FEATURES OF VASCULATURE IN PATIENTS WITH RETINA ARTERIAL MACROANEURYSM USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To assess morphologic characteristics of retinal arterial macroaneurysm (RAM) and their vascular changes using optical coherence tomography angiography (OCTA). METHODS: This observational study included 31 eyes of 29 participants diagnosed with RAM based on fundus fluorescein angiography in Tianjin Medical University Eye Hospital. Multimodal imaging modalities, including fundus photography, fluorescein angiography, and OCTA, were used to examine RAMs. The demographic and clinical characteristics of the RAMs were recorded. RESULTS: Depending on the fundus fluorescein angiography examination, 40 cases of RAM were confirmed in 29 patients. Twenty-three patients were female (79%), and six patients were male (21%). Two patients had binocular RAM, and four eyes had more than one RAMs. Relying on the OCTA technology, RAMs have four different vascular morphology types (i.e., distended, meshed, malformed, and occult types). In the distended type, round or encircled thrombi caused asymmetrical or symmetrical distention of retinal arteriolar, leading to separate true lumen and false thrombus lumen in RAM. In the meshed type, the meshed or dendritic vascular network around the RAM was likely to be the neovascularization due to the ischemia and hypoxia of the arteriolar wall. Finally, in the malformed and occult type, the RAM usually regressed, and the retinal arterioles were remodeled to distorted or normal arterioles accompanied by capillary degradation. CONCLUSION: Relying on the OCTA technology, we found that the RAMs have four different types of vascular morphology. Each group of RAM has different vascular features. The application of OCTA in patients with RAM furthers our understanding of the vasculature of RAMs.

Cerebral venous sinus thrombosis caused by traumatic brain injury complicating thyroid storm: a case report and discussion.

INTRODUCTION: Cerebral venous sinus thrombosis (CVST) is an uncommon cerebrovascular disease with diverse predisposing factors. We report a case of CVST caused by a thyroid storm induced by traumatic brain injury. CASE PRESENTATION: A 29-year-old male patient with a history of Graves' disease with hyperthyroidism presented to our hospital with head trauma of cerebral contusion and laceration in both frontal lobes confirmed by admission CT scan. He received mannitol to lower intracranial pressure, haemostatic therapy, and antiepileptic treatment. Eight days later, he presented with signs of thyroid storms, such as tachycardia, hyperthermia, sweating and irritation, and his thyroid function tests revealed high levels of TPO-Ab, TR-Ab, TG-Ab, FT3 and FT4. Then, he entered a deep coma. His brain CT showed a thrombosis of multiple venous sinuses, along with the opening of peripheral collateral vessels, congestive infarction with haemorrhage and brain swelling. He regained consciousness after treatment with antithyroid drugs, anticoagulants, respiratory support and a regimen of sedation/analgesia. After a half-year follow-up, most of the patient's blocked cerebral venous sinuses had been recanalized, but there were still some sequelae, such as an impaired fine motor performance of the right hand and verbal expression defects. CONCLUSIONS: CVST can be induced by thyroid storms, and trauma-related thyroid storms can develop on the basis of hyperthyroidism. The purpose of this case report is to raise clinicians' awareness and improve their ability to diagnose CVST early in patients with traumatic brain injury complicating thyroid storms to improve the neurological prognosis among similar patients.

Analysis of hypervirulent Klebsiella pneumoniae and classic Klebsiella pneumoniae infections in a Chinese hospital.

AIMS: To evaluate the clinical and genetic virulence characteristics of critically ill patients with hypervirulent Klebsiella pneumoniae (hvKP) and classic KP (cKP) infection. METHODS AND RESULTS: The patients included in this retrospective study (n = 225) were grouped according to their hvKP (n = 114) or cKP (n = 111) status, and their clinical characteristics were analysed and compared. Cox multivariate analysis was conducted to determine the risk factors for hvKP infection. Length of hospital stay, length of intensive care unit stay, duration of mechanical ventilation and 28-day survival rate were similar between the groups. However, the incidence of septic shock was higher in the hvKP group (16.7%) than in the cKP group (8.1%). CONCLUSIONS: There was a high rate of hvKP infection in this population. Compared to patients with cKP infection, those with hvKP infection showed a higher probability of having septic shock; nevertheless, survival and length of hospital stay were similar between the groups. Risk factors for hvKP infection included hospital-acquired infection and renal insufficiency. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents relevant information on the characteristics of hvKP infection in a Chinese population, and this promotes early diagnosis and supports the view that the prevalence of hvKP is high in China.

The role of optical coherence tomography angiography in distinguishing ischemic versus non-ischemic central retinal vein occlusion.

INTRODUCTION: To observe macular microvascular changes in patients with ischemic and non-ischemic central retinal vein occlusion (CRVO) by optical coherence tomography angiography (OCTA), and explore the value of OCTA in differentiating ischemic and non-ischemic CRVO. METHODS: Cross sectional study. Fifty patients diagnosed as CRVO with macular edema were included. Macular edema in all patients were regressive after three consecutive anti-VEGF treatment. Patients were divided into ischemic and non-ischemic group according to ultra-wide-angle fundus fluorescein angiography (UWFFA). All patients underwent BCVA, IOP, color fundus photography, UWFFA and OCTA. The following parameters were measured: (1) Vessel density (VD): superficial and deep whole VD (SVD, DVD), superficial and deep central fovea VD (SFVD, DFVD), superficial and deep parafoveal VD (SPFVD, DPFVD); (2) Central foveal retinal thickness (CRT); (3) Area of foveal avascular zone (FAZ), perimeter of FAZ (PERIM), avascular index of FAZ (AI) and VD within a width of 300 microns around the FAZ region (FD-300). Comparison between ischemic and non-ischemic group was performed by two independent sample t-tests. Receiver operating characteristic (ROC) curve analysis was used to measure the area under the curve (AUC) of VD for predicting ischemic CRVO. RESULTS: There were no significant differences in IOP, SFVD, DFVD and CRT between ischemic and non-ischemic group, and significant differences in age, BCVA, SVD, SPFVD, DVD, DPFVD, FAZ area, PERIM, AI and FD-300 between ischemic and non-ischemic group. ROC curve analysis showed AUC of DVD and DPFVD in predicting ischemic CRVO was highest (0.962). the threshold was 38.40%, and the sensitivity was 100%, but the specificity of DVD (92.3%) was significantly higher than that of DPFVD (84.6%). Therefore, DVD ≤ 38.40% can be used as the best threshold for determining ischemic CRVO. CONCLUSION: OCTA can quantitatively evaluate the macular microvascular structure of CRVO, which is helpful to distinguish ischemic from non-ischemic CRVO.

Novel mutations of the USH2A gene cause Usher syndrome in five Chinese families.

BACKGROUND: Usher syndrome (USH) is a leading disorder of deaf-blindness. The phenotypic and genetic heterogeneity of USH makes the diagnosis of this disorder difficult. However, diagnosis can be facilitated by employing molecular approaches, especially for diseases without pronounced pathognomonic symptoms. Therefore, this study aimed to reveal the genetic defects in five USH patients using clinical targeted exome sequencing (TES). METHODS: USH patients and their family members from five unrelated Chinese USH families were recruited and subjected to TES. Ophthalmic information was obtained for all patients to ensure a meaningful interpretation. The TES data were analysed using an established bioinformatics pipeline to identify causative mutations. Further verification by Sanger sequencing and cosegregation analysis were performed on available family members. RESULTS: We identified genetic mutations in five USH patients using TES. Seven mutations, four of which were novel, were identified in the USH2A gene. One proband (F1-II-3) was found to have a homozygous mutation inherited from nonconsanguineous parents, and another proband (F5-III-1) was found to carry three USH2A gene mutations. CONCLUSION: In conclusion, the study revealed the importance of TES in the clinical diagnosis of USH patients with variable phenotypes. The correlation between USH2A gene mutations and clinical phenotypes will help to refine the clinical diagnosis of USH.

Increased normalized lactate load is associated with higher mortality in both sepsis and non-sepsis patients: an analysis of the MIMIC-IV database.

BACKGROUND: The present study aimed to evaluate the association between normalized lactate load, an index that incorporates the magnitude of change and the time interval of such evolution of lactate, and 28-day mortality in sepsis and non-sepsis patients. We also compared the accuracy of normalized lactate load in predicting mortality between these two populations. METHODS: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database. We defined lactate load as the sum of the area under the lactate concentration curve; we also defined normalized lactate load as the lactate load divided by time. The performance of maximum lactate, mean lactate and normalized lactate load in predicting 28-day mortality in sepsis and non-sepsis patients were compared by receiver-operating characteristic curves analysis. RESULTS: A total of 21,333 patients were included (4219 sepsis and 17,114 non-sepsis patients). Non-survivors had significantly higher normalized lactate load than survivors in sepsis and non-sepsis patients. The maximum lactate, mean lactate, and normalized lactate load AUCs were significantly greater in sepsis patients than in non-sepsis patients. Normalized lactate load had the greatest AUCs in predicting 28-day mortality in both sepsis and non-sepsis patients. Sensitivity analysis showed that the AUC of normalized lactate load increased in non-sepsis patients when more lactate measurement was obtained, but it was not improved in sepsis patients. CONCLUSIONS: Normalized lactate load has the strongest predictive power compared with maximum or mean lactate in both sepsis and non-sepsis patients. The accuracy of normalized lactate load in predicting mortality is better in sepsis patients than in non-sepsis patients.

Proteomic Analysis of Plasma sEVs Reveals That TNFAIP8 Is a New Biomarker of Cell Proliferation in Diabetic Retinopathy.

Small extracellular vesicles (sEVs) derived from the plasma have been increasingly recognized as important vehicles of intercellular communication and potential sources of new biomarkers for multiple diseases. In this study, proteomic profiles of plasma sEVs from normal subjects and diabetic patients with or without diabetic retinopathy (DR) were systematically compared using iTRAQ-based quantitative proteomics. Among a total of 901 identified proteins in plasma sEVs (false discovery rate (FDR) < 1%), 90 proteins were found to have significantly changed levels in DR. Based on the findings from the proteomic analysis, the role of tumor necrosis factor-α-induced protein 8 (TNFAIP8) in promoting human retinal microvascular endothelial cell (HRMEC) proliferation was investigated. The enzyme-linked immunosorbent assay (ELISA) showed that TNFAIP8 levels in plasma sEVs and vitreous are elevated in DR, whereas not statistically different in large EVs (lEVs) and plasma. In addition, in vitro experiments demonstrated that 4-hydroxynonenal (4-HNE) increased the expression of TNFAIP8 in HRMECs. TNFAIP8 significantly increased HRMECs cell viability and promote cell migration and tube formation, and the depletion of TNFAIP8 impaired HRMEC proliferation. We demonstrated that TNFAIP8 in plasma sEVs could be used as a potential biomarker of DR. Functional studies suggested that TNFAIP8 might be an important mediator of angiogenesis in DR.

Effect of increased positive end-expiratory pressure on intracranial pressure and cerebral oxygenation: impact of respiratory mechanics and hypovolemia.

BACKGROUND: To evaluate the impact of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP) in animals with different respiratory mechanics, baseline ICP and volume status. METHODS: A total of 50 male adult Bama miniature pigs were involved in four different protocols (n = 20, 12, 12, and 6, respectively). Under the monitoring of ICP, brain tissue oxygen tension and hemodynamical parameters, PEEP was applied in increments of 5 cm H2O from 5 to 25 cm H2O. Measurements were taken in pigs with normal ICP and normovolemia (Series I), or with intracranial hypertension (via inflating intracranial balloon catheter) and normovolemia (Series II), or with intracranial hypertension and hypovolemia (via exsanguination) (Series III). Pigs randomized to the control group received only hydrochloride instillation while the intervention group received additional chest wall strapping. Common carotid arterial blood flow before and after exsanguination at each PEEP level was measured in pigs with intracranial hypertension and chest wall strapping (Series IV). RESULTS: ICP was elevated by increased PEEP in both normal ICP and intracranial hypertension conditions in animals with normal blood volume, while resulted in decreased ICP with PEEP increments in animals with hypovolemia. Increasing PEEP resulted in a decrease in brain tissue oxygen tension in both normovolemic and hypovolemic conditions. The impacts of PEEP on hemodynamical parameters, ICP and brain tissue oxygen tension became more evident with increased chest wall elastance. Compare to normovolemic condition, common carotid arterial blood flow was further lowered when PEEP was raised in the condition of hypovolemia. CONCLUSIONS: The impacts of PEEP on ICP and cerebral oxygenation are determined by both volume status and respiratory mechanics. Potential conditions that may increase chest wall elastance should also be ruled out to avoid the deleterious effects of PEEP.

Association between normalized lactate load and mortality in patients with septic shock: an analysis of the MIMIC-III database.

BACKGROUND: An index of dynamic lactate change that incorporates both the magnitude of change and the time interval of such change, termed "normalized lactate load," may reflect the hypoxic burden of septic shock. We aimed to evaluate the association between normalized lactate load and 28-day mortality in adult septic shock patients. METHODS: Patients with septic shock were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Lactate load was defined as the sum of the area under the curve (AUC) of serial lactate levels using the trapezoidal rule, and normalized lactate load was defined as the lactate load divided by time. Receiver-operating characteristic curves were constructed to determine the performance of initial lactate, maximum lactate and normalized lactate load in predicting 28-day mortality. RESULTS: A total of 1371 septic shock patients were included, and the 28-day mortality was 39.8%. Non-survivors had significantly higher initial lactate (means ± standard deviations: 3.9 ± 2.9 vs. 2.8 ± 1.7 mmol/L), maximum lactate (5.8 ± 3.8 vs. 4.3 ± 2.2 mmol/L), lactate load (94.3 ± 71.8 vs. 61.1 ± 36.4 mmol·hr./L) and normalized lactate load (3.9 ± 3.0 vs. 2.5 ± 1.5 mmol/L, all p <  0.001). The AUCs of initial lactate, maximum lactate and normalized lactate load were 0.623 (95% confidence interval: 0.596-0.648, with a cut-off value of 4.4 mmol/L), 0.606 (0.580-0.632, with a cut-off value of 2.6 mmol/L) and 0.681 (0.656-0.706, with a cut-off value of 2.6 mmol/L), respectively. The AUC of normalized lactate load was significantly greater than both initial lactate and maximum lactate (all p <  0.001). In the multivariate logistic regression model, normalized lactate load was identified as an independent risk factor for 28-day mortality. CONCLUSIONS: Normalized lactate load is an independent risk factor for 28-day mortality in adult septic shock patients. Normalized lactate load had better accuracy than both initial and maximum lactate in determining the prognosis of septic shock patients.

Mst1 deletion reduces septic cardiomyopathy via activating Parkin-related mitophagy.

Cardiomyocyte function and viability are highly modulated by mammalian Ste20-like kinase 1 (Mst1)-Hippo pathway and mitochondria. Mitophagy, a kind of mitochondrial autophagy, is a protective program to attenuate mitochondrial damage. However, the relationship between Mst1 and mitophagy in septic cardiomyopathy has not been explored. In the present study, Mst1 knockout mice were used in a lipopolysaccharide (LPS)-induced septic cardiomyopathy model. Mitophagy activity was measured via immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay. Pathway blocker and small interfering RNA were used to perform the loss-of-function assay. The results demonstrated that Mst1 was rapidly increased in response to LPS stress. Knockout of Mst1 attenuated LPS-mediated inflammation damage, reduced cardiomyocyte death, and improved cardiac function. At the molecular levels, LPS treatment activated mitochondrial damage, such as mitochondrial respiratory dysfunction, mitochondrial potential reduction, mitochondrial ATP depletion, and caspase family activation. Interestingly, in response to mitochondrial damage, Mst1 deletion activated mitophagy which attenuated LPS-mediated mitochondrial damage. However, inhibition of mitophagy via inhibiting parkin mitophagy abolished the protective influences of Mst1 deletion on mitochondrial homeostasis and cardiomyocyte viability. Overall, our results demonstrated that septic cardiomyopathy is linked to Mst1 upregulation which is followed by a drop in the protective mitophagy.

Targeted exome sequencing identified a novel USH2A mutation in a Chinese usher syndrome family: a case report.

BACKGROUND: Usher syndrome is a disease with a heterogeneous phenotype and genotype. Our purpose was to identify the gene mutation in a Chinese family with Usher syndrome type 2 and describe the clinical features. CASE PRESENTATION: A 23-year-old man complained of a 10-year duration of nyctalopia and a 3-year decline in visual acuity of both eyes accompanied by congenital dysaudia. To clarify the diagnosis, the clinical symptoms were observed and analysed in combination with comprehensive ophthalmologic examinations as well as genetic analysis (targeted exome sequencing, TES). A typical clinical presentation of Usher syndrome of the fundus was found, including a waxy yellow-like disc, bone-spicule formations and retinal vessel stenosis. Optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) showed loss of the ellipsoid zone and a reduction in paracaval vessel density in both eyes. Genetic analysis identified a novel homozygous c.8483_8486del (p.Ser2828*) mutation in USH2A. The mutation resulted in premature termination of translation and caused the deletion of 19 fibronectin type 3 domains (FN3), transmembrane (TM) region and PDZ-binding motif domain, which play an important role in protein binding. After combining the clinical manifestations and genetic results, the patient was diagnosed with Usher syndrome type 2. CONCLUSION: We found a novel c.8483_8486del mutation in the USH2A gene through TES techniques. The results broaden the spectrum of mutations in Usher syndrome type 2 and suggest that a combination of clinical information and molecular diagnosis via TES could help Usher syndrome patients obtain a better diagnosis.

Resveratrol Protects the Myocardium in Sepsis by Activating the Phosphatidylinositol 3-Kinases (PI3K)/AKT/Mammalian Target of Rapamycin (mTOR) Pathway and Inhibiting the Nuclear Factor-κB (NF-κB) Signaling Pathway.

BACKGROUND Sepsis combined with myocardial injury is an important cause of septic shock and multiple organ failure. However, the molecular mechanism of sepsis-induced myocardial dysfunction has not yet been thoroughly studied. Resveratrol has been an important research topic due its organ-protection function, but the specific mechanism is unclear. The purpose of this study was to explore the mechanism of organ injury in sepsis and to investigate the molecular mechanism of resveratrol in myocardial protection in sepsis. MATERIAL AND METHODS A classical Sprague-Dawley rat model of sepsis peritonitis was constructed for further experiments. The PI3K inhibitor LY294002 and resveratrol were used to intervene in a rat model of cardiomyopathy. HE staining was used to observe pathological changes. Cardiomyocyte apoptosis was detected by TUNEL assay. Western blot analysis was used to detect the level of maker proteins. RESULTS The PI3K inhibitors could promote cardiac abnormalities and apoptosis, but resveratrol showed the opposite effect. The upregulation function of the PI3K inhibitor on the expression of NF-kappaB, IL-6, IL-1ß, and TLR4 in LPS rats was not obvious, but the expression of TNF-a in LPS+LY294002 rats was increased by 22.85% compared with that in LPS rats (P<0.05). Compared with the LPS group, the expression of NF-kappaB, TNF-alpha, IL-6, IL-1ß, and TLR4 in the LPS+resveratrol group was decreased. The expression of p-PI3K, p-AKT, and p-mTOR in LPS+LY294002 was reduced. The expression p-PI3K, p-AKT, and p-mTOR in the myocardium of the LPS+resveratrol group was increased. CONCLUSIONS Resveratrol can protect the myocardium in sepsis by activating the PI3K/AKT/mTOR signaling pathway and inhibiting the NF-kappaB signaling pathway and related inflammatory factors.

Intracranial pressure responsiveness to positive end-expiratory pressure in different respiratory mechanics: a preliminary experimental study in pigs.

BACKGROUND: Respiratory mechanics affects the effect of positive end-expiratory pressure (PEEP) on intracranial pressure (ICP). Respiratory mechanics of the lung and the chest wall was not differentiated in previous studies. In the present study, we investigated the influence of the following possible determinants of ICP responsiveness to PEEP: chest wall elastance (ECW), lung elastance (EL), and baseline ICP. METHODS: Eight healthy Bama miniature pigs were studied. The increase of EL was induced by instillation of hydrochloride, and the increase of ECW was induced by strapping the animals' chest wall and abdomen. A balloon-tipped catheter was placed intracranially for inducing intracranial hypertension. Six experimental conditions were investigated in sequence: 1) Normal; 2) Stiff Chest Wall; 3) Lung Injury; 4) Lung Injury + Stiff Chest Wall; 5) Lung Injury + Stiff Chest Wall + Intracranial Hypertension and 6) Lung Injury + Intracranial Hypertension. PEEP was gradually increased in a 5 cm H2O interval from 5 to 25 cm H2O in each condition. Blood pressure, central venous pressure, ICP, airway pressure and esophageal pressure were measured. RESULTS: Hydrochloride instillation significantly increased EL in conditions with lung injury. ECW significantly increased in the conditions with chest wall and abdomen strapping (all p <  0.05). ICP significantly increased with increments of PEEP in all non-intracranial hypertension conditions (p <  0.001). The greatest cumulative increase in ICP was observed in the Stiff Chest Wall condition (6 [5.3, 6.8] mm Hg), while the lowest cumulative increase in ICP was observed in the Lung Injury condition (2 [1.3, 3.8] mm Hg). ICP significantly decreased when PEEP was increased in the intracranial hypertension conditions (p <  0.001). There was no significant difference in cumulative ICP change between the two intracranial hypertension conditions (p = 0.924). CONCLUSIONS: Different respiratory mechanics models can be established via hydrochloride induced lung injury and chest wall and abdominal strapping. The effect of PEEP on ICP is determined by respiratory mechanics in pigs with normal ICP. However, the responsiveness of ICP to PEEP is independent of respiratory mechanics when there is intracranial hypertension.

Intracranial pressure responsiveness to positive end-expiratory pressure is influenced by chest wall elastance: a physiological study in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Respiratory system elastance (ERS) is an important determinant of the responsiveness of intracranial pressure (ICP) to positive end-expiratory pressure (PEEP). However, lung elastance (EL) and chest wall elastance (ECW) were not differentiated in previous studies. We tested the hypothesis that patients with high ECW or a high ECW/ERS ratio have greater ICP responsiveness to PEEP. METHODS: An esophageal balloon catheter was placed to measure esophageal pressure. PEEP was increased from 5 to 15 cmH2O. Airway pressure and esophageal pressure were measured and EL, ECW and ERS were calculated at the two PEEP levels. Patients were classified into either an ICP responder group or a non-responder group based on whether the change of ICP after PEEP adjustment was greater than or less than the median of the overall study population. RESULTS: The magnitude of the increase in esophageal pressure (median [interquartile range]) at end-expiratory occlusion was significantly increased in the responder group compared with that in the non-responder group (4.1 [2.7-4.1] versus 2.7 [0.0-2.7] cmH2O, p = 0.033) after PEEP adjustment. ECW and the ECW/ERS ratio were significantly higher in ICP responders than in non-responders at both low PEEP (p = 0.021 and 0.017) and high PEEP (p = 0.011 and 0.025) levels. No significant differences in ERS and EL were noted between the two groups at both PEEP levels. CONCLUSIONS: Patients with greater ICP responsiveness to increased PEEP exhibit higher ECW and a higher ECW/ERS ratio, suggesting the importance of ECW monitoring.

Bispectral Index Can Reliably Detect Deep Sedation in Mechanically Ventilated Patients: A Prospective Multicenter Validation Study.

BACKGROUND: Excessively deep sedation is prevalent in mechanically ventilated patients and often considered suboptimal. We hypothesized that the bispectral index (BIS), a quantified electroencephalogram instrument, would accurately detect deep levels of sedation. METHODS: We prospectively enrolled 90 critically ill mechanically ventilated patients who were receiving sedation. The BIS was monitored for 24 hours and compared with the Richmond Agitation Sedation Scale (RASS) evaluated every 4 hours. Deep sedation was defined as a RASS of -3 to -5. Threshold values of baseline BIS (the lowest value before RASS assessment) and stimulated BIS (the highest value after standardized assessment) for detecting deep sedation were determined in a training set (45 patients, 262 RASS assessments). Diagnostic accuracy was then analyzed in a validation set (45 patients, 264 RASS assessments). RESULTS: Deep sedation was only prescribed in 6 (6.7%) patients, but 76 patients (84.4%) had at least 1 episode of deep sedation. Thresholds for detecting deep sedation of 50 for baseline and 80 for stimulated BIS were identified, with respective areas under the receiver-operating characteristic curve of 0.771 (95% confidence interval, 0.714-0.828) and 0.805 (0.752-0.857). The sensitivity and specificity of baseline BIS were 94.0% and 66.5% and of stimulated BIS were 91.0% and 66.5%. When baseline and stimulated BIS were combined, the sensitivity, specificity, and clinical utility index were 85.0% (76.1%-91.1%), 85.9% (79.5%-90.7%), and 66.9% (57.8%-76.0%), respectively. CONCLUSIONS: Combining baseline and stimulated BIS may help detect deep sedation in mechanically ventilated patients.

Ultrasound measurement of optic nerve diameter and optic nerve sheath diameter in healthy Chinese adults.

BACKGROUND: Measurement of optic nerve sheath diameter (ONSD) is a fast and non-invasive method in detecting elevated intracranial pressure. However, the reported normal range of ONSD was inconsistent. The objective of the study was to determine the normal range of ONSD in healthy Chinese adults. METHODS: Eyeball transverse diameter (ETD), optic nerve diameter (OND), and ONSD were measured by ultrasound examination in healthy adult volunteers. The OND and ONSD were assessed 3 mm behind the globe. The section showing maximal transverse diameter of the eyeball was frozen and the diameter was measured. Each ETD, OND and ONSD was examined twice and the mean value was calculated. RESULTS: A total of 519 healthy volunteers were included in the study. The median (interquartile range) of ETD, OND and ONSD were 22.3 (21.6 to 23.1) mm, 3.2 (2.9 to 3.4) mm, and 5.1 (4.7 to 5.4) mm, respectively. The 95% percentile of ONSD was 5.9 mm. There was no significant difference in ETD, OND or ONSD between male and female, or between left and right eye. ONSD was significantly correlated with OND (r = 0.62, P < 0.001), and the median OND/ONSD ratio (interquartile range) was 0.63 (0.59 to 0.67). CONCLUSIONS: The median and the 95% percentile of sonographic measurement of ONSD are 5.1 mm and 5.9 mm in healthy Chinese adults. The ONSD is correlated with OND, while independent of gender, age, height, weight and ETD. The median OND/ONSD ratio is 0.63 and this parameter warrants further investigation in patients with brain injury.

Cytoprotective effects of urinary trypsin inhibitor on astrocytes injured by sustained compression.

Decreased cell membrane integrity is a primary pathological change observed in traumatic brain injury (TBI) that activates a number of complex intercellular and intracellular pathological events, leading to further neural injury. In this paper, we assessed the effects of urinary trypsin inhibitor (UTI) on astrocyte membrane integrity by determining the percentage of lactate dehydrogenase (LDH) released after sustained compression injury using a hydrostatic pressure model of mechanical-like TBI. Astrocytes isolated from SD rat pups were injured by sustained compression. At a pressure of 0.3 MPa for 5 min, a significant increase in LDH release was observed compared with control samples. Astrocytes displayed extensive structural disruption of mitochondrial cristae reflected in their swelling. Based on our initial results, injured astrocytes were treated with UTI at a final concentration of 500, 1,000, 3,000 or 5,000 U/ml for 24 h. The percentage of LDH released from injured astrocytes was significantly decreased when 1,000 and 3,000 U/ml of UTI were used. In a separate experiment, astrocytes were treated with UTI at a final concentration of 1,000 U/ml immediately, or at 30 min, 2, 6, or 24 h after sustained compression. The percentage of LDH release was significantly reduced (P < 0.05) when astrocytes were treated with UTI immediately or 30 min later. Together, our results suggest that UTI may have protective effects on astrocytes injured by sustained compression injury. Furthermore, the early administration (<2 h after injury) of UTI may result in a better outcome compared with delayed administration.

Combination of extracorporeal membrane oxygenation and continuous renal replacement therapy in critically ill patients: a systematic review.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is used in critically ill patients presenting acute cardiac and/or pulmonary dysfunctions, who are at high risk of developing acute kidney injury and fluid overload. Continuous renal replacement therapy (CRRT) is commonly used in intensive care units (ICU) to provide renal replacement and fluid management. We conducted a review to assess the feasibility, efficacy and safety of the combination of ECMO and CRRT and to illustrate the indications and methodology of providing renal replacement therapy during the ECMO procedure. METHOD: We searched for all published reports of a randomized controlled trial (RCT), quasi-RCT, or other comparative study design, conducted in patients undergoing ECMO plus CRRT. Two reviewers independently selected potential studies and extracted data. We used the modified Jadad scale and the Newcastle-Ottawa for quality assessment of RCTs and non-RCTs, respectively. Statistical analyses were performed using RevMan 5.2. RESULTS: We identified 19 studies meeting the eligibility criteria (seven cohort, six case control, one historically controlled trial and five studies of technical aspects). There are three major methods for performing CRRT during ECMO: 'independent CRRT access', 'introduction of a hemofiltration filter into the ECMO circuit (in-line hemofilter)' and 'introduction of a CRRT device into the ECMO circuit'. We conducted a review with limited data synthesis rather than a formal meta-analysis because there could be greater heterogeneity in a systematic review of non-randomized studies than that of randomized trials. For ECMO survivors receiving CRRT, overall fluid balance was less than that in non-CRRT survivors. There was a higher mortality and a longer ECMO duration when CRRT was added, which may reflect a relatively higher severity of illness in patients who received ECMO plus CRRT. CONCLUSIONS: The combination of ECMO and CRRT in a variety of methods appears to be a safe and effective technique that improves fluid balance and electrolyte disturbances. Prospective studies would be beneficial in determining the potential of this technique to improve the outcome in critically ill patients.

Papillary vitreous detachment as a possible accomplice in non-arteritic anterior ischaemic optic neuropathy.

AIM: To evaluate the role of papillary vitreous detachment in the pathogenesis of non-arteritic anterior ischaemic optic neuropathy (NAION) by comparing the features of vitreopapillary interface between NAION patients and normal individuals. METHODS: This study included 22 acute NAION patients (25 eyes), 21 non-acute NAION patients (23 eyes) and 23 normal individuals (34 eyes). All study participants underwent swept-source optical coherence tomography to assess the vitreopapillary interface, peripapillary wrinkles and peripapillary superficial vessel protrusion. The statistical correlations between peripapillary superficial vessel protrusion measurements and NAION were analysed. Two NAION patients underwent standard pars plana vitrectomy. RESULTS: Incomplete papillary vitreous detachment was noted in all acute NAION patients. The prevalence of peripapillary wrinkles was 68% (17/25), 30% (7/23) and 0% (0/34), and the prevalence of peripapillary superficial vessel protrusion was 44% (11/25), 91% (21/23) and 0% (0/34) in the acute, non-acute NAION and control groups, respectively. The prevalence of peripapillary superficial vessel protrusion was 88.9% in the eyes without retinal nerve fibre layer thinning. Furthermore, the number of peripapillary superficial vessel protrusions in the superior quadrant was significantly higher than that in the other quadrants in eyes with NAION, consistent with the more damaged visual field defect regions. Peripapillary wrinkles and visual field defects in two patients with NAION were significantly attenuated within 1 week and 1 month after the release of vitreous connections, respectively. CONCLUSION: Peripapillary wrinkles and superficial vessel protrusion may be signs of papillary vitreous detachment-related traction in NAION. Papillary vitreous detachment may play an important role in NAION pathogenesis.

[Predictive value of postoperative serum procalcitonin concentration for moderate to severe acute respiratory distress syndrome in patients undergoing cardiopulmonary bypass surgery].

OBJECTIVE: To explore the changes of serum procalcitonin (PCT) level in patients with moderate and severe acute respiratory distress syndrome (ARDS) after cardiac surgery under cardiopulmonary bypass (CPB), and try to find out the best cut-off of PCT to predict the progression to moderate and severe ARDS. METHODS: Medical records of patients undergoing cardiac surgery with CPB in Fujian Provincial Hospital from January 2017 to December 2019 were retrospectively analyzed. Adult patients who were admitted in intensive care unit (ICU) for more than 1 day and had PCT values on the first postoperative day were enrolled. Clinical data such as patient demographics, past history, diagnosis, and New York Heart Association (HYHA) classification, and the operation mode, procedure duration, CPB duration, aortic clamp duration, intraoperative fluid balance, calculation of 24 hours postoperative fluid balance and vasoactive-inotropic score (VIS); 24 hours postoperative C-reactive protein (CRP), N-terminal B-type natriuretic peptide precursor (NT-proBNP) and PCT levels were collected. Two clinicians independently made the diagnosis of ARDS according to the Berlin definition, and the diagnosis was established only in patients with a consistent diagnosis. The differences in each parameter were compared between patients with moderate to severe ARDS and those without or with mild ARDS. Analysis of the ability of PCT to predict moderate to severe ARDS was evaluated by receiver operator characteristic curve (ROC curve). Multivariate Logistic regression was conducted to determine the risk factors of the development of moderate to severe ARDS. RESULTS: 108 patients were finally enrolled, including 37 patients with mild ARDS (34.3%), 35 patients with moderate ARDS (32.4%), 2 patients with severe ARDS (1.9%), and 34 patients without ARDS. Compared with patients with no or mild ARDS, patients with moderate to severe ARDS were older (years old: 58.5±11.1 vs. 52.8±14.8, P < 0.05), with a higher proportion of combined hypertension [45.9% (17/37) vs. 25.4% (18/71), P < 0.05], longer operative time (minutes: 363.2±120.6 vs. 313.5±97.6, P < 0.05), and higher mortality (8.1% vs. 0, P < 0.05), but there were no differences in the VIS score, incidence of acute renal failure (ARF), CPB duration, aortic clamp duration, and intraoperative bleeding, transfusion volume, and fluid balance between the two groups. Serum PCT and NT-proBNP levels in patients with moderate to severe ARDS at postoperative day 1 were significantly higher than those in patients with no or mild ARDS [PCT (µg/L): 16.33 (6.96, 32.56) vs. 2.21 (0.80, 5.76), NT-proBNP (ng/L): 2 405.0 (1 543.0, 6 456.5) vs. 1 680.0 (1 388.0, 4 667.0), both P < 0.05]. ROC curve analysis showed that the area under the curve (AUC) for PCT to predict the occurrence of moderate to severe ARDS was 0.827 [95% confidence interval (95%CI) was 0.739-0.915, P < 0.05]. When PCT cut-off value was 7.165 µg/L, the sensitivity was 75.7% and the specificity was 84.5%, for differentiating patients who developed moderate to severe ARDS from who did not. Multivariate Logistic regression showed that age and the elevated PCT concentration were independent risk factors for the development of moderate to severe ARDS [age: odds ratio (OR) = 1.105, 95%CI was 1.037-1.177, P = 0.002; PCT: OR = 48.286, 95%CI was 10.282-226.753, P < 0.001]. CONCLUSIONS: Patients with moderate to severe ARDS undergoing CPB cardiac surgery have a higher serum concentration of PCT than patients with no or mild ARDS. Serum PCT level may be a promising biomarker to predict the development of moderate to severe ARDS, the cut-off value is 7.165 µg/L.