VC Group Research Articles

Effect of high-dose intravenous vitamin C on prognosis in patients with SARS-CoV-2 pneumonia

BackgroundUntil now, the coronavirus disease 2019 (COVID-19) pandemic has affected more than 2.5 million individuals worldwide, with approximately 170,000 deaths. Currently, no treatments with robust evidence of clinical benefit exist, and utilization of experimental agents have been recommended by national and international guidelines as a part of clinical studies. MethodIn this retrospective study, a total of 323 patients severe acute respiratory syndrome due to PCR-documented COVID-19 infection admitted in our unit were included. Patients were categorized into two groups as those who did or did not receive high dose intravenous vitamin C. we examined the effect of high dose intravenous vitamin C administered in addition to other commonly used agents on prognosis in patients with COVID-19 pneumonia. ResultsAs compared to patients who did not receive vitamin C, those in the VC group were not significantly different in terms of the length of hospital stay (p=0.05), re-admission rate (p=0.943), admission to intensive care, need for advanced oxygen support (p=0.488), need for advanced medical treatment (p<0.001), and mortality (p=0.52). ConclusionThe limited evidence based on small samples precludes definitive conclusions regarding the potential efficacy of high dose vitamin C in these patients, indicating the need for further assessment within the context of clinical research.

Combined effect of vitamin C and vitamin D3 on intestinal epithelial barrier by regulating Notch signaling pathway

BackgroundTight junction proteins play crucial roles in maintaining the intestinal mucosal barrier. Although previous studies have shown that Notch signaling is closely related to tight junction proteins, the mechanism remains unclear. This study was performed to investigate whether vitamin C combined with vitamin D3 affects intestinal mucosal barrier stability via the Notch signaling pathway.MethodsIntestinal epithelial barrier and notch signaling pathway were studied using guinea pig and SW480 cells. The guinea pigs were randomized into four groups (n = 6 in each group): control group (C, 200 IU/kg d VD3 + 100 mg/kg d VC), low VC group (LVC, 200 IU/kg d VD3 + 10 mg/kg d VC), medium VC group (MVC, 200 IU/kg d VD3 + 100 mg/kg d VC), and high VC group (HVC, 200 IU/kg d VD3 + 200 mg/kg d VC). Except for the control group, the other three groups were freely drinked with 2% dextran sodium sulfate solution for 4 days. And the control group was free to drink distilled water. The following cell groups were used: control group (SW480 cells without intervention); LPS group (100 ng/mL LPS); VD3 group (0.1 μmol/L VD3); VC + VD3 group (0.1, 1, 5, 10 μmol/mL VC + 0.1 μmol/L VD3).ResultsElectron microscopy analysis revealed that both low and high doses of vitamin C combined with vitamin D3 maintained dextran sodium sulfate-induced ulcerative colitis in the guinea pig intestinal epithelium tight junction. Compared with the control group, the expression level of ZO-1 mRNA in the colon tissue of the high-dose vitamin C group was significantly increased. In SW480 cell experiments, compared with the control group, cell migration and repair following treatment with different concentrations of vitamin C combined with vitamin D3 were significantly improved and the protein expression of Notch-1 was increased, whereas the protein expression of claudin-2 was significantly decreased. Thus, our results demonstrate that an appropriate amount of vitamin C combined with vitamin D3 can regulate the expression of claudin-2 by regulating Notch-1, relieve destruction of the intestinal mucosal barrier, and promote the repair of damage to the cell mucosal barrier.ConclusionsWe found that vitamin C combined with vitamin D3 protected against dextran sodium sulfate-induced ulcerative colitis in the guinea pig intestinal mucosa.

Respiratory tactics during cardiopulmonary bypass in cardiac surgery

An important place in the structure of the causes of postoperative respiratory failure in cardiac surgery is occupied by atelectasis of the lung tissue, which is formed during cardiopulmonary bypass (CPB). The incidence of this complication makes 54–92%.The objective: to evaluate the effectiveness of various respiratory support techniques during CPB.Subjects and methods. 60 patients were randomly included in the study. CPAP Group (positive airway pressure +5 cm H2O) and VC Group (lung ventilation during CPB with parameters: tidal volume 3 ml/kg, respiratory rate 6/min, positive end-expiratory pressure +5 cm H2O).Results. The oxygenation index in VC Group was higher than in CPAP Group at the stages after the end of CPB (289.6 ± 100.0 in VC Group and 223.1 ± 152.0 in CPAP Group), at the end of surgery (in VC Group 318,7 ± 73.8 and in CPAP Group 275.2 ± 90.0) The frequency of intraoperative (VC 16% and CPAP 43%) and postoperative recruiting lung maneuvers (VC 7% and CPAP 26%) in VC Group was lower versus CPAP Group. The incidence of atelectasis in VC Group (10%) decreased compared to CPAP (36.6%).Conclusion: Low-volume ventilation during cardiopulmonary bypass has a more favorable effect on the oxygenating function compared to respiratory support in the CPAP mode.

Effects of different types and doses of whey protein on the physiological and intestinal flora in D-galactose induced aging mice

The elderly usually suffer from many diseases. Improving the quality of life of the elderly is an urgent social issue. In this present study, D-galactose treated aging mice models were used to reveal the effects of different animal sources and different doses of whey protein (WP) on the immune indexes organs and intestinal flora. A total of 9 groups were set up, including normal control (NC), negative control (NS), positive control (Vc), low-, medium- and high-doses of cow WP intervention groups (CL, CM and CH for short, correspondingly) and low-, medium- and high-doses of goat WP intervention groups (GL, GM and GH for short, correspondingly). The body weight gain, thymus/body weight ratio, superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, spleen immunoglobulins G (IgG), spleen interleukin-2 (IL-2) and spleen interleukin-2 (IL-6) were measured. Then, the intestinal contents were collected, and 16s genes of intestinal bacteria were sequenced to reveal the changes in bacterial flora structure. WP intervention significantly increased the weight gain, thymus/body ratio and SOD activity, but decrease the content of MDA. WP intervention increased some immune indicators. All the WP treated aging mice showed similar values of physiological indexes to that of the Vc group, even better. The relative abundance of Lactobacillus and Stenotrophomonas was increased and decreased, respectively, by both cow and goat WP. Lactobacillus may be involved in regulating the functional repair of organisms. In contrast, Stenotrophomonas might play a negative role in the immune and antioxidant capacity of the body. Combining physiological indicators and intestinal flora structure, low-concentration WP for cow and goat might be optimal for aging models.

Metabolic mechanism of Prunella vulgaris in treatment of ethanol-induced oxidative stress in rats based on metabonomics

Prunella vulgaris(PV) is an edible and traditional medicinal herb which has a wide range application in fighting inflammation and oxidative stress, and protecting liver. Now it has been used to treat various types of liver diseases and has significant clinical efficacy. This study aims to investigate the effects of PV on ethanol-induced oxidative stress injury in rats and its metabolic mechanism. The rats were divided into control group, model group, PV group, and VC group. The liver protection of PV was identified by measuring pharmacological indexes such as antioxidant and anti-inflammatory activity. The metabolic mechanism of long-term ethanol exposure and the metabolic regulation mechanism of PV treatment were studied by LS-MS metabonomics. The pharmacological investigation indicated that ethanol could significantly decrease the contents of SOD, GSH-Px, CAT and other antioxidant enzymes in liver and increase the content of MDA. At the same time, PV could significantly reduce the contents of inflammatory factors(TNF-α, IL-6 and IL-1β) and liver function markers(ALT, AST, ALP) in serum. What's more, long-term ethanol exposure could significantly cause liver injury, while PV could protect liver. Metabolomics based on multiple statistical analyses showed that long-term ethanol exposure could cause significant metabolic disorder, and fatty acids, phospholipids, carnitines and sterols were the main biomarkers. Meanwhile, pathway analysis and enrichment analysis showed that the β oxidation of branched fatty acids was the main influencing pathway. Also, PV could improve metabolic disorder of liver injury induced by ethanol, and amino acids, fatty acids, and phospholi-pids were the main biomarkers in PV treatment. Metabolic pathway analysis showed that PV mainly regulated metabolic disorder of ethanol-induced liver injury through phenylalanine, tyrosine and tryptophan biosynthetic pathways. This study could provide a new perspective on the hepatoprotective effect of natural medicines, such as PV.

107 Administration of antioxidants improves serum total antioxidant capacity, testosterone, and seminal quality of Magra rams

Oxidative stress is one of the most important factors responsible for poor quality of semen, and it is defined as an imbalance between the formation of reactive oxygen species (ROS, including hydroxyl radicals, superoxide anions, and hydrogen peroxide) and antioxidant capacity of semen. Antioxidants act as a powerful defence system against ROS attack in sperm cells by decreasing oxidative stress and they improve semen quality, which could be useful in the management of male infertility. Magra is a dual-purpose (wool and meat) hardy sheep breed that originated in the eastern and southern parts of the Bikaner district of Rajasthan, India. The present study evaluated the effects of the administration of vitamin E with selenium or vitamin C on serum antioxidants, testosterone, and seminal quality of Magra rams. Twenty-one Magra rams, aged between 1.5 and 2.5 years, were randomly assigned to treatment at weekly intervals with administration of either 1mL of vitamin E (tocopherol, 50mg mL−1) and selenium (1.5mg sodium selenite; n=7; VES), 8mL of vitamin C (250mg mL−1 sodium ascorbate; n=7; VC), or 1mL of saline (n=7; control) subcutaneously for 5 consecutive weeks. After the fourth week, semen and blood were collected twice a week for 5 consecutive weeks and assayed for seminal quality parameters, serum testosterone, and serum antioxidants. Data obtained were analysed statistically using te SPSS software (version 25.0; IBM Corp.). Mean values were compared using Duncan’s multiple range test. The semen parameters sperm motility, sperm concentration, live sperm percentage, and% HOST (hypo-osmotic swelling test)-positive sperm were significantly elevated, whereas reaction time and percentage of abnormal sperm were lower in both the treated groups compared with controls (P&amp;lt;0.05). Seminal pH declined significantly in the VES group (P&amp;lt;0.05), whereas it was not different between the VC and control groups of rams (P&amp;gt;0.05). Glutathione peroxidase, superoxide dismutase, and total antioxidant capacity concentrations were higher in serum and seminal plasma of treated rams (P&amp;lt;0.05). Serum testosterone concentrations were significantly elevated in VES and VC groups (P&amp;lt;0.05). We concluded that the administration of vitamin E and selenium or vitamin C improves the serum testosterone production and seminal quality of rams.

Effects of Vitamin C Supplementation on The Blood Oxidative Stress and Antibody Titre Against Histophilus Somni Vaccination in Calves.

IntroductionThe purpose of this study was to determine the effects of vitamin C supplementation on blood oxidative stress biomarkers and antibody response to vaccination in calves.Material and methodsThirty-four clinically healthy 2 week old Japanese Black calves were randomly assigned to two groups. Seventeen calves formed the VC group which received 1,000 mg of vitamin C daily from 2 to 8 weeks of age, and the other 17 calves of the control group did not receive supplementation. All calves received an inactivated Histophilus somni vaccine at 4 and 8 weeks of age. Blood samples were taken at 2, 4, 8 and 12 weeks of age.ResultsThe concentration of the serum reactive oxygen metabolites (d-ROMs), and the oxidative stress index (OSI), which is calculated from the d-ROMs and biological antioxidant potential, were significantly lower at 8 weeks of age in the VC group than in the control group (P < 0.05). The antibody titres to H. somni in the VC group were significantly higher than those in the control group at 12 weeks of age after the second vaccination (P < 0.05).ConclusionVitamin C supplementation to calves may reduce oxidative stress and enhance the antibody production after vaccination with H. somni.

Training Propulsion via Acceleration of the Trailing Limb.

Walking function, which is critical to performing many activities of daily living, is commonly assessed by walking speed. Walking speed is dependent on propulsion, which is governed by ankle moment and the posture of the trailing limb during push-off. Here, we present a new gait training paradigm that utilizes a dual belt treadmill to train both components of propulsion by accelerating the belt of the trailing limb during push-off. Accelerations require participants to produce greater propulsive force to counteract inertial effects, and increases extension of the trailing limb through increased belt velocity. We hypothesized that one session of training in this paradigm would produce after effects in propulsion mechanics and, consequently, walking speed. We tested the training paradigm on healthy young adults at two acceleration magnitudes-7 m/s2 (HA) and 2 m/s2 (LA)-and compared their results to a third control group (VC) that walked at a higher velocity during training. Results show that the HA group significantly increased walking speed following training (mean ± s.e.m: 0.073 ± 0.013 m/s, p < 0.001). The change in walking speed in the LA and VC groups was not significant (LA: 0.032 ± 0.013 m/s, VC: -0.003 ± 0.013 m/s). Responder analysis showed that changes in push-off posture and in activation of ankle plantar-flexor muscles contributed to the greater increases in gait speed measured in the HA group compared to the LA and VC groups. The duration of after effects post training suggest that the measured changes in neuromotor coordination are consistent with use-dependent learning.

Immunomodulatory effect of Acanthopanax senticosus polysaccharide on immunosuppressed chickens

The immunomodulatory effect of Acanthopanax senticosus polysaccharide (ASPS) on immunosuppressed chickens induced by cyclophosphamide (Cy) was observed in this study. Four hundred 7-day-old chickens were randomly divided into 4 groups: vaccinated control group (VC group), Cy-challenged control group (Cy group), Cy-challenged + low-dose ASPS group (ASPSL + Cy group), and Cy-challenged + high-dose ASPS group (ASPSH + Cy group). All groups except the VC group were injected with Cy at a dose of 80 mg/kg/day of BW for 3 successive days to induce immunosuppression. At the age of 10 d, the ASPSL + Cy group and ASPSH + Cy group were intramuscularly injected with 0.2 mL of ASPS at the dose of 100 and 200 mg/mL/day, respectively, once a day for 3 successive days. The Cy group was injected with saline solution in the same way as the 2 ASPS groups. At the age of 14 d, the chickens were vaccinated with Newcastle disease (ND) vaccine in all groups. On day 7, 14, 21, and 28 after the vaccination, BW, lymphocyte proliferation, the serum antibody titers of the ND vaccine, the proportion of CD4+ and CD8+ T lymphocytes, and the concentrations of interferon gamma and IL-2 were determined. The results showed that chickens were injected with Cy at a dose of 80 mg/kg of BW for 3 d displayed lower immune responses than the control group, indicating that the immunosuppressive model was successfully established. At most time points, both high and low doses of ASPS could significantly promote lymphocyte proliferation; enhance BW, antibody titers, and the proportion of CD4+ and CD8+ T lymphocytes; and raised the concentrations of interferon gamma and IL-2 in Cy-treated chickens compared with those in the Cy control group (P < 0.05). These results indicated that ASPS could resist immunosuppression induced by Cy and may be a new-type immune adjuvant to improve vaccination in normal and immunosuppressed chickens.

Mycobiome changes in the vitreous of post fever retinitis patients.

Fungi have been associated with various diseases of the eye like keratitis, uveitis and endophthalmitis. Despite this fact, fungal microbiome (mycobiome) studies compared to the bacterial microbiome studies have remained neglected. In the present study, using metagenomic sequencing, the mycobiomes of the vitreous of healthy control individuals (VC, n = 15) and individuals with post fever retinitis + non-PFR uveitis (PFR+, n = 9) were analysed and compared. The results indicated that Ascomycota was the most predominant phylum in both VC and PFR+ groups. Further, at the genera level it was observed that the abundance of 17 fungal genera were significantly different in post fever retinitis (PFR, n = 6) group compared to control group. Of these 17 genera, it was observed that 14 genera were relatively more abundant in PFR group and the remaining 3 genera in the VC group. Genus Saccharomyces, a commensal of the gut and skin, was predominantly present in the vitreous of both the cohorts, however it was significantly less abundant in PFR group. Further, significant increase in the genera that have a pathogenic interaction with the host were observed in PFR group. On the whole the mycobiome in both the groups differed significantly and formed two distinct clusters in the heatmap and Principal co-ordinate analysis. These results demonstrate significant changes in the mycobiome from the vitreous of post fever retinitis patients compared to healthy controls thus implying that dysbiotic changes in the fungal vitreous microbiome are associated with PFR.

Carvacrol inhibits the excessive immune response induced by influenza virus A via suppressing viral replication and TLR/RLR pattern recognition

Ethnopharmacological relevanceCarvacrol, a monoterpene phenol from Mosla chinensis Maxim, which is a commonly Chinese herbal medicine. The most important pharmacology of it is dispelling exogenous evils by increasing perspiration. And it is the gentleman medicine in the Chinese herbal compound prescription of Xin-Jia-Xiang-Ru-Yin, mainly for the treatment of summer colds with dampness including influenza virus A infection. Aim of the studyOur preliminary study verified that the Xin-Jia-Xiang-Ru-Yin could inhibit acute lung injury of mice with influenza virus A infection. And there have been some reports implicating the high antimicrobial activity of carvacrol for a wide range of product preservation, but little research including the effects of it on viral infection. The aim of this study was to reveal the antiviral effects of carvacrol, the main constituent in Mosla chinensis Maxim. Materials and methodsInitially, C57BL/6 mice were grouped and intranasally administered FM1 virus to construct viral infection models. After treatment with ribavirin and carvacrol for 5 days, all mice were euthanized, and specimens were immediately obtained. Histology, flow cytometry and Meso Scale Discovery (MSD) analysis were used to analyze pathological changes in lung tissue, the expression levels of cytokines and the differentiation and proportion of CD4+ T cells subsets, while Western blot and qRT-PCR were used to detect the expression of related proteins and mRNA. ResultsCarvacrol attenuated lung tissue damage, the proportions of Th1, Th2, Th17 and Treg in CD4+ T cells and the relative proportions of Th1/Th2 and Th17/Treg cells. Carvacrol inhibited the expression of inflammation-associated cytokines including IFN-γ, IL-2, IL-4, IL-5, IL-12 and TNF-ɑ, IL-1, IL-10, IL-6. Decreased levels of TLR7, MyD88, IRAK4, TRAK6, NF-κB, RIG-I, IPS-I and IRF mRNA in carvacrol-treated mice were observed comparing to the mice in VC group. Further, the total expression of RIG-I, MyD88 and NF-κB proteins had increased significantly in the VC group but reduced obviously in the group treated with ribavirin or carvacrol. ConclusionsThese results indicate that carvacrol is a potential alternative treatment for the excessive immune response induced by influenza virus A infection, the cold-fighting effect of Mosla chinensis Maxim may depend on the anti-virus of carvacrol.

S1175 Clinical Response to Treatment for Acute Kidney Injury (AKI) in Patients With Cirrhosis

INTRODUCTION: The development of acute kidney injury (AKI) is associated with increase in morbidity/mortality in patients with cirrhosis. Revised ICA criteria now classify AKI into three stages (1: Cr increase by 0.3 mg/dl or 50–100% increase from baseline; 2: Cr increase by 100-200%;3: Cr increase by > 200% or Cr > 4 mg/dl) with management based on stage and response to therapy. AIM: To characterize cirrhotic patients admitted with AKI and response to therapy based on ICA AKI stages. METHODS: Retrospective study of inpatients with cirrhosis at single center from 1/2015–05/2019 who received treatment for AKI. Treatment was administered at the discretion of the treating hepatologist and included volume expansion (VE; albumin, lactated ringer, normal saline), vasoconstrictors (VC; midodrine or norepinephrine), and octreotide. Progression and regression of AKI and incidence of liver transplant were analyzed. RESULTS: One hundred seventy-nine patients (97M, 82F, mean age 59) were reviewed (40% Caucasians, 35% Hispanics, 9% Asians, 3% Black). Main cirrhosis etiologies included alcohol (36%), HCV (19%), NASH (11%), cryptogenic (8%) and others. At presentation mean MAP was 69 mmHg and mean Na MELD 31. Mean serum values included Na 130 mEq/l, TB 9 mg/dl, creatinine 2.0 mg/dL, INR 2.0. 135/179 patients had AKI present at admission. 104 (58%) patients developed Stage 1, 43 (24%) developed Stage 2, 32 (18%) developed Stage 3 AKI. 69 patients received VE only, 110 patients received VC and VE (Table 1). In VC group, 37% remained in same stage AKI as at admission, 45% progressed to higher stage AKI, 18% regressed to lower AKI stage (Table 2). Peak stages of AKI were Stage 1 (18%), Stage 2 (16%), and Stage 3 (66%). In VE group, 39% developed regression of AKI, 39% had no change, 22% had progression. Peak stages of AKI were Stage 1 (38%), Stage 2 (23%), Stage 3 (39%). 34% received liver transplant, 49% died, 4% were LTFU, 13% alive. Patients who received VE for AKI had higher response to treatment (P < 0.05) compared to VC group. Patients with AKI stage 2 and stage 3 at admission had higher odds of remaining in same stage of AKI regardless of receiving vasoconstrictors (table 3). Patients with lower MAP at presentation had higher mortality rate (P = 0.002). CONCLUSION: Development of AKI is associated with high rate of mortality and need for LT. Regression to lower stage of AKI noted in 20/179 (11%) of patients receiving vasoconstrictors. The lowest response rates to VC were seen in those with Stage 3 AKI.Table 1Table 2Table 3

Abstract 1732: Hybrid-nanoengineering of an effective combination therapy for pancreatic cancer

Abstract Introduction: A novel proprietary nano-combination therapy (Hybrid-Nanoengineering) combination of paclitaxel and bioavailable curcumin (nano-paclitaxel-curcumin or NPC) has been created and shown to be stable as a dry powder and was effective in treating pancreatic cancer in preclinical models. Experimental Methods: The highly aggressive L3.6PL model of orthotopic pancreatic cancer is typically lethal within 30 days. Three L3.6PL tumor spheroids were introduced into the pancreas of each of 40 nude mice with a vehicle control and treatment group. On 5 of the 20 mice in each treatment group 5x105 cells were implanted to act as sentinels for the orthotopic growth. After 5 days, treatment was initiated with 10 mg/kg (paclitaxel equivalent) every 4 days. The NPC was resuspended with saline to a 1 mg/ml final concentration and the vehicle group received saline (VC) in an equivalent volume. The NPC dose was adjusted on day 17 to 20 mg/kg, q4d as there was no observed flank tumor growth inhibition. Treatment was continued for 25 days before treatment was halted on day 42. Results 1: Tumor response was low at the initial 10 mg/kg dose and after 12 days when the flank tumors had reached ~600 mm3, the treatment was adjusted to 20 mg/kg, q4d. 17/20 of the VC control animals died or were euthanized by day 42, whereas in the NPC group 13/20 animals survived for an unexpected 65% survival rate with this aggressive tumor. The mean orthotopic tumor weight was 2.53 g and 0.81 g for the VC and NPC groups respectively, indicating a significant reduction in tumor volume with treatment in addition to the significant survival benefit with the NPC drug treatment. Results 2: At day 42 a decision to halt the combination therapy was made and two groups of 5 were randomized from the surviving NPC group animals. One group received a nano-curcumin (NC) at 40 mg/kg, q4d and one no treatment (C) for an additional 23 days. Tumors were excised and the average tumor volumes were 1.39 g for the "C" group and 0.54 g for the "NC" animals. Discussion: The NPC formulation provided dramatic and unexpected survival benefit at a relatively low dose of paclitaxel and was well tolerated by the mice already burdened with an aggressive pancreatic tumor. In fact, by allowing the tumors to escape initially at the 10 mg/kg, q4d dose, and reaching nearly 600 mm3 (flank sentinel tumors), this was an extreme challenge and the 20 mg/kg, q4d dose provided a significant benefit to overall survival, tumor burden and animal health. In a previous study with Panc-1 xenograft tumors, a clear benefit was shown with the nano-paclitaxel-curcumin over nab-paclitaxel with similar tumor volumes at half the dose (not shown). Citation Format: Mewa Singh, Michael R. Briggs. Hybrid-nanoengineering of an effective combination therapy for pancreatic cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1732.

PL02: Double Sequential External Defibrillation for Refractory Ventricular Fibrillation: the DOSE VF pilot randomized controlled trial

Introduction: Despite recent advances in resuscitation, some patients remain in ventricular fibrillation (VF) after multiple defibrillation attempts during out-of-hospital cardiac arrest (OHCA). Vector change defibrillation (VC) and double sequential external defibrillation (DSED) have been proposed as alternate therapeutic strategies for OHCA patients with refractory VF. The primary objective was to determine the feasibility, safety and sample size required for a future cluster randomized controlled trial (RCT) with crossover comparing VC or DSED to standard defibrillation for patients experiencing refractory VF. Secondary objectives were to evaluate the intervention effect on VF termination and return of spontaneous circulation (ROSC). Methods: We conducted a pilot cluster RCT with crossover in four Canadian paramedic services and included all treated adult OHCA patients who presented in VF and received a minimum of three defibrillation attempts. In addition to standard cardiac arrest care, each EMS service was randomly assigned to provide continued standard defibrillation (control), VC or DSED. Services crossed over to an alternate defibrillation strategy after six months. Prior to the launch of the trial, 2,500 paramedics received in-person training for VC and DSED defibrillation using a combination of didactic, video and simulated scenarios. Results: Between March 2018 and September 2019, 152 patients were enrolled. Monthly enrollment varied from 1.4 to 6.1 cases per service. With respect to feasibility, 89.5% of cases received the defibrillation strategy they were randomly allocated to, and 93.1% of cases received a VC or DSED shock prior to the sixth defibrillation attempt. There were no reported cases of defibrillator malfunction, skin burns, difficulty with pad placement or concerns expressed by paramedics, patients, families, or ED staff about the trial. In the standard defibrillation group, 66.6% of cases resulted in VF termination, compared to 82.0% in VC and 76.3% of cases in the DSED group. ROSC was achieved in 25.0%, 39.3% and 40.0% of standard, VC and DSED groups, respectively. Conclusion: Findings from our pilot RCT suggest the DOSE VF protocol is feasible and safe. VF termination and ROSC were higher with VC and DSED compared to standard defibrillation. The results of this pilot trial will allow us to inform a multicenter cluster RCT with crossover to determine if alternate defibrillation strategies for refractory VF may impact patient-centered, clinical outcomes

Intermittent administration of parathyroid hormone improves bone quality and quantity around implants in rat tibiae

ObjectivesIntermittent injection of parathyroid hormone (PTH) is used to treat osteoporosis. The concept of bone quality was updated 20 years ago; however, these updates have not been adopted in implant dentistry. This study aimed to investigate the effects of intermittent administration of PTH on bone quality around implants in rat tibiae. MethodsGrade IV-titanium-threaded implants that were 3.5 mm long and 2.0 mm wide were placed in a randomly selected side of the proximal tibiae of 12-week-old female Wistar rats. Three weeks after implant placement, the rats were randomly divided into PTH-administration and saline-injection groups (PTH and VC, respectively; n = 7 per group). Micro-computed tomographical, histomorphometric, and immunohistochemical analyses were performed to evaluate bone quality and quantity surrounding the implants. ResultsPTH significantly increased bone volume and bone mineral density in bones not associated with the implants as compared to these values in the VC group. PTH significantly increased bone area and the amount of collagen within the total inside areas of all implant threads compared to that observed in VC. Moreover, PTH significantly increased the number of osteoblasts, osteocytes, and osteoclasts in the total inside and/or outside areas of all implant threads and altered the ratio of type I and III collagen to total collagen fibers. ConclusionsWithin the limitations of this study, intermittent administration of PTH improved both bone quantity and bone quality based on the types and numbers of bone cells and the types of collagen fibers surrounding implants placed into rat tibiae.

High dose haemodialysis and haemodiafiltration parameters and the relationship with advanced vascular calcification

BackgroundVascular calcification (VC) is a risk factor for cardiovascular disease in end-stage renal disease (ESRD) patients undergoing maintenance haemodialysis (MHD). However, evidence is still insufficient about the association between dialysis parameters and VC. Thus, this study was to evaluate association of dialysis parameters with VC.MethodsWe enrolled 297 ESRD patients undergoing MHD at six distinct centers in Korea. Study participants were categorized into 3 groups by the scoring system of abdominal aortic calcification based on lateral lumbar radiography (no VC group: 0, mild VC group: 1–7 and advanced VC group: 8–24). We compared the features of dialysis parameters according to the severity of VC. Multivariate logistic regression analysis was used to calculate adjusted odd ratios (ORs) and 95% confidence interval (CI) for mild and advanced VC in each haemodialysis parameter (adjusted OR [95% CI]).ResultsPooled Kt/V (spKt/V), equilibrated Kt/V (eKt/V), standard Kt/V (stdKt/V) and the proportion of haemodiafiltration were increased along with the severity of VC. Multivariate regression analysis indicated that advanced VC was positively associated with spKt/V (5.27 [1.51–18.41]), eKt/V (6.16 [1.45–26.10]), stdKt/V (10.67 [1.74–65.52]) and haemodiafiltration (3.27 [1.74 to 6.16]).ConclusionHigh dose dialysis and haemodiafiltration were significantly associated with advanced VC.

Preoperative restrictive pulmonary dysfunction influences the survival after gastrectomy for elderly patients with gastric carcinoma.

We aimed to evaluate the prognostic impact of pulmonary dysfunctions and their relationships with other possible prognostic factors, especially sarcopenia, in elderly patients with gastric carcinoma (GC). In total, 402 elderly GC patients (≥ 75years) who underwent radical gastrectomy were retrospectively reviewed. Restrictive and obstructive pulmonary dysfunction were defined as %VC < 80% and FEV1.0% < 70%, respectively. Forty-two patients (10.4%) had a low %VC, which was associated with ASA-PS, comorbidity and sarcopenia while correlating with neither the FEV1.0% nor pathological variables. The overall survival in the low %VC group was significantly worse than that in the high %VC group, especially in those with pStage I/II diseases. The survival was not stratified by FEV1.0%. Non-gastric cancer-related deaths were more prevalent in the low %VC group than in the high %VC group. The cancer-specific survival showed no significant differences between the two groups. A multivariate analysis revealed a low %VC to be the most powerful predictor of a poor survival among all independent variables, including sex, age, comorbidity, total gastrectomy, and pStage. Patients with both a low %VC and sarcopenia showed an extremely poor survival. Preoperative restrictive pulmonary dysfunction was independently associated with poor survival outcomes, especially when present in combination with sarcopenia, due to an increased risk of death from non-cancer-related causes.

Double sequential external defibrillation for refractory ventricular fibrillation: The DOSE VF pilot randomized controlled trial

ObjectivesThe primary objective was to determine the feasibility and safety of a cluster randomized controlled trial (RCT) with crossover comparing vector change defibrillation (VC) or double sequential external defibrillation (DSED) to standard defibrillation for patients experiencing refractory ventricular fibrillation (VF). Secondary objectives were to assess the rates of VF termination (VFT) and return of spontaneous circulation (ROSC). MethodsWe conducted a pilot cluster RCT with crossover in four Canadian paramedic services including all treated adult OHCA patients who presented in VF and received a minimum of three successive defibrillation attempts. Each EMS service was randomly assigned to provide standard defibrillation, VC or DSED. Agencies crossed over to an alternate defibrillation strategy after six months. Results152 patients were enrolled. With respect to feasibility, 89.5% of cases received the defibrillation strategy they were randomly allocated to, and 93.1% of cases received a VC or DSED shock prior to the sixth defibrillation attempt. There were no safety concerns reported. In the standard group, 66.6% of cases resulted in VFT, compared to 82.0% in VC and 76.3% in the DSED group. ROSC was achieved in 25.0%, 39.3% and 40.0% of standard, VC and DSED groups, respectively. ConclusionsOur findings suggest the DOSE-VF protocol is feasible and safe. Rates of VFT and ROSC were higher in the VC and DSED than standard defibrillation. The results of this pilot trial will allow us to inform a multicenter cluster RCT with crossover to determine if alternate defibrillation strategies for refractory VF may impact clinical outcomes.

P549 A virtual clinic enhances the quality use of anti-TNF dose intensification and rates of treatment success using a treat-to-target approach compared with standard outpatient care in Crohn’s disease

Abstract Background Virtual clinics (VC) represent a novel model-of-care which promote quality use of biologics and facilitate a treat-to-target (T2T) approach. We aimed to evaluate the clinical and process-driven outcomes of intensified anti-TNF therapy for secondary loss of response (SLoR) in a VC compared with standard outpatient care (SoC). Methods A retrospective multicenter, parallel observational cohort study of patients with Crohn’s disease (CD) who underwent anti-TNF dose intensification to address SLoR with up to 2-years of follow-up was undertaken. Objective assessments of disease activity and anti-TNF trough levels at SLoR then during subsequent 6-month semesters were compared longitudinally between VC and SoC groups. ‘Anti-TNF escalation success’ was the primary endpoint, defined as achieved when two consecutive 6-month semesters of objective assessment demonstrated inactive disease. Dose intensification was defined as ‘appropriate’ if there was both objective evidence of disease activity, plus anti-TNF trough levels at or below the lower limit of the therapeutic range prior to intensification. ‘Treatment escalation failure’ was defined by the occurrence of one or more of biologic switching, discontinuation or further intensification; recommencement of corticosteroids, or IBD-related surgery. Results 149 patients (69 VC vs. 80 SoC) underwent infliximab (n = 94) or adalimumab (n = 55) dose intensification with similar baseline patient, disease and treatment characteristics between cohorts. The median duration of follow-up post dose-intensification was 1.9 and 1.5 years for the SoC and VC cohorts respectively (p = 0.37). There were higher rates of appropriate dose intensification (82.6 vs. 40.0%, p &amp;lt; 0.01) across the VC cohort. Higher proportions of anti-TNF escalation success (60.9 v 35.0%, p &amp;lt; 0.01), biomarker remission (i.e., C-Reactive Protein (&amp;lt;5mg/l) and faecal calprotectin (&amp;lt;150 μg/ml) normalisation, log-rank tests, p = 0.06 and p &amp;lt; 0.01 respectively), tight disease monitoring (84.1 vs. 28.8%, p &amp;lt; 0.01) and de-escalation of intensified therapy (21.3 vs. 10.0%, p = 0.03) were also achieved by the VC cohort following dose-intensification. Conclusion This study favoured a VC-led model of care over standard outpatient-based IBD care in facilitating an effective T2T approach to CD management. A VC model of care improved quality use of intensified anti-TNF therapy through processes that promoted appropriate dose intensification and encouraged more frequent anti-TNF dose de-escalation. Moreover, tight semester-based monitoring using a T2T-based strategy facilitated by the VC was associated with improved treatment outcomes.

Selection criteria and colpotomic approach for safe minimally invasive radical hysterectomy in early-stage cervical cancer.

ObjectiveTo evaluate oncologic outcomes of minimally invasive radical hysterectomy (RH) in early cervical cancer before and after the application of parametrial invasion (PMI) criterion on magnetic resonance imaging (MRI) and vaginal colpotomy (VC).MethodsA total of 216 International Federation of Gynecology and Obstetrics stage IB–IIA cervical cancer patients who underwent minimally invasive RH was identified between April 2006 and October 2018. Patients were classified into the pre-PMI intracorporeal or VC (IVC) (n=117) and post-PMI VC groups (n=99). In the pre-PMI IVC group, PMI criterion (intact stromal ring) on MRI was not applied and the patients received IVC. In the post-PMI VC group, surgical candidates were selected using the PMI criterion on MRI and all patients received VC only. Oncologic outcomes and prognostic factors associated with disease recurrence were analyzed.ResultsThe rate of positive vaginal cuff margins in the pre-PMI IVC group was higher than that in the post-PMI VC group (11.1% vs. 1.0%, p=0.003). Two-year disease-free survival was different between the 2 groups (84.5% in pre-PMI IVC vs. 98.0% in post-PMI VC groups, p=0.005). Disrupted stromal ring on MRI (hazard ratio [HR]=20.321; 95% confidence interval [CI]=4.903–84.218; p<0.001) and intracorporeal colpotomy (HR=3.059; 95% CI=1.176–7.958; p=0.022) were associated with recurrence.ConclusionThe intact cervical stromal ring on MRI might identify the low-risk group of patients in terms of PMI and lymphovascular/stromal invasion in early cervical cancer. Minimally invasive RH should be performed in optimal candidates with an intact stromal ring on MRI, using VC.