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Cureus Jul 2024Heterotaxy is a syndrome characterized by a spectrum of anatomical anomalies in organ lateralization due to embryological errors. It frequently involves intrathoracic...
Heterotaxy is a syndrome characterized by a spectrum of anatomical anomalies in organ lateralization due to embryological errors. It frequently involves intrathoracic organs, especially the heart, leading to congenital abnormalities. Abdominal organs can also be affected, causing clinical features such as sepsis from asplenia or intestinal volvulus; however, these are less studied. Currently, there is no data on the relationship between heterotaxy and malignancy. We present an interesting case of an elderly adult admitted for a workup of newly diagnosed pancreatic ductal carcinoma, who was found to have heterotaxy of the stomach and spleen, with eventual tumor invasion of these organs. This case suggests that heterotaxy may increase the risk of gastrointestinal malignancy and result in a poorer prognosis due to the complexity of tumor resection involving additional organs.
PubMed: 38957513
DOI: 10.7759/cureus.63664 -
TheScientificWorldJournal 2024The medicinal plant . is used to treat cardiovascular disease, chronic fatigue, low libido, as well as increased diuresis. However, studies considering the toxicity of...
The medicinal plant . is used to treat cardiovascular disease, chronic fatigue, low libido, as well as increased diuresis. However, studies considering the toxicity of this plant are scarce. Develop an aqueous extract of considering traditional use and determine the average lethality (LD), signs, and symptoms of toxicity. The extract was obtained by immersing the root bark in ultrapure water for 18 hours at 4°C, under constant stirring. The test extract was administered in a single dose of 2.000 mg/kg by gavage to rats. Signs and symptoms of toxicity were determined according to the Hippocratic screening test and compared with the control group. In addition, a necropsy was performed for macroscopic evaluation of the organs in the abdominal cavity. A powder was obtained from aqueous extracts that showed the same organoleptic characteristics and emulsification capacity as those presented by the fresh root when prepared according to popular tradition. The LD was greater than the test dose with three animals surviving. On the other hand, necropsy of dead rats showed necrosis and reduction in lung mass, in addition to the presence of foam and excessive distension of the stomach and intestines. The main symptoms of toxicity were anesthesia, ataxia, sedation, loss of muscle strength, and excessive drowsiness in the first 24 hours. There was no difference between the control and extract groups with regard to body mass, food, and water intake, as well as in macroscopy of the heart, liver, lungs, intestines, spleen, pancreas, and kidneys. The aqueous extract of the was considered nontoxic or of very low toxicity. However, it is capable of altering the activity of the central nervous system and causing disorders in the respiratory and digestive systems.
Topics: Animals; Plant Extracts; Rats; Plant Bark; Male; Plant Roots; Lethal Dose 50; Female; Toxicity Tests, Acute; Rats, Wistar; Models, Animal
PubMed: 38957454
DOI: 10.1155/2024/8991384 -
Frontiers in Endocrinology 2024This study aimed to construct a machine learning model using clinical variables and ultrasound radiomics features for the prediction of the benign or malignant nature of...
OBJECTIVE
This study aimed to construct a machine learning model using clinical variables and ultrasound radiomics features for the prediction of the benign or malignant nature of pancreatic tumors.
METHODS
242 pancreatic tumor patients who were hospitalized at the First Affiliated Hospital of Guangxi Medical University between January 2020 and June 2023 were included in this retrospective study. The patients were randomly divided into a training cohort (n=169) and a test cohort (n=73). We collected 28 clinical features from the patients. Concurrently, 306 radiomics features were extracted from the ultrasound images of the patients' tumors. Initially, a clinical model was constructed using the logistic regression algorithm. Subsequently, radiomics models were built using SVM, random forest, XGBoost, and KNN algorithms. Finally, we combined clinical features with a new feature RAD prob calculated by applying radiomics model to construct a fusion model, and developed a nomogram based on the fusion model.
RESULTS
The performance of the fusion model surpassed that of both the clinical and radiomics models. In the training cohort, the fusion model achieved an AUC of 0.978 (95% CI: 0.96-0.99) during 5-fold cross-validation and an AUC of 0.925 (95% CI: 0.86-0.98) in the test cohort. Calibration curve and decision curve analyses demonstrated that the nomogram constructed from the fusion model has high accuracy and clinical utility.
CONCLUSION
The fusion model containing clinical and ultrasound radiomics features showed excellent performance in predicting the benign or malignant nature of pancreatic tumors.
Topics: Humans; Pancreatic Neoplasms; Machine Learning; Female; Male; Retrospective Studies; Ultrasonography; Middle Aged; Aged; Adult; Nomograms; Radiomics
PubMed: 38957447
DOI: 10.3389/fendo.2024.1381822 -
Frontiers in Pharmacology 2024The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin's antioxidant and anticancer... (Review)
Review
The bioactive compounds present in citrus fruits are gaining broader acceptance in oncology. Numerous studies have deciphered naringenin's antioxidant and anticancer potential in human and animal studies. Naringenin (NGE) potentially suppresses cancer progression, thereby improving the health of cancer patients. The pleiotropic anticancer properties of naringenin include inhibition of the synthesis of growth factors and cytokines, inhibition of the cell cycle, and modification of several cellular signaling pathways. As an herbal remedy, naringenin has significant pharmacological properties, such as anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and anti-cancer activities. The inactivation of carcinogens following treatment with pure naringenin, naringenin-loaded nanoparticles, and naringenin combined with anti-cancer agents was demonstrated by data and studies. These studies included colon cancer, lung neoplasms, breast cancer, leukemia and lymphoma, pancreatic cancer, prostate tumors, oral squamous cell carcinoma, liver cancer, brain tumors, skin cancer, cervical and ovarian cancers, bladder neoplasms, gastric cancer, and osteosarcoma. The effects of naringenin on processes related to inflammation, apoptosis, proliferation, angiogenesis, metastasis, and invasion in breast cancer are covered in this narrative review, along with its potential to develop novel and secure anticancer medications.
PubMed: 38957397
DOI: 10.3389/fphar.2024.1406619 -
Scandinavian Journal of Gastroenterology Jul 2024: International guidelines currently recommend the use of molecular testing in patients with advanced pancreatic cancer. The rate of actionable molecular alterations is...
Molecular testing for personalized therapy is underutilized in patients with borderline resectable and locally advanced pancreatic cancer - real world data from the NORPACT-2 study.
: International guidelines currently recommend the use of molecular testing in patients with advanced pancreatic cancer. The rate of actionable molecular alterations is low. The utility of molecular testing in patients with borderline resectable (BRPC) or locally advanced (LAPC) pancreatic cancer in real world clinical practice is unclear. 188 consecutive patients included in a prospective, population-based study (NORPACT-2) in patients with BRPC and LAPC (2018-2020) were reviewed. Molecular testing was performed at the discretion of the treating oncologist and was not recommended as a routine investigation by the national guidelines. All patients were considered fit to undergo primary chemotherapy and potential surgical resection. The frequency and the results of molecular testing (microsatellite instability (MSI) and/or KRAS status) were assessed. Thirty patients (16%) underwent molecular testing. MSI tumour was detected in one (3.6%) of 28 tested patients. The patient received immunotherapy and subsequently underwent surgical resection. Histological assessment of the resected specimen revealed a complete response. KRAS wild type was detected in one (14.3%) of seven tested patient. Patients who initiated FOLFIRINOX as the primary chemotherapy regimen ( = 0.022), or were being treated at one of the eight hospital trusts ( = 0.001) were more likely to undergo molecular testing. Molecular testing was rarely performed in patients with BRPC or LAPC. Routine molecular testing for all patients with BRPC and LAPC should be considered to increase identification of targetable mutations and improve outcomes.
PubMed: 38957079
DOI: 10.1080/00365521.2024.2373115 -
Endocrine, Metabolic & Immune Disorders... Jul 2024Diabetes mellitus is a common chronic metabolic disease characterized by a high incidence and disability rate. Intestinal flora refers to the microbial community that...
Diabetes mellitus is a common chronic metabolic disease characterized by a high incidence and disability rate. Intestinal flora refers to the microbial community that lives in the intestines and plays a crucial role in maintaining intestinal health and the human immune system. In recent years, an increasing body of research has revealed a close relationship between intestinal flora and diabetes. The pathophysiological mechanisms between them have also been constantly uncovered, and the regulation of intestinal flora has shown promising efficacy in the adjuvant treatment of diabetes. This study mainly summarized the characteristics and mechanisms of intestinal flora in patients with diabetes in recent years, as well as the methods of regulating intestinal flora to prevent and treat diabetes, and prospected the future research direction. This will offer a theoretical basis for the clinical adjuvant treatment of diabetes with intestinal flora and the development of new drugs.
PubMed: 38956918
DOI: 10.2174/0118715303308965240624054156 -
Current Diabetes Reviews Jul 2024Diabetes mellitus (DM), arising from pancreatic β-cell dysfunction and disrupted alpha-amylase secretion, manifests as hyperglycemia. Synthetic inhibitors of...
BACKGROUND
Diabetes mellitus (DM), arising from pancreatic β-cell dysfunction and disrupted alpha-amylase secretion, manifests as hyperglycemia. Synthetic inhibitors of alphaamylase like acarbose manage glucose but pose adverse effects, prompting interest in plantderived alternatives rich in antioxidants and anti-inflammatory properties.
OBJECTIVE
The current review investigates plant-based alpha-amylase inhibitors, exploring their potential therapeutic roles in managing DM. Focusing on their ability to modulate postprandial hyperglycemia by regulating alpha-amylase secretion, it assesses their efficacy, health benefits, and implications for diabetes treatment.
METHOD
This review examines plant-derived alpha-amylase inhibitors as prospective diabetic mellitus treatments using PubMed, Google Scholar, and Scopus data.
RESULTS
Plant-derived inhibitors, including A. deliciosa, B. egyptiaca, and N. nucifera, exhibit anti-inflammatory and antioxidant properties, effectively reducing alpha-amylase levels in diabetic conditions. Such alpha-amylase inhibitors showed promising alternative treatment in managing diabetes with reduced adverse effects.
CONCLUSION
The current literature concludes that plant-derived alpha-amylase inhibitors present viable therapeutic avenues for diabetes management by modulating alpha-amylase secretion by regulating inflammatory, oxidative stress, and apoptotic mechanisms involved in the pathogenesis of diabetes. Further investigation into their formulations and clinical efficacy may reveal their more comprehensive diabetes therapeutic significance, emphasizing their potential impact on glucose regulation and overall health.
.PubMed: 38956911
DOI: 10.2174/0115733998304373240611110224 -
Molecular Therapy : the Journal of the... Jul 2024Chronic pancreatitis (CP) is marked by progressive fibrosis and the activation of pancreatic stellate cells (PSC), accompanied by the destruction of pancreatic...
Chronic pancreatitis (CP) is marked by progressive fibrosis and the activation of pancreatic stellate cells (PSC), accompanied by the destruction of pancreatic parenchyma, leading to the loss of acinar cells (ACs). Few researches explored the mechanism by which damaged ACs (DACs) contribute to PSC activation and pancreatic fibrosis. Currently, there are no effective drugs for curing CP or limiting the progression of pancreatic fibrosis. In this research, co-culture with intact acinar cells (IACs) suppressed PSC activation, while co-culture with DACs did the opposite. Krüppel-like factor 4 (KLF4) was significantly upregulated in DACs and was established as the key molecule that switches ACs from PSC-suppressor to PSC-activator. We revealed the exosomes of IACs contributed to the anti-activated function of IACs-CS on PSC. MiRNome profiling showed that let-7 family is significantly enriched in IACs-derived exosomes (>30% miRNome), which partially mediates IACs' suppressive impacts on PSC. Furthermore, it has been observed that the enrichment of let-7 in exosomes was influenced by the expression level of KLF4. Mechanistic studies demonstrated that KLF4 in ACs upregulated Lin28A, thereby decreasing let-7s levels in ACs-derived exosomes, and thus promoting PSC activation. We utilized an adeno-associated virus specifically targeting KLF4 in ACs (shKLF4-pAAV) to suppress PSC activation in CP, resulting in reduced pancreatic fibrosis. IACs-derived exosomes hold potential as potent weapons against PSC activation via let-7s, while activated KLF4/Lin28A signaling in DACs diminished such functions. ShKLF4-pAAV holds promise as a novel therapeutic approach for CP.
PubMed: 38956871
DOI: 10.1016/j.ymthe.2024.06.030 -
International Journal of Cancer Jul 2024There are no clear guidelines regarding the optimal treatment sequence for advanced pancreatic cancer, as head-to-head phase III randomised trials are missing. We assess...
There are no clear guidelines regarding the optimal treatment sequence for advanced pancreatic cancer, as head-to-head phase III randomised trials are missing. We assess real-world effectiveness of three common sequential treatment strategies by emulating a hypothetical randomised trial. This analysis included 1551 patients with advanced pancreatic cancer from the prospective, clinical cohort study Tumour Registry Pancreatic Cancer receiving FOLFIRINOX (n = 613) or gemcitabine/nab-paclitaxel (GEMNAB; n = 938) as palliative first-line treatment. We used marginal structural modelling to compare overall survival (OS) and time to deterioration (TTD) of health-related quality of life (HRQoL) between three common first- to second-line treatment sequences, adjusting for time-varying potential confounding. The sequences were: FOLFIRINOX→GEMNAB, GEMNAB→FOLFOX/OFF and GEMNAB→nanoliposomal irinotecan (NALIRI) + 5-fluorouracil. Outcome was also calculated stratified by patients' prognostic risk according to the Pancreatic Cancer Score. Median OS and TTD of HRQoL independent of risk were 10.7 [8.9, 11.9] and 6.4 [4.8, 7.7] months for FOLFIRINOX→GEMNAB, 8.4 [7.4, 9.7] and 5.8 [4.6, 7.1] months for GEMNAB→FOLFOX/OFF and 8.9 [7.8, 10.4] and 4.6 [4.1, 6.1] months for GEMNAB→NALIRI+5-fluorouracil. Compared to FOLFIRINOX→GEMNAB, OS and TTD were worse for poor-risk patients with GEMNAB→FOLFOX/OFF (OS: HR 2.09 [1.47, 2.98]; TTD: HR 1.97 [1.19, 3.27]) and those with GEMNAB→NALIRI+5-fluorouracil (OS: HR 1.35, [0.76, 2.39]; TTD: HR 2.62 [1.56, 4.42]). Brackets denote 95%-confidence intervals. The estimated real-world effectiveness of the three treatment sequences evaluated were largely comparable. Poor-risk patients might benefit from intensified treatment with FOLFIRINOX→GEMNAB in terms of clinical and patient-reported outcomes. Future randomised trials on sequential treatments in advanced pancreatic cancer are warranted.
PubMed: 38956837
DOI: 10.1002/ijc.35071 -
Journal of Anesthesia, Analgesia and... Jul 2024Pancreatic surgery is associated with a significant risk for acute kidney injury (AKI) and clinically relevant postoperative pancreatic fistula (CR-POPF). This...
BACKGROUND
Pancreatic surgery is associated with a significant risk for acute kidney injury (AKI) and clinically relevant postoperative pancreatic fistula (CR-POPF). This investigation evaluated the impact of intraoperative volume administration, vasopressor therapy, and blood pressure management on the primary outcome of AKI and the secondary outcome of a CR-POPF after pancreatic surgery.
METHODS
This retrospective single-center cohort investigated 200 consecutive pancreatic surgeries (January 2018-December 2021). Patients were categorized for the presence/absence of AKI (Kidney Disease Improving Global Outcomes) and CR-POPF. After univariate analysis, multivariable models were constructed to control for the univariate cofactor differences in the primary and secondary outcomes.
RESULTS
AKI was identified in 20 patients (10%) with significant univariate differences in demographics (body mass index and gender), comorbidities, indices of chronic renal insufficiency, and an increased AKI Risk score. Surgical characteristics, intraoperative fluid, vasopressor, and blood pressure management were similar in patients with and without AKI. Patients with AKI had increased blood loss, lower urine output, and packed red blood cell administration. After multivariate analysis, male gender (OR = 7.9, 95% C.I. 1.8-35.1) and the AKI Risk score (OR = 6.3, 95% C.I. 2.4-16.4) were associated with the development of AKI (p < 0.001). Intraoperative and postoperative volume, vasopressor administration, and intraoperative hypotension had no significant impact in the multivariate analysis. CR-POPF occurred in 23 patients (11.9%) with no significant contributing factors in the multivariate analysis. Patients who developed AKI or a CR-POPF had an increase in surgical complications, length of stay, discharge to a skilled nursing facility, and mortality.
CONCLUSION
In this analysis, intraoperative volume administration, vasopressor therapy, and a blood pressure < 55 mmHg for more than 10 min were not associated with an increased risk of AKI. After multivariate analysis, male gender and an elevated AKI Risk score were associated with an increased likelihood of AKI.
PubMed: 38956707
DOI: 10.1186/s44158-024-00176-0