HD Group Research Articles

The Efficacy of a Lower Dose of Everolimus in Patients with Advanced Neuroendocrine Tumors

Background: Everolimus at 10 mg daily is approved to treat patients with advanced grade 1/2 neuroendocrine tumors (NETs), although it may lead to significant toxicity. Grade 3 or higher drug-related adverse events and drug discontinuation occur in approximately one-fourth of cases. However, phase I trials have demonstrated that doses from 5 mg daily efficiently inhibit NET cell signaling. Objectives and Methods: This multicenter retrospective study compared the time to treatment failure (TTF) in patients with NETs who received a mean daily dose of 7–10 mg (higher dose [HD]) or ≤6 mg (lower dose [LD]) of everolimus. Results: Ninety-two patients were included: 74 (80%) in the HD group and 18 (20%) in the LD group. At a median follow-up of 4.2 years, the median time to treatment failure (TTF) was 9.2 months for the HD and 7.2 months for the LD groups (p = 0.85). The TTF did not significantly differ between the LD and the HD groups (HR: 1.24; 95% CI: 0.68–2.25; p = 0.47), even after adjusting for age at treatment initiation, the NET grade, and the treatment line. Conclusion: Everolimus doses from 5 to 6 mg/day seem to be equally as effective as higher doses, but lower doses are potentially associated with less toxicity and lower costs. These findings support validation through a randomized clinical trial.

Host–microbe interaction-mediated resistance to DSS-induced inflammatory enteritis in sheep

BackgroundThe disease resistance phenotype is closely related to immunomodulatory function and immune tolerance and has far-reaching implications in animal husbandry and human health. Microbes play an important role in the initiation, prevention, and treatment of diseases, but the mechanisms of host–microbiota interactions in disease-resistant phenotypes are poorly understood. In this study, we hope to uncover and explain the role of microbes in intestinal diseases and their mechanisms of action to identify new potential treatments.MethodsFirst, we established the colitis model of DSS in two breeds of sheep and then collected the samples for multi-omics testing including metagenes, metabolome, and transcriptome. Next, we made the fecal bacteria liquid from the four groups of sheep feces collected from H-CON, H-DSS, E-CON, and E-DSS to transplant the fecal bacteria into mice. H-CON feces were transplanted into mice named HH group and H-DSS feces were transplanted into mice named HD group and Roseburia bacteria treatment named HDR groups. E-CON feces were transplanted into mice named EH group and E-DSS feces were transplanted into mice in the ED group and Roseburia bacteria treatment named EDR groups. After successful modeling, samples were taken for multi-omics testing. Finally, colitis mice in HD group and ED group were administrated with Roseburia bacteria, and the treatment effect was evaluated by H&E, PAS, immunohistochemistry, and other experimental methods.ResultsThe difference in disease resistance of sheep to DSS-induced colitis disease is mainly due to the increase in the abundance of Roseburia bacteria and the increase of bile acid secretion in the intestinal tract of Hu sheep in addition to the accumulation of potentially harmful bacteria in the intestine when the disease occurs, which makes the disease resistance of Hu sheep stronger under the same disease conditions. However, the enrichment of harmful microorganisms in East Friesian sheep activated the TNFα signalling pathway, which aggravated the intestinal injury, and then the treatment of FMT mice by culturing Roseburia bacteria found that Roseburia bacteria had a good curative effect on colitis.ConclusionOur study showed that in H-DSS-treated sheep, the intestinal barrier is stabilized with an increase in the abundance of beneficial microorganisms. Our data also suggest that Roseburia bacteria have a protective effect on the intestinal barrier of Hu sheep. Accumulating evidence suggests that host–microbiota interactions are associated with IBD disease progression.2GpPdtDdh9Lk52sebv8JARVideo

Association Between Gut Microbiome Composition and Physical Characteristics in Patients with Severe Motor and Intellectual Disabilities: Perspectives from Microbial Diversity.

The human gut environment undergoes substantial changes as a host ages. This investigation centered on the gut microbiome diversity among patients with severe motor and intellectual disabilities (SMID), examining the association between the gut microbiome composition and physical characteristics with varying levels of diversity. Fourteen subjects were investigated, with physical and defecation status, blood biochemical test, gut microbiome profiling, and fecal metabolites used to divide the patients into a high-diversity group (HD, eight patients) and a low-diversity group (LD, six patients). Findings indicated that the microbiome of the LD group showed delayed maturation reminiscent of neonates and lactating infants. Analysis of the fecal bile acids (BAs) revealed a markedly diminished proportion of deoxycholic acid in the secondary BAs in the LD group, suggestive of inadequate conversion from primary to secondary BAs. Furthermore, the LD group presented with loose stools. The LD group exhibited a higher degree of physical severity, with all patients bedridden and fed via gastrostomy with only enteral formula received. The composition of the gut microbiome and BAs in the LD group was found to differ from those of healthy individuals and the HD group, indicating a potentially immature gut environment for these individuals.

Analysis of neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as inflammatory biomarkers in chronic kidney disease: impact of parathyroidectomy.

Secondary hyperparathyroidism (SHPT) is one of the causes for inflammation in CKD. We assessed the impact of parathyroidectomy (PTX) on neutrophil-to-lymphocyte (N/L) and platelet-to-lymphocyte (P/L) ratios in SHPT patients. A total of 118 patients [hemodialysis (HD, n = 81), and transplant recipients (TX, n = 37)] undergoing PTX between 2015 and 2021 were analyzed. There was a significant reduction in calcium and PTH levels in both groups, in addition to an increase in vitamin D. In the HD group, PTX did not alter N/L and P/L ratios. In the TX group, there was a reduction in N/L and P/L ratios followed by a significant increase in total lymphocyte count. N/L and P/L ratios are not reliable biomarkers of inflammation in SHPT patients undergoing PTX. Uremia, which induces a state of chronic inflammation in dialysis patients, and the use of immunosuppression in kidney transplant recipients are some of the confounding factors that prevent the use of this tool in clinical practice.

Single-cell transcriptome sequencing reveals altered peripheral blood immune cells in patients with severe tuberculosis

Tuberculosis is a serious global health burden, resulting in millions of deaths each year. Several circulating cell subsets in the peripheral blood are known to modulate the host immune response to Mycobacterium tuberculosis (Mtb) infection in different ways. However, the characteristics and functions of these subsets to varying stages of tuberculosis infection have not been well elucidated. Peripheral blood immune cells (PBICs) were isolated from healthy donors (HD group), individuals with mild tuberculosis (MI group), and individuals with severe tuberculosis (SE group). CD4+ naive T cells and CD8+ T cells were decreased in the SE and MI groups, while CD14+ monocytes were increased in the SE group. Further analysis revealed increased activated CD4+ T cells, transitional CD8+ T cells, memory-like NK cells, and IGHG3highTTNhighFCRL5high B cells were increased in all patients with tuberculosis (SE and MI group). In contrast, Th17 cells, cytotoxic NK cells, and cytotoxic CD4+ T cells were decreased. Moreover, the increase of CD14+CD16+ monocytes correlated with severe tuberculosis, and the GBP5highRSAD2high neutrophils were unique to patients with severe tuberculosis. Cellular communication analysis revealed that CD8+ T cells exhibited the highest incoming interaction strength in the SE group. The increased CD8+ T cell incoming interactions are associated with the MHC-I and LCK pathways, with HLA-(A-E)-CD8A, HLA-(A-E)-CD8B, and LCK-(CD8A+CD8B) being ligand–receptor pairs. Patients with tuberculosis, especially severe tuberculosis, have profound changes in peripheral blood immune cell profiles. CD8+ T cells showed the highest incoming interaction strength in patients with severe tuberculosis, with the main signals being MHC-I and LCK pathways.

Effect of crowding stress on liver health, gut permeability and gut microbiota of genetically improved farmed tilapia (GIFT, Oreochromis niloticus)

This study investigated the effects of crowding stress on liver and gut health in genetically improved farmed tilapia (GIFT, Oreochromis niloticus). Fish averaging 18.90 ± 0.01 g were reared at low (LD, 5 g/L) or high densities (HD, 100 g/L) for 14 days. The analysis revealed that the HD group significantly increased serum cortisol, glucose and adrenocorticotropic hormone (ACTH) levels in GIFT (P < 0.05). Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were elevated in the HD group (P < 0.05). TUNEL staining of liver tissues revealed that the fluorescence intensity indicating apoptosis was significantly higher in the HD group (P < 0.05). Additionally, the HD group exhibited increased expression of p53 and Caspase3 in the liver (P < 0.05). In comparison to the LD group, the HD group showed a significant increase in gut superoxide dismutase (SOD) and catalase (CAT) activities, as well as malondialdehyde (MDA) content (P < 0.05). The expressions of inflammatory-related genes (tnfα, il-1β, il-8, and il-6) and pro-apoptotic genes (p53 and Caspase7) were significantly upregulated in the gut of the HD group (P < 0.05). Serum contents of D-lactate and diamine oxidase (DAO) were significantly elevated in HD group as comparison to LD group (P < 0.05), and significantly higher serum FITC-CM-dextran was observed in HD group versus LD group following oral gavage (P < 0.05). Furthermore, the HD group down-regulated the expressions of gut tight junction proteins (tjp2a, hif-1a, and zo-1) (P < 0.05), and significantly up-regulated the protein expression of phosphorylated myosin light chain 2 (P-MLC2) (P < 0.05). The 16S rDNA gene sequencing results indicated that the relative abundance of Cetobacterium was significantly lower (P < 0.05), and Enterovibrio and Weissella were significantly higher in the HD group (P < 0.05). Overall, crowding stress negatively affects GIFT liver and gut health, which is caused by inducing hepatic and intestinal apoptosis, impairing intestinal barrier function, and disrupting the gut microbiota.

The effect of dietary supplementation of Lycium barbarum leaves on the growth performance, organ indexes and intestinal microflora of rats.

This study was conducted to investigate both fruit and different levels of leaf supplementation on the growth performance, organ indices and intestinal microflora of rats. Twenty-five healthy male Sprague-Dawley rats were randomly divided into five groups. The rats in the control (NC) and positive control (PC) groups were fed by gavage a basal diet and a basal diet with 4 g/kg of L. barbarum fruit homogenate, respectively. The test (LD, MD, and HD) groups were fed basal diets with additional 2, 4, and 8 g/kg of L. barbarum leaf homogenate, respectively. The feeding period was 35 d. The result revealed that the rats in the LD group had the highest average weight gain (p < 0.05). The cardiac and renal indexes in the LD and MD groups were significantly higher than in NC group, respectively (p < 0.05). Diversity analysis revealed that adding low concentrations of L. barbarum leaf homogenates markedly reduced the Shannon index of the rats cecum (p < 0.05). The relative abundance of Verrucomicrobiota was higher in the LD group than those in other groups (p < 0.05). The relative abundance of Actinobacteriota was found significantly higher in PC group than others (p < 0.05). The relative abundance of Akkermansia in LD group was the highest (p < 0.05). The relative abundance of Romboutsia in the PC group was considerably higher than that in other groups. The relative abundance of Candidatus_Saccharimonas in the supplementation groups was appreciably lower than those found in other groups. The relative abundance of Alloprevotella was significantly lower in PC, LD, and MD groups than in NC and HD groups (p < 0.05). The relative abundance of Oscillibacter was significantly higher in HD group than in other groups (p < 0.05). Thus, L. barbarum leaf homogenate fed to rats could increase their growth performance, internal organ weights and additionally enhance the relative abundance of beneficial bacteria. Therefore, based on the obtained data in the current study, a dose of L. barbarum leaf homogenate supplemented with 2 g/kg in diet is recommended, however, further studies are required to confirm, especially in animals.

Does The Serum Zinc Level Affect the Quality of Life in Dialysis Patients? A Report from Iran

Background: Zinc deficiency is a common finding among ESRD and dialysis patients and may affect their quality of life. Objectives: This study aimed to evaluate the serum level of zinc and its correlation with the quality-of-life score in dialysis patients. Methods: A cross-sectional study was conducted in 2018 on dialysis patients. Patients’ information and clinical data, their serum zinc levels, and quality of life assessed by the SF-36 questionnaire were collected. The Spearman correlation test was used to assess the correlation between serum zinc levels and the Physical (PCS) and Mental (MCS) Component Summary scores of the SF-36 questionnaire in general and in different subgroups. P-values less than 0.05 were considered significant. Results: In the HD group, PCS and MCS scores were significantly correlated (P = 0.0001), while this correlation was not observed in the PD group. Additionally, there was a positive correlation between zinc levels and PCS and MCS scores in the HD group but not in the PD group (P = 0.0001). In the PD group, only age negatively correlated with the PCS score (P = 0.03), without any other significant correlations with other study variables. Multivariate analysis revealed that zinc level was an independent predictor of PCS and MCS scores in the HD group (P &lt; 0.001). In the PD group, age (P = 0.02) and zinc level (P = 0.03) were independent predictors of PCS score but not MCS score. Conclusions: There is a positive correlation between serum zinc levels and both the physical and mental aspects of quality of life in dialysis patients.

Can Vitamin D Supplementation Improve Inflammation in Relapsing-Remitting Multiple Sclerosis Patients?

(1) Background: Studies indicate that vitamin D (VitD) may reduce inflammation in multiple sclerosis (MS). The aim of the study was to assess the effect of supplementation with different doses of VitD on inflammation in relapsing-remitting MS (RRMS) patients. (2) Methods: The effect of 6-month supplementation with different doses of oral VitD (2000 IU/day) in a high-dose group (HD, n = 23) and a low-dose group (15,960 IU/month) (LD, n = 29) on selected markers of inflammation was assessed in 52 RRMS patients. (3) Results: Females constituted the majority of participants (63.46%). The median age [years] was 39.5 [34.5-49.8] and 47 [40.0-55.0] in the HD and LD groups, respectively. Significant differences were observed in age (p = 0.028), body weight (p = 0.014) and height (p = 0.001) between the study groups. Considering the BMI, statistically significant differences were not found (p = 0.496). The median 25(OH)D concentration [ng/mL] increased from 23.023 [15.578-25.76] in the HD group and 28.318 [20.644-32.232] in the LD group to 29.819 [24.937-38.064] and 30.837 [25.382-36.789], respectively (p < 0.01), and the increase was significantly higher in the HD group (p = 0.01). Hypovitaminosis D was found in most patients (71.2%) initially, and serum VitD levels were still <30.0 ng/mL in 46.2% of the participants at the follow-up. A significant increase in the levels of IL-4, IL-6, IL-17A, IL-22, IL-23 and TNF -α [pg/mL] and a decrease in IL-10 levels were reported during the study (p < 0.01). A significant positive correlation was observed between 25(OH)D serum levels and sCD40L (R = 0.33; p < 0.05) and TNF-α (R = 0.28; p < 0.05), and a significant negative correlation was reported between 25(OH)D and IL-23 (R = -0.32; p < 0.01) at the beginning of the study. (4) Conclusions: In RRMS patients, the doses of VitD were probably too low to induce beneficial effects on inflammation. Further studies are warranted to determine the effect of VitD supplementation on inflammatory markers in MS patients.

Safety and immunogenicity of the intranasal H3N2 M2-deficient single-replication influenza vaccine alone or coadministered with an inactivated influenza vaccine (Fluzone High-Dose Quadrivalent) in adults aged 65–85 years in the USA: a multicentre, randomised, double-blind, double-dummy, phase 1b trial

Older adults (aged ≥65 years) show increased susceptibility to severe disease with influenza virus infection, accounting for 70-85% of annual influenza-related fatalities in the USA. Stimulating mucosal antibodies and T cells might enhance the low vaccine effectiveness seen in older adults for currently licensed inactivated influenza vaccines, which induce mainly serum antibodies. We aimed to evaluate the safety and immunogenicity of the intranasal H3N2 M2-deficient single-replication (M2SR) vaccine, alone or coadministered with a licensed inactivated influenza vaccine (Fluzone High-Dose Quadrivalent; hereafter referred to as Fluzone HD), in older adults. In this multicentre, randomised, double-blind, double-dummy, phase 1b trial, individuals aged 65-85 years who were considered healthy or with stable chronic conditions with no recent (<6 months) influenza vaccinations were recruited from five clinical trial sites in the USA and randomly assigned (3:3:3:1) using a permuted block design to receive the H3N2 M2SR vaccine and Fluzone HD, the H3N2 M2SR vaccine and placebo, Fluzone HD and placebo, or placebo alone. All participants received a single intranasal spray and a single intramuscular injection, whether active or placebo, to maintain masking. The primary outcome was to assess the safety of H3N2 M2SR, administered alone or with Fluzone HD, in the safety analysis set, which included all participants who were randomly assigned and received treatment. Serum and mucosal antibodies were assessed as a secondary endpoint, and cell-mediated immunity as an exploratory endpoint, in participants in the per-protocol population, which included individuals in the safety analysis set without major protocol deviations. This trial is registered with ClinicalTrials.gov, NCT05163847. Between June 14 and Sept 15, 2022, 305 participants were enrolled and randomly assigned to receive the H3N2 M2SR vaccine plus placebo (n=89), H3N2 M2SR vaccine plus Fluzone HD (n=94), Fluzone HD plus placebo (n=92), or placebo alone (n=30). All randomly assigned participants were included in the safety analysis set. The most frequently reported local symptoms up to day 8 in groups that received M2SR were rhinorrhoea (43% [38 of 89] in the H3N2 M2SR plus placebo group and 38% [36 of 94] in the H3N2 M2SR plus Fluzone HD group), nasal congestion (51% [45 of 89] and 35% [33 of 94]), and injection-site pain (8% [seven of 89] and 49% [46 of 94]), and the most frequently reported solicited systemic symptoms were sore throat (28% [25 of 89]) for M2SR and decreased activity (26% [24 of 94]) for the M2SR plus Fluzone HD group. In the Fluzone HD plus placebo group, the most frequently reported local symptom was injection-site pain (48% [44 of 92]) and systemic symptom was muscle aches (22% [20 of 92]). The frequency of participants with any treatment-emergent adverse event related to vaccination was low across all groups (2-5%). One serious adverse event was reported, in a participant in the Fluzone HD plus placebo group. M2SR with Fluzone HD induced seroconversion (≥four-fold increase in haemagglutination inhibition antibodies from baseline to day 29) in 44 (48%) of 91 participants, compared with 28 (31%) of 90 participants who seroconverted in the Fluzone HD plus placebo group (p=0·023). M2SR with Fluzone HD also induced mucosal and cellular immune responses. The H3N2 M2SR vaccine coadministered with Fluzone HD in older adults was well tolerated and provided enhanced immunogenicity compared with Fluzone HD administered alone, suggesting potential for improved efficacy of influenza vaccination in this age group. Additional studies are planned to assess efficacy. US Department of Defense.

Effect of Dialysis Modality and Membrane Permeability on FGF 23 Level and Cardiovascular Calcification in ESRD Patients

Abstract Introduction Cardiovascular disease is the most common cause of death in patients with chronic kidney disease (CKD) and vascular calcification is one of the strongest predictors of cardiovascular risk. The prevalence of vascular calcification increases as glomerular filtration rate (GFR) declines and calcification occurs years earlier in CKD patients than in the general population. (26). Aim of the Study To study the effect of hemodialysis modality in controlling FGF-23and to determine the impact of FGF23 on cardiovascular calcification Patients and Methods We selected 50 patients ESRD maintained on hemodialysis divided into 2 groups, Group 1: comprised of 25 patients maintained on hemodialysis with high flux dialyzer and Group 2: comprised of 25 maintained on weekly session of hemodiafiltration and comparison between both groups regarding FGF23 serum level in addition to cardiovascular screening for calcifications using ECHO, Carotid intima-media thickness, and carotid duplex. Results we found that Post dialysis FGF23 was significantly lower in “hemodiafiltration patients” than ‘hemodialysis patients” and Reduction ratio was significantly higher in “hemodiafiltration patients”(P &amp;lt; 0.001).ECHO score and carotid duplex score were insignificantly different between both groups, but carotid intima-media thickness was significantly higher in haemodialysis patients (P value 0.035). Post HDF FGF 23 had a significant positive correlation with IMT (r = 0.579, P = 0.008). Serum FGF23 post-HD and HDF had significant positive correlation with serum Calcium (r = 0.659, P = 0.002), (r = 0.474, P = 0.035), PTH (r = 0.485, P = 0.03), (r = 547, P = 0.013) and CRP (r = 0.646, P = 0.002), (r = 707, P &amp;lt; 0.001) and serum Phosphorus (r = 0.462, P = 0.04), (r = 478, P = 0.033) respectively. In HD group Carotid Duplex Score had significant positive correlation with serum Ca (r = 0.469, P = 0.037), while in HDF group Carotid Duplex Score had significant positive correlation with PTH (r = 0.59, P = 0.006). Conclusion Using online HDF technique showed a significant reduction of FGF23 and improvement of carotid intima-media thickness calcification score.

Effects of Astragalus complanatus Flavonoids (FAC) on Immune Function and Liver Fibrosis in Alcohol-Induced Liver Rats by Mediating TNF-α Signaling Pathway

This study investigated the effects of Astragalus complanatus flavonoids on immune function and liver fibrosis in alcohol-induced liver rats. 80 healthy ACL female rats were grouped as healthy group, alcohol liver group (AL group), low-dose group (30 mg/kg) (LD group), and high-dose group (120 mg/kg) (HD group). ALT and AST were measured by CD4+ and CD8+ were measured by flow cytometry. Radioimmunoassay measured HA, LN, PC-III, and IV-c, while Western blot measured TNF-α/TLR4/MYD88/NF-kB. The liver cells from healthy group were neatly arranged with clear boundaries, disordered in the alcohol liver group with blurred lobules, with a large number of vacuoles and inflammatory cell infiltrations. The liver cells from 2 intervention groups were relatively clearly arranged and intracellular vacuoles were reduced. The ALT and AST levels in AL group were highest than healthy group (P &lt; 0.05), followed by LD (P &lt; 0.05) and HD group (P &lt; 0.05). Compared with healthy group, the CD4+ and CD4+/CD8+ content in the AL group decreased and CD8+ increased (P &lt; 0.05). In comparison with AL group, CD4+ and CD4+/CD8+ level increased and CD8+ decreased (P &lt; 0.05) in LD and HD group with increased HD group (P &lt; 0.05). The expressions of HA, LN, PC-III, IV-c, TNF-α, TLR4, MYD88, and NF-kB in healthy group were lower than AL group (P &lt; 0.05) and lowly expressed in AL group and highly expressed in HD group (P &lt; 0.05). The flavonoids of Astragalus complanatus can therefore reduce the degree of liver fibrosis in alcohol-induced rats and improve the immunity of rats by inhibiting cytokines in the TNF-α signaling pathway (Fig. 1).

Effects of Different Stocking Densities on the Growth, Antioxidant Status, and Intestinal Bacterial Communities of Carp in the Rice–Fish Co-Culture System

Common carp (Cyprinus carpio) is a freshwater fish commonly farmed in rice fields, yet there were few studies on the intestinal functions and microbial community structure of common carp in the rice–carp co-culture system. Therefore, this study aimed to explore the effects of different stocking densities on the growth, antioxidant status, and intestinal bacterial composition of common carp in this system. This study was divided into three different stocking densities, including low density (LD, 10 fish, 52.9 g/m2), medium density (MD, 20 fish, 105.8 g/m2), and high density (HD, 30 fish, 158.7 g/m2), with a culturing period of 60 days. The results indicated that HD treatment inhibited the growth of common carp, as evidenced by the reduced final weight, WG, and SGR. In serum, the TG content in the HD group and the Cor content in the MD group were significantly increased. Meanwhile, HD treatment induced oxidative stress, manifesting specifically as increased SOD and CAT activities in the intestine or serum while reducing Gpx, GSH, and T-AOC in the serum. The 16S rDNA analysis indicated that the Simpson and Shannon indices of intestinal microbiota in the HD group were significantly higher than those in the LD group. At the phylum level, Proteobacteria, Cyanobacteria, and Firmicutes were dominant microbial communities in two groups. In addition, there was a significant difference between the two groups in the abundances of Actinobacterota and Bifidobacterium. Based on growth performances, biochemical indicators, and microbial diversity in rice–carp co-culture, low density (52.9 g/m2) may be more suitable in the rice–carp co-culture systems. In summary, this study contributes to a better understanding of common carp response to different stocking densities in the rice–carp co-culture system.

Gastrointestinal delivery of bitter hop extract reduces appetite and food cravings in healthy adult women undergoing acute fasting

BackgroundDietary restrictions or reductions such as fasting for weight loss are often difficult to adhere to due to increased appetite and food cravings. Recently, gastrointestinal delivery of bitter hops has been shown to be effective at reducing appetite in men. Our aim was to determine the effect of a bitter hop extract on appetite and cravings in women, using a 24 h, water-only fast. MethodsThis was a randomized, double-blind, cross-over treatment study. Thirty adult women were recruited and required to fast for 24 h from 1800 h to 1800 h on three occasions and given an ad libitum meal to break each fast. Treatments of either a placebo or one of two doses (high dose; HD: 250 mg or low dose; LD: 125 mg) of a bitter hop-based appetite suppressant (Amarasate®) were given twice per day at 16 and 20 h into the fast. ResultsThe HD and LD treatment groups exhibited a significant (p < 0.05) reduction in appetite and cravings for food when compared to the placebo control. Two participants reported loose stools and one reported heartburn while on the HD treatment, and one participant reported loose stools while on the LD treatment. ConclusionThese data suggest that appetite suppressant co-therapy may be useful in reducing hunger during fasting in women and shows that gastrointestinal delivery of bitter compounds may also be an effective method of reducing cravings for food.This trial received ethical approval from the Northen B New Zealand Human Disability and Ethics committee (Northern B Health and Disability Ethics Committee (2022 EXP 10995) and was prospectively registered with the Australian New Zealand Clinical Trial Registry (ACTRN12622000107729).

Effect of desflurane anesthesia on flash visual evoked potential monitoring in patients undergoing spine surgery: study protocol for a randomized controlled trial

BackgroundFlash visual evoked potentials (FVEPs) are a reliable method for protecting visual function during spine surgery in prone position. However, the popularization and application of FVEPs remain limited due to the unclear influence of various anesthetics on FVEPs. Exploring the effects of anesthetic drugs on FVEP and establishing appropriate anesthesia maintenance methods are particularly important for promoting and applying FVEP. According to the conventional concept, inhaled narcotic drugs significantly affect the success of FVEP monitoring, FVEP extraction, and interpretation. Nonetheless, our previous study demonstrated that sevoflurane-propofol balanced anesthesia was a practicable regimen for FVEPs. Desflurane is widely used in general anesthesia for its rapid recovery properties. As the effect of desflurane on FVEP remains unclear, this trial will investigate the effect of different inhaled concentrations of desflurane anesthesia on amplitude of FVEPs during spine surgery, aiming to identify more feasible anesthesia schemes for the clinical application of FVEP.Methods/ designA total of 70 patients undergoing elective spinal surgery will be enrolled in this prospective, randomized controlled, open-label, patient-assessor-blinded, superiority trial and randomly assigned to the low inhaled concentration of desflurane group (LD group) maintained with desflurane-propofolremifentanil-balanced anesthesia or high inhaled concentration of desflurane group (HD group) maintained with desflurane-remifentanil anesthesia maintenance group at a ratio of 1:1. All patients will be monitored for intraoperative FVEPs, and the baseline will be measured half an hour after induction under total intravenous anesthesia (TIVA). After that, patients will receive 0.5 minimum alveolar concentration (MAC) of desflurane combined with propofol and remifentanil for anesthesia maintenance in the LD group, while 0.7–1.0 MAC of desflurane and remifentanil will be maintained in the HD group. The primary outcome is the N75-P100 amplitude 1 h after the induction of anesthesia. We intend to use the dual measure evaluation, dual data entry, and statistical analysis by double trained assessors to ensure the reliability and accuracy of the results.DiscussionThis randomized controlled trial aims to explore the superiority effect of low inhaled concentration of desflurane combined with propofolremifentanil-balanced anesthesia versus high inhaled concentration of desflurane combined with remifentanil anesthesia on amplitude of FVEPs. The study is meant to be published in a peer-reviewed journal and might guide the anesthetic regimen for FVEPs. The conclusion is expected to provide high-quality evidence for the effect of desflurane on FVEPs and aim to explore more feasible anesthesia schemes for the clinical application of FVEPs and visual function protection.Trial registrationThis study was registered on clinicaltrials.gov on July 15, 2022. ClinicalTrials.gov Identifier: NCT05465330.

Standard-definition White-light, High-definition White-light versus Narrow-band Imaging Endoscopy for Detecting Colorectal Adenomas: A Multicenter Randomized Controlled Trial.

This study aimed to compare the performance of standard-definition white-light endoscopy (SD-WL), high-definition white-light endoscopy (HD-WL), and high-definition narrow-band imaging (HD-NBI) in detecting colorectal lesions in the Chinese population. This was a multicenter, single-blind, randomized, controlled trial with a non-inferiority design. Patients undergoing endoscopy for physical examination, screening, and surveillance were enrolled from July 2017 to December 2020. The primary outcome measure was the adenoma detection rate (ADR), defined as the proportion of patients with at least one adenoma detected. The associated factors for detecting adenomas were assessed using univariate and multivariate logistic regression. Out of 653 eligible patients enrolled, data from 596 patients were analyzed. The ADRs were 34.5% in the SD-WL group, 33.5% in the HD-WL group, and 37.5% in the HD-NBI group (P=0.72). The advanced neoplasm detection rates (ANDRs) in the three arms were 17.1%, 15.5%, and 10.4% (P=0.17). No significant differences were found between the SD group and HD group regarding ADR or ANDR (ADR: 34.5% vs. 35.6%, P=0.79; ANDR: 17.1% vs. 13.0%, P=0.16, respectively). Similar results were observed between the HD-WL group and HD-NBI group (ADR: 33.5% vs. 37.7%, P=0.45; ANDR: 15.5% vs. 10.4%, P=0.18, respectively). In the univariate and multivariate logistic regression analyses, neither HD-WL nor HD-NBI led to a significant difference in overall adenoma detection compared to SD-WL (HD-WL: OR 0.91, P=0.69; HD-NBI: OR 1.15, P=0.80). HD-NBI and HD-WL are comparable to SD-WL for overall adenoma detection among Chinese outpatients. It can be concluded that HD-NBI or HD-WL is not superior to SD-WL, but more effective instruction may be needed to guide the selection of different endoscopic methods in the future. Our study's conclusions may aid in the efficient allocation and utilization of limited colonoscopy resources, especially advanced imaging technologies.

#605 Shared decision-making intervention regarding dialysis modality in patients with CKD stage 5

Abstract Background and Aims Patients with kidney failure must make complicated decisions about the dialysis modalities used either at home or in-hospital. Different options have varying levels of impact on patients’ physical and psychological conditions and their social life. The purpose of this study was to evaluate the implementation of an intervention designed to achieve shared decision making (SDM) in patients’ options for dialysis. Method SDM was performed after consent was written for stage 5 chronic kidney disease patients before dialysis, and 435 cases were performed in 408 patients from December 16, 2019 to June 30, 2021. Among these, 101 patients were compared by SDM measurement scale, patient satisfaction, disease recognition scale survey, and dialysis method. Results The average age of participants was 56 years, with a gender composition of 55 males (54.5%) and 46 females (45.5%). Following SDM, the final dialysis methods decided upon by patients and clinicians were peritoneal dialysis (67 patients, 66.3%), hemodialysis (22 patients, 21.8%), and kidney transplantation (1 patient, 1.0%). Looking at the items, “My doctor and I chose treatment together” (94% in the PD group, 87.5% in the HD group, P = .012) and “My doctor and I agreed on a course of treatment” (97% in the PD group, 81.3% in the HD group, P = .058), the group of patients that selected treatment with PD had a significantly higher percentage of positive answers of 4 points or higher in comparison to the group of patients that selected HD Conclusion Among participating patients, SDM was effective when used to decide on dialysis treatment, and patients were satisfied with the dialysis method decision process. On the disease awareness scale, those who participated in this project had relatively high positive and low negative perceptions, so it can be concluded that SDM was relatively effective. The implementation of SDM was helpful in selecting patients’ best dialysis methods, and SDM scale results were higher in the peritoneal dialysis group than in the hemodialysis group.

#2677 A propensity score-matched analysis of kidney replacement therapy outcomes for older adults stratified by frailty severity

Abstract Background and Aims Older people living with frailty who receive kidney replacement therapy (KRT) experience higher mortality and hospital readmission compared to their non-frail counterparts [1–3]. Shared decision making with older people regarding the optimal KRT modality (haemodialysis [HD], peritoneal dialysis [PD], or kidney transplant [TX]) can present challenges due to the lack of research comparing KRT modalities stratified by frailty severity. The Hospital Frailty Risk Score (HFRS), which uses routinely collected clinical data to categorise frailty severity, has been shown to predict outcomes in advanced chronic kidney disease (CKD) [4]. However, the HFRS has not been used to compare outcomes across KRT modalities. This single-centre project aims to explore outcomes between KRT modalities for older people stratified by HFRS frailty severity. Method Adults aged 60 years or older starting KRT at our institution between December 2012 and January 2022 were included. HFRS was calculated at first estimated glomerular filtration rate (eGFR) result below 15 mL/min/1.73 m2 and at start of KRT. Patients were stratified by KRT modality and their frailty severity (categorized as low, intermediate, or high according to their HFRS score). TX patients were then matched to 1:2 to HD patients and 1:1 to PD patients, based on patient age, HFRS category, and Charlson Comorbidity Index (CCI) at KRT start. Outcomes of interest were hospital readmission and mortality, both overall and within 1 year of KRT initiation. Descriptive statistics compared HD, PD, and TX groups. Results Twenty TX, 20 PD, and 40 HD matched patients were included. Age (HD vs PD vs TX: 68.5 vs 67.6 vs 68.3 years, p = 0.50), proportion of males (57.5% vs 70.0% vs 55.0%, p = 0.66), and CCI (15.0 vs 13.0 vs 13.0, p = 0.95) were similar between cohorts. Frailty, as assessed by the HFRS, worsened or remained the same for most patients in all 3 cohorts between first eGFR &amp;lt; 15 and KRT start (81.0% vs 93.0% vs 83.0%, p = 0.61). All patients were either of low (85.0% vs 80.0% vs 85.0%) or intermediate (15.0% vs 20.0% vs 15.0%) frailty status at time of KRT start and the proportion of patients in each category did not vary with modality (p = 0.92). Re-hospitalization within 1 year of starting KRT was similar between groups (32.5% vs 25.0% vs 10.0%, p = 0.12). Kaplan-Meier survival analyses also demonstrated similar survival among groups at 1 year (75.0% vs 95.0% vs 90.0%, log-rank p = 0.09), but better survival among TX patients overall (0.0% vs 66.1% vs 79.4%, log-rank p = 0.02). Overall and 1 year Kaplan-Meier survival for patients stratified by KRT modality and HFRS are shown in Fig. 1. Conclusion TX may optimize longer term survival for older people with low and intermediate frailty status and kidney failure. Furthermore, the HFRS appears to be a useful prognostic tool that could inform shared decision making with older patients regarding KRT modality choice.

184 The metabolism of vitamin D is modulated by vitamin C supplementation during porcine reproductive and respiratory syndrome challenge in post-weaning piglets

Abstract This study evaluated the impact of different dietary vitamin D sources combined or not with vitamin C on serum 25(OH)D3 concentrations and the expression of genes related to antimicrobial peptides and to the metabolism of vitamin D, vitamin C, calcium (Ca), and phosphorus (P). From weaning (d 21) until d 68, 27 piglets were fed a post-weaning diet supplemented with: 1,500 IU of vitamin D3 (CTR; n = 9); 200 IU of vitamin D3 + 2,000 IU of 25(OH)D3 (HD; n = 8); or HD + 500 mg/kg of vitamin C (HD+C; n = 10). From d 40 to 68 piglets were exposed to porcine reproductive and respiratory syndrome (PRRS) using a natural disease challenge model. At d 68, after blood collection, all piglets were euthanized for the collection of lung and kidney samples. The concentrations of serum 25(OH)D3 were determined by HPLC and the mRNA expression of genes of interest was assessed by qPCR. Data were analyzed in a one-way analysis of variance with three treatments. At d 40 (after 19 d of supplementation), serum 25(OH)D3 concentrations were greatest for HD+C (22.48 ± 1.25 ng/mL), intermediate for HD (17.43 ± 0.84 ng/mL), and least for CTR (8.54 ± 0.65 ng/mL) treatments (P &amp;lt; 0.01). At d 68 (after 28 d of PRRS challenge) these values were greatest for HD (14.64 ± 2.77 ng/mL), intermediate for CTR (6.22 ± 0.59 ng/mL), and least for HD+C (2.18 ± 0.13 ng/mL; P &amp;lt; 0.01). No treatments effect was detected on pulmonary CYP27B1, RXRα, SLC23A1, RIGI, PR-39, and pBD1. In lungs, VDR expression was least for HD+C (P ≤ 0.06) whereas MDA5 expression was greatest for HD+C (P ≤ 0.07), and SLC23A2 expression was greatest for HD (P ≤ 0.09; Table 1). No treatments effect was detected on expression of renal FGFR1, KL, RXRα, SLC23A1, SLC23A2, and TPRV5. In kidney, CYP27B1 expression was greatest for HD+C groups (P = 0.03) and CYP24A expression was greatest for HD (P = 0.01). Renal EGR1 and NPT2c expressions were greatest for CTR groups and least for HD+C (P = 0.09) whereas WNK4 expression was greatest for HD+C and least for CTR (P = 0.10). Renal VDR expression was greatest for HD groups and least for HD+C (P ≤ 0.05). In conclusion, vitamin C supplementation increased serum 25(OH)D3 concentrations in pre-challenged piglets. These concentrations were reduced by vitamin C supplementation after PRRS challenge, which may be related to a greater synthesis of the active form of vitamin D in the kidney. Little effects were detected on pulmonary antimicrobial peptides, but the gene expression related to renal P reabsorption was influenced by HD+C whereas Ca reabsorption was apparently not impacted by treatments.

Aspirin is Not for Everyone: Discharge to Non-home Facilities After Total Hip and Knee Arthroplasty Increases Risk of Venous Thromboembolism

BackgroundPatients discharged to non-home facilities (NHD) after total hip arthroplasty (THA) and total knee (TKA) arthroplasty experience higher rates of adverse events and may require more aggressive venous thromboembolism (VTE) chemoprophylaxis. Our aim was to compare the rates of VTE in NHD patients and those discharged home (HD) after THA/TKA. Our secondary aim was to determine VTE rates within HD and NHD groups when stratified by chemoprophylactic regimen. MethodsA retrospective cohort of primary THA and TKA patients were stratified into HD and NHD, then allocated into groups by chemoprophylactic regimen on discharge: aspirin alone (AA), more aggressive (MA) chemoprophylaxis, and other regimens (other). The primary outcome was VTE. Rates of VTE in HD and NHD patients, as well as AA and MA regimens, were analyzed using a generalized linear regression model. ResultsSix thousand three hundred seventy-nine patients were included with 1.03% experiencing VTE. HD had lower rates of VTE compared to NHD (0.83% vs 2.17%, P < .001). AA had similar rates of VTE compared to MA (0.99% vs 1.08%, P = .82). NHD patients had a lower VTE rate with MA vs AA prophylaxis (1.47% vs 3.83%, P = .016). HD patients treated with AA vs MA had no difference in VTE rates (0.76% vs 0.96%, P = .761). ConclusionsNHD patients have higher rates of VTE than HD patients. However, NHD patients have significantly lower rates of VTE on MA chemoprophylaxis compared to those on AA. Providers should consider prescribing MA VTE chemoprophylaxis for NHD patients. Prospective, randomized studies are necessary to confirm these recommendations.