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Trials Jul 2024Body weight loss (BWL) after gastrectomy impact on the short- and long-term outcomes. Oral nutritional supplement (ONS) has potential to prevent BWL in patients after...
The efficacy of simple oral nutritional supplements versus usual care in postoperative patients with gastric cancer: study protocol for a multicenter, open-label, parallel, randomized controlled trial.
BACKGROUND
Body weight loss (BWL) after gastrectomy impact on the short- and long-term outcomes. Oral nutritional supplement (ONS) has potential to prevent BWL in patients after gastrectomy. However, there is no consistent evidence supporting the beneficial effects of ONS on BWL, muscle strength and health-related quality of life (HRQoL). This study aimed to evaluate the effects of ONS formulated primarily with carbohydrate and protein on BWL, muscle strength, and HRQoL.
METHODS
This will be a multicenter, open-label, parallel, randomized controlled trial in patients with gastric cancer who will undergo gastrectomy. A total of 120 patients who will undergo gastrectomy will be randomly assigned to the ONS group or usual care (control) group in a 1:1 ratio. The stratification factors will be the clinical stage (I or ≥ II) and surgical procedures (total gastrectomy or other procedure). In the ONS group, the patients will receive 400 kcal (400 ml)/day of ONS from postoperative day 5 to 7, and the intervention will continue postoperatively for 8 weeks. The control group patients will be given a regular diet. The primary outcome will be the percentage of BWL (%BWL) from baseline to 8 weeks postoperatively. The secondary outcomes will be muscle strength (handgrip strength), HRQoL (EORTC QLQ-C30, QLQ-OG25, EQ-5D-5L), nutritional status (hemoglobin, lymphocyte count, albumin), and dietary intake. All analyses will be performed on an intention-to-treat basis.
DISCUSSION
This study will provide evidence showing whether or not ONS with simple nutritional ingredients can improve patient adherence and HRQoL by reducing BWL after gastrectomy. If supported by the study results, nutritional support with simple nutrients will be recommended to patients after gastrectomy for gastric cancer.
TRIAL REGISTRATION
jRCTs051230012; Japan Registry of Clinical Trails. Registered on Apr. 13, 2023.
Topics: Humans; Stomach Neoplasms; Gastrectomy; Dietary Supplements; Quality of Life; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Treatment Outcome; Weight Loss; Administration, Oral; Middle Aged; Male; Female; Adult; Aged; Nutritional Status; Time Factors; Hand Strength; Muscle Strength
PubMed: 38961505
DOI: 10.1186/s13063-024-08169-8 -
Journal of Medical Case Reports Jul 2024Myasthenic crisis (MC) is a life-threatening complication of myasthenia gravis (MG), necessitating ventilation. Achieving a safe and timely diagnosis of myasthenic...
BACKGROUND
Myasthenic crisis (MC) is a life-threatening complication of myasthenia gravis (MG), necessitating ventilation. Achieving a safe and timely diagnosis of myasthenic crisis with atypical, isolated presentation is a considerable challenge particularly in elderly patients, where myasthenia gravis can present with isolated dysarthria in rare instances, giving a clinical impression of lacunar stroke.
CASE PRESENTATION
We present a compelling case of a 73-year-old Caucasian female presenting with abrupt onset of isolated dysarthria. Despite initial treatment for a presumed lacunar stroke, subsequent evaluations led to her diagnosis of a myasthenic crisis. Within 72 h of admission, the patient developed dysphagia and shortness of breath, requiring supplemental oxygen. The case highlights the sequential progression of events from the atypical presentation of isolated dysarthria and its course to the management of a myasthenic crisis.
CONCLUSION
Our reported case focuses on the discussion of myasthenia that mimicked a lacunar stroke and was finally diagnosed at a critical time of medical crisis. This case highlights the imperative notion that isolated dysarthria in elderly individuals warrants vigilant monitoring for possible myasthenia gravis, given the low incidence of lacunar stroke presenting with only dysarthria.
Topics: Humans; Myasthenia Gravis; Aged; Dysarthria; Female; Diagnosis, Differential; Stroke, Lacunar; Cholinesterase Inhibitors; Deglutition Disorders; Dyspnea
PubMed: 38961428
DOI: 10.1186/s13256-024-04617-w -
BMC Surgery Jul 2024Acute mesenteric ischaemia (AMI) is a life-threatening disease where early diagnosis is critical to avoid morbidity and mortality from extensive irreversible bowel...
BACKGROUND
Acute mesenteric ischaemia (AMI) is a life-threatening disease where early diagnosis is critical to avoid morbidity and mortality from extensive irreversible bowel necrosis. Appropriate prediction of presence of bowel necrosis is currently not available but would help to choose the optimal method of treatment. The study aims to identify combinations of biomarkers that can reliably identify AMI and distinguish between potentially reversible and irreversible bowel ischaemia.
METHODS
This is a prospective multicentre study. Adult patients with clinical suspicion of AMI (n = 250) will be included. Blood will be sampled on admission, at and after interventions, or during the first 48 h of suspicion of AMI if no intervention undertaken. Samples will be collected and the following serum or plasma biomarkers measured at Tartu University Hospital laboratory: intestinal fatty acid-binding protein (I-FABP), alpha-glutathione S-transferase (Alpha- GST), interleukin 6 (IL-6), procalcitonin (PCT), ischaemia-modified albumin (IMA), D-lactate, D-dimer, signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) and lipopolysaccharide-binding protein (LBP). Additionally, more common laboratory markers will be measured in routine clinical practice at study sites. Diagnosis of AMI will be confirmed by computed tomography angiography, surgery, endoscopy or autopsy. Student's t or Wilcoxon rank tests will be used for comparisons between transmural vs. suspected (but not confirmed) AMI (comparison A), confirmed AMI of any stage vs suspected AMI (comparison B) and non-transmural AMI vs transmural AMI (comparison C). Optimal cut-off values for each comparison will be identified based on the AUROC analysis and likelihood ratios calculated. Positive likelihood ratio > 10 (> 5) and negative likelihood ratio < 0.1 (< 0.2) indicate high (moderate) diagnostic accuracy, respectively. All biomarkers with at least moderate accuracy will be entered as binary covariates (using the best cutoffs) into the multivariable stepwise regression analysis to identify the best combination of biomarkers for all comparisons separately. The best models for each comparison will be used to construct a practical score to distinguish between no AMI, non-transmural AMI and transmural AMI.
DISCUSSION
As a result of this study, we aim to propose a score including set of biomarkers that can be used for diagnosis and decision-making in patients with suspected AMI.
TRIAL REGISTRATION
NCT06212921 (Registration Date 19-01-2024).
Topics: Humans; Biomarkers; Prospective Studies; Mesenteric Ischemia; Acute Disease; Adult; Predictive Value of Tests
PubMed: 38961419
DOI: 10.1186/s12893-024-02491-3 -
BMC Pediatrics Jul 2024Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to...
BACKGROUND
Adipose tissue is significantly involved in inflammatory bowel disease (IBD). Vitamin D can affect both adipogenesis and inflammation. The aim of this study was to compare the production of selected adipokines, potentially involved in the pathogenesis of IBD - adiponectin, resistin, retinol binding protein 4 (RBP-4), adipocyte fatty acid binding protein and nesfatin-1 in children with IBD according to the presence of 25-hydroxyvitamin D (25(OH)D) deficiency.
METHODS
The study was conducted as a case-control study in pediatric patients with IBD and healthy children of the same sex and age. In addition to adipokines and 25(OH)D, anthropometric parameters, markers of inflammation and disease activity were assessed in all participants.
RESULTS
Children with IBD had significantly higher resistin levels regardless of 25(OH)D levels. IBD patients with 25(OH)D deficiency only had significantly lower RBP-4 compared to healthy controls and also compared to IBD patients without 25(OH)D deficiency. No other significant differences in adipokines were found in children with IBD with or without 25(OH)D deficiency. 25(OH)D levels in IBD patients corelated with RBP-4 only, and did not correlate with other adipokines.
CONCLUSIONS
Whether the lower RBP-4 levels in the 25(OH)D-deficient group of IBD patients directly reflect vitamin D deficiency remains uncertain. The production of other adipokines does not appear to be directly related to vitamin D deficiency.
Topics: Humans; Vitamin D Deficiency; Male; Female; Child; Case-Control Studies; Adipokines; Adolescent; Vitamin D; Retinol-Binding Proteins, Plasma; Resistin; Nucleobindins; Adiponectin; Calcium-Binding Proteins; Fatty Acid-Binding Proteins; DNA-Binding Proteins; Biomarkers; Inflammatory Bowel Diseases
PubMed: 38961351
DOI: 10.1186/s12887-024-04890-0 -
BMC Microbiology Jul 2024Gut microbiota is closely related to the occurrence and development of colorectal cancer (CRC). However, the differences in bacterial co-abundance groups (CAGs) between...
BACKGROUND & AIMS
Gut microbiota is closely related to the occurrence and development of colorectal cancer (CRC). However, the differences in bacterial co-abundance groups (CAGs) between tumor tissue (TT) and normal tissue (NT), as well as their associations with clinical features, are needed to be clarified.
METHODS
Bacterial 16 S rRNA sequencing was performed by using TT samples and NT samples of 251 patients with colorectal cancer. Microbial diversity, taxonomic characteristics, microbial composition, and functional pathways were compared between TT and NT. Hierarchical clustering was used to construct CAGs.
RESULTS
Four CAGs were grouped in the hierarchical cluster analysis. CAG 2, which was mainly comprised of pathogenic bacteria, was significantly enriched in TT samples (2.27% in TT vs. 0.78% in NT, p < 0.0001). CAG 4, which was mainly comprised of non-pathogenic bacteria, was significantly enriched in NT samples (0.62% in TT vs. 0.79% in NT, p = 0.0004). In addition, CAG 2 was also significantly associated with tumor microsatellite instability (13.2% in unstable vs. 2.0% in stable, p = 0.016), and CAG 4 was positively correlated with the level of CA199 (r = 0.17, p = 0.009).
CONCLUSIONS
Our research will deepen our understanding of the interactions among multiple bacteria and offer insights into the potential mechanism of NT to TT transition.
Topics: Humans; Colorectal Neoplasms; Bacteria; Male; Gastrointestinal Microbiome; Female; RNA, Ribosomal, 16S; Middle Aged; Aged; Microsatellite Instability; Adult; DNA, Bacterial; Aged, 80 and over; Phylogeny; Cluster Analysis
PubMed: 38961349
DOI: 10.1186/s12866-024-03402-5 -
BMC Gastroenterology Jul 2024Platelet dysfunction plays a critical role in the pathogenesis of inflammatory bowel disease (IBD). Despite clinical observations indicating abnormalities in platelet... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Platelet dysfunction plays a critical role in the pathogenesis of inflammatory bowel disease (IBD). Despite clinical observations indicating abnormalities in platelet parameters among IBD patients, inconsistencies persist, and these parameters lack standardization for diagnosis or clinical assessment.
METHODS
A comprehensive search was conducted in the PubMed, Embase, Web of Science, and Cochrane Library databases for relevant articles published up to December 16th, 2023. A random-effects model was employed to pool the weighted mean difference (WMD) and 95% confidence interval (95% CI) of platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) between IBD patients and healthy controls, and subgroup analyses were performed.
RESULTS
The meta-analysis included 79 articles with 8,350 IBD patients and 13,181 healthy individuals. The results revealed significantly increased PLT and PCT levels (WMD: 69.910, 95% CI: 62.177, 77.643 10/L; WMD: 0.046%, 95% CI: 0.031%, 0.061%), and decreased MPV levels (WMD: -0.912, 95% CI: -1.086, -0.739 fL) in IBD patients compared to healthy individuals. No significant difference was found in PDW between the IBD and control groups (WMD: -0.207%, 95% CI: -0.655%, 0.241%). Subgroup analysis by disease type and disease activity showed no change in the differences for PLT, PCT, and MPV in the ulcerative colitis and Crohn's disease groups, as well as the active and inactive groups. Notably, the active group exhibited significantly lower PDW levels than the control group (WMD: -1.138%, 95% CI: -1.535%, -0.741%).
CONCLUSIONS
Compared with healthy individuals, IBD patients display significantly higher PLT and PCT and significantly lower MPV. Monitoring the clinical manifestations of platelet abnormalities serves as a valuable means to obtain diagnostic and prognostic information. Conversely, proactive measures should be taken to prevent the consequences of platelet abnormalities in individuals with IBD.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42023493848.
Topics: Humans; Platelet Count; Mean Platelet Volume; Inflammatory Bowel Diseases; Blood Platelets; Blood Platelet Disorders
PubMed: 38961334
DOI: 10.1186/s12876-024-03305-9 -
Cellular & Molecular Biology Letters Jul 2024Pancreatic cancer (PC) is one of the most malignant cancers with highly aggressiveness and poor prognosis. N6-methyladenosine (m6A) have been indicated to be involved in...
BACKGROUND
Pancreatic cancer (PC) is one of the most malignant cancers with highly aggressiveness and poor prognosis. N6-methyladenosine (m6A) have been indicated to be involved in PC development. Glucan Branching Enzyme 1 (GBE1) is mainly involved in cell glycogen metabolism. However, the function of GBE1 and Whether GBE1 occurs m6A modification in PC progression remains to be illustrated.
METHODS
The clinical prognosis of GBE1 was analyzed through online platform. The expression of GBE1 was obtained from online platform and then verified in normal and PC cell lines. Lentivirus was used to generated GBE1 stable-overexpression or knockdown PC cells. Cell Counting Kit (CCK-8), colony formation assay, sphere formation assay and flow cytometry assay were conducted to analyze cell proliferation and stemness ability in vitro. Subcutaneous and orthotopic mouse models were used to verify the function of GBE1 in vivo. RNA immunoprecipitation (RIP) assay, RNA stability experiment and western blots were conducted to explore the molecular regulation of GBE1 in PC.
RESULTS
GBE1 was significantly upregulated in PC and associated with poor prognosis of PC patients. Functionally, GBE1 overexpression facilitated PC cell proliferation and stemness-like properties, while knockdown of GBE1 attenuated the malignancy of PC cells. Importantly, we found the m6A modification of GBE1 RNA, and WTAP and IGF2BP3 was revealed as the m6A regulators to increase GBE1 mRNA stability and expression. Furthermore, c-Myc was discovered as a downstream gene of GBE1 and functional rescue experiments showed that overexpression of c-Myc could rescue GBE1 knockdown-induced PC cell growth inhibition.
CONCLUSIONS
Our study uncovered the oncogenic role of GBE1/c-Myc axis in PC progression and revealed WTAP/IGF2BP3-mediated m6A modification of GBE1, which highlight the potential application of GBE1 in the targeted therapy of PC.
Topics: Humans; Cell Proliferation; RNA-Binding Proteins; Proto-Oncogene Proteins c-myc; Cell Line, Tumor; Animals; Neoplastic Stem Cells; Pancreatic Neoplasms; Gene Expression Regulation, Neoplastic; Mice; Up-Regulation; Mice, Nude; Prognosis
PubMed: 38961325
DOI: 10.1186/s11658-024-00611-8 -
Scientific Reports Jul 2024This study aimed to construct a non-invasive diagnostic nomogram based on high-frequency ultrasound and magnetic resonance imaging results for early liver cirrhosis...
This study aimed to construct a non-invasive diagnostic nomogram based on high-frequency ultrasound and magnetic resonance imaging results for early liver cirrhosis patients with chronic hepatitis B (CHB) which cannot be detected by conventional non-invasive examination methods but can only be diagnosed through invasive liver puncture for pathological examination. 72 patients with CHB were enrolled in this prospective study, and divided into S4 stage of liver cirrhosis and S0-S3 stage of non-liver cirrhosis according to pathological findings. Binary logistic regression analysis was performed to identify independent predictors, and a diagnostic nomogram was constructed for CHB-related early cirrhosis. It was validated and calibrated by bootstrap self-extraction. Binary logistic regression analysis showed that age (OR 1.14, 95% CI (1.04-1.27)), right hepatic vein diameter (OR 0.43, 95% CI 0.23-0.82), presence or absence of nodules (OR 31.98, 95% CI 3.84-266.08), and hepatic parenchymal echogenicity grading (OR 12.82, 95% CI 2.12-77.51) were identified as independent predictive indicators. The nomogram based on the 4 factors above showed good performance, with a sensitivity and specificity of 90.70% and 89.66%, respectively. The area under the curve (AUC) of the prediction model was 0.96, and the predictive model showed better predictive performance than APRI score (AUC 0.57), FIB-4 score (AUC 0.64), INPR score (AUC 0.63), and LSM score (AUC 0.67). The calibration curve of the prediction model fit well with the ideal curve, and the decision curve analysis showed that the net benefit of the model was significant. The nomogram in this study can detect liver cirrhosis in most CHB patients without liver biopsy, providing a direct, fast, and accurate practical diagnostic tool for clinical doctors.
Topics: Humans; Liver Cirrhosis; Male; Female; Nomograms; Middle Aged; Prospective Studies; Hepatitis B, Chronic; Adult; Ultrasonography; Magnetic Resonance Imaging; Liver
PubMed: 38961222
DOI: 10.1038/s41598-024-66560-6 -
Scientific Reports Jul 2024Precision-cut liver slices (PCLS) are increasingly used as a model to investigate anti-fibrotic therapies. However, many studies use PCLS from healthy animals treated...
Precision-cut liver slices (PCLS) are increasingly used as a model to investigate anti-fibrotic therapies. However, many studies use PCLS from healthy animals treated with pro-fibrotic stimuli in culture, which reflects only the early stages of fibrosis. The effects of different culture conditions on PCLS from cirrhotic animals has not been well characterized and there is no consensus on optimal methods. In this study, we report a method for the collection and culture of cirrhotic PCLS and compare the effect of common culture conditions on viability, function, and gene expression. Additionally, we compared three methods of RNA isolation and identified a protocol with high yield and purity. We observed significantly increased albumin production when cultured with insulin-transferrin-selenium and dexamethasone, and when incubated on a rocking platform. Culturing with insulin-transferrin-selenium and dexamethasone maintained gene expression closer to the levels in fresh slices. However, despite stable viability and function up to 4 days, we found significant changes in expression of key genes by day 2. Interestingly, we also observed that cirrhotic PCLS maintain viability in culture longer than slices from healthy animals. Due to the influence of matrix stiffness on fibrosis and hepatocellular function, it is important to evaluate prospective anti-fibrotic therapies in a platform that preserves tissue biomechanics. PCLS from cirrhotic animals represent a promising tool for the development of treatments for chronic liver disease.
Topics: Animals; Rats; Liver; Liver Cirrhosis; Dexamethasone; Male; RNA; Insulin; Rats, Sprague-Dawley; Selenium; Tissue Culture Techniques
PubMed: 38961190
DOI: 10.1038/s41598-024-66235-2 -
Scientific Reports Jul 2024Characteristics of livers and spleens of people with multiple sclerosis (pwMS) could constitute good biomarkers of MS-related characteristics such as the disability...
Characteristics of livers and spleens of people with multiple sclerosis (pwMS) could constitute good biomarkers of MS-related characteristics such as the disability status. To test the hypothesis "the gross anatomical features of livers and spleens, are not similar between pwMS with different disease characteristics" a cross-sectional study was conducted on pwMS seen at the Isfahan MS clinic, Iran, from February until December 2023. Definitive, otherwise-healthy, pwMS were enrolled after an initial laboratory evaluation. Presence/absence and grading of non-alcoholic fatty liver disease (NAFLD) and the span of spleen were determined by a radiologist using high-resolution abdominopelvic ultrasonography. 193 pwMS (160 women) were enrolled. Of whom, 143 (74.1%) were receiving first-line disease-modifying therapies (DMTs), 24 (12.4%) fingolimod, and 26 (13.5%) rituximab. The span of spleen was negatively associated with EDSS (adjusted β [SE] - 4.08 [1.52], p < 0.01), as well as 6 m-CDW (adjusted β [SE] - 6.94 [3.56], p = 0.05), unlike age, DMTs, and MS duration (all with p > 0.05). Receiver operating characteristic analysis showed, spleen span performs significant but poor in discrimination of EDSS > 1 from EDSS = 1 (area under curve [AUC] 0.62, SE 0.05, p < 0.01), yet, significant and fair in discrimination of presence from absence of 6 m-CDW (AUC 0.72, SE 0.06, p < 0.01). Other findings were unremarkable. Further longitudinal, prospective studies are warranted to confirm whether smaller spleens are predictive of higher disability accrual rate in pwMS. Particularly, findings require further validation in untreated/treatment-naïve pwMS, and ones with higher EDSS scores.
Topics: Humans; Female; Spleen; Cross-Sectional Studies; Adult; Male; Multiple Sclerosis; Ultrasonography; Middle Aged; Non-alcoholic Fatty Liver Disease; Liver; Iran
PubMed: 38961187
DOI: 10.1038/s41598-024-66216-5