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Cureus May 2024() infection is widely recognized for its association with gastric diseases. Prior studies on the relationship between infection and biliary diseases have faced...
Exploring the Relationship Between Helicobacter pylori Infection and Biliary Diseases: A Comprehensive Analysis Using the United States National Inpatient Sample (2016-2020).
BACKGROUND
() infection is widely recognized for its association with gastric diseases. Prior studies on the relationship between infection and biliary diseases have faced constraints, including inadequate control of confounding factors and small sample sizes. This study aims to explore the association between infection and biliary diseases using a large, population-based sample with adequate control for various covariates.
METHODS
The National Inpatient Sample (NIS) from 2016 to 2020 was used to investigate the association between infection and biliary diseases. We identified patients with infection using the International Classification of Diseases, Tenth Revision (ICD-10) code (B96.81). Descriptive analysis and inferential statistics, including univariate and multivariate regression, were performed to explore the relationship between and selected biliary diseases. Results: Overall, 32,966,720 patients were analyzed. Among them, 736,585 patients had biliary diseases (n=1,637 with and n=734,948 without ). The baseline characteristics revealed notable differences in demographics and healthcare variables between both groups. Univariate regression analysis demonstrated significant associations between infection and various biliary diseases such as gallbladder stones, gallbladder cancer, cholangitis, acute cholecystitis, and biliary pancreatitis, with the highest risk for chronic cholecystitis (odds ratio: 5.21; 95% confidence interval: 4.1-6.62; p<0.0001). Multivariate regression analysis, after adjusting for various covariates, confirmed these associations, providing insights into the potential causal relationship between and biliary diseases.
CONCLUSION
This study strengthens the evidence suggesting a potential association between infection and biliary diseases. The findings need to be validated in prospective clinical studies.
PubMed: 38939288
DOI: 10.7759/cureus.61238 -
Cureus May 2024Palmar fasciitis and polyarthritis syndrome (PFPAS) is an exceedingly rare rheumatologic condition characterized by fibrotic changes in the palmar fascia with joint...
Palmar fasciitis and polyarthritis syndrome (PFPAS) is an exceedingly rare rheumatologic condition characterized by fibrotic changes in the palmar fascia with joint pains. It is known to be associated with gynecological malignancy, especially ovarian adenocarcinoma, gastric cancer, pancreatic, prostate, breast, and lung cancer. We present a unique case of a 75-year-old Caucasian female with PFPAS preceding the diagnosis of ovarian cancer by eight months. Our case highlights the importance of considering PFPAS as a potential paraneoplastic syndrome. It underscores the need for increased awareness and further studies to enhance the early detection of underlying malignancies in patients presenting with similar nonspecific hand symptoms.
PubMed: 38939277
DOI: 10.7759/cureus.61248 -
Cureus May 2024There have been no case reports of non-occlusive mesenteric ischemia (NOMI) following head trauma. Our two patients with non-surgical traumatic intracerebral hemorrhage...
There have been no case reports of non-occlusive mesenteric ischemia (NOMI) following head trauma. Our two patients with non-surgical traumatic intracerebral hemorrhage succumbed to NOMI one week after the injury. Both were women over age 80 years and were clinically improving before NOMI occurred. One patient had been eating since admission, while the other had not, which prompted the initiation of enteral nutrition on day 5. The patients shared many characteristics: 1) over age 80 years; 2) minor brain contusion; 3) constipation for a week; 4) minimal abdominal symptoms; 5) rapidly developing leukocytosis, hyperglycemia, hypernatremia, and elevated blood urea nitrogen; 6) massive diarrhea with a small amount of blood on the same day that laboratory data became abnormal; and 7) fever and shock developed shortly after diarrhea appeared. Because of the fulminant worsening of the condition, shock status, and old age, surgical intervention was considered high risk and not performed in either patient. In retrospect, if NOMI had been diagnosed earlier when the acute pancreatitis-like symptoms began, surgical intervention may have saved their lives. Clinicians should be aware that NOMI can occur after relatively minor head trauma, which can cause death if the diagnosis is delayed.
PubMed: 38939261
DOI: 10.7759/cureus.61227 -
DEN Open Apr 2025A 79-year-old Japanese woman, who had undergone pancreaticoduodenectomy 6 months prior to presentation owing to pancreatic cancer, complained of jaundice with high...
A 79-year-old Japanese woman, who had undergone pancreaticoduodenectomy 6 months prior to presentation owing to pancreatic cancer, complained of jaundice with high fever. Computed tomography revealed proximal bile duct dilatation with complete hepaticojejunostomy anastomotic stricture (HJAS). We performed a single-balloon endoscopy for biliary drainage. The presence of a scar-like feature surrounding the anastomosis was identified as the HJAS. White-light imaging during single-balloon endoscopy revealed that the HJAS contained a milky whitish area (MWA), suggesting that a membranous and fibrosis layer affected continuous inflammation around the center of the anastomosis (within a scar-like feature). Endoscopic dilatation was performed using an endoscopic injection needle, with the MWA used as an indicator. A 23-gauge endoscopic injection needle was used to penetrate the center of the blind lumen within the MWA, and a pinhole was created in the stricture. After confirming the position of the proximal bile duct using a contrast medium with the needle, an endoscopic guidewire with a cannula was inserted into the pinhole. A through-the-scope sequential balloon dilator was used to dilate the stricture, and a plastic stent was inserted into the proximal bile duct. This endoscopic intervention led to positive outcomes. In cases of complete HJAS occlusion, an endoscopic approach to the bile duct is difficult because the anastomotic opening of the HJAS is not visible. Thus, puncturing within the MWA, which can be used as a scar-like landmark within a complete membranous HJAS, is considered a useful endoscopic strategy.
PubMed: 38939119
DOI: 10.1002/deo2.396 -
JACS Au Jun 2024This study highlights the novel potential of molecular aggregates as inhibitors of a disease-related protein. Enzyme inhibitors have been studied and developed as...
This study highlights the novel potential of molecular aggregates as inhibitors of a disease-related protein. Enzyme inhibitors have been studied and developed as molecularly targeted drugs and have been applied for cancer, autoimmune diseases, and infections. In many cases, enzyme inhibitors that are used for therapeutic applications interact directly with enzymes in a molecule-to-molecule manner. We found that the aggregates of a small compound, Mn007, inhibited bovine pancreatic DNase I. Once Mn007 molecules formed aggregates, they exhibited inhibitory effects specific to DNases that require divalent metal ions. A DNase secreted by causes streptococcal toxic shock syndrome (STSS). STSS is a severe infectious disease with a fatality rate exceeding 30% in patients, even in this century. disrupts the human barrier system against microbial infections through the secreted DNase. Until now, the discovery/development of a DNase inhibitor has been challenging. Mn007 aggregates were found to inhibit the DNase secreted by , which led to the successful suppression of growth in human whole blood. To date, molecular aggregation has been outside the scope of drug discovery. The present study suggests that molecular aggregation is a vast area to be explored for drug discovery and development because aggregates of small-molecule compounds can inhibit disease-related enzymes.
PubMed: 38938790
DOI: 10.1021/jacsau.4c00210 -
Molecular Therapy. Nucleic Acids Jun 2024Small interfering RNAs (siRNAs) are revolutionizing the treatment of liver-associated indications. Yet, robust delivery to extrahepatic tissues remains a challenge....
Small interfering RNAs (siRNAs) are revolutionizing the treatment of liver-associated indications. Yet, robust delivery to extrahepatic tissues remains a challenge. Conjugating lipids (e.g., docosanoic acid [DCA]) to siRNA supports extrahepatic delivery, but tissue accumulation remains lower than that achieved in liver by approved siRNA therapeutics. Early evidence suggests that functionalizing DCA with a head group (e.g., phosphatidylcholine [PC]) may enhance delivery to certain tissues. Here, we report the first systematic evaluation of the effect of PC head group chemistry on the extrahepatic distribution of DCA-conjugated siRNAs. We show that functionalizing DCA with a PC head group enhances siRNA accumulation in heart, muscle, lung, pancreas, duodenum, urinary bladder, and fat. Varying the size of the linker between the phosphate and choline moiety of the PC head group altered the extrahepatic accumulation of siRNA, with the optimal linker length being different for different tissues. Increasing PC head group valency also improved extrahepatic accumulation in a tissue-specific manner. This study demonstrates the structural impact of the PC moiety on the biodistribution of lipid-conjugated siRNA and introduces multiple novel PC variants for the chemical optimization of DCA-conjugated siRNA. These chemical variants can be used in the context of other lipids to increase the repertoire of conjugates for the extrahepatic distribution of siRNAs.
PubMed: 38938759
DOI: 10.1016/j.omtn.2024.102230 -
Advances in Pharmacological and... 2024Nutritional supplements are gaining traction for their effects in mitigating the impacts of various health conditions. In particular, many supplements are being proposed...
Nutritional supplements are gaining traction for their effects in mitigating the impacts of various health conditions. In particular, many supplements are being proposed to reduce the impacts of type 2 diabetes (T2D), a metabolic condition that has reached global epidemic proportions. Recently, a supplement of oleic acid (OA) and succinic acid (SA; 1 : 1, w/w) was reported to improve glycaemic control in type 2 diabetic (T2D) Sprague-Dawley (S-D) rats through ameliorating insulin release and sensitivity. Here, we investigate the effects of the supplement (OA and SA) on hepatic and pancreatic function in T2D S-D rats. Eighteen (18) S-D rats were rendered diabetic and were divided into three equal groups: diabetic control, diabetic treatment, and diabetic glibenclamide. Another 12 S-D rats were obtained and served as the normal groups. The animals were treated daily with the vehicle, OA and SA (800 mg/kg body weight (bw); 1 : 1), or glibenclamide (10 mg/kg bw) which served as the positive control. The findings indicated that treatment with the supplement resulted in a 35.69 ± 4.22% reduction (=0.006) in blood glucose levels (BGL). Analysis of hepatic enzymes depicted that the nutritional supplement reduced the activity of the gluconeogenesis enzyme, glucose-6-phosphatase (G6P) while improved the activity of catabolic enzymes such as glucose-6-phosphate dehydrogenase (G6PD) and pyruvate kinase (PK). Furthermore, the supplement attenuated oxidative stress through restoration of catalase (CAT) and superoxide dismutase (SOD), while reducing malondialdehyde (MDA) levels. Finally, the supplement showed no liver or kidney toxicity and improved the size and number of pancreatic islets of Langerhans, indicating its potential application in treating T2D. The study highlighted that a supplement of the two organic acids may be beneficial in reducing the rate of pathogenesis of type 2 diabetes. Therefore, it may offer therapeutic value as a dietary or nutritional supplement in the approach against diabetes and its complications.
PubMed: 38938594
DOI: 10.1155/2024/5556722 -
Frontiers in Immunology 2024This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved...
This report details a case of pancreatic cancer with liver metastasis that exhibited a positive immune response to personalized immunization therapy. Our study involved the identification of neoantigens and their corresponding immunogenic peptides using an in-house bioinformatic pipeline. This process included the identification of somatic mutations through DNA/RNA sequencing of solid tumor tissue and blood liquid biopsy. Computational prediction techniques were then employed to identify novel epitopes, followed by the design and manufacture of patient-specific immunization peptides. In combination with standard-of-care chemotherapy, the patient received a sequence of 5 biweekly prime injections followed by 2 boost injections 2 and 5 months later. The peptides were emulsified in Montanide and the injection-site was conditioned with nivolumab and imiquimod. The combined regimen of peptide immunization and chemotherapy resulted in a notable decline in CA19-9 tumor marker levels following both prime and boost applications. Subsequent MRI assessments revealed a reduction in the size of liver metastases several months post-immunization initiation. Importantly, the patient showed and improved overall survival and reported an improved quality of life without experiencing significant treatment-related adverse effects. This case underscores the potential benefits of personalized peptide-based immunization as an adjunctive therapy in the treatment of advanced pancreatic cancer, showcasing promising outcomes in tumor marker reduction, tumor shrinkage, and enhanced patient well-being.
Topics: Humans; Pancreatic Neoplasms; Antigens, Neoplasm; Liquid Biopsy; Precision Medicine; Cancer Vaccines; Liver Neoplasms; Male; Peptides; Middle Aged; Vaccines, Subunit; Immunization; Female; Biomarkers, Tumor
PubMed: 38938562
DOI: 10.3389/fimmu.2024.1414737 -
Frontiers in Endocrinology 2024Insulin resistance (IR) and beta cell dysfunction are the major drivers of type 2 diabetes (T2D). Genome-Wide Association Studies (GWAS) on IR have been predominantly...
Insulin resistance (IR) and beta cell dysfunction are the major drivers of type 2 diabetes (T2D). Genome-Wide Association Studies (GWAS) on IR have been predominantly conducted in European populations, while Middle Eastern populations remain largely underrepresented. We conducted a GWAS on the indices of IR (HOMA2-IR) and beta cell function (HOMA2-%B) in 6,217 non-diabetic individuals from the Qatar Biobank (QBB; Discovery cohort; n = 2170, Replication cohort; n = 4047) with and without body mass index (BMI) adjustment. We also developed polygenic scores (PGS) for HOMA2-IR and compared their performance with a previously derived PGS for HOMA-IR (PGS003470). We replicated 11 loci that have been previously associated with HOMA-IR and 24 loci that have been associated with HOMA-%B, at nominal statistical significance. We also identified a novel locus associated with beta cell function near gene, tagged by rs61552983 ( = 4.38 × 10). Moreover, our best performing PGS (Q-PGS4; Adj R = 0.233 ± 0.014; = 1.55 x 10) performed better than PGS003470 (Adj R = 0.194 ± 0.014; = 5.45 x 10) in predicting HOMA2-IR in our dataset. This is the first GWAS on HOMA2 and the first GWAS conducted in the Middle East focusing on IR and beta cell function. Herein, we report a novel locus in that is implicated in beta cell dysfunction. Inclusion of under-represented populations in GWAS has potentials to provide important insights into the genetic architecture of IR and beta cell function.
Topics: Humans; Insulin Resistance; Genome-Wide Association Study; Female; Male; Middle Aged; Multifactorial Inheritance; Diabetes Mellitus, Type 2; Adult; Qatar; Polymorphism, Single Nucleotide; Insulin-Secreting Cells; Aged; Body Mass Index; Cohort Studies; Genetic Predisposition to Disease
PubMed: 38938516
DOI: 10.3389/fendo.2024.1384103 -
International Journal of Genomics 2024related hypertriglyceridemia occurs due to biallelic variants of this gene. Here, genotype-phenotype architecture of all pathogenic variants is investigated among...
related hypertriglyceridemia occurs due to biallelic variants of this gene. Here, genotype-phenotype architecture of all pathogenic variants is investigated among heterozygous and homozygous individuals. Clinical heterogeneity of various types of the variants is also described, and pancreatitis in more than half of homozygotes carrying chain-termination variants is highlighted as well. For this study, patients were selected who had a plasma triglyceride level above 250 mg/dL. The coding and intronic regions of the gene were amplified using the Sanger sequencing to investigate the presence of variants. The genotypes, lipid profiles, and detailed clinical features were documented for all -related patients and heterozygous individuals. Pathogenicity of the variants was predicted and categorized using available bioinformatics tools such as MutationTaster and PolyPhen-2 and ACMG criteria. MetaDome and Phyre2 were applied for structural and functional in silico analyses. 40% (12 out of 30) of variants were chain-termination (nonsense and frameshift) variants. These types of variants were determined in 60.53% of patients. 55% of these patients showed pancreatitis followed by lipemia retinalis (29%), abdominal pain (24%), hepatosplenomegaly (24%), and xanthomas (18%). The mean age of onset was about 22 years old. In at least 50% of 38 homozygous individuals, the TG level was more than 2000 mg/dL. More than 25% of heterozygous individuals showed at least one symptom. Pancreatitis and a severe form of HTG were found in 5 and 2% of heterozygous individuals, respectively. The main clinical features of -related hypertriglyceridemia include pancreatitis, lipemia retinalis, abdominal pain, hepatosplenomegaly, and xanthomas. Nonsense and frameshift homozygous variants usually lead to a severe form of hypertriglyceridemia. Pancreatitis is one of the main consequences of these types of mutations; thus, it is important to consider this point when evaluating asymptomatic individuals. Heterozygous individuals may become symptomatic due to the role of unknown modifying agent including environmental genetic factors.
PubMed: 38938447
DOI: 10.1155/2024/6653857