Asymmetry and rehabilitation of the subjective visual vertical in unilateral vestibular hypofunction patients.

Aims: Patients with acute unilateral peripheral vestibular hypofunction (AUVP) show postural, ocular motor, and perceptive signs on the diseased side. The subjective visual vertical (SVV) test measures the perceived bias in earth-vertical orientation with a laser line in darkness. This study was aimed at (1) examining whether SVV bias could depend on preset line orientation and angles, and (2) investigating whether vestibular rehabilitation (VR) can improve SVV normalization. To our knowledge, SVV symmetry/asymmetry and impact of VR on SVV normalization have never been documented in the literature. Participants and methods: We investigated the SVV bias in a retrospective study (Study 1: n = 42 AUVP patients) comparing the data recorded for line orientation to the ipsilateral and contralateral sides at preset angles of 15° and 30°. We investigated the effects of VR on SVV normalization in a prospective study (Study 2: n = 20 AUPV patients) in which patients were tilted in the roll plane using a support tilted to the hypofunction side with the same amplitude as the SVV bias. This VR protocol was performed twice a week for 4 weeks. Supplementary data on body weight distribution and medio-lateral position of the center of foot pressure (CoP) were obtained using posturography recordings. Results: Study 1 showed asymmetrical values of the SVV bias. On average, the SVV errors were significantly higher for ipsilateral compared to contralateral line orientation (6.98° ± 3.7° vs. 4.95° ± 3.6°; p < 0.0001), and for 30° compared to 15° preset angle (6.76° ± 4.2° vs. 5.66° ± 3.3°; p < 0.0001). Study 2 showed a fast SVV normalization with VR. Non-pathological SVV bias (below ±2°) was found after only 3 to 5 VR sessions while pathological SVV values were still observed at the same time after symptoms onset in patients without VR (1.25° ± 1.46° vs. 4.32° ± 2.81°, respectively; p < 0.0001). A close temporal correlation was observed in the time course of body weight distribution, mediolateral CoP position, and SVV bias over time, suggesting beneficial effects of the VR protocol at both the perceptive and postural levels. Conclusion: We recommend routine assessment of the ipsilateral and contralateral SVV bias separately for a better evaluation of otolith organs imbalance that can trigger chronic instability and dizziness. The SVV bias and the postural impairment caused by the imbalanced otolith inputs after unilateral vestibular loss can be rapidly normalized by tilting the patients in the roll plane, an additional means in the physiotherapist's toolbox. The protocol likely reweights the visual and somatosensory cues involved in the perception of verticality.

The Subjective Visual Vertical and Electrocochleography Tests in Individuals with Meniere's Disease.

Introduction: Meniere's disease is an inner ear disorder not associated with central brain structure involvement. Although the ECochG test has been commonly used to diagnose Meniere's disease recently, it has not demonstrated high sensitivity. Therefore, it is recommended that other complementary tests alongside the ECochG test be used to diagnose Meniere's disease. The SVV test has gained popularity recently for this reason, and in this study, it was decided to use the SVV test in both static and dynamic modes, along with the ECochG test, as a tool for diagnosing Meniere's disease and evaluating its diagnostic features. Materials and Methods: The study was conducted on 53 patients with confirmed unilateral Meniere's disease and a normal group. Means were calculated with a 95% confidence interval for the groups, and the corresponding graphs were plotted. Independent t-tests were used to examine the difference in SVV results between the normal and Meniere's groups. The ROC curve was then used to determine the cutoff point and calculate. Results: After investigating the cutoff point for the three SVV conditions (tilted towards the lesion), a cutoff point of 2.1 degrees with a sensitivity and specificity of approximately 0.7 was identified as the best condition for distinguishing the Meniere's group from the healthy group. Conclusion: Finally, based on the findings, it can be concluded that the SVV test has relatively low sensitivity for diagnosing Meniere's disease. Therefore, more than relying solely on its results to identify Meniere's disease is required, and it is suggested that other measures alongside the ECochG and SVV tests be included in future studies for further investigation.

Focused Update on Clinical Testing of Otolith Organs.

Sensing gravity through the otolith receptors is crucial for bipedal stability and gait. The overall contribution of the otolith organs to eye movements, postural control, and perceptual functions is the basis for clinical testing of otolith function. With such a wide range of contributions, it is important to recognize that the functional outcomes of these tests may vary depending on the specific method employed to stimulate the hair cells. In this article, we review common methods used for clinical evaluation of otolith function and discuss how different aspects of physiology may affect the functional measurements in these tests. We compare the properties and performance of various clinical tests with an emphasis on the newly developed video ocular counter roll (vOCR), measurement of ocular torsion on fundus photography, and subjective visual vertical or horizontal (SVV/SVH) testing.

Seneca valley virus 3C protease blocks EphA2-Mediated mTOR activation to facilitate viral replication.

The Seneca Valley virus (SVV) is a recently discovered porcine pathogen that causes vesicular diseases and poses a significant threat to the pig industry worldwide. Erythropoietin-producing hepatoma receptor A2 (EphA2) is involved in the activation of the AKT/mTOR signaling pathway, which is involved in autophagy. However, the regulatory relationship between SVV and EphA2 remains unclear. In this study, we demonstrated that EphA2 is proteolysed in SVV-infected BHK-21 and PK-15 cells. Overexpression of EphA2 significantly inhibited SVV replication, as evidenced by decreased viral protein expression, viral titers, and viral load, suggesting an antiviral function of EphA2. Subsequently, viral proteins involved in the proteolysis of EphA2 were screened, and the SVV 3C protease (3Cpro) was found to be responsible for this cleavage, depending on its protease activity. However, the protease activity sites of 3Cpro did not affect the interactions between 3Cpro and EphA2. We further determined that EphA2 overexpression inhibited autophagy by activating the mTOR pathway and suppressing SVV replication. Taken together, these results indicate that SVV 3Cpro targets EphA2 for cleavage to impair its EphA2-mediated antiviral activity and emphasize the potential of the molecular interactions involved in developing antiviral strategies against SVV infection.

Seneca Valley virus 3C protease cleaves OPTN (optineurin) to Impair selective autophagy and type I interferon signaling.

Seneca Valley virus (SVV) causes vesicular disease in pigs, posing a threat to global pork production. OPTN (optineurin) is a macroautophagy/autophagy receptor that restricts microbial propagation by targeting specific viral or bacterial proteins for degradation. OPTN is degraded and cleaved at glutamine 513 following SVV infection via the activity of viral 3C protease (3C[pro]), resulting in N-terminal and a C-terminal OPTN fragments. Moreover, OPTN interacts with VP1 and targets VP1 for degradation to inhibit viral replication. The N-terminal cleaved OPTN sustained its interaction with VP1, whereas the degradation capacity targeting VP1 decreased. The inhibitory effect of N-terminal OPTN against SVV infection was significantly reduced, C-terminal OPTN failed to inhibit viral replication, and degradation of VP1 was blocked. The knockdown of OPTN resulted in reduced TBK1 activation and phosphorylation of IRF3, whereas overexpression of OPTN led to increased TBK1-IRF3 signaling. Additionally, the N-terminal OPTN diminished the activation of the type I IFN (interferon) pathway. These results show that SVV 3C[pro] targets OPTN because its cleavage impairs its function in selective autophagy and type I IFN production, revealing a novel model in which the virus develops diverse strategies for evading host autophagic machinery and type I IFN response for survival.Abbreviations: Co-IP: co-immunoprecipitation; GFP-green fluorescent protein; hpi: hours post-infection; HRP: horseradish peroxidase; IFN: interferon; IFNB/IFN-ß: interferon beta; IRF3: interferon regulatory factor 3; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MOI: multiplicity of infection; OPTN: optineurin; PBS: phosphate-buffered saline; SVV: Seneca Valley virus; SQSTM1: sequestosome 1; TAX1BP1: Tax1 binding protein 1; TBK1: TANK binding kinase 1; TCID50: 50% tissue culture infectious doses; UBAN: ubiquitin binding in TNIP/ABIN (TNFAIP3/A20 and inhibitor of NFKB/NF-kB) and IKBKG/NEMO; UBD: ubiquitin-binding domain; ZnF: zinc finger.

Modification of cortical electrical activity in stroke survivors with abnormal subjective visual vertical: An eLORETA study.

Objectives: Balance impairment is among the main complications of stroke. The gravity-based subjective vertical (SV) is considered an important reference for upright posture and navigation affected by stroke. The correlation between injury location and pathological perception of verticality remains controversial. This study aimed to evaluate the cortico-cortical network of vertical perception among patients with the right hemisphere stroke and abnormal visual-vertical perception compared with healthy individuals. Materials and methods: This observational cross-sectional study included 40 patients with the right hemisphere stroke and 35 healthy participants. All patients had abnormal visual-vertical perception. The EEG connectivity analysis was conducted through the exact low-resolution brain electromagnetic tomography analysis (eLORETA). Results: Stroke survivors manifested a power spectral density that reduced within the beta-2 frequency band in the left hemisphere and increased within the beta-3 frequency band in the right hemisphere compared with controls (p < 0.01). The lagged-phase synchronization was increased within alpha-1, beta-2, and beta-3 bands and decreased in stroke survivors compared with controls in the vestibular network involved in visual-vertical perception (p < 0.01). Conclusion: The results of this study demonstrated variations in the function and functional connectivity of cortical areas involved in the visual-vertical perception that are mainly located in the vestibular cortex.

Seneca Valley Virus Degrades STING via PERK and ATF6-Mediated Reticulophagy.

Seneca Valley Virus (SVV), a member of the Picornaviridae family, is an emerging porcine virus that can cause vesicular disease in pigs. However, the immune evasion mechanism of SVV remains unclear, as does its interaction with other pathways. STING (Stimulator of interferon genes) is typically recognized as a critical factor in innate immune responses to DNA virus infection, but its role during SVV infection remains poorly understood. In the present study, we observed that STING was degraded in SVV-infected PK-15 cells, and SVV replication in the cells was affected when STING was knockdown or overexpressed. The STING degradation observed was blocked when the SVV-induced autophagy was inhibited by using autophagy inhibitors (Chloroquine, Bafilomycin A1) or knockdown of autophagy related gene 5 (ATG5), suggesting that SVV-induced autophagy is responsible for STING degradation. Furthermore, the STING degradation was inhibited when reticulophagy regulator 1 (FAM134B), a reticulophagy related receptor, was knocked down, indicating that SVV infection induces STING degradation via reticulophagy. Further study showed that in eukaryotic translation initiation factor 2 alpha kinase 3 (PERK)/activating transcription factor 6 (ATF6) deficient cells, SVV infection failed to induce reticulophagy-medaited STING degradation, indicating that SVV infection caused STING degradation via PERK/ATF6-mediated reticulophagy. Notably, blocking reticulophagy effectively hindered SVV replication. Overall, our study suggested that SVV infection resulted in STING degradation via PERK and ATF6-mediated reticulophagy, which may be an immune escape strategy of SVV. This finding improves the understanding of the intricate interplay between viruses and their hosts and provides a novel strategy for the development of novel antiviral drugs.

Seneca Valley virus 3Cpro antagonizes type I interferon response by targeting STAT1-STAT2-IRF9 and KPNA1 signals.

IMPORTANCE: Type I interferon (IFN) signaling plays a principal role in host innate immune responses against invading viruses. Viruses have evolved diverse mechanisms that target the Janus kinase-signal transducer and activator of transcription (STAT) signaling pathway to modulate IFN response negatively. Seneca Valley virus (SVV), an emerging porcine picornavirus, has received great interest recently because it poses a great threat to the global pork industry. However, the molecular mechanism by which SVV evades host innate immunity remains incompletely clear. Our results revealed that SVV proteinase (3Cpro) antagonizes IFN signaling by degrading STAT1, STAT2, and IRF9, and cleaving STAT2 to escape host immunity. SVV 3Cpro also degrades karyopherin 1 to block IFN-stimulated gene factor 3 nuclear translocation. Our results reveal a novel molecular mechanism by which SVV 3Cpro antagonizes the type I IFN response pathway by targeting STAT1-STAT2-IRF9 and karyopherin α1 signals, which has important implications for our understanding of SVV-evaded host innate immune responses.

Targeting GBM with an Oncolytic Picornavirus SVV-001 alone and in combination with fractionated Radiation in a Novel Panel of Orthotopic PDX models.

BACKGROUND: Animal models representing different molecular subtypes of glioblastoma multiforme (GBM) is desired for developing new therapies. SVV-001 is an oncolytic virus selectively targeting cancer cells. It's capacity of passing through the blood brain barrier makes is an attractive novel approach for GBM. MATERIALS AND METHODS: 23 patient tumor samples were implanted into the brains of NOD/SCID mice (1 × 105 cells/mouse). Tumor histology, gene expression (RNAseq), and growth rate of the developed patient-derived orthotopic xenograft (PDOX) models were compared with the originating patient tumors during serial subtransplantations. Anti-tumor activities of SVV-001 were examined in vivo; and therapeutic efficacy validated in vivo via single i.v. injection (1 × 1011 viral particle) with or without fractionated (2 Gy/day x 5 days) radiation followed by analysis of animal survival times, viral infection, and DNA damage. RESULTS: PDOX formation was confirmed in 17/23 (73.9%) GBMs while maintaining key histopathological features and diffuse invasion of the patient tumors. Using differentially expressed genes, we subclassified PDOX models into proneural, classic and mesenchymal groups. Animal survival times were inversely correlated with the implanted tumor cells. SVV-001 was active in vitro by killing primary monolayer culture (4/13 models), 3D neurospheres (7/13 models) and glioma stem cells. In 2/2 models, SVV-001 infected PDOX cells in vivo without harming normal brain cells and significantly prolonged survival times in 2/2 models. When combined with radiation, SVV-001 enhanced DNA damages and further prolonged animal survival times. CONCLUSION: A panel of 17 clinically relevant and molecularly annotated PDOX modes of GBM is developed, and SVV-001 exhibited strong anti-tumor activities in vitro and in vivo.

Standardized blood volume changes monitored by capnodynamic hemodynamic variables: An experimental comparative study in pigs.

BACKGROUND: The capnodynamic method, based on Volumetric capnography and differential Fick mathematics, assess cardiac output in mechanically ventilated subjects. Capnodynamic and established hemodynamic monitoring parameters' capability to depict alterations in blood volume were investigated in a model of standardized hemorrhage, followed by crystalloid and blood transfusion. METHODS: Ten anesthetized piglets were subjected to controlled hemorrhage (450 mL), followed by isovolemic crystalloid bolus and blood re-transfusion. Intravascular blood volume, and all hemodynamic variables, were determined twice after each intervention. The investigated hemodynamic variables were: cardiac output and stroke volume for capnodynamics and pulse contour analysis, respectively, pulse pressure and stroke volume variability and mean arterial pressure. One-way ANOVA and Tukey's test for multiple comparisons were used to identify significant changes. Trending was assessed by correlation and concordance. RESULT: Concordance against intravascular volume changes for capnodynamic cardiac output and stroke volume were 96 and 94%, with correlations r = .78 and .68, (p < .0001) with significant changes for 6 and 5 of the 6 measuring points, respectively. Mean arterial pressure and pulse pressure variation had a concordance of 85% and 87%, r = .67 (p < .0001) and r = -.45 (p < .0001), respectively, and both changed significantly for 3 of 6 measuring points. Pulse contour stroke volume variation, stroke volume and cardiac output, showed concordance and correlation of 76%, r = -.18 (p = .11), 63%, r = .28 (p = .01) and 50%, r = .31 (p = .007), respectively and significant change for 1, 1 and 0 of the measuring points, respectively. CONCLUSION: Capnodynamic cardiac output and stroke volume did best depict the changes in intravascular blood volume. Pulse contour parameters did not follow volume changes in a reliable way.

Directed Evolution of Seneca Valley Virus in Tumorsphere and Monolayer Cell Cultures of a Small-Cell Lung Cancer Model.

The Seneca Valley virus (SVV) is an oncolytic virus from the picornavirus family, characterized by a 7.3-kilobase RNA genome encoding for all the structural and functional viral proteins. Directed evolution by serial passaging has been employed for oncolytic virus adaptation to increase the killing efficacy towards certain types of tumors. We propagated the SVV in a small-cell lung cancer model under two culture conditions: conventional cell monolayer and tumorspheres, with the latter resembling more closely the cellular structure of the tumor of origin. We observed an increase of the virus-killing efficacy after ten passages in the tumorspheres. Deep sequencing analyses showed genomic changes in two SVV populations comprising 150 single nucleotides variants and 72 amino acid substitutions. Major differences observed in the tumorsphere-passaged virus population, compared to the cell monolayer, were identified in the conserved structural protein VP2 and in the highly variable P2 region, suggesting that the increase in the ability of the SVV to kill cells over time in the tumorspheres is acquired by capsid conservation and positively selecting mutations to counter the host innate immune responses.

Evaluation of fluid responsiveness with dynamic superior vena cava collapsibility index in mechanically ventilated patients.

BACKGROUND: This study aimed to evaluate the predictive accuracy of the superior vena cava collapsibility index measured by transesophageal echocardiography and compare the index with stroke volume variation measured by FloTrac™/Vigileo™ in mechanically ventilated patients. METHODS: In the prospective study, a total of 60 patients were enrolled for elective general surgery under mechanical ventilation, where all patients received 10 ml/kg of Ringer's lactate. Five kinds of related data were recorded before and after the fluid challenge, including the superior vena cava collapsibility index (SVC-CI), the ratio of E/e', cardiac index (CI), stroke volume variation (SVV), and central venous pressure (CVP). Based on the collected data after the fluid challenge, we classified the patients as responders (FR group) if their CI increased by at least 15% and the rest were non-responders (NR). RESULTS: Twenty-five of 52 (48%) of the patients were responders, and 27 were non-responders (52%). The SVC-CI was higher in the responders (41.90 ± 11.48 vs 28.92 ± 9.05%, P < 0.01). SVC-CI was significantly correlated with △CI FloTrac (r = 0.568, P < 0.01). The area under the ROC curve (AUROC) of SVC-CI was 0.838 (95% CI 0.728 ~ 0.947, P < 0.01) with the optimal cutoff value of 39.4% (sensitivity 64%, specificity 92.6%). And there was no significant difference in E/e' between the two groups (P > 0.05). The best cutoff value for SVV was 12.5% (sensitivity 40%, specificity 89%) with the AUROC of 0.68 (95% CI 0.53 ~ 0.826, P < 0.05). CONCLUSIONS: The SVC-CI and SVV can predict fluid responsiveness effectively in mechanically ventilated patients. And SVC-CI is superior in predicting fluid responsiveness compared with SVV. The E/e' ratio and CVP cannot predict FR effectively. TRIAL REGISTRATION: Chinese clinical trial registry (ChiCTR2000034940).

Evaluation of pre-induction dynamic arterial elastance as an adjustable predictor of post-induction hypotension: A prospective observational study.

STUDY OBJECTIVE: Dynamic arterial elastance (Eadyn) has been suggested as a functional measure of arterial load. We aimed to evaluate whether pre-induction Eadyn can predict post-induction hypotension. DESIGN: Prospective observational study. PATIENTS: Adult patients undergoing general anesthesia with invasive and non-invasive arterial pressure monitoring systems. MEASUREMENTS: We collected invasive and non-invasive Eadyns (n = 38 in each), respectively. In both invasive and non-invasive Eadyns, pre-induction Eadyns were obtained during one-minute tidal and deep breathing in each patient before anesthetic induction. Post-induction hypotension was defined as a decrease of >30% in mean blood pressure from the baseline value or any absolute mean blood pressure value of <65 mmHg for 10 min after anesthetic induction. The predictabilities of Eadyns for the development of post-induction hypotension were tested using receiver-operating characteristic curve analysis. MAIN RESULTS: Invasive Eadyn during deep breathing showed significant predictability with an area under the curve (AUC) of 0.78 (95% Confidence interval [CI], 0.61-0.90, P = 0.001). But non-invasive Eadyn during tidal breathing (AUC = 0.66, 95% CI, 0.49-0.81, P = 0.096) and deep breathing (AUC = 0.53, 95% CI, 0.36-0.70, P = 0.75), and invasive Eadyn during tidal breathing (AUC = 0.66, 95% CI, 0.41-0.74, P = 0.095) failed to predict post-induction hypotension. CONCLUSION: In our study, invasive pre-induction Eadyn during deep breathing -could predict post-induction hypotension. Despite its invasiveness, future studies will be needed to evaluate the usefulness of Eadyn as a predictor of post-induction hypotension because it is an adjustable parameter.

The effects of COVID-19 on the vestibular system.

Introduction: The symptoms and severity of SARS-CoV-2 infection vary greatly across the spectrum, from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome and even death. Dizziness is a frequently reported symptom of SARS-CoV-2 viral infection. However, the extent to which this symptom results from the effect of SARS-CoV-2 on the vestibular system remains unclear. Materials and methods: In the present single-center, prospective cohort study, patients with a previous SARS-CoV-2 infection underwent a vestibular assessment consisting of the Dizziness Handicap Inventory to assess dizziness during and after infection, a clinical examination, the video head impulse test, and the subjective visual vertical test. When the subjective visual vertical test result was abnormal, vestibular-evoked myogenic potentials were performed. Vestibular testing results were compared to pre-existing normative data of healthy controls. In addition, we performed a retrospective data analysis of patients admitted to hospital presenting with acute symptoms of dizziness who were also diagnosed with acute SARS-CoV-2 infection. Results: A total of 50 participants have been enrolled. During and after the SARS-CoV-2 infection, women were significantly more likely than men to suffer from dizziness. A significantly reduced semicircular canal or otolith function was not observed in either women or men. Acute SARS-CoV-2 infection was diagnosed in nine patients who presented to the emergency room with acute vestibular syndrome. Six of the patients exhibited acute unilateral peripheral vestibulopathy upon diagnosis. A different patient was diagnosed with vestibular migraine, and two individuals had a posterior inferior cerebellar artery infarct revealed by magnetic resonance imaging. Discussion/conclusion: Overall, a persisting structural affection of the vestibular system by SARS-CoV-2 seems to be unlikely and could not be confirmed by vHIT, SVV, and VEMPS in our study. It seems possible but unlikely that SARS-CoV-2 induces acute vestibulopathy. Nevertheless, dizziness is a common symptom in patients with COVID-19, which should be taken and worked through seriously.

Seneca Valley virus replicons are packaged in trans and have the capacity to overcome the limitations of viral transgene expression.

Oncolytic viruses (OVs) promote the anti-tumor immune response as their replication, and the subsequent lysis of tumor cells, triggers the activation of immune-sensing pathways. Arming OVs by expressing transgenes with the potential to promote immune cell recruitment and activation is an attractive strategy to enhance OVs' therapeutic benefit. For picornaviruses, a family of OVs with clinical experience, the expression of a transgene is limited by multiple factors: genome physical packaging limits, high rates of recombination, and viral-mediated inhibition of transgene secretion. Here, we evaluated strategies for arming Seneca Valley virus (SVV) with relevant immunomodulatory transgenes. Specificially in the contex of arming SVV, we evaluated transgene maximum size and stabiltity, transgene secretion, and the impact of transgene inclusion on viral fitness. We find that SVV is not capable of expressing secreted payloads and has a transgene packaging capacity of ∼10% of viral genome size. To enable transgene expression, we developed SVV replicons with greater transgene size capacity and secretion capabilities. SVV replicons can be packaged in trans by virus in co-infected cells to express immunomodulatory transgenes in surrounding cells, thus providing a means to enhance the potential of this therapeutic to augment the anti-tumor immune response.

Effect of goal-directed fluid therapy based on plasma colloid osmotic pressure on the postoperative pulmonary complications of older patients undergoing major abdominal surgery.

BACKGROUND: As an important component of accelerated rehabilitation surgery, goal-directed fluid therapy (GDT) is one of the optimized fluid therapy strategies and is closely related to perioperative complications and mortality. This article aimed to study the effect of combining plasma colloid osmotic pressure (COP) with stroke volume variation (SVV) as a target for intraoperative GDT for postoperative pulmonary complications in older patients undergoing major abdominal surgery. METHODS: In this study, older patients (n = 100) undergoing radical resection of gastroenteric tumors were randomized to three groups: Group C (n1 = 31) received a conventional infusion regimen, Group S1 (n2 = 34) received GDT based on SVV, and Group S2 (n3 = 35) received GDT based on SVV and COP. The results were recorded, including the lung injury score (LIS); PaO2/FiO2 ratio; lactic acid value at the times of beginning (T0) and 1 h (T1), 2 h (T2), and 3 h (T3) after liquid infusion in the operation room; the total liquid infusion volume; infusion volumes of crystalline and colloidal liquids; urine production rate; pulmonary complications 7 days after surgery; and the severity grading of postoperative pulmonary complications. RESULTS: The patients in the S2 group had fewer postoperative pulmonary complications than those in the C group (P < 0.05) and the proportion of pulmonary complications of grade 1 and higher than grade 2 in S2 group was significantly lower than that in C group (P <0.05); the patients in the S2 group had a higher PaO2/FiO2 ratio than those in the C group (P < 0.05), lower LIS than those in the S1 and C groups (P < 0.05), less total liquid infusion than those in the C group (P < 0.05), and more colloidal fluid infusion than those in the S1 and C groups (P < 0.05). CONCLUSION: The findings of our study show that intraoperative GDT based on COP and SVV can reduce the incidence of pulmonary complications and conducive to shortening the hospital stay in older patients after gastrointestinal surgery. TRIAL REGISTRATION: Chinese Clinical Trial. no. ChiCTR2100045671. Registry at www.chictr.org.cn on April 20, 2021.

In vitro and in vivo antiviral activity of monolaurin against Seneca Valley virus.

Introduction: Surveillance of the Seneca Valley virus (SVV) shows a disproportionately higher incidence on Chinese pig farms. Currently, there are no vaccines or drugs to treat SVV infection effectively and effective treatment options are urgently needed. Methods: In this study, we evaluated the antiviral activity of the following medium-chain fatty acids (MCFAs) or triglycerides (MCTs) against SVV: caprylic acid, caprylic monoglyceride, capric monoglyceride, and monolaurin. Results: In vitro experiments showed that monolaurin inhibited viral replication by up to 80%, while in vivo studies showed that monolaurin reduced clinical manifestations, viral load, and organ damage in SVV-infected piglets. Monolaurin significantly reduced the release of inflammatory cytokines and promoted the release of interferon-γ, which enhanced the viral clearance activity of this type of MCFA. Discussion: Therefore, monolaurin is a potentially effective candidate for the treatment of SVV infection in pigs.

Accuracy of stroke volume variation and pulse pressure variation in predicting fluid responsiveness undergoing one-lung ventilation during thoracic surgery: a systematic review and meta-analysis.

Background: Stroke volume variation (SVV) and pulse pressure variation (PPV) are based on the interaction between the heart and lungs during mechanical ventilation. However, debate continues as to whether SVV and PPV can accurately predict fluid responsiveness during the one-lung ventilation (OLV). We therefore undertook a systematic review and meta-analysis of clinical trials that investigated the diagnostic value of SVV and PPV in predicting fluid responsiveness undergoing OLV during thoracic surgery. Methods: The MEDLINE, EMBASE, WANFANG, and CENTRAL databases were systematically searched for studies on the use of SVV and/or PPV in patients undergoing OLV from 2010 to 2021. Heterogeneity was assessed using I2 statistics. The funnel diagram analysis was used to test publication bias. A fixed-effects model was used to calculate the pooled values of sensitivity, specificity, the diagnostic odds ratio (DOR), and the relevant 95% confidence intervals (95% CIs). The summary receiver operating characteristic (SROC) curves were estimated, and the areas under the SROC curve were calculated. Results: In total nine studies, comprising 452 patients were ultimately included in this meta-analysis, including 217 (48%) responders and 235 (52%) nonresponders. After combining the correlation coefficients, a slight heterogeneity was found between SVV and PPV in these selected studies (I2 SVV =19.7%, I2 PPV =15.3%), and the funnel diagram also showed that the P values of SVV and PPV were 0.33 and 0.26. After the pooled analysis, the respective sensitivity of SVV and PPV in predicting fluid responsiveness was 0.66 and 0.61, the specificity was 0.62 and 0.53, the positive likelihood ratios were 1.7 and 1.3, the negative likelihood ratios were 0.55 and 0.74, and the DORs were 3 and 2. The areas under the SROC curve of SVV and PPV were 0.68 and 0.60, respectively, according to STATA SE16 software, and the combined areas under the receiver operating characteristic (ROC) curve of SVV and PPV were 0.681 and 0.604, respectively, according to MedCalc19.0.4 software. Conclusions: Current evidence suggests that SVV and PPV are not suitable for guiding intraoperative fluid therapy due to their poor ability to predict fluid responsiveness in patients undergoing OLV, and we need a better indicator instead.

Reliability of stroke volume or pulse pressure variation as dynamic predictors of fluid responsiveness in laparoscopic surgery: a systematic review.

The reliability of stroke volume variation (SVV) and pulse pressure variation (PPV) in predicting fluid responsiveness during laparoscopic surgery remains unclear. We conducted the present systematic review to summarize the current evidence. We reviewed studies that investigated the reliability of SVV and PPV in laparoscopic surgery. Seven studies were included in the final analysis. Two studies demonstrated that the area under the receiver operating characteristic curve (AUROC) for SVV was less than 0.8, and five studies reported that the AUROC was > 0.8. The pooled AUROC for SVV and PPV was more than 0.8 with high heterogeneities between the included studies. Most individual studies have suggested that SVV and PPV are sufficiently reliable for predicting fluid responsiveness during laparoscopic surgery. However, the limited number of patients, varied apparatus used to define fluid responsiveness, diverse definitions of fluid responsiveness, and different fluids used to perform fluid challenges in the included studies render firm conclusions about SVV's and PPV's reliability impossible.

First report and genetic characterization of Seneca Valley virus (SVV) in Chile.

Seneca Valley virus (SVV) is a non-enveloped RNA virus and the only member of the Senecavirus A (SVA) species, in the Senecavirus genus, Picornaviridae family. SVV infection causes vesicular lesions in the oral cavity, snout and hooves of pigs. This infection is clinically indistinguishable from trade-restrictions-related diseases such as foot-and-mouth disease. Other clinical manifestations include diarrhoea, anorexia, lethargy, neurological signs and mortality in piglets during their first week of age. Before this study, Chile was considered free of vesicular diseases of swine, including SVV. In April 2022, a suspected case of vesicular disease in a swine farm was reported in Chile. The SVV was confirmed and other vesicular diseases were ruled out. An epidemiological investigation and phylogenetic analyses were performed to identify the origin and extent of the outbreak. Three hundred ninety-five samples from 44 swine farms were collected, including faeces (208), oral fluid (28), processing fluid (14), fresh semen (61), environmental samples (80) and tissue from lesions (4) for real-time RT-PCR detection. Until June 2022, the SVV has been detected in 16 out of 44 farms, all epidemiologically related to the index farm. The closest phylogenetic relationship of the Chilean SVV strain is with viruses collected from swine in California in 2017. The direct cause of the SVV introduction has not yet been identified; however, the phylogenetic analyses suggest the USA as the most likely source. Since the virus remains active in the environment, transmission by fomites such as contaminated feed cannot be discarded. Further studies are needed to determine the risk of the introduction of novel SVV and other transboundary swine pathogens to Chile.