BMC Medicine最新文献

Background: Celiac disease (CeD) is an autoimmune condition characterized by an aberrant immune response triggered by the ingestion of gluten, which damages epithelial cells lining the small intestine. Small intestinal epithelial cells (sIECs) play key roles in the enzymatic digestion and absorption of nutrients, maintaining gut barrier integrity, and regulating immune response. Chronic inflammation and tissue damage associated with CeD disrupt the intricate network of metabolic processes in sIECs that support these functions, impairing their ability to perform their essential roles. However, the specific disrupted metabolic processes underlying sIECs dysfunction in CeD remain largely undefined.

Methods: To address this knowledge gap, personalized, sex-specific genome-scale models of sIECs metabolism were constructed using transcriptional data from intestinal biopsies of 42 subjects with active CeD, CeD in remission (on a gluten-free diet), and non-CeD controls. These models were computationally simulated under relevant dietary conditions for each group of subjects to assess the activity of several metabolic tasks essential for sIECs function and to profile metabolite secretion into the bloodstream and intestinal lumen.

Results: Significant alterations in the activity of 28 essential metabolic tasks were observed in active CeD and remission CeD, impacting critical processes integral to sIECs function such as oxidative stress regulation, nucleotide synthesis and DNA repair, energy production, and polyamine and amino acid metabolism. Additionally, altered secretion profiles of several metabolites, encompassing amino acids, vitamins, polyamines, lipids, and fatty acids, into the bloodstream were detected in active CeD and remission CeD patients. These findings were partially supported by comparisons with independent external datasets and further corroborated through extensive review of existing literature. Furthermore, a drug target analysis was performed, identifying 22 FDA-approved drugs that target genes encoding impaired sIECs metabolic functions in CeD, potentially helping to restore their normal activity.

Conclusions: This study unveils new insights into the metabolic reprogramming of sIECs in CeD, highlighting specific dysregulated metabolic processes that compromise cellular functions essential for gut health. These findings offer a foundation for developing therapeutic interventions targeting impaired metabolic processes in CeD.

Background: Infrared molecular fingerprinting has been identified as a new minimally invasive technological tool for disease diagnosis. While the utility of cross-molecular infrared fingerprints of serum and plasma for in vitro cancer diagnostics has been recently demonstrated, their potential for stratifying and predicting the prognosis of lung cancer remained unexplored. This study investigates the capability of this approach to predict survival and stratify lung cancer patients.

Methods: Molecular fingerprinting through vibrational spectroscopy is employed to probe lung cancer. Fourier-transform infrared (FTIR) spectroscopy is applied to blood sera from 160 therapy-naive lung cancer patients, who were followed for up to 4 years. Machine learning is then utilized to evaluate the prognostic utility of this new approach. Additionally, a case-control study involving 501 individuals is analyzed to investigate the relationship between FTIR spectra and disease progression.

Results: Overall, we establish a strong correlation between the infrared fingerprints and disease progression, specifically in terms of tumor stage. Furthermore, we demonstrate that infrared fingerprinting provides insights into patient survival at performance levels comparable to those of tumor stage and relevant blood-based biomarkers.

Conclusions: Identifying the combined capacity of infrared fingerprinting to complement primary lung cancer diagnostics and to assist in the assessment of lung cancer survival represents the first proof-of-concept study underscoring the potential of this profiling platform. This may provide new avenues for the development of tailored, personalized treatment decision-making.

Background: Demonstrating mortality reduction in new colorectal cancer (CRC) screening programs through randomized clinical trials (RCTs) is challenging. We systematically reviewed single-round program performance outcomes using a stepwise approach proposed by the World Endoscopy Organization CRC Screening Committee framework.

Methods: The MEDLINE, EMBASE, Central, and Ichushi Web databases were searched until October 28, 2024, to find RCTs comparing guaiac-based and immunochemical fecal occult blood testing (gFOBT and FIT), flexible sigmoidoscopy (FS), computed tomographic colonography (CTC), and total colonoscopy (TCS). Paired reviewers screened studies, extracted data, and assessed bias risk. A Bayesian random-effects network meta-analysis was conducted, and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. The primary outcome was advanced neoplasia (AN) detection, and the secondary outcomes were participation and colorectal cancer (CRC) detection, all during the first screening round.

Results: Eighteen RCTs (437,072 invitees) were included. The risk of bias was low or raised some concerns for screening participation, but it was high for detection outcomes. In the network meta-analysis of 15 RCTs not allowing crossover, the FIT-based program had a higher AN detection rate than the gFOBT-based program (relative risk [RR] 2.48; 95% credible interval [CrI] 1.52-4.21; moderate certainty). AN detection rates were not different in the CTC- (RR 1.01; CrI 0.43-2.23; very low certainty) and TCS-based (RR 1.03; CrI 0.54-1.78; low certainty) programs compared with the FS-based program. All the visualization modality programs had higher AN detection rates than the FIT-based program (FS: RR 2.13 [CrI 1.38-3.77]; CTC 2.16 [1.11-4.51]; and TCS 2.19 [1.43-3.48]; all with low certainty). Low event rates precluded definitive conclusions regarding CRC detection (very low to low certainty). The TCS-based program had the worst participation rate (very low to low certainty). Comparative data allowing crossover were limited.

Conclusions: This is the first network meta-analysis that evaluates program-level initial performance indicators. FIT-based programs likely detect more AN cases than gFOBT-based programs, while FS-, CTC-, and TCS-based programs may outperform FIT. Due to limitations in first-round results, long-term outcomes should be assessed after 10-15 years.

Background: The communication of health and risk information is an integral part of patient-physician interaction. Effective communication of risk information for cardiovascular diseases and diabetes has been shown to improve medication adherence, increase physical activity levels, and improve dietary control. Patients who understand their risk profile are better able to work towards modifying their lifestyle behaviours as part of a shared decision-making process with physicians. This scoping review examines the evidence on patient-physician risk communication strategies, approaches and interventions for CVDs and diabetes management in primary care and secondary outpatient settings.

Methods: A comprehensive database search for quantitative and qualitative studies was conducted in PubMed, Embase, Web of Science, Scopus, CINAHL, PsycINFO, and Cochrane Library from 1st January 2000 to 3rd October 2023. Two reviewers independently performed the screening of articles. Studies that report on patient-physician risk communication processes were included. Data were extracted and analysed using descriptive summaries and narrative synthesis. Results are reported in accordance with PRISMA-ScR guidelines. Included articles were appraised for quality following JBI critical appraisal and MMAT tools.

Results: A total of 8378 articles published between 1st Jan 2000 to 3rd October 2023 were screened. After a full-text review of 88 articles, a total of 30 articles, consisting of 15 qualitative, 14 quantitative and 1 mixed method studies were included. Common areas of inquiry among articles include: (1) understanding and recalling risk information, (2) strategies and approaches used by physicians to communicate risk, and (3) interventions to improve the communication of risk. Studies reveal how physicians use a range of strategies, approaches and interventions to discuss risk with patients. We present and discuss each theme narratively in detail.

Conclusions: There is a critical need for further research into risk communication strategies for cardiovascular diseases (CVDs) and diabetes, with a focus on developing targeted approaches that enhance patients' understanding of their risk profiles. Evidence-based guidelines should assist healthcare professionals improve risk communication within clinical settings, with the goal of facilitating patient comprehension of health risks that can sustain lifestyle changes. Misalignment in communication may lead to dissatisfaction and confusion, which may impede the effective management of chronic conditions.

Background: Cardiometabolic disorders are the leading cause of mortality and contribute substantially to the First Nations Health Gap in Australia. Central obesity is the major contributor to metabolic syndrome. We investigated factors associated with central obesity and how normal-weight central obesity is associated with cardiometabolic disorders among Aboriginal and Torres Strait Islander Australians (hereafter respectfully referred to as 'Indigenous Australians').

Methods: This study used the 2018-2019 Australian Bureau of Statistics (ABS) National Aboriginal and Torres Strait Islander Health Survey dataset. A total of weighted 4864 Indigenous adults (18 + years) were included. Normal-weight central obesity refers to individuals with a normal body mass index (BMI) but with an elevated waist circumference (WC ≥ 102 cm for males and ≥ 88 cm for females). Main outcomes included self-reported type 2 diabetes, hypertension, high cholesterol and heart disease. Multi-level logistic regression models were used to examine the relationship between explanatory variables and outcomes.

Results: The overall prevalence of central obesity was 46.2% (95% confidence interval [CI]: 42.8, 49.72) in males and 67.7% (95% CI: 64.90, 70.4) in females. Physical inactivity increased the risk of central obesity in males (odds ratio [OR] = 1.34; 95% CI: 1.09, 1.65), while daily consumption of soft drinks was associated with central obesity in females (OR = 1.35; 95% CI: 1.12, 1.62). Males living in very remote areas had a lower risk of central obesity, while females in very remote areas had a higher risk. Our findings also showed that females with normal-weight central obesity had a higher risk of hypertension (OR = 3.29; 95% CI: 1.95, 9.62) and higher total cholesterol (OR = 4.62; 95% CI: 2.22, 9.62). Similarly, males with normal-weight central obesity were associated with a higher risk of type 2 diabetes (OR = 4.13; 95% CI: 1.23, 13.94).

Conclusions: This was the first study to report that approximately 12% of Indigenous Australians with normal BMI have central obesity. Relying solely on BMI to identify such high-risk individuals may be inadequate for early intervention. Public health initiatives targeting obesity should include individuals with a normal BMI and central obesity.

Background: Appropriate complementary feeding practices (CFPs) play a key role for ensuring optimal health, growth and development for children 6-23 months. The purpose of this study was to determine the prevalence and associated factors of CFPs of mothers or primary caregivers having children 6-23 months in Thanh Phu rural district of Ben Tre province, Vietnam.

Methods: Three hundred fifty eight child-mother pairs participated in a cross-sectional study. Weight and height of children were measured by trained nutritionists using standard measurement tools and procedure. Mothers or primary caregivers were interviewed about maternal, child, and household characteristics, awareness of the food environment, household food insecurity (HFI), and CFPs using a structured questionnaire. Chi square test, Fisher exact test, t-test, and multivariate logistic regression were used to evaluate associations between CFPs and independent variables.

Results: The percentages of children with appropriate minimum dietary diversity (MDD), minimum meal frequency (MMF), and minimum acceptable diet (MAD) were 71.5%, 40.8%, and 31.6%, respectively. MDD was negatively associated with younger child, the child's sickness in the last 2 weeks, caregivers being fathers, not breastfeeding, lower monthly household income, and use of untreated drinking water after controlling for covariates (p < 0.05). Factors associated with poorer MMF included older child, not breastfeeding, and maternal biological status. Conversely, purchasing foods at the street vendors and appropriate MDD was positively associated with better MMF (p < 0.05). Maternal biological status, marital status of mothers, breastfeeding, and HFI were all associated with MAD (p < 0.05).

Conclusions: These results revealed that inappropriate complementary feeding practices among children aged 6-23 months in rural disadvantaged areas of Southern region remained a significant challenge for nutrition improvement of young children in Vietnam. Child age, HFI, use of untreated drinking water, lower monthly income, mother's marital status, not breastfeeding, and source of purchased foods were associated with poor CFPs. Solutions for improving CFPs for children should address these underlying causes.

Background: This study aimed to determine whether associations of antenatal maternal anaemia with smaller corpus callosum, caudate nucleus, and putamen volumes previously described in children at age 2-3 years persisted to age 6-7 years in the Drakenstein Child Health Study (DCHS).

Methods: This neuroimaging sub-study was nested within the DCHS, a South African population-based birth cohort. Pregnant women were enrolled (2012-2015) and mother-child dyads were followed prospectively. A sub-group of children had magnetic resonance imaging at 6-7 years of age (2018-2022). Mothers had haemoglobin measurements during pregnancy and a proportion of children were tested postnatally. Maternal anaemia (haemoglobin < 11 g/dL) and child anaemia were classified using WHO and local guidelines. Linear modeling was used to investigate associations between antenatal maternal anaemia status, maternal haemoglobin concentrations, and regional child brain volumes. Models included potential confounders and were conducted with and without child anaemia to assess the relative roles of antenatal versus postnatal anaemia.

Results: Overall, 157 children (Mean [SD] age of 75.54 [4.77] months; 84 [53.50%] male) were born to mothers with antenatal haemoglobin data. The prevalence of maternal anaemia during pregnancy was 31.85% (50/157). In adjusted models, maternal anaemia status was associated with smaller volumes of the total corpus callosum (adjusted percentage difference, - 6.77%; p = 0.003), left caudate nucleus (adjusted percentage difference, - 5.98%, p = 0.005), and right caudate nucleus (adjusted percentage difference, - 6.12%; p = 0.003). Continuous maternal haemoglobin was positively associated with total corpus callosum (β = 0.239 [CI 0.10 to 0.38]; p < 0.001) and caudate nucleus (β = 0.165 [CI 0.02 to 0.31]; p = 0.027) volumes. In a sub-group (n = 89) with child haemoglobin data (Mean [SD] age of 76.06 [4.84]), the prevalence of antenatal maternal anaemia and postnatal child anaemia was 38.20% (34/89) and 47.19% (42/89), respectively. There was no association between maternal and child anaemia (χ² = 0.799; p = 0.372), and child anaemia did not contribute to regional brain volume differences associated with maternal anaemia.

Conclusions: Associations between maternal anaemia and regional child brain volumes previously reported at 2-3 years of age were consistent and persisted to 6-7 years of age. Findings support the importance of optimising antenatal maternal health and reinforce these brain regions as a future research focus.

Background: Postoperative delirium is the most common complication in older patients and is associated with surgery-induced inflammation. Although inflammation plays a key role in delirium, the potential benefits of a comprehensive anti-inflammatory approach to managing perioperative systemic inflammation remain underexplored. This study evaluated whether a perioperative anti-inflammatory bundle strategy, combining dexmedetomidine, glucocorticoids, ulinastatin, and nonsteroidal anti-inflammatory drugs, reduces the risk of postoperative delirium in older patients undergoing hip fracture surgery.

Methods: This dual-center, double-blind, placebo-controlled, parallel-group, pilot study was conducted from August 2023 to January 2024 at two tertiary university hospitals. A total of 132 patients aged ≥ 65 years with an American Society of Anesthesiologists physical status of 2 or 3 scheduled for elective hip fracture surgery were screened and randomized to receive either an anti-inflammatory drug bundle or a placebo. The primary outcome was postoperative delirium, identified within the first three postoperative days. Postoperative blood inflammatory markers and acute pain were measured for mediation analysis.

Results: Of the 132 patients randomized, 123 (93%) completed the trial (mean age, 82 years; 75% women). The prevalence of postoperative delirium was significantly lower in the anti-inflammatory bundle group (15%, 9/62) compared to the placebo group (44%, 27/61) (risk difference, - 30 percentage points [95% CI, - 45 to - 15]; relative risk [RR], 0.33 [95% CI, 0.17 to 0.64]; P = 0.001). No major adverse events were reported in either group. The postoperative CRP level in the anti-inflammatory bundle group was significantly lower (predicted mean difference: - 29.4 [95% CI: - 46.5, - 12.2] mg·L^-1; adjusted P < 0.001). Mediation analysis showed a significant indirect association between the anti-inflammatory bundle and postoperative delirium through reduced systemic inflammation (odds ratio [OR], 0.61 [95% CI, 0.26 to 0.87]).

Conclusions: This study demonstrates that a perioperative anti-inflammatory bundle significantly reduces the prevalence of postoperative delirium in older patients undergoing hip fracture surgery, without major side effects. Systemic inflammation mediates the protective effect of the intervention. These findings provide preliminary evidence supporting the anti-inflammatory bundle strategy, paving the way for large-scale multicenter trials to optimize postoperative delirium prevention strategies.

Trial registration: This study was registered in the Chinese Clinical Trial Registry (ChiCTR2300074303) by Ayixia Nawan on August 3, 2023, prior to patient enrollment.

Background: Irritable bowel syndrome (IBS) is a debilitating disorder affecting 4-9% of the global population. It is a multifaceted disorder with complex and varied causes. This review aims to consolidate the evidence regarding IBS risk factors by examining existing systematic reviews and meta-analyses, covering potential genetic, immunological, psychological, and dietary causes.

Methods: Systematic literature searches were conducted in MEDLINE, Embase and Cochrane library databases. Study selection and data extraction were conducted independently by four authors, with discrepancies resolved by consensus with a senior author. Systematic reviews examining risk factors of IBS development were eligible for review. Results were narratively synthesized. Quality of reviews were analysed using AMSTAR 2, and evidence were appraised using GRADE methodology.

Results: A total of 69 systematic reviews were included in this study. Most reviews were of "critically low" quality, while the remaining were "low" quality. Common shortcomings included the absence of a list of excluded studies with justifications for their exclusion and inadequate consideration of the risk of bias in individual studies. Eight major categories of risk factors for IBS identified were as follows: dietary, genetic, environmental, psychological, gut microbiome, socio-economic, physiological, and pathological, albeit overlaps exist. The most frequently reported risk factors for IBS development were female gender and anxiety disorders, with overall GRADE evaluation of "low"; depression and gastroenteritis, with overall GRADE evaluation of "moderate".

Conclusions: Clinical practice should prioritize recognition of these risk factors. Future reviews should improve their reporting of results based on the PRISMA guidelines, to enhance the quality of research in this field.

Protocol registration: PROSPERO CRD42023493739.

Background: Uterine serous carcinoma and carcinosarcoma are aggressive forms of endometrial cancer with poor survival outcomes. Trastuzumab, a human epidermal growth factor receptor-2 (HER2)-directed monoclonal antibody, has demonstrated tumoricidal efficacy. However, clinical data regarding its efficacy in uterine serous carcinoma are limited, and there are no clinical data available for uterine carcinosarcoma. Therefore, this study aimed to ascertain the efficacy and safety of adding trastuzumab to carboplatin and paclitaxel as a frontline treatment for advanced-stage HER2-overexpressing uterine serous carcinoma and carcinosarcoma.

Methods: This retrospective study used deidentified data from electronic health records from the TriNetX Research Network. Participants were identified using International Classification of Diseases codes, and HER2 positivity was confirmed through immunohistochemistry or fluorescence in situ hybridisation. Propensity score matching was employed to reduce confounders, and survival outcomes and adverse events were assessed.

Results: Following propensity score matching, 280 patients with advanced HER2-positive uterine serous carcinoma or carcinosarcoma were analysed. The group of patients treated with carboplatin/paclitaxel + trastuzumab (CP + T) showed a significantly prolonged median overall survival compared to those treated exclusively with CP (41 months versus 25.2 months, hazard ratio [HR] = 0.51, p = 0.002) in both advanced-stage uterine carcinosarcoma and serous carcinoma. Specifically, patients with uterine carcinosarcoma experienced a prolonged survival benefit (HR = 0.39, p < 0.0001) when trastuzumab was added to their chemotherapy regimen, which surpassed the survival benefit observed in patients with uterine serous carcinoma (HR = 0.56, p = 0.04). However, patients who received trastuzumab experienced increased rates of hypertension, diarrhoea, and left ventricular systolic dysfunction.

Conclusions: The addition of trastuzumab to frontline chemotherapy is effective in treating HER2-overexpressing uterine serous carcinoma and carcinosarcoma, particularly uterine carcinosarcoma. However, careful monitoring of adverse cardiac events is needed.