Association between septic shock and tracheal injury score in intensive care unit patients with invasive ventilation: a prospective single-centre cohort study in China.

OBJECTIVES: There was no evidence regarding the relationship between septic shock and tracheal injury scores. Investigate whether septic shock was independently associated with tracheal injury scores in intensive care unit (ICU) patients with invasive ventilation. DESIGN: Prospective observational cohort study. SETTING: Our study was conducted in a Class III hospital in Hebei province, China. PARTICIPANTS: Patients over 18 years of age admitted to the ICU between 31 May 2020 and 3 May 2022 with a tracheal tube and expected to be on the tube for more than 24 hours. PRIMARY AND SECONDARY OUTCOME MEASURES: Tracheal injuries were evaluated by examining hyperaemia, ischaemia, ulcers and tracheal perforation by fiberoptic bronchoscope. Depending on the number of lesions, the lesions were further classified as moderate, severe or confluent. RESULTS: Among the 97 selected participants, the average age was 56.6±16.5 years, with approximately 64.9% being men. The results of adjusted linear regression showed that septic shock was associated with tracheal injury scores (ß: 2.99; 95% CI 0.70 to 5.29). Subgroup analysis revealed a stronger association with a duration of intubation ≥8 days (p=0.013). CONCLUSION: Patients with septic shock exhibit significantly higher tracheal injury scores compared with those without septic shock, suggesting that septic shock may serve as an independent risk factor for tracheal injury. TRIAL REGISTRATION NUMBER: ChiCTR2000037842, registered 03 September 2020. Retrospectively registered, https://www.chictr.org.cn/edit.aspx?pid=57011&htm=4.

Effect of opioids on constipation in critically ill patients: A meta-analysis.

OBJECTIVES: This meta-analysis evaluated the effect of opioids on constipation in ICU patients. REVIEW METHOD USED: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang DATA databases. REVIEW METHODS: Random or fixed-effects meta-analyses were used. Subgroup analysis was performed according to the definition of constipation (three vs. six days), opioids (fentanyl vs. morphine), study design (prospective vs. retrospective), adjustment of confounders (No vs. Yes), and patient's age (adults vs. children). We used sensitivity analysis to test the robustness of results with significant statistical heterogeneity. RESULTS: Seven studies (2264 patients) were included. Opioid use in ICU patients was associated with an increased risk of constipation (relative risk [RR]=1.14; 95% confidence interval [CI]=1.05 to 1.24; I2=49.8%). Subgroup analysis further showed that adjustment form, category of opioid, study design, and patient's age significantly influenced the relationship between opioid use and the risk of constipation. Sensitivity analysis confirmed the robustness of pooled results. CONCLUSION: Opioids significantly increase the risk of constipation in critically ill patients, especially children. It is worth noting that the adjustment of the constipation definition used for ICU significantly influenced the relationship between opioid use and the risk of constipation. Therefore, It is necessary to clearly define ICU constipation and conduct time-based layered treatment. Additional prospective studies are needed to investigate the consistent definition of ICU constipation.

Fungal Endophthalmitis in a Case of Rhino-Orbito-Cerebral Mucormycosis: Successfully Treated With Amphotericin B Colloidal Dispersion.

Background: Rhino-orbito-cerebral mucormycosis (ROCM) is an acute, fulminant, opportunistic fungal infection that usually occurs in diabetes or immunocompromised patients. Amphotericin B combined with surgical debridement remains the standard treatment, although it is controversial due to its lager nephrotoxicity. Thus far, no studies have reported the treatment for ROCM-associated fungal endophthalmitis because the exact pathogenesis and transmission routes in ROCM remain unclear. Here, we reported a case of ROCM complicated with fungal endophthalmitis treated favorably with amphotericin B colloidal dispersion (ABCD) in combination with other antifungals and surgical debridement. Case Presentation: A 34-year-old woman with diabetes was admitted to our hospital owing to right-sided headache for 8 days, blindness with swelling in the right eye for 5 days, and blindness in the left eye for 1 day. MRI showed that the patient had sphenoid sinus, sinuses, frontal lobe lesions, and proptosis of the right eye. Metagenomic sequencing revealed that the patient had Rhizopus oryzae infection. During hospitalization, the patient received intravenous ABCD, oral posaconazole, and topical amphotericin B and underwent surgical debridement. After 67 days of treatment, the patient's condition was significantly improved, and limb muscle strength showed grade V. Rhizopus oryzae showed negative results, and conjunctival swelling decreased. Additionally, no nephrotoxicity occurred during treatment. After discharge, the patient's treatment was transitioned to oral posaconazole and she was free of complaints during the 30-day follow-up without any additional treatment for ROCM. Conclusion: Treatment with ABCD combined with other antifungal drugs and surgical debridement for ROCM complicated with fungal endophthalmitis showed remarkable efficacy and good safety. Hence, this regimen is a promising treatment strategy for this fatal disease.

MiRNA-196-5p Promotes Proliferation and Migration in Cholangiocarcinoma via HAND1/Wnt/ß-Catenin Signaling Pathway.

Accumulating evidence has indicated the crucial role of microRNA-196 in mediating tumor progression, while its significance in cholangiocarcinoma (CCA) remains unclear. In this study, we provided the first evidence that the expression level of miR-196-5p is elevated in both CCA cell lines and clinic specimen. MiR-196-5p inhibition notably suppressed cell proliferation as well as metastasis in CCA cell line HuCCT1. Furthermore, the interaction between miR-196-5p and its downstream molecule HAND1 was verified. Moreover, a series of rescue assay verified that both HAND1 and ß-catenin silencing could reverse the abnormal elevated cell proliferation and migration brought by miR-196-5p elevation, indicating that HAND1/Wnt/ß-catenin signaling pathway activation is essential for miR-196-5p to exert its roles. In summary, we successfully depict the oncogenic role of miR-196-5p in promoting cell proliferation and migration in CCA via HAND1/Wnt/ß-catenin axis.

Clinical role of serum histone deacetylase 4 measurement in acute ischemic stroke: Relation to disease risk, severity, and prognosis.

OBJECTIVE: Histone deacetylase 4 (HDAC4) is engaged in the pathophysiology of acute ischemic stroke (AIS) through modulating atherosclerosis, inflammation and neurocyte death. This study aimed to investigate the clinical role of HDAC4 in AIS. METHODS: Serum samples were collected from 176 AIS patients and 80 controls for HDAC4 detection by enzyme-linked immunosorbent assay (ELISA). In AIS patients, disease severity was assessed by National Institute of Health Stroke Scale (NIHSS) score and their recurrence-free survival (RFS) and overall survival (OS) were calculated, inflammatory cytokines and adhesion molecules were detected by ELISA. RESULTS: HDAC4 was declined in AIS patients vs. controls (p < 0.001), it also had certain ability of distinguishing AIS patients from controls with an area under curve of 0.748 (95% confidence interval: 0.689-0.806). Among AIS patients, HDAC4 was negatively linked with NIHSS score (p < 0.001) but no other clinical features (all p > 0.05). Moreover, HDAC4 was negatively related to interleukin (IL)-17 (p = 0.010) and tumor necrosis factor alpha (p = 0.001), while it was not correlated with IL-1ß (p = 0.081) or IL-6 (p = 0.074). Furthermore, HDAC4 was negatively associated with intercellular cell adhesion molecule-1 (p < 0.001) and vascular cell adhesion molecule-1 (p = 0.003). During a median follow-up of 19.0 months, 17 (9.7%) patients had recurrence and 10 (5.7%) patients died. Additionally, high HDAC4 was linked with prolonged RFS (p = 0.044) but not OS (p = 0.079). CONCLUSION: HDAC4 possesses the potential to monitor disease risk, inflammation and estimate recurrence of AIS, while further study with larger scale is needed to verify our findings.

Low tricuspid annular plane systolic excursion is associated with a poor outcome in patients with COVID-19: A systematic review and meta-analysis.

ABSTRACT: Background: This systematic review and meta-analysis aimed to assess whether tricuspid annular plane systolic excursion (TAPSE) could be used as a prognostic tool in patients with coronavirus disease 19 (COVID-19). METHODS: Studies on the relationship between TAPSE and COVID-19 since February 2021. Standardized mean difference (SMD) and 95% confidence intervals were used to assess the effect size. The potential for publication bias was assessed using a contour-enhanced funnel plot and Egger test. A meta-regression was performed to assess if the difference in TAPSE between survivors and nonsurvivors was affected by age, sex, hypertension or diabetes. RESULTS: Sixteen studies comprising 1579 patients were included in this meta-analysis. TAPSE was lower in nonsurvivors (SMD -3.24 (-4.23, -2.26), P < .00001; I2 = 71%), and a subgroup analysis indicated that TAPSE was also lower in critically ill patients (SMD -3.85 (-5.31, -2.38,), P < .00001; I2 = 46%). Heterogeneity was also significantly reduced, I2 < 50%. Pooled results showed that patients who developed right ventricular dysfunction had lower TAPSE (SMD -5.87 (-7.81, -3.92), P = .004; I2 = 82%). There was no statistically significant difference in the TAPSE of patients who sustained a cardiac injury vs those who did not (SMD -1.36 (-3.98, 1.26), P = .31; I2 = 88%). No significant publication bias was detected (P = .8147) but the heterogeneity of the included studies was significant. A meta-regression showed that heterogeneity was significantly greater when the incidence of hypertension was <50% (I2 = 91%) and that of diabetes was <30% (I2 = 85%). CONCLUSION: Low TAPSE levels are associated with poor COVID-19 disease outcomes. TAPSE levels are modulated by disease severity, and their prognostic utility may be skewed by pre-existing patient comorbidities. TRIAL RETROSPECTIVELY REGISTERED FEBRUARY ,: PROSPERO CRD42021236731.

Effect of prone position ventilation on right heart function in patients with acute respiratory distress syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a severe respiratory disease with a high mortality rate. It is characterized by acute onset of pulmonary edema, hypoxemia, and the need of mechanical ventilation. As the primary treatment, ventilation has been considered effective in treating patients with ARDS. Recently, numerous studies have shown that prone position ventilation demonstrates more efficacy compared with traditional supine position. However, the potential impact of the non-physiological prone position on patients remains unclear. Current study aims to evaluate the effect of prone position ventilation on right heart function in ARDS patients. METHODS: Following Berlin Diagnostic Criteria, 80 eligible patients were recruited and randomly assigned into prone position ventilation group and supine position ventilation group. Different ventilation methods were implemented in these two groups. RESULTS: Both positions showed the beneficial effects, as evidenced by decreased PV score and APACHE II score, enhanced blood gas index and right heart function parameters, and the prognosis analysis. However, compared with those receiving SPV treatment, the patients demonstrated greater benefits from PPV treatment, with significant differences in PV score (p < 0.01) and APACHE II score (p < 0.001), blood gas index such as PAPm (p < 0.05), and right heart function indicators (p < 0.05). CONCLUSION: Prone position mechanical ventilation is more beneficial than supine position ventilation in improving the blood gas status of patients with moderate to severe ARDS, and it is more helpful to reduce the load on the right heart and promote the recovery of patients.

Application of P(jv-a) CO2 in monitoring cerebral oxygen supply-demand balance in injured brain.

Transcranial Doppler sonography (TCD) assayed cerebral blood flow (CBF) may vary between different intracranial pathologies. Blood gas analysis of the jugular bulb provides a novel way to estimate the global relationship between CBF and oxygen metabolism. In this study, 25 patients with brain trauma, spontaneous intracerebral hemorrhage, and acute cerebral infarction were recruited. Jugular venous oxygen saturation (SjvO2) increased significantly at different time points after hyperventilation (p < 0.05). A negative correlation between the partial pressure of CO2 between jugular venous bulb and radial artery blood (P(jv-a)CO2) and CBF could be observed in acute brain injury and spontaneous intracerebral hemorrhage groups, while P(jv-a)CO2 and CBF show positive correlation in acute cerebral infarction group. Our results suggest that serial P(jv-a)CO2 analysis combing with SjvO2 can be utilized to monitor the change of CBF for patients undergoing craniocerebral surgery.

17ß-estradiol rescues damages following traumatic brain injury from molecule to behavior in mice.

Traumatic brain injury (TBI) is a public health concern, and causes cognitive dysfunction, emotional disorders, and neurodegeration, as well. The currently available treatments are all symptom-oriented with unsatifying efficacy. It is highly demanded to understand its underlying mechanisms. Controlled cortical impact (CCI) was used to induce TBI in aged female mice subjected to ovariectomy. Brain damages were assessed with neurological severity score, brain infarction and edema. Morris water maze and elevated plus maze were applied to evaluate the levels of anxiety. Apoptosis in the hippocampus was assayed with Fluoro-Jade B staining and TUNEL staining. Western blot was employed to measure the expression of NMDA receptor subunits and phosphorylation of ERK1/2, and biochemical assays were used to estimate oxidative stress. 17beta-Estradiol (E2) was intraperitoneally administered at 10-80 µg/kg once per day for 7 consecutive days before or after CCI. Chronic administration of E2 both before and immediately after CCI conferred neuroprotection, reducing neurological severity score, brain infarction, and edema in TBI mice. Additionally, E2 improved many aspects of deleterious effects of TBI on the hippocampus, including neuronal apoptosis, dysfunction in spatial memory, reduction in NR2B, enhancement of oxidative stress, and activation of ERK1/2 pathway. The present study provides clue for the notion that E2 has therapeutic potential for both prevention and intervention of TBI-induced brain damages.

Cerebral hemorrhage therapy by targeting VEGF and HGF in a preclinical trial in rats.

Cerebral hemorrhage is the most common type of human cerebrovascular disease and frequently causes paralysis, vegetative state and mortality. The modulatory actions of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are vital in the human nervous system. The present study investigated the association between cerebral hemorrhage and the expression of VEGF and HGF in a rat model of cerebral hemorrhage. The therapeutic potential of cerebral hemorrhage was also evaluated using targeted drugs for VEGF and HGF in the cerebral hemorrhage rat model. Behavioral and preclinical changes and the survival rates of rats were assessed after treatment with VEGF receptor (VEGFR) and HGF receptor (HGFR). The results of Tarlov scores demonstrated that movement of limbs and coordination when walking were significantly improved in moderate and severe hemorrhage lesions in the VEGFR plus HGFR­treated group and mainly alleviated in primary hemorrhage lesions compared with rats in the single VEGFR or HGFR­treated groups and the control group (**P<0.01). Decreasing expression levels of VEGF and HGF were observed in the neural tissue of animals treated with VEGFR plus HGFR compared with the control group (**P<0.01). These preclinical observations indicated that VEGF and HGF serve a function in the pathological injury and repair of cerebral tissue in rats with cerebral hemorrhages. The therapeutic benefits of VEGFR plus HGFR suggested that VEGFR plus HGFR may be candidate drugs for cerebral hemorrhage, and thus offer a promising treatment for clinicians and doctors.