230/130 mm Hg when the ECMO catheter was removed, and then the diagnosis of phaeochromocytoma was suspected. Computed tomography showed a left suprarenal tumour. The tumour size was 5.8 cm × 5.7 cm with central necrosis. The vanillylmandelic acid concentration was 63.15 mg/24 h. Post-operation, pathology confirmed phaeochromocytoma. To our knowledge, this is the first case report of a patient with cardiogenic shock induced by phaeochromocytoma crisis mimicking hyperthyroidism which was successfully resuscitated by VA ECMO.

Serum exosome microRNA panel as a noninvasive biomarker for molecular diagnosis of fulminant myocarditis.

Exosome-derived microRNAs (miRNAs) are potential diagnostic biomarkers. However, little is known about their effectiveness as diagnostic biomarkers of fulminant myocarditis (FM). This study aimed to explore serum exosomal miRNAs as potential biomarkers for FM diagnosis. Peripheral blood samples were collected from 99 patients with FM, 32 patients with nonfulminant myocarditis (NFM), and 105 healthy controls (HCs). The miRNA expression profiles of serum exosomes were determined using next-generation sequencing, and differentially expressed miRNAs were further analyzed by quantitative reverse transcriptase polymerase chain reaction. A logistic regression model was constructed using a training cohort (n = 120) and then validated using an independent cohort (n = 106). The area under the receiver operating characteristic curve was used to evaluate diagnostic accuracy. In FM patients, hsa-miR-30a, hsa-miR-192, hsa-miR-146a, hsa-miR-155, and hsa-miR-320a were validated as significantly and differentially expressed candidates that could serve as potential markers for diagnosing FM. In addition, the miRNA panel (hsa-miR-155 and hsa-miR-320a) from the multivariate logistic regression model demonstrated high accuracy in the diagnosis of FM and was able to distinguish FM from HCs and NFM. Moreover, the diagnostic value of the miRNA panel was greater than that of CRP and cTn alone or together. The miRNA panel provided the excellent diagnostic capability for FM.

[Research progress of septic retina and optic nerve damage].

The main mechanisms of sepsis induced organ damage are microcirculation dysfunction, host immune response imbalance, mitochondrial dysfunction, etc. As one of the most metabolically active organs in the human body, the retina can be damaged in sepsis. Studies have shown that nearly 50% of patients with sepsis have changes such as slow retinal blood flow, exudation, hemorrhage, and retinal microaneurysm formation, which are far higher than clinicians' expectations. For individuals, the importance of the eyeball has always surpassed this organ itself. Even the slight deterioration of visual ability may be closely related to daily activities. However, the ICU physicians are mainly concerned with the dysfunction of the "large" organs, it is only noticed when the patient has an irreversible visual impairment. In addition, the eyes can also "reflect" the severity of the disease and predict the prognosis. Therefore, it is necessary to re-understand and pay more attention to this organ in sepsis. This article reviews the epidemiology, clinical manifestations, possible pathogenic factors, pathogenesis, and treatment of septic retinal and optic nerve injury, to raise the concern about "eyeball" injury in septic patients.

Inhibition of miR-155 alleviates sepsis-induced inflammation and intestinal barrier dysfunction by inactivating NF-κB signaling.

MicroRNA-155 (miR-155) is implicated in the pathological processes of sepsis. However, the function and regulatory mechanism of miR-155 in sepsis-induced inflammation and intestinal barrier dysfunction remain unknown. In this study, mouse models of sepsis were established by caecal ligation and puncture (CLP). To reduce miR-155 expression, the mice were injected for three consecutive days with an miR-155 inhibitor (80 mg/kg) before CLP. The serum DAO concentration was measured by ELISA, and histological changes in the intestine were identified by H&E staining 24 h after CLP. FITC-dextran assays were used to evaluate intestinal permeability. MiR-155 gene expression was evaluated with RT-PCR, and relative protein expression was assessed by Western blotting. NCM460 cells were transfected with an miR-155 mimic/miR-155 inhibitor or pretreated with an NF-κB inhibitor before LPS treatment, and the cytokines levels, miR-155 gene expression and relative protein expression were measured. Sepsis increased miR-155, DAO and FITC-dextran levels and reduced Occludin and ZO-1 expression. Mice injected with the miR-155 inhibitor recovered from the damages. Transfection of NCM460 cells with the miR-155 mimic elevated the NF-κB (P65) and p-NF-κB (p-P65) localization and expression in the nucleus, which was reversed by the miR-155 inhibitor. Pretreatment with an NF-κB inhibitor suppressed inflammation, improved cell permeability to FITC-dextran and increased Occludin and ZO-1 levels. Transfection with the miR-155 inhibitor decreased TNF-α and IL-6 levels, reduced cell permeability to FITC-dextran and increased ZO-1 and Occludin expression. The effects induced by transfection with the miR-155 mimic, including elevated TNF-α and IL-6 levels, hyperpermeability to FITC-dextran and reduced ZO-1 and Occludin expression, were partly rescued by pretreatment with the NF-κB inhibitor. These findings reveal that the miR-155 inhibitor alleviates inflammation and intestinal barrier dysfunction by inactivating NF-κB signaling during sepsis.

[Study on the extracorporeal membrane oxygenation inter-hospital transport during coronavirus disease 2019 epidemic: based on the transport experience of 6 cases of severe H1N1 influenza virus pneumonia on extracorporeal membrane oxygenation].

OBJECTIVE: To provide a reference for extracorporeal membrane oxygenation (ECMO) inter-hospital transport during coronavirus disease 2019 (COVID-19), based on the transport experience of 6 patients with severe H1N1 influenza virus pneumonia using ECMO. METHODS: Clinical data of patients with severe H1N1 influenza virus pneumonia implemented by ECMO in the First Affiliated Hospital of Wannan Medical College from October 2018 to December 2019 were retrospective analyzed, including general information, ECMO transport distance, time, clinical parameters before and after ECMO, including the patients' oxygenation index (PaO2/FiO2), respiratory rate (RR), pulse blood oxygen saturation (SpO2), arterial blood carbon dioxide partial pressure (PaCO2), and pH value, various complications during transport, mechanical ventilation time, patients' prognosis and other indicators. Experience from the aspects of personal protection, transport process and equipment, team cooperation, mid-transit monitoring, quality control, etc., was summarized to provide suggestions for patients with severe COVID-19 using ECMO during inter-hospital transport and protection. RESULTS: A total of 6 patients with severe H1N1 influenza virus pneumonia were transported on ECMO. All patients were transported to the intensive care unit (ICU) of the First Affiliated Hospital of Wannan Medical College by the ECMO transport team after the establishment of ECMO in the local hospital. The transfer distance was 11 to 197 km, with an average of (93.8±58.6) km; the transfer time was 30 to 150 minutes, with an average of (79.2±40.6) minutes. Two patients experienced a drop in ECMO flow and SpO2 during the process, and the main reason was insufficient volume, which was improved after fluid resuscitation and posture adjustment. All patients maintained SpO2 above 0.93. Six patients survived and were discharged. ECMO assisted time was 4-9 days, with an average of (6.5±1.5) days; mechanical ventilation time was 7-24 days, and median time was 10.0 (8.0, 14.5) days. No H1N1 transmission occurred in medical personnel. To achieve good therapeutic effect, the main experience was to choose the proper timing and mode of ECMO; intact transportation vehicles and equipment to reduce or avoid mechanical complications; the effective management of respiration and circulation during the transportation to avoid ventilation-associated lung injury (VALI) and serious hypoxemia; the appropriate space for the transfer team to quickly handle various critical situations; and personal protection to avoid infection. CONCLUSIONS: With an experienced ECMO transport team, good transport equipment, comprehensive protection measures, reasonable transport procedures, and a perfect emergency plan, it is safe to use ECMO transport for COVID-19 patients.

[Role and mechanism of splenic myeloid-derived suppressor cells in sepsis-induced adrenal injury in mice].

OBJECTIVE: To investigate the role and mechanism of splenic myeloid-derived suppressor cells (MDSCs) in sepsis-induced adrenal injury (SAI). METHODS: Thirty male C57 mice aged 6-8 weeks were randomly divided into normal control group (n = 5), sham operation group (Sham group, n = 5), sepsis model group [cecal ligation and perforation (CLP) group, n = 10] and sepsis+splenectomy group (CLPS group, n = 10). The sepsis model of mice was reproduced by CLP method. In Sham group, only the cecum was opened and separated, then closed, without CLP. In CLPS group, the spleen was removed before CLP. In normal control group, no challenge was given. After 24 hours, the rats were sacrificed by anesthesia, and peripheral blood, spleen, bone marrow, and bilateral adrenal glands were harvested. The pathological of adrenal gland was assessed by hematoxylin-eosin (HE) staining under optical microscope. The ratio of MDSCs in peripheral blood, spleen and bone marrow was determined by flow cytometry. The expressions of MDSCs surface antigen CD11b, Gr-1 and interleukins (IL-6, IL-1ß) mRNA in adrenal tissue were measured by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Western Blot was used to detect the expressions of mammalian rapamycin target protein (mTOR) pathway related proteins including total mTOR (T-mTOR), phosphorylation of mTOR (p-mTOR) and caspase-3. RESULTS: The adrenal cortex and medulla of the normal control group and Sham group were intact and the structure was clear under optical microscope, while in the CLP group, the adrenal gland showed edema, cortical hemorrhage and cell edema. Compared with the CLP group, the adrenal tissue injury was significantly reduced in the CLPS group. Compared with the normal control group and Sham group, MDSCs ratio in the peripheral blood was significantly increased and significantly reduced in the spleen in the CLP group, but there was no significant difference in bone marrow, the expression levels of CD11b, Gr-1, IL-6, IL-1ß mRNA and caspase-3 protein were increased significantly and p-mTOR protein expression was significantly decreased in adrenal tissue, there was no significant difference in the expression of T-mTOR protein. Compared with the CLP group, in the CLPS group, the MDSCs ratio in the peripheral blood was significantly decreased (0.143±0.011 vs. 0.324±0.023, P < 0.01), the expression levels of CD11b, Gr-1, IL-6 , IL-1ß mRNA and caspase-3 protein in adrenal gland were significantly decreased [CD11b mRNA (2-ΔΔCt): 2.90±0.56 vs. 5.74±0.13, Gr-1 mRNA (2-ΔΔCt): 2.71±0.14 vs. 4.59±0.46, IL-6 mRNA (2-ΔΔCt): 2.44±0.64 vs. 5.17±1.04, IL-1ß mRNA (2-ΔΔCt): 3.58±0.52 vs. 4.44±0.26, caspase-3 protein (caspase-3/GAPDH): 0.05±0.01 vs. 0.13±0.02, all P < 0.01], the p-mTOR protein expression was significantly increased (p-mTOR/GAPDH: 0.61±0.11 vs. 0.27±0.04, P < 0.01). CONCLUSIONS: The spleen is the major source of MDSCs in SAI. Splenectomy can attenuate SAI by reducing mobilization of MDSCs and activating the mTOR signaling pathway.

Evaluation of diaphragm ultrasound in predicting extubation outcome in mechanically ventilated patients with COPD.

BACKGROUND: To explore the value of the right hemi-diaphragmatic excursion (DE) and its variation in predicting extubation outcome in mechanically ventilated patients with COPD. METHODS: All included patients with COPD received mechanical ventilation (MV) and were ready to wean from MV. After patients passed the 30 min spontaneous breathing trail (SBT), extubation was considered to be feasible, and the right DE measured by ultrasound at 0 min, 5 min, and 30 min of SBT were named as DE0, DE5, and DE30, respectively. RESULTS: Twenty-five patients succeeded extubation; 12 patients failed. The area under receiver operator characteristic curve (AUCROC) of DE30 and ΔDE30-5 (the variation between 30 and 5 min) were 0.762 and 0.835; a cutoff value of DE30 > 1.72 cm and ΔDE30-5 > 0.16 cm were associated with a successful extubation with a sensitivity of 76% and 84%, a specificity of 75% and 83.3%, respectively. The predictive probability equation of the DE30 plus ∆DE30-5 was P = 1/[1 + e-(-5.625+17.689×∆DE30-5+1.802×DE30)], a cutoff value of P > 0.626 was associated with a successful extubation with the AUCROC of 0.867, a sensitivity of 92%, and a specificity of 83.3%. CONCLUSION: The combination of DE30 and ∆DE30-5 could improve the predictive value and could be used as the predictor of extubation outcome in mechanically ventilated patients with COPD.

[Application of Narcotrend index and Richmond agitation-sedation score in sedation assessment of patients with short-term mechanical ventilation after pancreatoduodenectomy: a randomized controlled trial].

OBJECTIVE: To explore the feasibility of Narcotrend index (NTI) for digital monitoring of light sedation depth in patients undergoing short-term mechanical ventilation after pancreaticoduodenectomy. METHODS: A prospective randomized controlled trial was conducted. Patients with mechanical ventilation for 12-48 hours after pancreaticoduodenectomy admitted to department of critical care medicine of the First Affiliated Hospital of Wannan Medical College from January 2016 to December 2018 were enrolled. They were randomly divided into two groups, and NTI and Richmond agitation-sedation score (RASS) were used to guide light sedation treatment respectively. The implementation effect of light sedation, duration of mechanical ventilation, dosage of sedative drugs, occurrence of adverse events (accidental extubation, delirium, cardiovascular events) and stress response [cortisol, epinephrine, norepinephrine, C-reactive protein (CRP)] were compared between the two groups. RESULTS: A total of 87 patients were enrolled in this study, of whom 45 received NTI-guided sedation assessment and 42 received RASS-guided sedation assessment. There were no significant differences in gender, age, body mass index (BMI), liver function classification, operation time, blood loss, conversion to laparotomy and acute physiology and chronic health evaluation II (APACHE II) score between the two groups. During sedation treatment, the light sedation compliance rate after light sedation, 2, 4, 6 hours and cumulative compliance period number (Dt) in NTI group were higher than those in RASS group [71.1% (32/45) vs. 50.0% (21/42), 80.0% (36/45) vs. 54.8% (23/42), 88.9% (40/45) vs. 59.5% (25/42), 83.9% (642/765) vs. 62.8% (475/756), all P < 0.05]. The dosage of dexmedetomidine in NTI group was higher than that in RASS group (µg×kg-1×h-1: 0.60±0.10 vs. 0.54±0.12, P < 0.01), but more patients in RASS group receiveda larger dose of propofol to maintain sedation [ratio of use of propofol: 64.3% (27/42) vs. 37.8% (17/45), dose of propofol (mg/h): 47.82±7.31 vs. 30.83±10.35, both P < 0.05]. The sedation duration and duration of mechanical ventilation in NTI group were lower than those in RASS group (hours: 15.68±2.43 vs. 17.29±2.43, 16.27±2.42 vs. 18.25±2.04, both P < 0.01). There were no significant differences in hypertension, bradycardia, accidental extubation and delirium between the two groups during sedation treatment, but the incidence of hypotension in RASS group was higher than that in NTI group [35.7% (15/42) vs. 13.3% (6/45), P < 0.05]. Compared with RASS group, epinephrine, norepinephrine and the levels of CRP at treatment of 6 hours with light sedation and 2 hours after tracheal catheter removal in NTI group were decreased [epinephrine (pg/L): 138.35±18.60 vs. 157.50±19.91, 136.24±40.40 vs. 150.46±20.22; norepinephrine (pg/L): 347.34±45.46 vs. 393.75±49.77, 340.59±50.95 vs. 376.37±49.70; CRP (µg/L): 62.26±18.78 vs. 71.31±10.32, 53.30±14.47 vs. 64.26±14.69, all P < 0.05], and cortisol level 6 hours after treatment with light sedation was lower than that of RASS group (nmol/L: 327.03±41.04 vs. 358.12±70.01, P < 0.05). CONCLUSIONS: The application of NTI monitoring to guide light sedation therapy for patients with short-term mechanical ventilation after pancreaticoduodenectomy can better achieve the goal of light sedation.