Derivation and validation of a quantitative risk prediction model for weaning and extubation in neurocritical patients.

Background: Patients with severe neurological conditions are at high risk during withdrawal and extubation, so it is important to establish a model that can quantitatively predict the risk of this procedure. Methods: By analyzing the data of patients with traumatic brain injury and tracheal intubation in the ICU of the affiliated hospital of Hangzhou Normal University, a total of 200 patients were included, of which 140 were in the modeling group and 60 were in the validation group. Through binary logistic regression analysis, 8 independent risk factors closely related to the success of extubation were screened out, including age ≥ 65 years old, APACHE II score ≥ 15 points, combined chronic pulmonary disease, GCS score < 8 points, oxygenation index <300, cough reflex, sputum suction frequency, and swallowing function. Results: Based on these factors, a risk prediction scoring model for extubation was constructed with a critical value of 18 points. The AUC of the model was 0.832, the overall prediction accuracy was 81.5%, the specificity was 81.6%, and the sensitivity was 84.1%. The data of the validation group showed that the AUC of the model was 0.763, the overall prediction accuracy was 79.8%, the specificity was 84.8%, and the sensitivity was 64.0%. Conclusion: These results suggest that the extubation risk prediction model constructed through quantitative scoring has good predictive accuracy and can provide a scientific basis for clinical practice, helping to assess and predict extubation risk, thereby improving the success rate of extubation and improving patient prognosis.

Pretreatment with geniposide mitigates myocardial ischemia/reperfusion injury by modulating inflammatory response through TLR4/NF-κB pathway.

Geniposide (GEN), a medical herb, is known for its therapeutic applications in cardiovascular diseases, though its efficacy in treating myocardial ischemia/reperfusion injury (MI/RI) is yet to be fully elucidated. This study is an endeavor to explore the potential protective mechanism of GEN against MI/RI. To simulate the MI/RI condition, the left anterior descending artery was occluded for 30 min, followed by a reperfusion period of 120 min in a rat model. Three dosages (50, 100, or 150 mg/kg) of GEN were intraperitoneally injected to the Sprague-Dawley rats once a day, for seven days before the ligation of the artery. The rats were categorized into sham group, MI/RI group, and three different dosages GEN-treated groups. As the results showed, the pretreatment with GEN mitigated myocardial injury, reduced infarct volume, inhibited apoptosis, enhanced superoxide dismutase activity, and decreased malondialdehyde and myeloperoxidase activity, as well as serum creatine kinase-MB and lactate dehydrogenase levels. Moreover, GEN ameliorated MI/RI by downregulating protein expression of toll-like receptor 4, myeloid differentiation primary response 88, and p-nuclear factor-κB. In conclusion, the pretreatment of GEN may be considered as a potential therapeutic option for MI/RI.

TERLIPRESSIN COMBINED WITH NOREPINEPHRINE IN THE TREATMENT OF SEPTIC SHOCK: A SYSTEMATIC REVIEW.

ABSTRACT: Objective: The objective of this study was to provide an in-depth analysis of the advantages and potential research directions concerning the utilization of terlipressin (TP) in combination with norepinephrine (NE) for the management of septic shock. Methods: A systematic search was conducted across five major electronic databases, namely, PubMed, Cochrane, Embase, ScienceDirect, and MEDLINE, using the Boolean method. The search encompassed articles published until May 22, 2023. Randomized controlled trials investigating the efficacy of TP combined with NE in the treatment of patients with septic shock were considered for inclusion. Results: A total of seven trials met the inclusion criteria. The combination therapy of TP and NE exhibited potential benefits in the treatment of adult patients suffering from septic shock. Furthermore, the concurrent administration of TP with NE demonstrated improvements in cardiac output and central venous pressure. However, it is important to acknowledge the presence of certain risks and potential adverse events, including an elevated risk of peripheral ischemia. Conclusions: The available evidence supports the notion that early combination therapy involving NE and TP holds promise in terms of reducing the required dosage of NE, enhancing renal perfusion, and improving microcirculation in patients diagnosed with septic shock.

Geniposide alleviates pressure overload in cardiac fibrosis with suppressed TGF-ß1 pathway.

BACKGROUND: Cardiac fibrosis is one of the main contributors to the pathogenesis of heart failure. Geniposide (GE), a major iridoid in gardenia fruit extract, has recently been reported to improve skeletal muscle fibrosis through the modulation of inflammation response. This investigation aimed to illuminate the cardio-protective effect and the potential mechanism of GE in cardiac fibrosis. MATERIAL AND METHODS: A transverse aortic contraction (TAC) induction mice model was established and GE (0 mg/kg; 10 mg/kg; 20 mg/kg; 40 mg/kg) was administered by oral gavage daily for 4 weeks. Hemodynamic parameters, Masson's trichrome stain, and hematoxylin-eosin (HE) staining were estimated and cardiomyocyte fibrosis, interstitial collagen levels, and hypertrophic markers were analyzed using qPCR and western blot. In vitro, H9C2 cells were exposed to the Ang II (1 µM) pretreated with GE (0.1 µM, 1 µM, and 10 µM). Cardiomyocyte apoptosis was detected. Moreover, the transforming growth factor ß1 (TGF-ß1)/Smad2 pathway was assessed in vivo and in vitro. RESULTS: GE significantly ameliorated TAC-induced cardiac hypertrophy, ventricular remodeling, myocardial fibrosis, and improved cardiac function in vivo, and it inhibited Ang II-induced cardiomyocyte apoptosis in vitro. We further observed that the inflammatory channel TGF-ß1/Smad2 pathway was suppressed by GE both in vivo and in vitro. CONCLUSION: These results indicate that GE inhibited myocardial fibrosis and improved hypertrophic cardiomyocytes with attenuated the TGF-ß1/Smad2 pathway and proposed to be an important therapeutic of cardiac fibrosis reduced by TAC.

Quartz-Enhanced Photoacoustic Spectroscopy-Conductance Spectroscopy for Gas Mixture Analysis.

A novel spectroscopic method, named quartz-enhanced photoacoustic spectroscopy-conductance spectroscopy (QEPAS-CS), was first developed for gas mixture analysis. In QEPAS-CS, the advantage of photoacoustic detection and conductance analysis was realized by a quartz tuning fork (QTF). Two-component gas analysis was done by photoacoustic detection and conductance detection. For an explicit application, natural spider silk was used as a water vapor transducer to modify the QTF, making a conductance sensing channel. A 2004 nm laser diode was used as an excitation source for a photoacoustic sensing channel. Such a QEPAS-CS sensor was used for H2O/CO2 gas mixture analysis in a cell incubator. This provides a solution to calibrate an infrared photoacoustic spectroscopy gas sensor. This example effectively confirms the capacity of multigas analysis by the QEPAS-CS sensor.

Clamp-type quartz tuning fork enhanced photoacoustic spectroscopy.

In this Letter, clamp-type quartz tuning fork enhanced photoacoustic spectroscopy (Clamp-type QEPAS) is proposed and realized through the design, realization, and testing of clamp-type quartz tuning forks (QTFs) for photoacoustic gas sensing. The clamp-type QTF provides a wavefront-shaped aperture with a diameter up to 1 mm, while keeping Q factors > 104. This novel, to the best of our knowledge, design results in a more than ten times increase in the area available for laser beam focusing for the QEPAS technique with respect to a standard QTF. The wavefront-shaped clamp-type prongs effectively improve the acoustic wave coupling efficiency. The possibility to implement a micro-resonator system for clamp-type QTF is also investigated. A signal-to-noise enhancement of ∼30 times has been obtained with a single-tube acoustic micro resonator length of 8 mm, ∼20% shorter than the dual-tube micro-resonator employed in a conventional QEPAS system.

[Clinical study of fluid resuscitation guided by peripheral perfusion index in patients with septic shock].

OBJECTIVE: To explore the guiding effect of peripheral perfusion index (PI) on fluid resuscitation in patients with septic shock. METHODS: Sixty-five patients with septic shock who were diagnosed according to relevant criteria of septic shock and admitted to the department of critical care medicine of the Affiliated Hospital of Hangzhou Normal University from September 2017 to December 2020 were included. Patients were divided into the conventional treatment group (30 cases) and PI guidance group (35 cases) by random number method. Both groups of patients were treated with the bundle according to clinical guidelines. Sputum, urine and blood were collected for pathogenic microorganism culture before the application of antibiotics, and vasoactive drugs were given. Both groups need to achieve all the following resuscitation goals within 6 hours: urine output > 0.5 mL×kg-1×h-1, mean arterial pressure (MAP) ≥ 65 mmHg (1 mmHg ≈ 0.133 kPa), central venous pressure (CVP) was 8-12 mmHg, and central venous oxygen saturation (ScvO2) ≥ 0.70. There was no further resuscitation in the conventional treatment group after the goals were achieved. In addition to these four goals, the PI guidance group was expected to achieve PI ≥ 1.4. Heart rate (HR), CVP, MAP, ScvO2, blood lactic acid (Lac), the time of fluid negative balance, intensive care unit (ICU) mortality and 28-day mortality between the two groups were compared before and after 6 hours of fluid resuscitation. RESULTS: Before fluid resuscitation, there were no statistically significant differences in all indicators between two groups. After 6 hours fluid resuscitation, the four treatment goals in PI guidance group were slightly lower than those of the conventional treatment group [HR (times/min): 96.5±12.1 vs. 97.7±7.9, MAP (mmHg): 83.2±6.2 vs. 82.1±7.5, ScvO2: 0.661±0.077 vs. 0.649±0.051, CVP (mmHg): 10.8±2.7 vs. 10.4±2.1], there were no statistically significant differences between the two groups (all P > 0.05); the Lac level of the PI guidance group after resuscitation was lower than that of the conventional treatment group, and the difference was statistically significant (mmol/L: 4.8±1.3 vs. 5.9±1.4, P < 0.05); the duration of fluid negative balance in the PI guidance group was earlier than that in the conventional treatment group [days: 3.0 (2.0, 3.0) vs. 3.5 (3.0, 4.0), P < 0.05]. The ICU mortality and 28-day mortality in the PI guidance group were lower than those in the conventional treatment group [ICU mortality rate: 37.1% (13/35) vs. 50.0% (15/30), 28-day mortality rate: 57.1% (20/35) vs. 60.0% (18/30)], but the differences were not statistically significant (both P > 0.05). CONCLUSIONS: The peripheral PI can be used as an important indicator of fluid resuscitation in patients with septic shock. PI guiding fluid resuscitation in patients with septic shock can reduce Lac levels, shorten the duration of fluid negative balance and reduce the risk of fluid overload.

Spider Silk-Improved Quartz-Enhanced Conductance Spectroscopy for Medical Mask Humidity Sensing.

Spider silk is one of the hottest biomaterials researched currently, due to its excellent mechanical properties. This work reports a novel humidity sensing platform based on a spider silk-modified quartz tuning fork (SSM-QTF). Since spider silk is a kind of natural moisture-sensitive material, it does not demand additional sensitization. Quartz-enhanced conductance spectroscopy (QECS) was combined with the SSM-QTF to access humidity sensing sensitively. The results indicate that the resonance frequency of the SSM-QTF decreased monotonously with the ambient humidity. The detection sensitivity of the proposed SSM-QTF sensor was 12.7 ppm at 1 min. The SSM-QTF sensor showed good linearity of ~0.99. Using this sensor, we successfully measured the humidity of disposable medical masks for different periods of wearing time. The results showed that even a 20 min wearing time can lead to a >70% humidity in the mask enclosed space. It is suggested that a disposable medical mask should be changed <2 h.

The predictive performance of the lactate clearance rate combined with the APACHE II score in the prediction of sepsis-associated acute kidney injury in 7 days.

Background: The purpose of this study was to evaluate the accuracy of the lactate clearance rate (LCR) combined with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in the prediction of sepsis-associated acute kidney injury (SAKI). Methods: Sepsis patients were divided into the SAKI group and non-SAKI group. Arterial blood lactate was collected at 0 h (before treatment), 2 h, 4 h, 6 h, and 8 h (after treatment), and the LCR was calculated. The physiological parameters and laboratory test results were used to calculate the APACHE II score and the Sequential Organ Failure Assessment (SOFA) score. The receiver operating characteristic (ROC) curves of LCR, APACHE II score and SOFA score for predicting patients with SAKI were drawn. Two single indicators with high areas under the curves (AUCs) were selected to calculate the joint probability through regression analysis, and the prediction efficiency corresponding to each curve was analyzed. Results: There were significant differences in LCR between different groups and time periods (Fgroup=17.44, Pgroup ≤0.0001, Ftime =11.71, Ptime =0.0014). After 8 h of treatment, there was a significant difference in the overall compliance rate between the 2 groups (P<0.0001). In addition, after 24 h of treatment, the APACHE II score in the SAKI group was significantly higher than that in the non-SAKI group (P=0.0007), and SOFA score was also significantly higher than that in the non-SAKI group (P=0.0001). ROC curve showed that the 0-8 h LCR and APACHE II scores had a high predictive performance for the acute kidney injury (AKI) occurrence in sepsis patients, and AUCs were 0.7637 and 0.7517, respectively, while the combined AUC of the 2 indicators was 0.7975. Conclusions: The 0-8 h LCR combined with APACHE II score can improve the early predictive value of SAKI, reduce the risk of AKI in patients with sepsis/septic shock, and reduce the social and family burden, which is worthy of clinical application.

Neuroprotective Effect of Stroke Pretreated Mesenchymal Stem Cells Against Cerebral Ischemia/Reperfusion Injury in Rats.

BACKGROUND: Mesenchymal stem cells (MSCs) have been shown to enhance neurological recovery after stroke. A rat middle cerebral artery occlusion model was designed to assess neuroprotective effects of stroke pretreated MSCs on cerebral ischemia/reperfusion injury. METHODS: MSCs were isolated and cultured in medium with 10% fetal bovine serum, normal control serum, or stroke serum (SS). MSCs were then injected into rats (n = 6 in each group) 1 day after middle cerebral artery occlusion, and feeding continued for 28 days. A battery of behavioral tests, 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, enzyme-linked immunosorbent assay, and terminal deoxynucleotidyl transferase dUTP nick end labeling assay were used to assess neural injury. To detect enhancement of neuronal regeneration and angiogenesis, immunofluorescence and Western blotting were performed to assess expression of trophic factors and growth factors. RESULTS: After treatment, behavior of rats improved significantly. Infarction area, brain lesion, and apoptosis cells were significantly decreased in the SS-MSCs group compared with the other groups. SS-MSCs also modulated inflammation by attenuating inflammatory cytokines. Furthermore, the number of neurogenesis-positive cells and expression of trophic factors and growth factors were significantly higher in the SS-MSCs group compared with the others. MSCs cultured with fetal bovine serum and normal control serum showed differences in expression of trophic factors and growth factors, but the results were not as good as with SS-MSCs. CONCLUSIONS: Administration of SS-MCSs after reperfusion led to neuroprotection by inducing the recovery process, including improving pathological changes, behavioral improvement, neurogenesis, suppression of apoptosis and inflammation, and angiogenesis.

Prevalence and phenotypic characterization of carbapenem-resistant Klebsiella pneumoniae strains recovered from sputum and fecal samples of ICU patients in Zhejiang Province, China.

OBJECTIVE: To understand the prevalence and transmission of carbapenem-resistant Klebsiella pneumoniae (CRKP) in ICU patients in Zhejiang Province, China, and determined the genetic and phenotypic characteristics of these CRKP strains. MATERIALS AND METHODS: A total of 202 ICU patients from eight tertiary hospitals were recruited and 55 non-duplicate CRKP strains were collected during July and August in 2017. These strains were subjected to determination of MICs, carriage of carbapenemase genes and tet(A) variants, PFGE, MLST and virulence potential using G. mellonella larvae infection model. RESULTS: A total of 55 CRKP strains were recovered from 42 patients, representing a carriage rate of 20.8%. CRKP strains were recovered from both the intestinal and respiratory tract of 13 patients. Importantly, strains isolated from sputum and fecal samples often displayed identical PFGE profiles, suggesting that CRKP may also colonize the respiratory tract. The most dominant ST type of these CRKP strains was ST11, accounting for 78% (43/55) of the test strains. The majority of CRKP strains were resistant to multiple antibiotics, with the exception of tigecycline and ceftazidime/avibactam. Interestingly, 32 strains were found to harbor the tet(A) variant, which is known to confer reduced tigecycline susceptibility. Assessment of the virulence potential of these CRKP strains by string test showed that results were negative for 53 of the 55 test strains. However, further assessment of virulence potential using a G. mellonella larvae infection model showed that CRKP isolated from sputum consistently exhibited a higher virulence level than strains recovered from fecal samples. CONCLUSION: CRKP is highly prevalent in ICU patients in Zhejiang Province with strains isolated from respiratory exhibiting higher virulence potential than those from GI tract. These data provide essential insight into development of new infection control measures to halt the transmission of CRKP in clinical settings.

Vascular oxidative stress increases dendritic cell adhesion and transmigration induced by homocysteine.

Atherosclerosis is a long-term chronic inflammatory and immunological disease. Endothelial dysfunction and the dendritic cell (DC) immune response are pivotal early events in atherogenesis. This study investigated the effects and possible mechanisms of action of homocysteine (Hcy) on DC adhesion to and transmigration between endothelial cells (ECs), and indicated a novel immunoregulatory mechanism by which Hcy induces atherogenesis. When ECs were stimulated with increasing concentrations of Hcy, immunofluorescence showed that endothelial reactive oxygen species (ROS) generation strikingly increased, while nitrite assay showed that nitric oxide (NO) release markedly decreased. Furthermore, DC adhesion and transmigration were significantly increased when ECs were activated by Hcy. However, pretreatment of ECs with antioxidant before Hcy markedly attenuated the induction of DC adhesion and transmigration, dependent on the intracellular ROS decrease and endothelial NO increase. In conclusion, DC adhesion and transmigration are significantly increased by vascular oxidative stress under conditions of elevated Hcy levels. These findings provide insight into the inflammatory processes and immune responses occurring in atherosclerosis induced by Hcy.