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Alterations of gut microbiota are associated with blood pressure: a cross-sectional clinical trial in Northwestern China.
Lv, J, Wang, J, Yu, Y, Zhao, M, Yang, W, Liu, J, Zhao, Y, Yang, Y, Wang, G, Guo, L, et al
Journal of translational medicine. 2023;21(1):429
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Hypertension (HTN) is a complex and modifiable risk factor for cardiovascular diseases (CVDs) and stroke, while a diverse range of endogenous and environmental factors contribute to both HTN onset and progression. The adult gut microbiota (GM) consists of trillions of microorganisms and maintains the gut immunity and whole-body homeostasis. The aim of this study was to investigate the GM characteristics in HTN subjects in Northwestern China, and evaluate the associations of GM with blood pressure levels based on sex differences. This study was a cross-sectional study. Participants were randomly selected for the HTN and control groups. A total of 36 HTN subjects (24 females and 12 males) and 18 controls (9 females and 9 males) were randomly selected for metagenomic analysis. Results showed a positive association between GM characteristics and alterations and HTN in both females and males. Thus, GM dysbiosis underlies HTN pathogenesis. Authors conclude that further studies are needed to elucidate the underlying mechanisms and potential therapeutic interventions targeting GM for HTN prevention and management
Abstract
BACKGROUND The human gut microbiota (GM) is involved in the pathogenesis of hypertension (HTN), and could be affected by various factors, including sex and geography. However, available data directly linking GM to HTN based on sex differences are limited. METHODS This study investigated the GM characteristics in HTN subjects in Northwestern China, and evaluate the associations of GM with blood pressure levels based on sex differences. A total of 87 HTN subjects and 45 controls were recruited with demographic and clinical characteristics documented. Fecal samples were collected for 16S rRNA gene sequencing and metagenomic sequencing. RESULTS GM diversity was observed higher in females compared to males, and principal coordinate analysis showed an obvious segregation of females and males. Four predominant phyla of fecal GM included Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria. LEfSe analysis indicated that phylum unidentified_Bacteria was enriched in HTN females, while Leuconostocaceae, Weissella and Weissella_cibaria were enriched in control females (P < 0.05). Functionally, ROC analysis revealed that Cellular Processes (0.796, 95% CI 0.620 ~ 0.916), Human Diseases (0.773, 95% CI 0.595 ~ 0.900), Signal transduction (0.806, 95% CI 0.631 ~ 0.922) and Two-component system (0.806, 95% CI 0.631 ~ 0.922) could differentiate HTN females as effective functional classifiers, which were also positively correlated with systolic blood pressure levels. CONCLUSIONS This work provides evidence of fecal GM characteristics in HTN females and males in a northwestern Chinese population, further supporting the notion that GM dysbiosis may participate in the pathogenesis of HTN, and the role of sex differences should be considered. Trial registration Chinese Clinical Trial Registry, ChiCTR1800019191. Registered 30 October 2018 - Retrospectively registered, http://www.chictr.org.cn/ .
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Antitumor Activity and Safety of Dostarlimab Monotherapy in Patients With Mismatch Repair Deficient Solid Tumors: A Nonrandomized Controlled Trial.
André, T, Berton, D, Curigliano, G, Sabatier, R, Tinker, AV, Oaknin, A, Ellard, S, de Braud, F, Arkenau, HT, Trigo, J, et al
JAMA network open. 2023;(11):e2341165
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Abstract
IMPORTANCE Mismatch repair deficiency (dMMR) occurs in various cancers, and these tumors are attractive candidates for anti-programmed cell death 1 therapies, such as dostarlimab, a recently approved immune checkpoint inhibitor. OBJECTIVE To assess the antitumor activity and safety of dostarlimab in patients with advanced or recurrent dMMR solid tumors. DESIGN, SETTING, AND PARTICIPANTS The GARNET trial was a phase 1, open-label, single-group, multicenter study that began enrolling May 8, 2017. Participants had advanced or recurrent dMMR and microsatellite instability-high (MSI-H) or polymerase epsilon (POLE)-altered solid tumors. The data cut for this interim analysis was from November 1, 2021, with median follow-up of 27.7 months. INTERVENTIONS Patients received 500 mg of dostarlimab intravenously every 3 weeks for 4 doses, then 1000 mg every 6 weeks until disease progression, discontinuation, or withdrawal. MAIN OUTCOMES AND MEASURES The primary objective was to evaluate objective response rate and duration of response in patients with dMMR solid tumors by blinded independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1. RESULTS The efficacy population included 327 patients (median [range] age, 63 [24-85] years; 235 [71.9%] female; 7 [2.1%] Asian, 6 [1.8%] Black, and 206 [63.0%] White patients), with 141 patients (43.1%) with dMMR endometrial cancer, 105 patients (32.1%) with dMMR colorectal cancer, and 81 patients (24.8%) with other dMMR tumor types. All patients had at least 1 previous line of therapy. Objective response rate assessed per blinded independent central review for dMMR solid tumors was 44.0% (95% CI, 38.6% to 49.6%). Median duration of response was not reached (range, ≥1.18 to ≥47.21 months); 72.2% of responders (104 of 144) had a response lasting 12 or more months. Median progression-free survival was 6.9 months (95% CI, 4.2 to 13.6 months); probability of progression-free survival at 24 months was 40.6% (95% CI, 35.0% to 46.1%). Median overall survival was not reached (95% CI, 31.6 months to not reached). The most frequent immune-related adverse events were hypothyroidism (25 [6.9%]), alanine aminotransferase increase (21 [5.8%]), and arthralgia (17 [4.7%]). No new safety concerns were identified. CONCLUSIONS AND RELEVANCE In this nonrandomized controlled trial, dostarlimab was a well-tolerated treatment option with rapid, robust, and durable antitumor activity in patients with diverse dMMR solid tumors. These findings suggest that dostarlimab provides meaningful long-term benefit in a population with high unmet need. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02715284.
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Effects of an urban forest healing program on cancer-related fatigue in cancer survivors.
Park, KH, Lee, H, Park, EY, Sung, JH, Song, MK, An, M, Bang, E, Baek, SY, Do, Y, Lee, S, et al
Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer. 2023;(1):4
Abstract
PURPOSE This study aimed to examine the effects of an eight-session structured urban forest healing program for cancer survivors with fatigue. BACKGROUND Cancer-related fatigue (CRF) is a complex and multifactorial common symptom among cancer survivors that limits quality of life (QoL). Although health benefits of forest healing on physiological, physical, and psychological aspect as well as on the immune system have been reported in many studies, there is limited evidence on the efficacy of specialized forest program for cancer survivors. METHOD A single-blinded, pre-test and post-test control group clinical trial was conducted with -75 cancer survivors assigned to either the forest healing group or the control group. The intervention was an eight-session structured urban forest program provided at two urban forests with easy accessibility. Each session consists of three or four major activities based on six forest healing elements such as landscape, phytoncides, anions, sounds, sunlight, and oxygen. Complete data of the treatment-adherent sample (≥ 6 sessions) was used to examine whether sociodemographic, clinical, physiological (respiratory function, muscle strength, balance, 6-min walking test) and psychological (distress, mood state, sleep quality, QoL) characteristics at baseline moderated the intervention effect on fatigue severity at 9 weeks. RESULTS Significant time-group interactions were observed muscle strength, balance, 6-min walking test, distress, fatigue, moods, and QoL. The mean difference in fatigue between pre- and post-forest healing program was 9.1 (95% CI 6.2 to 11.9), 11.9 (95% CI 7.6 to 16.1) in moods, and -93.9 (95% CI -123.9 to -64.0) in QoL, showing significant improvements in forest healing group, but no significant improvements in the control group. CONCLUSION This study suggests that a forest healing program positively impacts the lives of cancer survivors, by addressing both physical and psychological challenges associated with CRF. TRIAL REGISTRATION NUMBER KCT0008447 (Date of registration: May 19, 2023).
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The Effect of Cold-Water Hydrotherapy According to Sebastian Kneipp for Immune Stimulation: A Nonrandomized, Controlled, Explorative, Mixed-Methods Clinical Study.
Schulte, K, Blakeslee, SB, Kandil, FI, Stock-Schröer, B, Seifert, G
Journal of integrative and complementary medicine. 2022;(9):749-756
Abstract
Highlights Home-based hydrotherapy leads to fewer missed kindergarten-days in total. In the application group, more fever days could be registered. Hydrotherapy, according to the hormesis principle by Sebastian Kneipp, aims to reduce infections of the lower respiratory tract. Parents participation motivated by increase in applicable health knowledge for their children. Objectives: This study investigates the effect of cold-water hydrotherapy stimulation according to the hormesis principle by Sebastian Kneipp on the number of missing kindergarten-days, fever days, and respiratory tract infections in children aged 3-6 years. Study design: A nonrandomized, controlled, explorative, mixed-methods clinical study. Intervention: The hydrotherapeutic intervention treated children aged 3-6 years with Kneipp arm affusions over 6 weeks. The control group received no intervention. Number of missed kindergarten-days, fever days, and respiratory tract infections were assessed by means of a digital diary. Through a self-developed structured questionnaire, sociodemographic data of both groups were compared and reason for participation in the study was recorded and qualitatively evaluated. Results: Twenty children participants and their parents in the intervention group and 18 in the control group were evaluated. The intervention was conducted at home by the parents. Statistical analysis revealed no significant differences between the groups but still showed intermediate effect sizes (indicating an underpowered study). These effect sizes point to a potentially lower proportion of children in the application group versus the control group with missed kindergarten-days in total (d = 0.67), days missed due to fever (d = 0.29), and infections of the lower respiratory tract (d = 0.60). In a future study, these parameters will thus serve as promising factors for evaluation. Parent's stated reasons for participation interest were to improve health, increase their own health knowledge, and because of their interest in alternative therapies and to support research. Conclusions: Cold-water hydrotherapy stimulation, according to the hormesis principle by Sebastian Kneipp, did reduce the number of days absent in kindergarten in total in the intervention group and lower respiratory tract infections occurred less frequently. Parent' participation interest demonstrated a desire to increase health literacy and implement this with their own children. Due to the small sample size, the results should be interpreted cautiously. Clinical Trial Registration Number: German Register of Clinical Trials (DRKS): ID 00017562.
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Influence of dietary supplementation of short-chain fatty acid sodium propionate in people living with HIV (PLHIV).
Brauckmann, V, Nambiar, S, Potthoff, A, Höxtermann, S, Wach, J, Kayser, A, Tiemann, C, Schuppe, AK, Brockmeyer, NH, Skaletz-Rorowski, A
Journal of the European Academy of Dermatology and Venereology : JEADV. 2022;(6):881-889
Abstract
BACKGROUND Non-AIDS-associated chronic diseases in HIV+ patients have been on the rise since the advent of antiretroviral therapy. Especially cardiovascular diseases and disruption in the gastrointestinal tract have limited health-related quality of life (QoL). Several of those complications have been associated with chronic systemic inflammation. Short-chain fatty acids (SCFA), with propionate as one of the major compounds, have been described as an important link between gut microbiota and the immune system, defining the pro- and the anti-inflammatory milieu through direct and indirect regulation of T-cell homeostasis. The effects of dietary supplementation of sodium propionate (SP) in people living with HIV (PLHIV) have not yet been investigated prior to this study. OBJECTIVES To investigate the impact of SP uptake among PLHIV and its relevance to improve QoL, the study aimed to investigate metabolic, immunological, microbiome and patient-reported QoL-related changes post-SP supplementation with follow-up. METHODS A prospective, non-randomized, controlled, monocentric interventional study was conducted in WIR, Center for Sexual Health and Medicine, in Bochum, Germany. 32 HIV+ patients with unaltered ART-regimen in the last three months were included. Participants were given SP for a duration of 12 weeks in the form of daily oral supplementation and were additionally followed-up for another 12 weeks. RESULTS The supplementation of SP was well tolerated. We found an improvement in lipid profiles and long-term blood glucose levels. A decrease in pro-inflammatory cytokines and a depletion of effector T cells was observed. Regulatory T cells and IL-10 decreased. Furthermore, changes in taxonomic composition of the microbiome during follow-up were observed and improvement of items of self-reported life-quality assessment. CONCLUSION Taken together, the beneficial impact of SP in PLHIV reflects its potential in improving metabolic parameters and modulating pro-inflammatory immune responses. Thus, possibly reducing the risk of cardiovascular disorders and facilitating long-term improvement of the gut flora.
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The Curative Effect of Shuangshen Decoction Combined with Immunological Preparations in the Treatment of Pediatric Nephrotic Syndrome and Its Influence on the Rate of Complicated Infection and Recurrence.
Han, N, Xie, J, Li, Q, Li, H, Wang, X, Sheng, Y
Computational and mathematical methods in medicine. 2022;:3355462
Abstract
BACKGROUND To explore the curative effect of Shuangshen Decoction combined with immunological preparations in the treatment of pediatric nephrotic syndrome and its influence on concurrent infection and recurrence rate. METHODS Ninety children with nephrotic syndrome were divided into the routine group and the combined group. The routine group received conventional treatment and immune agents, and the combined group was treated with Shuangshen Decoction on the basis of the routine group. The clinical indexes of the two groups were analyzed and followed up. The infection rate and recurrence rate were calculated. RESULTS The TCM syndrome scores in the combined group were significantly lower than those in the routine group. The total effective rate of the combined group was significantly higher than that of the routine group. The recurrence rate and infection rate of the combined group were significantly lower than those of the routine group. The incidence of adverse reactions in the combined group was significantly lower than that in the routine group. CONCLUSION Shuangshen Decoction combined with immune preparations is effective in treating pediatric nephrotic syndrome and can reduce the incidence of adverse reactions, infection rate, and recurrence rate.
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Effects of nutritional support combined with insulin therapy on serum proteins, inflammatory factors, pentraxin-3, and serum amylase levels in patients with diabetic ketoacidosis complicated with acute pancreatitis.
Yin, C, Lu, S, Wei, D, Xiong, J, Zhu, L, Yan, S, Meng, R
Medicine. 2021;(51):e27920
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To explore the effects of nutritional support combined with insulin therapy on serum protein, procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), pentraxin-3 (PTX-3), and serum amylase (AMS) levels in patients with diabetic ketoacidosis complicated with acute pancreatitis.A total of 64 patients with diabetic ketoacidosis complicated with acute pancreatitis admitted to our hospital from January 2018 to February 2019 were enrolled in this prospective study. They were divided into the study group and the control group according to the random number table method, with 32 patients in each group. Patients in the study group were given nutritional support combined with insulin therapy, and patients in the control group were given insulin therapy.There were no significant differences in general data including age, gender, body mass index, course and type of diabetes, acute physiology and chronic health evaluation II, RANSON, CT grades between the 2 groups before treatment (all P > .05). After 7 days of treatment, the clinical efficacy of the study group was significantly higher than that of the control group (study group vs control group, 94.44% vs 75.00%, P < .05). After 7 days of treatment, the levels of prealbumin and albumin in the study group were significantly higher than those in the control group (P < .05). After 7 days of treatment, the levels of PCT, CRP, TNF-α, PTX-3, and AMS in the 2 groups were significantly lower than those before treatment (P < .05), and the levels of PCT, CRP, TNF-α, PTX-3, and AMS in the study group were significantly lower than those in the control group. After 7 days of treatment, the levels of IgG, IgM, and IgA in the 2 groups were significantly higher than those before treatment, and the levels of IgG, IgM, and IgA in the study group were significantly higher than those in the control group (P < .05).Nutritional support combined with insulin is obviously effective in the treatment of diabetic ketoacidosis complicated with acute pancreatitis, which can improve serum protein levels, reduce inflammatory response, improve immune function, and is worthy of clinical application.
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Analgesic effects of breast- and formula feeding during routine childhood immunizations up to 1 year of age.
Viggiano, C, Occhinegro, A, Siano, MA, Mandato, C, Adinolfi, M, Nardacci, A, Caiazzo, AL, Viggiano, D, Vajro, P
Pediatric research. 2021;(5):1179-1184
Abstract
BACKGROUND Data on analgesic effects of breast/formula milk sucking while receiving routine childhood immunizations are available only in early infancy, have rarely been compared in the same study, and are not accompanied by information on mothers' satisfaction/acceptance. Here we aimed to compare the analgesic effect of both methods vs. held-only controls up to 1 year of age, and verify mothers' satisfaction. METHODS Two to 12 months children subjected to vaccine were allocated into three groups: breastfed, formula-fed, and held-only controls. A video recording was performed to analyze pain parameters: crying latency/duration and specific scales [FLACC (Face, Legs, Activity, Cry, and Consolability), NIPS (Neonatal Infant Pain Scale)]. After the procedure, mothers filled in a satisfaction questionnaire. RESULTS One-hundred and sixty-two children were recruited: 54 breastfed, 35 formula fed, and 73 controls. Breastfed showed the longest crying latency, and together with formula fed, had the shortest duration and lowest pain scores. Most mothers appreciated not only the respective feeding-mediated pain mitigation method used, but also the simply-holding procedure. In all cases, they felt reassured, with an unexpected frequent underestimation of their child's pain during the shot. CONCLUSIONS The analgesic effect of breastfeeding during vaccination extends also to children >6 months old, and is obtained by formula too. Embracing the child may help to reassure mothers. IMPACT We confirmed the analgesic effect of breastfeeding during the vaccination procedures in early infancy. We show for the first time that this effect is extended also to children up to 1 year of age, and it may be obtained by formula feeding as well. Most mothers appreciated pain mitigation not only through feeding, but also the simply-holding procedure. In all cases, mothers felt reassured, with an unexpected frequent underestimation of their child' pain during the shot. The promotion of these easily feasible and well-accepted strategies should be further encouraged within health professionals during vaccination procedures.
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Cytokine-specific autoantibodies shape the gut microbiome in autoimmune polyendocrine syndrome type 1.
Petersen, AØ, Jokinen, M, Plichta, DR, Liebisch, G, Gronwald, W, Dettmer, K, Oefner, PJ, Vlamakis, H, Chung, DC, Ranki, A, et al
The Journal of allergy and clinical immunology. 2021;(3):876-888
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BACKGROUND Gastrointestinal dysfunction is a frequent and disabling manifestation of autoimmune polyendocrine syndrome type 1 (APS-1), a rare monogenic multiorgan autoimmune disease caused by the loss of central AIRE-controlled immune tolerance. OBJECTIVES This study aimed to understand the role of the gut microbiome in APS-1 symptoms and potentially alleviate common gastrointestinal symptoms by probiotic intervention. METHODS This study characterized the fecal microbiomes of 28 patients with APS-1 and searched for associations with gastrointestinal symptoms, circulating anti-cytokine autoantibodies, and tryptophan-related metabolites. Additionally, daily doses of the probiotic Lactobacillus rhamnosus GG were administered for 3 months. RESULTS Of 581 metagenomic operational taxonomic units (mOTUs) characterized in total, 14 were significantly associated with patients with APS-1 compared with healthy controls, with 6 mOTUs depleted and 8 enriched in patients with APS-1. Four overabundant mOTUs were significantly associated with severity of constipation. Phylogenetically conserved microbial associations with autoantibodies against cytokines were observed. After the 3-month intervention with the probiotic L rhamnosus GG, a subset of gastrointestinal symptoms were alleviated. L rhamnosus GG abundance was increased postintervention and corresponded with decreased abundances of Alistipes onderdonkii and Collinsella aerofaciens, 2 species positively associated with severity of diarrhea in patients with APS-1. CONCLUSIONS The APS-1 microbiome correlates with several APS-1 symptoms, some of which are alleviated after a 3-month L rhamnosus GG intervention. Autoantibodies against cytokines appear to shape the gut microbiome by positively correlating with a taxonomically consistent group of bacteria.
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Use of the Tissue Common Rejection Module Score in Kidney Transplant as an Objective Measure of Allograft Inflammation.
Zarinsefat, A, Guerra, JMA, Sigdel, T, Damm, I, Sarwal, R, Chan-On, C, Szabo, G, Aguilar-Frasco, JL, Ixtlapale-Carmona, X, Salinas-Ramos, C, et al
Frontiers in immunology. 2020;:614343
Abstract
Long-term kidney transplant (KT) allograft outcomes have not improved as expected despite a better understanding of rejection and improved immunosuppression. Previous work had validated a computed rejection score, the tissue common rejection module (tCRM), measured by amplification-based assessment of 11 genes from formalin-fixed paraffin-embedded (FFPE) biopsy specimens, which allows for quantitative, unbiased assessment of immune injury. We applied tCRM in a prospective trial of 124 KT recipients, and contrasted assessment by tCRM and histology reads from 2 independent pathologists on protocol and cause biopsies post-transplant. Four 10-μm shaves from FFPE biopsy specimens were used for RNA extraction and amplification by qPCR of the 11 tCRM genes, from which the tCRM score was calculated. Biopsy diagnoses of either acute rejection (AR) or borderline rejection (BL) were considered to have inflammation present, while stable biopsies had no inflammation. Of the 77 biopsies that were read by both pathologists, a total of 40 mismatches in the diagnosis were present. The median tCRM scores for AR, BL, and stable diagnoses were 4.87, 1.85, and 1.27, respectively, with an overall significant difference among all histologic groups (Kruskal-Wallis, p < 0.0001). There were significant differences in tCRM scores between pathologists both finding inflammation vs. disagreement (p = 0.003), and both finding inflammation vs. both finding no inflammation (p < 0.001), along with overall significance between all scores (Kruskal-Wallis, p < 0.001). A logistic regression model predicting graft inflammation using various clinical predictor variables and tCRM revealed the tCRM score as the only significant predictor of graft inflammation (OR: 1.90, 95% CI: 1.40-2.68, p < 0.0001). Accurate, quantitative, and unbiased assessment of rejection of the clinical sample is critical. Given the discrepant diagnoses between pathologists on the same samples, individuals could utilize the tCRM score as a tiebreaker in unclear situations. We propose that the tCRM quantitative score can provide unbiased quantification of graft inflammation, and its rapid evaluation by PCR on the FFPE shave can become a critical adjunct to help drive clinical decision making and immunosuppression delivery.