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Cureus May 2024Chylothorax is a rare condition that results from thoracic duct disruption with malignant and nonmalignant etiologies manifesting as a pleural effusion. Typically,...
Chylothorax is a rare condition that results from thoracic duct disruption with malignant and nonmalignant etiologies manifesting as a pleural effusion. Typically, chylothorax in the setting of cirrhosis is associated with the migration of chylous ascites. We present the case of a 64-year-old male with prior liver transplant who presented with new-onset transudative chylothorax without chylous ascites who responded to transjugular intrahepatic portosystemic shunt revision, diuresis, and serial thoracentesis.
PubMed: 38916011
DOI: 10.7759/cureus.60996 -
Journal of Cancer Research and Clinical... Jun 2024Cholangiocarcinoma (CCA) is a rare tumor with a poor prognosis and poses significant therapeutic challenges. Herein, we investigated the mechanism of efficacy of I seed...
OBJECTIVES
Cholangiocarcinoma (CCA) is a rare tumor with a poor prognosis and poses significant therapeutic challenges. Herein, we investigated the mechanism of efficacy of I seed implantation therapy in CCA, focusing on the induction of reactive oxygen species (ROS)-mediated apoptosis and the involvement of glutathione peroxidase 2 (GPX2).
MATERIALS AND METHODS
Human cholangiocarcinoma cell lines QBC939 and RBE were purchased for in vitro studies. In vivo studies were performed using a rabbit VX2 CCA model. Apoptosis and proliferation were detected by TUNEL staining and clone formation, respectively. ROS generation was detected by dihydroethidium staining. Histological evaluation was performed by hematoxylin and eosin staining. Protein expression was determined by Western blotting and immunohistochemistry.
RESULTS
Our results demonstrate that I seeds effectively inhibited tumor growth in the rabbit VX2 tumor model and promoted the apoptosis of CCA cells in vitro in a dose-dependent manner. Molecular analyses indicate a marked increase in reactive oxygen species (ROS) levels following treatment with I seeds, suggesting the involvement of ROS-mediated apoptosis in the therapeutic mechanism. Furthermore, the downregulation of glutathione peroxidase 2 (GPX2) was observed, indicating its potential role in modulating ROS-mediated apoptosis in CCA.
CONCLUSION
I seed implantation therapy exerts therapeutic effects on CCA by inducing ROS-mediated apoptosis. The downregulation of GPX2 may contribute to enhanced ROS accumulation and apoptotic cell death. These findings provide mechanistic insights into the therapeutic potential of I seed implantation for CCA and highlight ROS-mediated apoptosis and GPX2 regulation as promising targets for further investigation and therapeutic intervention in this malignancy.
Topics: Cholangiocarcinoma; Iodine Radioisotopes; Animals; Reactive Oxygen Species; Glutathione Peroxidase; Apoptosis; Humans; Bile Duct Neoplasms; Rabbits; Cell Line, Tumor; Cell Proliferation; Xenograft Model Antitumor Assays
PubMed: 38914724
DOI: 10.1007/s00432-024-05840-0 -
JAMA Network Open Jun 2024Congenital heart disease (CHD) is the most common human organ malformation, affecting approximately 1 of 125 newborns globally.
IMPORTANCE
Congenital heart disease (CHD) is the most common human organ malformation, affecting approximately 1 of 125 newborns globally.
OBJECTIVES
Assessing the performance of 2 diagnostic tests using minimal amounts of dried blood spots (DBS) to identify high-risk CHD compared with controls in a Swedish cohort of neonates.
DESIGN, SETTING, AND PARTICIPANTS
This diagnostic study took place in Sweden between 2019 and 2023 and enrolled full-term babies born between 2005 and 2023. All cases were identified through centralized pediatric cardiothoracic surgical services in Lund and Gothenburg, Sweden. Controls were followed up for 1 year to ensure no late presentations of high-risk CHD occurred. Cases were verified through surgical records and echocardiography.
EXPOSURE
High-risk CHD, defined as cases requiring cardiac surgical management during infancy due to evolving signs of heart failure or types in which the postnatal circulation depends on patency of the arterial duct. Using 3-μL DBS samples, automated quantitative tests for NT-proBNP and interleukin 1 receptor-like 1 (IL-1 RL1; formerly known as soluble ST2) were compared against established CHD screening methods.
MAIN OUTCOMES AND MEASURES
Performance of DBS tests to detect high-risk CHD using receiver operating characteristic curves; Bland-Altman and Pearson correlation analyses to compare IL-1 RL1 DBS with plasma blood levels.
RESULTS
A total of 313 newborns were included (mean [SD] gestational age, 39.4 [1.3] weeks; 181 [57.8%] male). Mean (SD) birthweight was 3495 (483) grams. Analyzed DBS samples included 217 CHD cases and 96 controls. Among the CHD cases, 188 participants (89.3%) were high-risk types, of which 73 (38.8%) were suspected prenatally. Of the 188 high-risk cases, 94 (50.0%) passed pulse oximetry screening and 36 (19.1%) were initially discharged after birth without diagnoses. Combining NT-proBNP and IL-1 RL1 tests performed well in comparison with existing screening methods and enabled additional identification of asymptomatic babies with receiver operating characteristic area under the curve 0.95 (95% CI, 0.93-0.98).
CONCLUSIONS AND RELEVANCE
In this diagnostic study, NT-proBNP and IL-1 RL1 DBS assays identified high-risk CHD in a timely manner, including in asymptomatic newborns, and improved overall screening performance in this cohort from Sweden. Prospective evaluation of this novel approach is warranted.
Topics: Humans; Infant, Newborn; Heart Defects, Congenital; Neonatal Screening; Dried Blood Spot Testing; Biomarkers; Female; Male; Sweden; Natriuretic Peptide, Brain; Peptide Fragments; Case-Control Studies; Interleukin-1 Receptor-Like 1 Protein
PubMed: 38913376
DOI: 10.1001/jamanetworkopen.2024.18097 -
The Indian Journal of Radiology &... Jul 2024The aim of this study was to examine the imaging manifestations of post-endoscopic retrograde cholangiopancreatography (ERCP) specific complications by computed...
The aim of this study was to examine the imaging manifestations of post-endoscopic retrograde cholangiopancreatography (ERCP) specific complications by computed tomography to aid in its early and successful diagnosis and timely intervention. Forty-one cases of imaging having post-ERCP were complications were retrospectively collected and the spectrum of complications and their key imaging features and methods to improve their detection were analyzed. The most common complication detected in computed tomography (CT) post-ERCP was the presence of intra-abdominal collections seen in 21 patients (51.2%). Pancreatitis was seen in 20 of 41 patients (48.7%), while bowel perforation was present in 9 patients (21%). Pleural effusion was present in 8 patients (19.5%), liver abscess in 6 patients (14.6%), cholangitis in 4 patients (9.7%), gallbladder perforation in 4 patients (9.7%), displaced common bile duct stent in 3 patients (7.3%), possibility of main pancreatic duct cannulation in 2 patients (4.8%), vascular injury resulting in right hepatic artery pseudoaneurysm in 1 patient (2.4%), thrombosis of portal vein or its branches in 2 patients (4.8%), superior mesenteric vein thrombosis in 1 patient (2.4%), right hepatic vein thrombosis in 1 patient (2.4%), pulmonary thromboembolism in 2 patients (4.8%), duodenal inflammation in 1 patient (2.4%), bowel ileus in 4 patients (9.6%), and bowel obstruction in 1 patient (2.4%). Complications after ERCP can cause significant morbidity and mortality if not diagnosed early and treated appropriately. Familiarity with normal findings post-ERCP and knowledge of the imaging appearance of these complications are vital in the early management of these conditions.
PubMed: 38912237
DOI: 10.1055/s-0044-1779585 -
Iranian Journal of Public Health May 2024One of the most prevalent gastrointestinal tract ailments is gallstone disease (GD). Diet has been acknowledged as a modifiable GD risk factor. The Healthy Eating Index...
BACKGROUND
One of the most prevalent gastrointestinal tract ailments is gallstone disease (GD). Diet has been acknowledged as a modifiable GD risk factor. The Healthy Eating Index (HEI) is a scale for evaluating the quality of diets; therefore, this study aimed to determine whether the HEI-2015 score was associated with serum metabolic parameters in women with GD.
METHODS
This case-control study was conducted on a sample of 75 women diagnosed with GD and 75 healthy women at the Gastroenterology and Hepatology Clinic of Shahid Beheshti University of Medical Science in Tehran, Iran. Standard laboratory methods were employed to measure the biochemical parameters. The participants' habitual dietary intake was assessed using a validated food frequency questionnaire (FFQ). The HEI-2015 score was computed for all participants. The study employed multivariate logistic regression to identify the optimal predictor of GD. The Pearson Correlation was employed to determine the correlation between the HEI-2015 and serum metabolic parameters.
RESULTS
The study found a significant negative association between the risk of GD and serum HDL-c (OR: 0.84; 95% CI: 0.76-0.95, =0.008). Moreover, a significant positive association was detected between HOMAIR (OR: 3.27; 95% CI: 1.16-9.19, =0.025), and the risk of GD. The study did not find a statistically significant correlation between the HEI-2015 and serum parameters.
CONCLUSION
While an association was discovered between certain serum metabolic parameters and the risk of GD, the results do not provide a significant association between serum metabolic parameters and HEI-2015 score.
PubMed: 38912147
DOI: 10.18502/ijph.v53i5.15595 -
Journal of Indian Association of... 2024The aim is to study the various histopathological changes in the liver in pediatric patients with choledochal cyst (CC) and correlate with the presentation and type of...
AIM
The aim is to study the various histopathological changes in the liver in pediatric patients with choledochal cyst (CC) and correlate with the presentation and type of cyst.
METHODS
In a prospective observational study including all pediatric patients who underwent CC excision, histopathological changes of the liver in the form of cholestasis (CHS), portal inflammation (PI), bile duct proliferation (BDP), and fibrosis were studied and graded using a scoring system. They were analyzed in relation to age, sex, symptoms, and type of the cyst.
RESULTS
All 30 patients of CC showed various degrees of histopathological changes in the liver in the form of CHS, PI, BDP, and liver fibrosis. Patients <1 years had 9/13 (69.2%) cystic variety and those >1 years had 17/17 (100%) fusiform variety of CC ( < 0.001). Patients <1 years frequently presented with jaundice and hepatomegaly and those >1 years presented with pain abdomen ( < 0.002). Higher grades of liver fibrosis and BDP were seen in the cystic variety compared to the fusiform variety ( < 0.001). However, no significant association was found with CHS and PI ( > 1.23).
CONCLUSIONS
Histopathological changes in the liver of varying grades are seen in all patients of CC. Patients of CC <1 year presented frequently with jaundice, had the cystic type, and had a higher degree of liver damage on histopathology.
PubMed: 38912034
DOI: 10.4103/jiaps.jiaps_195_23 -
Journal of Cancer 2024There is growing evidence linking glutamine levels to the risk of gastrointestinal diseases, yet the presence of a causal relationship remains uncertain. In this study,...
There is growing evidence linking glutamine levels to the risk of gastrointestinal diseases, yet the presence of a causal relationship remains uncertain. In this study, we employed a Mendelian randomization (MR) approach to investigate potential causal associations between glutamine and colitis, inflammatory bowel disease (IBD), and digestive tumors. Genetic instrumental variables for glutamine exposure were identified from a genome-wide association study (GWAS) involving 114,751 participants. We pooled statistics from GWAS of gastrointestinal diseases in European populations, encompassing colitis (cases=1193, controls=461,740), IBD (cases=31,665, controls=33,977), Crohn's disease (cases=17,897, controls=33,977), ulcerative colitis (cases=1,239, controls=990), oesophageal cancer (cases=740, controls=372,016), gastric cancer (cases=6,563, controls=195,745), liver cell carcinoma (cases=168, controls=372,016), hepatic bile duct cancer (cases=418, controls=159,201), pancreatic cancer (cases=1,196, controls=475,049), and colon cancer (cases=1,494, controls=461,439). To ensure the validity of our findings, we utilized several analytical approaches including inverse variance weighted, weighted median, weighted mode, MR-Egger, and simple mode method. Using the IVW method, we found that glutamine levels were inversely associated with colon cancer (OR = 0.998; 95% CI: 0.997-1.000; P = 0.027), colitis (OR = 0.998; 95% CI: 0.997-1.000; P = 0.020), and IBD (OR = 0.551; 95% CI: 0.343-0.886; P = 0.014). Subgroup analysis revealed a negative association between glutamine and Crohn's disease (OR = 0.375; 95% CI: 0.253-0.557; P = 1.11E-06), but not with ulcerative colitis (OR = 0.508; 95% CI: 0.163-1.586; P = 0.244). Glutamine levels showed no significant correlation with oesophageal cancer (OR = 1.000; 95% CI: 0.999-1.001; P = 0.566), gastric cancer (OR = 0.966; 95% CI: 0.832-1.121; P = 0.648), liver cell carcinoma (OR = 1.000; 95% CI: 0.999-1.000; P = 0.397), hepatic bile duct cancer (OR = 0.819; 95% CI: 0.499-1.344; P = 0.430), and pancreatic cancer (OR = 1.130; 95% CI: 0.897-1.423; P = 0.301). Sensitivity analyses also supports this finding, affirming the reliability and robustness of our study. This study suggests that blood glutamine levels in European populations may lower the risk of colon cancer, colitis, and IBD, particularly Crohn's disease. Nevertheless, additional research involving a diverse range of ancestries is imperative to corroborate this causal relationship.
PubMed: 38911392
DOI: 10.7150/jca.96085 -
Hepatobiliary Surgery and Nutrition Jun 2024
Insights on liver-directed surgical innovations, targeted therapies, and immunotherapy for biliary tract cancer: navigating the new European Society for Medical Oncology (ESMO) Clinical Practice Guidelines.
PubMed: 38911219
DOI: 10.21037/hbsn-24-63 -
Hepatobiliary Surgery and Nutrition Jun 2024
PubMed: 38911198
DOI: 10.21037/hbsn-23-633 -
APL Bioengineering Jun 2024Previous lung-on-chip devices have facilitated significant advances in our understanding of lung biology and pathology. Here, we describe a novel lung-on-a-chip model in...
Previous lung-on-chip devices have facilitated significant advances in our understanding of lung biology and pathology. Here, we describe a novel lung-on-a-chip model in which human induced pluripotent stem cell-derived alveolar epithelial type II cells (iAT2s) form polarized duct-like lumens alongside engineered perfused vessels lined with human umbilical vein endothelium, all within a 3D, physiologically relevant microenvironment. Using this model, we investigated the morphologic and signaling consequences of the KRAS mutation, a commonly identified oncogene in human lung adenocarcinoma (LUAD). We show that expression of the mutant KRAS isoform in iAT2s leads to a hyperproliferative response and morphologic dysregulation in the epithelial monolayer. Interestingly, the mutant epithelia also drive an angiogenic response in the adjacent vasculature that is mediated by enhanced secretion of the pro-angiogenic factor soluble uPAR. These results demonstrate the functionality of a multi-cellular platform capable of modeling mutation-specific behavioral and signaling changes associated with lung adenocarcinoma.
PubMed: 38911024
DOI: 10.1063/5.0207228