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The association of fructose and fiber consumption and physical activity with non-alcoholic fatty liver disease in children and adolescents: a cross-sectional study

BMC Nutr. 2024 Oct 21;10(1):140. doi: 10.1186/s40795-024-00943-w.

ABSTRACT

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is emerging as the most prevalent liver disease in overweight and obese children. While no cure exists, dietary and lifestyle modifications have been shown to improve the condition. This study investigates the relationship between fructose and fiber consumption, physical activity, and NAFLD in children.

METHODS: A cross-sectional study was conducted on 378 overweight and obese children aged 6-13 years. NAFLD diagnosis was confirmed via ultrasound, and dietary intake was assessed using a 147-item food frequency questionnaire (FFQ). Physical activity was evaluated using the Modifiable Activity Questionnaire (MAQ). Multivariable logistic regression models were applied to determine the associations.

RESULTS: After excluding 53 participants due to incomplete data, 325 were included in the final analysis. The mean age was 9.2 ± 1.7 years, and 35% had NAFLD. No significant association was found between fructose intake and NAFLD (OR: 0.67, 95% CI: 0.35-1.29, P = 0.221). However, higher intake of legume fiber (OR: 0.48, 95% CI: 0.26-0.90, P = 0.03) and nut fiber (OR: 0.52, 95% CI: 0.28-0.95, P = 0.04) was significantly associated with a reduced risk of NAFLD. Physical activity showed a trend towards reduced NAFLD risk but was not statistically significant after adjustments (OR: 0.53, 95% CI: 0.22-1.04, P = 0.07).

CONCLUSIONS: While fructose intake was not significantly linked to NAFLD in this population, fiber from legumes and nuts appeared protective. Further prospective studies are needed to confirm these findings and clarify the role of physical activity in NAFLD prevention.

PMID:39434194 | DOI:10.1186/s40795-024-00943-w

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Normal saline versus lactated Ringer’s solution for acute pancreatitis resuscitation, an open-label multicenter randomized controlled trial: the WATERLAND trial study protocol

Trials. 2024 Oct 21;25(1):699. doi: 10.1186/s13063-024-08539-2.

ABSTRACT

BACKGROUND: Some evidence suggests that fluid resuscitation with lactated Ringer’s solution (LR) may have an anti-inflammatory effect on acute pancreatitis (AP) when compared to normal saline (NS) and may be associated with a decrease in severity, but existing single-center randomized controlled trials showed conflicting results. The WATERLAND trial aims to investigate the efficacy and safety of fluid resuscitation using LR compared to NS in patients with AP.

METHODS: The WATERLAND trial is an international multicenter, open-label, parallel-group, randomized, controlled, superiority trial. Patients will be randomly assigned in a 1:1 ratio to receive LR versus NS-based fluid resuscitation for at least 48 h. The primary outcome will be moderately severe or severe AP, according to the revision of the Atlanta classification. The secondary objectives of the WATERLAND trial are to determine the effect of LR versus NS fluid resuscitation on several efficacy and safety outcomes in patients with AP. A total sample of 720 patients, 360 in the LR group and 360 in the NS group, will achieve 90% power to detect a difference between the group proportions of 10%, assuming that the frequency of moderately severe or severe AP in the LR group will be 17%. A loss to follow-up of 10% of patients is expected, so the total sample size will be 396 patients in each treatment arm (792 patients overall). The test statistic used is the two-sided Z test with pooled variance set at a 0.05 significance level.

DISCUSSION: The WATERLAND study aims to improve the early management of AP. Fluid resuscitation is an inexpensive treatment available in any hospital center worldwide. If a better evolution of pancreatitis is demonstrated in one of the treatment arms, it would have important repercussions in the management of this frequent disease.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT05781243. Registration date on January 4, 2023. EudraCT number 2023-000010-18, first posted March 23, 2023.

PMID:39434191 | DOI:10.1186/s13063-024-08539-2

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Effects of multicomponent exercise intervention on cardiometabolic risk factors in children and young adults with cerebral palsy: a multiple-baseline trial

BMC Sports Sci Med Rehabil. 2024 Oct 21;16(1):219. doi: 10.1186/s13102-024-01006-0.

ABSTRACT

BACKGROUND: Adults with cerebral palsy (CP) have a high risk of cardiometabolic diseases. It is unknown whether this risk is elevated in young people with CP and whether exercise can reduce this risk. Therefore, we investigated the effects of the EXErcise for Cerebral Palsy (EXECP) intervention on cardiometabolic risk in children and young adults with CP and compared this risk to typically developing children and young adults (TDs).

METHODS: Ambulatory male and female participants with spastic CP, aged 9-24 years, and age- and sex-matched TDs without musculoskeletal disorders were recruited. Participants with CP were measured at baseline, after a three-month control period manifesting normal development, and after the three-month strength, gait, and flexibility training intervention. TDs were measured at baseline and after the control period. They did not attend the intervention. Cardiometabolic risk factors included body weight, body fat percentage, and skeletal muscle mass index assessed with bioimpedance; resting systolic and diastolic blood pressure and aortic pulse wave velocity assessed with a non-invasive oscillometric device; fasting plasma high-density and low-density lipoprotein cholesterol, triglyceride, and glucose levels. Data were analyzed with independent samples t-tests and linear mixed-effects models adjusted for sex and age.

RESULTS: The study involved 18 participants with CP (13 males, 9-22 year, mean 14.2 ± 4.4) and 17 TDs (12 males, 9-22 year, mean 14.6 ± 4.3). At baseline, participants with CP had a 1.0 (95% confidence interval (CI) [-2.0, -0.0]) kg/m2 lower skeletal muscle mass index than TDs. During the control period, no statistically significant between-group differences were observed in the change of any outcome. In the CP group, body weight (β = 1.87, 95% CI [1.04, 2.70]), fat percentage (β = 1.22 [0.07, 2.37], and blood glucose (β = 0.19, 95% CI [0.01, 0.37]) increased, while diastolic blood pressure (β=-2.31, 95% CI [-4.55, -0.06]) and pulse wave velocity (β=-0.44, 95% CI [-0.73, -0.16]) decreased. In the TD group, only body weight increased (β = 0.85, 95% CI [0.01, 1.68]) statistically significantly. In the CP group, no changes were observed during the intervention.

CONCLUSIONS: Young people with and without CP do not exhibit significant differences in most cardiometabolic risk factors. EXECP intervention may attenuate some adverse development trajectories occurring without the intervention but greater volume and intensity of aerobic exercise may be needed to reduce cardiometabolic risk.

TRIAL REGISTRATION: ISRCTN69044459; Registration date 21/04/2017.

PMID:39434176 | DOI:10.1186/s13102-024-01006-0

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Identification of three subtypes of ovarian cancer and construction of prognostic models based on immune-related genes

J Ovarian Res. 2024 Oct 21;17(1):208. doi: 10.1186/s13048-024-01526-w.

ABSTRACT

BACKGROUND: Immunotherapy has revolutionized the treatment of ovarian cancer (OC), but different immune microenvironments often constrain the efficacy of immunotherapeutic interventions. Therefore, there is an imperative to delineate novel immune subtypes for development of efficacious immunotherapeutic strategies.

METHODS: The immune subtypes of OC were identified by consensus cluster analysis. The differences in clinical features, genetic mutations, mRNA stemness (mRNAsi) and immune microenvironments were analyzed among subtypes. Subsequently, prognostic risk models were constructed based on differentially expressed genes (DEGs) of the immune subtypes using weighted correlation network analysis.

RESULTS: OC patients were classified into three immune subtypes with distinct survival rates and clinical features. Different subtypes exhibited varying tumor mutation burdens, homologous recombination deficiencies, and mRNAsi levels. Significant differences were observed among immune subtypes in terms of immune checkpoint expression and immunogenic cell death. Prognostic risk models were validated as independent prognostic factors demonstrated great predictive performance for survival of OC patients.

CONCLUSION: In this study, three distinct immune subtypes were identified based on gene sets related to vaccine response, with the C2 subtype exhibiting significantly worse prognosis. While no statistically significant differences in tumor mutation burden (TMB) were observed across the three subtypes, the homologous recombination deficiency (HRD) score and mRNA stemness index (mRNAsi) were notably elevated in the C2 group compared to the others. Immune infiltration analysis indicated that the C2 subtype may have an increased presence of regulatory T (Treg) cells, potentially contributing to a more favorable response to combination therapies involving PARP inhibitors and immunotherapy. These findings offer a precision medicine approach for tailoring immunotherapy in ovarian cancer patients. Moreover, the C3 subtype demonstrated significantly lower expression levels of immune checkpoint genes, a pattern validated by independent datasets, and associated with a better prognosis. Further investigation revealed that the immune-related gene FCRL5 correlates with ovarian cancer prognosis, with in vitro experiments showing that it influences the proliferation and migration of the ovarian cancer cell line SKOV3.

PMID:39434163 | DOI:10.1186/s13048-024-01526-w

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Malignancy risk factors based on endometrial polyp

BMC Womens Health. 2024 Oct 21;24(1):567. doi: 10.1186/s12905-024-03406-3.

ABSTRACT

AIMS: This study aims to examine cases identified with endometrial polyp and carcinoma originating from polyps in patients presenting with gynaecological problems, and to highlight the significance of risk factors contributing to malignancy.

MATERIALS AND METHODS: The study comprised 203 patients who visited our clinic between January 2019 and 2024 with various gynaecological problems and were identified with endometrial polyps after a clinical, radiographic, and laboratory assessment. We retrospectively analysed data from 191 benign endometrial polyps and hyperplasia without atypia and 12 patients with endometrial polyps and underlying endometrial hyperplasia with atypia and/or endometrial carcinoma, diagnosed histopathologically after hysteroscopic resection, retrieved from our hospital’s electronic archive system. Two hundred three participants were tested in the study, with 191 classifieds with benign tumours and 12 diagnosed with malignant tumours and atypical endometrial hyperplasia (premalignant). Cases were chosen according on consistent criteria for age, BMI, gravida, parity, abortion, educational level, smoking habits, operation history, and co-morbidities. After determining the sample size for the malignant group, patients from the control group were selected to be included in the study. Initially, patients with similar age and BMI distributions were included into the study. Next, the cases were analysed for similarities in gravida, parity, and abortion parameters, and those that matched were chosen. Following this step, the educational status was compared for resemblance, and examples with matching educational status were chosen. Consequently, the study covered a total of 34 patients, with 12 identified with malignant tumours and atypical endometrial hyperplasia (premalignant) and 22 with benign tumours. Two groups of cases were diagnosed with endometrial polyp, and risk factors that may cause the development of endometrial polyp and underlying carcinoma: age, gravida, parity, abortion, education level, smoking, previous operation history, comorbidity, gynaecological complaints, fasting blood sugar, CRP values, haemoglobin, and haematocrit were evaluated in terms of endometrial polyp sizes, endometrial thickness level, and endometrial polyp localization. By examining the pathological risk factors of these cases, particularly during the premenopausal period, the goal is to predict endometrial cancer, the most prevalent gynaecological cancer in women, along with its antecedents, and implement preventive measures proactively.

RESULTS: Age, BMI, gravida, parity, number of abortions, educational status, smoking status, operation history, co-morbidity, and complaint variables did not exhibit a statistically significant difference between the groups (p > 0.05). It was revealed that the FBG level, CRP level, Polyp length and Endometrial thickness level of the malignant group were statistically significantly higher than the benign group (p < 0.01) (p < 0.05). Upon analysing the FBG distribution among groups, it is noted that the ODDS ratio is 10.20 for FBG values of 122.5 and above (95% CI: 1.97 – 52.78). Upon analysing the CRP distribution by groups, it is noted that the ODDS ratio is 231 for CRP values of 9.7 and above (95% CI: 13.15 – 4058.67). Upon analysing the distribution of Polyp length based on groups, it was determined that the ODDS ratio is 13.5 for Polyp lengths of 2.25 and above (95% CI: 2.47 – 73.71). Upon analysing the distribution of EM thickness based on groups, it is shown that the ODDS ratio is 5.25 for EM thicknesses of 11 and above (95% CI: 1.09 – 25.21).

CONCLUSION: Endometrial polyps are common benign growths that are typically not seen as cancer precursors but may be linked to cancer in people with advanced age. It is vital to remember that in cases of endometrial polyps, variables such as increasing polyp length, endometrial thickness, fasting glucose level, and elevated CRP levels are significant risk factors for the development of cancer associated with polyps.

PMID:39434154 | DOI:10.1186/s12905-024-03406-3

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Efficacy and safety of immunosuppressants and monoclonal antibodies in adults with myasthenia gravis: a systematic review and network meta-analysis

J Transl Med. 2024 Oct 21;22(1):955. doi: 10.1186/s12967-024-05751-1.

ABSTRACT

Numerous clinical trials for myasthenia gravis (MG) treatment have been conducted recently, with satisfactory cognitive and clinical results. However, due to the limited evidence for direct comparison of the safety and effectiveness of various drugs, there is a need for further exploration of the advantages and disadvantages of different monoclonal antibodies and immunosuppressants. Thus, in the present network meta-analysis (NMA), we aimed to compare the efficacy and safety of immunosuppressants and monoclonal antibodies in treating MG. We systematically searched for randomized controlled trials published in PubMed, Embase, Web of Science, and the Cochrane Library between January 1, 2000 and March 6, 2024. Statistical analyses were performed using R software (version 4.2.3), JAGS, and STATA (version 15.0). The surface under the cumulative ranking curve (SUCRA) value was calculated to assess the potential efficacy of each drug and the likelihood of adverse events (AEs), with higher SUCRA values indicating better efficacy or a lower likelihood of AEs. This NMA included 21 randomized controlled trials involving 13 drugs and 1,657 patients. Based on changes in Quantitative MG and MG Composite scores, batoclimab was most likely to exert the best therapeutic effects, with SUCRA values of 99% and 92%, respectively. Rozanolixzumab performed better than the other drugs in terms of the MG Activities of Daily Living score (85%). Eculizumab exhibited the highest potential in reducing the 15-item revised version of the MG Quality of Life score (96%). Regarding safety, belimumab had the highest SUCRA value (85%), demonstrating the lowest likelihood of AEs. In conclusion, all immunosuppressants and monoclonal antibodies analyzed in this study were more effective than the placebo in treating MG, with rozanolixzumab and batoclimab potentially being the most effective. Regarding safety, rozanolixzumab exhibited a higher likelihood of AEs than did placebo. The conclusions guide the clinical selection of effective drugs and offer insights for future drug experiments.

PMID:39434135 | DOI:10.1186/s12967-024-05751-1

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A method for determining potential parental contamination: linkage disequilibrium-based log-likelihood ratio analysis for IVF-PGT

Reprod Biol Endocrinol. 2024 Oct 21;22(1):129. doi: 10.1186/s12958-024-01300-z.

ABSTRACT

BACKGROUND: At present, embryologists are attempting to use conventional in vitro fertilization (cIVF) as an alternative to intracytoplasmic sperm injection (ICSI) for preimplantation genetic testing (PGT). However, the potential parental contamination origin of sperm cells and cumulus cells is considered the main limiting factor in the inability of cIVF embryos to undergo PGT.

METHODS: In this study, we established an IVF-PGTA assay for parental contamination tests with a contamination prediction model based on allele frequencies and linkage disequilibrium (LD) to compute the log-likelihood ratio (LLR) under competing ploidy hypotheses, and then verified its sensitivity and accuracy. Finally, comparisons of the effectiveness of SNP-based analysis and LLR-based IVF-PGTA among 40 cIVF embryos was performed, based on both statistical analysis of the parental contamination rate and chromosomal ploidy concordance rate between TE biopsy and ICM isolations.

RESULTS: With IVF-PGTA assay, biopsies with 10% maternal contamination could be detected accurately, and contamination caused by sperm cells could be eliminated completely. Utilizing LLR-based or single Nucleotide Polymorphism (SNP) -based analyses, our comprehensive examination of 40 clinically discarded fresh cIVF embryos revealed an absence of paternal contamination. Strikingly, the LLR-based analysis uniquely revealed a mere instance of 24% maternal contamination within the trophectoderm cell (TE) biopsy of 5* embryo. Furthermore, it was solely through this analysis that embryo (9-F) was identified as a triploid of paternal origin.

CONCLUSIONS: In this study, we developed a new bioinformatics analysis method for identifying parental contamination during IVF-PGT, especially for couples with nonmale factor infertility.

PMID:39434113 | DOI:10.1186/s12958-024-01300-z

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Impact of PARP inhibitors on progression-free survival in platinum-sensitive recurrent epithelial ovarian cancer: a retrospective analysis

World J Surg Oncol. 2024 Oct 21;22(1):276. doi: 10.1186/s12957-024-03562-8.

ABSTRACT

OBJECTIVE: Poly (ADP-ribose) polymerase (PARP) inhibitors such as olaparib and niraparib have shown promise in extending progression-free survival (PFS) in patients with platinum-sensitive recurrent (PSR) epithelial ovarian cancer. In this retrospective study, we aimed to present our own data on the effect of PARP inhibitors on PFS in recurrent epithelial ovarian cancer.

METHODS: 82 patients diagnosed with PSR epithelial ovarian, tubal, or primary peritoneal cancer between May 2017 and September 2023 were initially enrolled from our hospital. However, 16 patients had prior exposure to PARP inhibitors during primary treatment, and 11 were lost to follow-up. Consequently, the study focused on 55 eligible patients. PFS was compared between patients receiving PARP inhibitor maintenance therapy and those who did not.

RESULTS: Among the 55 patients with PSR epithelial ovarian cancer, 18 received olaparib as maintenance therapy, 19 received niraparib, and 18 opted for observation. PARP inhibitor therapy significantly extended PFS (mean 24.0 months) compared to observation (mean 9.0 months, p = 0.0005), regardless of BRCA mutation status (HR = 0.20, 95% CI: 0.08-0.50). Subgroup analysis showed no statistical difference between olaparib and niraparib. Additionally, there was no PFS difference based on BRCA mutation status within both PARP inhibitor groups.

CONCLUSION: Our retrospective study demonstrates that PARP inhibitor maintenance therapy, including olaparib and niraparib, significantly prolongs PFS in patients with PSR epithelial ovarian, tubal, or primary peritoneal cancer, These findings support the broad utilization of PARP inhibitors as a standard maintenance therapy for PSR epithelial ovarian cancer irrespective of BRCA mutation status.

PMID:39434111 | DOI:10.1186/s12957-024-03562-8

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Global cancer statistics for adolescents and young adults: population based study

J Hematol Oncol. 2024 Oct 21;17(1):99. doi: 10.1186/s13045-024-01623-9.

ABSTRACT

BACKGROUND: Accurate and up-to-date estimates of the global cancer burden in adolescents and young adults (AYA) are scarce. This study aims to assess the global burden and trends of AYA cancer, with a focus on socioeconomic disparities, to inform global cancer control strategies.

METHODS: AYA cancer, defined as cancer occurring in individuals aged 15-39, was analyzed using data from the Global Burden of Disease (GBD) 2021 study and the Global Cancer Observatory (GLOBOCAN) 2022 project. We examined the global burden by age, sex, geographic location, and Human Development Index (HDI), as well as its temporal trends. Primary outcomes included age-standardized incidence and mortality rates (ASIR, ASMR) and the average annual percent change (AAPC).

RESULTS: In 2022, an estimated 1,300,196 incidental cases and 377,621 cancer-related deaths occurred among AYAs worldwide, with an ASIR of 40.3 per 100,000 and an ASMR of 11.8 per 100,000. The most common cancers were breast, thyroid, and cervical, while the leading causes of death were breast, cervical, and leukemia. The incidence and mortality were disproportionately higher among females (ASIR: 52.9 for females vs. 28.3 for males; ASMR: 13.1 for females vs. 10.6 for males). Countries with higher HDI experienced a higher incidence of AYA cancers (ASIR: 32.0 [low HDI] vs. 54.8 [very high HDI]), while countries with lower HDI faced a disproportionately higher mortality burden (ASMR: 17.2 [low HDI] vs. 8.4 [very high HDI]) despite their relatively low incidence. Disproportionality and regression measures highlighted significant HDI-related inequalities. AYA cancer incidence was stable from 2000 to 2011 (AAPC: – 0.04) but increased from 2012 to 2021 (AAPC: 0.53), driven by growing gonadal and colorectal cancers. Mortality decreased substantially from 2000 to 2011 (AAPC: – 1.64), but the decline slowed from 2012 (AAPC: – 0.32) probably due to increased deaths from gonadal cancers. These trends varied by sex, cancer type, geography, and HDI.

CONCLUSION: AYA cancers present a significant and growing global burden, with marked disparities across sex, geographic locations, and HDI levels. Policymakers should prioritize equitable resource allocation and implement targeted interventions to reduce these inequalities, particularly in low-HDI regions and with regard to gonadal cancers.

PMID:39434099 | DOI:10.1186/s13045-024-01623-9

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The impact of changing exposure to PM2.5 on mortality for US diplomats with multiple international relocations: a modelling study

Environ Health. 2024 Oct 22;23(1):89. doi: 10.1186/s12940-024-01127-6.

ABSTRACT

BACKGROUND: Current evidence linking long-term exposure to fine particulate matter (PM2.5) exposure and mortality is primarily based on persons that live in the same residence, city and/or country throughout the study, with few residential moves or relocations. We propose a novel method to quantify the health impacts of PM2.5 for United States (US) diplomats who regularly relocate to international cities with different PM2.5 levels.

METHODS: Life table methods were applied at an individual-level to US mortality statistics using the World Health Organization’s database of city-specific PM2.5 annual mean concentrations. Global Burden of Disease concentration-response (C-R) functions were used to estimate cause-specific mortality and days of life lost (DLL) for a range of illustrative 20-year diplomatic assignments for three age groups. Time lags between exposure and exposure-related mortality risks were applied. Sensitivity analysis of baseline mortality, exposure level, C-R functions and lags was conducted. The effect of mitigation measures, including the addition of air purifiers, was examined.

RESULTS: DLL due to PM2.5 exposure for a standard 20-year assignment ranged from 0.3 days for diplomats’ children to 84.1 days for older diplomats. DLL decreased when assignments in high PM2.5 cities were followed by assignments in low PM2.5 cities: 162.5 DLL when spending 20 years in high PM2.5 cities compared to 62.6 DLL when spending one of every four years (5 years total) in a high PM2.5 city for older male diplomats. Use of air purifiers and improved home tightness in polluted cities may halve DLL due to PM2.5 exposure. The results were highly sensitive to lag assumptions: DLL increased by 68% without inception lags and decreased by 59% without cessation lags for older male diplomats.

CONCLUSION: We developed a model to quantify health impacts of changing PM2.5 exposure for a population with frequent relocations. Our model suggests that alternating assignments in high and low PM2.5 cities may help reduce PM2.5-related mortality burdens. Adding exposure mitigation at home may help reduce PM2.5 related mortality. Further research on outcome-specific lag structures is needed to improve the model.

PMID:39434094 | DOI:10.1186/s12940-024-01127-6