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Endocrinology, Diabetes & Metabolism Jul 2024To determine the incidence, presentation, frequency and management of immune checkpoint inhibitors (ICI)-related endocrinopathies in a comprehensive cancer centre in...
OBJECTIVES
To determine the incidence, presentation, frequency and management of immune checkpoint inhibitors (ICI)-related endocrinopathies in a comprehensive cancer centre in Oman, particularly with programme death 1/programme death-ligand 1 (PD-1/PD-L1) inhibitors.
BACKGROUND
A high number of patients treated with PD-1/PD-L1 inhibitors for the management of solid tumours developed endocrinopathies.
METHODS
This is a retrospective study of patients admitted to Sultan Qaboos Comprehensive Cancer Care and Research Centre (SQCCCRC) from August 2021 to December 2022. All adults diagnosed with solid cancers and have received at least one dose of ICIs were included. Patients with incomplete data were excluded from the analysis. Data regarding the ICI-induced endocrinopathy were collected.
RESULTS
A total of 139 patients were included in the study of which 58% were females. The median age of the cohort was 56 years. The incidence of endocrine-related adverse events was 28%. The mean time for the development of endocrine adverse events after treatment initiation was 4.1 ± 2.8 months. Of the patients who developed toxicity, 90% had hypothyroidism. Ten patients developed hyperthyroidism, two patients were diagnosed with secondary adrenal insufficiency/hypophysitis and one patient developed Type 1 diabetes mellitus (DM). Using univariable logistic regression weight and body mass index (BMI) significantly impacted the development of endocrine immune-related adverse events (irAEs).
CONCLUSIONS
This is the first study from the Sultanate of Oman to assess PD-1/PDL-1 ICI-induced endocrinopathies. The most common endocrine adverse event is thyroid dysfunction, mainly hypothyroidism followed by hyperthyroidism. Hypophysitis, primary adrenal insufficiency and CIADM occur less frequently, but have a more significant effect on the patient's health. The treating physician should be aware of ICI-induced endocrinopathies, screening and treatment. Furthermore, our study showed that patients with a higher BMI have a greater risk of developing irAES. Further studies are needed to establish the predictors of endocrine irAEs.
Topics: Humans; Female; Male; Immune Checkpoint Inhibitors; Retrospective Studies; Middle Aged; Endocrine System Diseases; Neoplasms; Oman; Adult; Aged; Incidence; Cancer Care Facilities; Hypothyroidism
PubMed: 38932429
DOI: 10.1002/edm2.505 -
Viruses Jun 2024Increasing testing is key to achieving hepatitis C elimination. This retrospective study aimed to assess the testing cascade of patients at a regional hospital in...
Increasing testing is key to achieving hepatitis C elimination. This retrospective study aimed to assess the testing cascade of patients at a regional hospital in Victoria, Australia, who inject drugs or are living with hepatitis C, to identify missed opportunities for hepatitis C care. Adult hospital inpatients and emergency department (ED) attendees from 2018 to 2021 with indications for intravenous drug use (IDU) or hepatitis C on their discharge or ED summary were included. Data sources: hospital admissions, pathology, hospital pharmacy, and outpatients. We assessed progression through the testing cascade and performed logistic regression analysis for predictors of hepatitis C care, including testing and treatment. Of 79,923 adults admitted, 1345 (1.7%) had IDU-coded separations and 628 (0.8%) had hepatitis C-coded separations (N = 1892). Hepatitis C virus (HCV) status at the end of the study was unknown for 1569 (82.9%). ED admissions were associated with increased odds of not providing hepatitis C care (odds ratio 3.29, 95% confidence interval 2.42-4.48). More than 2% of inpatients at our hospital have an indication for testing, however, most are not being tested despite their hospital contact. As we work toward HCV elimination in our region, we need to incorporate testing and linkage strategies within hospital departments with a higher prevalence of people at risk of infection.
Topics: Humans; Retrospective Studies; Male; Hepatitis C; Female; Middle Aged; Adult; Inpatients; Hepacivirus; Substance Abuse, Intravenous; Hospitalization; Victoria; Aged; Emergency Service, Hospital; Mass Screening; Young Adult
PubMed: 38932269
DOI: 10.3390/v16060979 -
Viruses May 2024Hepatitis B core-related antigen (HBcrAg) reflects the activity of intrahepatic covalently closed circular DNA. HBcrAg can be detected even in chronic hepatitis B... (Review)
Review
Hepatitis B core-related antigen (HBcrAg) reflects the activity of intrahepatic covalently closed circular DNA. HBcrAg can be detected even in chronic hepatitis B patients in whom serum HBV DNA or hepatitis B surface antigen is undetectable. The HBcrAg measurement system was developed based on two concepts. One is a fully-automated and highly-sensitive HBcrAg assay (iTACT-HBcrAg) and the other is a point-of-care testing (POCT) that can be used in in resource-limited areas. iTACT-HBcrAg is an alternative to HBV DNA for monitoring HBV reactivation and predicting the development of hepatocellular carcinoma. This validated biomarker is available in routine clinical practice in Japan. Currently, international guidelines for the prevention of mother-to-child transmission recommend anti-HBV prophylaxis for pregnant women with high viral loads. However, over 95% of HBV-infected individuals live in countries where HBV DNA quantification is widely unavailable. Given this situation, a rapid and simple HBcrAg assay for POCT would be highly effective. Long-term anti-HBV therapy may have potential side effects and appropriate treatment should be provided to eligible patients. Therefore, a simple method of determining the indication for anti-HBV treatment would be ideal. This review provides up-to-date information regarding the clinical value of HBcrAg in HBV management, based on iTACT-HBcrAg or POCT.
Topics: Humans; Hepatitis B Core Antigens; Hepatitis B virus; DNA, Viral; Hepatitis B; Biomarkers; Sensitivity and Specificity; Point-of-Care Testing; Mass Screening; Carcinoma, Hepatocellular; Female; Hepatitis B, Chronic; Infectious Disease Transmission, Vertical; Viral Load; Pregnancy; Liver Neoplasms; Hepatitis B Surface Antigens
PubMed: 38932141
DOI: 10.3390/v16060848 -
Pharmaceuticals (Basel, Switzerland) May 2024Dasatinib is one of the tyrosine kinase inhibitors. The main use of these agents is inhibition of cancerous cell proliferation. The therapeutic importance of tyrosine...
BACKGROUND AND OBJECTIVES
Dasatinib is one of the tyrosine kinase inhibitors. The main use of these agents is inhibition of cancerous cell proliferation. The therapeutic importance of tyrosine kinase inhibitors raises the necessity of many types of investigations, especially the pharmacokinetic analysis of these drugs in humans. This analysis, along with other investigations and clinical research, will contribute to the overall knowledge of the drug. This study focused on the population pharmacokinetics of dasatinib. The objective of the study was to investigate the sources of the variability of dasatinib in a population pharmacokinetics study in healthy participants.
METHODS
We utilized 4180 plasma observations from 110 subjects who were administered SPRYCEL on two separate occasions under fasting conditions; data from 20% of the subjects (22 subjects) were extracted for the purpose of internal model evaluation and data from 88 subjects were used in modeling. The model was evaluated by visual predictive check of three different datasets. A two-compartmental model with first order absorption and transit compartment was considered the simplest base model to describe the data based on the corrected Bayesian information criterion evaluation. Covariates were tested through conditional sampling for the stepwise approach-screening procedure in Monolix 2020R1 version. Conditional sampling for the stepwise approach was used to include the correlated covariates within the base model in the forward inclusion step and then to eliminate them backwardly to ensure that the key covariates were kept in the model at the final stage.
RESULTS
The effect of body mass index on the absorption rate constant was considered as significant covariate in the final established model. Visual predictive check for simulations, 20% of the original dataset (internal dataset) and an external dataset demonstrated the appropriateness of the final model.
CONCLUSIONS
Population pharmacokinetic modeling was performed to describe dasatinib pharmacokinetics in healthy subjects. Body mass index was considered as a factor that might be used in the future along with studies on patients to adjust the dosing regimens.
KEY POINTS
Dasatinib is classified as a highly variable drug; this variability was demonstrated in the study by the effect of body mass index on the absorption rate constant.
PubMed: 38931339
DOI: 10.3390/ph17060671 -
Nutrients Jun 2024Preoperative malnutrition is a significant factor in patients with pancreatic tumors undergoing pancreaticoduodenectomy. The aim of this study was to assess the...
BACKGROUND
Preoperative malnutrition is a significant factor in patients with pancreatic tumors undergoing pancreaticoduodenectomy. The aim of this study was to assess the association between preoperative malnutrition and delayed discharge within a ten-day timeframe and potential correlations between preoperative malnutrition and postoperative surgical complications.
METHODS
A retrospective cohort study was conducted, recruiting a final sample of 79 patients with benign or malignant cephalic pancreatic tumors from 2015 to 2022. The risk of malnutrition was assessed using the Malnutrition Universal Screening Tool, while length of hospital stay and relevant clinical data were extracted from clinical documentation.
RESULTS
The preoperative malnutrition risk was high in 21.52% of the sample, moderate in 36.71%, and low in 41.77%. Body mass index (BMI) ( = 0.007) and postoperative surgical complications ( < 0.001) were significantly correlated with delayed discharge. No statistically significant differences were found between levels of malnutrition risk and delayed discharge ( = 0.122), or postoperative surgical complications ( = 0.874).
CONCLUSIONS
Postoperative complications and BMI emerge as significant risk factors. The limited sample size may have compromised the collection of homogeneous and significant data. Future studies should evaluate the implementation of personalized nutritional screening tools, nutritional assessment plans, and the involvement of specialized health professionals.
Topics: Humans; Malnutrition; Retrospective Studies; Male; Female; Pancreatic Neoplasms; Pancreaticoduodenectomy; Middle Aged; Postoperative Complications; Aged; Risk Factors; Nutrition Assessment; Length of Stay; Body Mass Index; Preoperative Period; Nutritional Status; Adult; Patient Discharge; Cohort Studies
PubMed: 38931194
DOI: 10.3390/nu16121839 -
Molecules (Basel, Switzerland) Jun 2024Secondary metabolites, bioactive compounds produced by living organisms, can unveil symbiotic relationships in nature. In this study, soilborne entomopathogenic...
Preliminary Screening on Antibacterial Crude Secondary Metabolites Extracted from Bacterial Symbionts and Identification of Functional Bioactive Compounds by FTIR, HPLC and Gas Chromatography-Mass Spectrometry.
Secondary metabolites, bioactive compounds produced by living organisms, can unveil symbiotic relationships in nature. In this study, soilborne entomopathogenic nematodes associated with symbiotic bacteria ( and ) were extracted from solvent supernatant containing secondary metabolites, demonstrating significant inhibitory effects against , , , , , and . The characterization of these secondary metabolites by Fourier transforms infrared spectroscopy revealed amine groups of proteins, hydroxyl and carboxyl groups of polyphenols, hydroxyl groups of polysaccharides, and carboxyl groups of organic acids. Furthermore, the obtained crude extracts were analyzed by high-performance liquid chromatography for the basic identification of potential bioactive peptides. Gas chromatography-mass spectrometry analysis of ethyl acetate extracts from identified major compounds including nonanoic acid derivatives, proline, paromycin, octodecanal derivatives, trioxa-5-aza-1-silabicyclo, 4-octadecenal, methyl ester, oleic acid, and 1,2-benzenedicarboxylicacid. Additional extraction from yielded functional compounds such as indole-3-acetic acid, phthalic acid, 1-tetradecanol, nemorosonol, 1-eicosanol, and unsaturated fatty acids. These findings support the potential development of novel natural antimicrobial agents for future pathogen suppression.
Topics: Chromatography, High Pressure Liquid; Anti-Bacterial Agents; Spectroscopy, Fourier Transform Infrared; Gas Chromatography-Mass Spectrometry; Symbiosis; Secondary Metabolism; Photorhabdus; Xenorhabdus; Microbial Sensitivity Tests; Animals
PubMed: 38930979
DOI: 10.3390/molecules29122914 -
Molecules (Basel, Switzerland) Jun 2024The content of chemical constituents in leaf extracts correlates positively with biological activities. The experimental objective was to carry out the phytochemical...
The content of chemical constituents in leaf extracts correlates positively with biological activities. The experimental objective was to carry out the phytochemical screening and purification of the major polyphenols from the leaves of . In addition, the anti- activity of the hydroalcoholic extract, fraction, subfractions and polyphenols purified were evaluated. After partitioning of the extract with ethyl acetate, the fractions were chromatographed on Sephadex LH-20 gel followed by RP-flash chromatography and monitored by TLC and RP-HPLC. The samples were characterized by mass spectrometry (LC-ESI-QTOF-MS) and subjected to the microdilution method in 96-well plates against strains of , and . Myricitrin (93.89%; /; / 463.0876), gallic acid (99.9%; /; / 169.0142), and ellagic acid (94.2%; /; / 300.9988) were recovered. The polyphenolic fraction (62.67% (/) myricitrin) and the ellagic fraction (67.86% (/) ellagic acid) showed the best antifungal performance (MIC between 62.50 and 500 μg/mL), suggesting an association between the majority constituents and the antifungal response of derivatives. However, there is a clear dependence on the presence of the complex chemical mixture. In conclusion, chromatographic strategies were effectively employed to recover the major polyphenols from the leaves of the species.
Topics: Polyphenols; Eugenia; Plant Leaves; Antifungal Agents; Plant Extracts; Microbial Sensitivity Tests; Candida; Tandem Mass Spectrometry; Spectrometry, Mass, Electrospray Ionization; Chromatography, High Pressure Liquid; Gallic Acid
PubMed: 38930827
DOI: 10.3390/molecules29122761 -
Microorganisms Jun 2024This study demonstrates that can produce exopolysaccharides (EPSs) using alternative carbon sources, such as sugarcane molasses and glycerol. After screening 22 strains...
This study demonstrates that can produce exopolysaccharides (EPSs) using alternative carbon sources, such as sugarcane molasses and glycerol. After screening 22 strains of Lactobacillus to determine which achieved the highest production of EPS based on dry weight at 37 °C, the strain Ke8 () was selected for new experiments. The EPS obtained using glycerol and glucose as carbon sources was classified as a heteropolysaccharide composed of glucose and mannose, containing 1730 g.mol, consisting of 39.4% carbohydrates and 18% proteins. The EPS obtained using molasses as the carbon source was characterized as a heteropolysaccharide composed of glucose, galactose, and arabinose, containing 1182 g.mol, consisting of 52.9% carbohydrates and 11.69% proteins. This molecule was characterized using Size Exclusion Chromatography (HPLC), Gas chromatography-mass spectrometry (GC-MS), Fourier-transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance spectroscopy (H-NMR). The existence of polysaccharides was confirmed via FT-IR and NMR analyses. The results obtained suggest that can grow in media that use alternative carbon sources such as glycerol and molasses. These agro-industry residues are inexpensive, and their use contributes to sustainability. The lack of studies regarding the use of for the production of EPS using renewable carbon sources from agroindustry should be noted.
PubMed: 38930541
DOI: 10.3390/microorganisms12061159 -
Microorganisms May 2024Colorectal cancer (CRC) stands as a significant global health concern, ranking second in mortality and third in frequency among cancers worldwide. While only a small... (Review)
Review
Colorectal cancer (CRC) stands as a significant global health concern, ranking second in mortality and third in frequency among cancers worldwide. While only a small fraction of CRC cases can be attributed to inherited genetic mutations, the majority arise sporadically due to somatic mutations. Emerging evidence reveals gut microbiota dysbiosis to be a contributing factor, wherein polyketide synthase-positive (pks+ ) plays a pivotal role in CRC pathogenesis. pks+ bacteria produce colibactin, a genotoxic protein that causes deleterious effects on DNA within host colonocytes. In this review, we examine the role of the gut microbiota in colon carcinogenesis, elucidating how colibactin-producer bacteria induce DNA damage, promote genomic instability, disrupt the gut epithelial barrier, induce mucosal inflammation, modulate host immune responses, and influence cell cycle dynamics. Collectively, these actions foster a microenvironment conducive to tumor initiation and progression. Understanding the mechanisms underlying pks+ bacteria-mediated CRC development may pave the way for mass screening, early detection of tumors, and therapeutic strategies such as microbiota modulation, bacteria-targeted therapy, checkpoint inhibition of colibactin production and immunomodulatory pathways.
PubMed: 38930493
DOI: 10.3390/microorganisms12061111 -
Microorganisms May 2024The extensive harvesting of , as a biomedicinal plant and a wild source of quaternary benzo[c]phenanthridine alkaloids, has led to a rapid decline in its population. An...
The extensive harvesting of , as a biomedicinal plant and a wild source of quaternary benzo[c]phenanthridine alkaloids, has led to a rapid decline in its population. An alternative approach to the production of these bioactive compounds, which are known for their diverse pharmacological effects, is needed. Production of these compounds using alkaloid-producing endophytic fungi is a promising potential approach. In this research, we isolated an alkaloid-producing endophytic fungus, strain MC503, from the roots of . Genomic analysis was conducted to elucidate its metabolic pathways and identify the potential genes responsible for alkaloid biosynthesis. High-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) analyses revealed the presence and quantified the content of sanguinarine (536.87 μg/L) and chelerythrine (393.31 μg/L) in the fungal fermentation extract. Based on our analysis of the morphological and micromorphological characteristics and the ITS region of the nuclear ribosomal DNA of the alkaloid-producing endophyte, it was identified as strain MC503. To the best of our knowledge, there is no existing report on from or other medicinal plants that produce sanguinarine and chelerythrine simultaneously. These findings provide valuable insights into the capability of to carry out isoquinoline alkaloid biosynthesis and lay the foundation for further exploration of its potential applications in pharmaceuticals.
PubMed: 38930470
DOI: 10.3390/microorganisms12061088