Investigation of genetic diversity using molecular and biochemical markers associated with powdery mildew resistance in different flax (Linum usitatissimum L.) genotypes.

Under greenhouse conditions, the resistance of 18 different genotypes of flax to powdery mildew was evaluated. To investigate genetic diversity and identify the molecular and biochemical markers linked to powdery mildew resistance in the tested genotypes, two molecular marker systems-start codon targeted (SCoT) and inter-simple sequence repeat (ISSR)-as well as a biochemical marker (protein profiles, antioxidant enzyme activity, and secondary metabolites) were used. Based on the results, the genotypes were classified into four categories: highly susceptible, susceptible, moderately susceptible, and moderately resistant. The genotypes differed significantly in powdery mildew severity: Polk had a severity of 92.03% and Leona had a severity of 18.10%. Compared to the other genotypes, the moderately resistant genotypes had higher levels of flavonoids, antioxidant enzymes, phenolics, and straw yield; nevertheless, their hydrogen peroxide and malondialdehyde levels were lower. Protein profiles revealed 93.75% polymorphism, although the ISSR marker displayed more polymorphism (78.4%) than the SCoT marker (59.7%). Specific molecular and biochemical markers associated with powdery mildew resistance were identified. The 18 genotypes of flax were divided into two major clusters by the dendrogram based on the combined data of molecular markers. The first main cluster included Leona (genotype number 7), considered moderate resistance to powdery mildew and a separate phenetic line. The second main cluster included the other 17 genotypes, which are grouped together in a sub-cluster. This means that, besides SCoT, ISSR markers can be a useful supplementary technique for molecular flax characterization and for identifying genetic associations between flax genotypes under powdery mildew infection.

A New Parametric Life Distribution with Modified Bagdonavicius-Nikulin Goodness-of-Fit Test for Censored Validation, Properties, Applications, and Different Estimation Methods.

In this paper, we first study a new two parameter lifetime distribution. This distribution includes "monotone" and "non-monotone" hazard rate functions which are useful in lifetime data analysis and reliability. Some of its mathematical properties including explicit expressions for the ordinary and incomplete moments, generating function, Renyi entropy, δ-entropy, order statistics and probability weighted moments are derived. Non-Bayesian estimation methods such as the maximum likelihood, Cramer-Von-Mises, percentile estimation, and L-moments are used for estimating the model parameters. The importance and flexibility of the new distribution are illustrated by means of two applications to real data sets. Using the approach of the Bagdonavicius-Nikulin goodness-of-fit test for the right censored validation, we then propose and apply a modified chi-square goodness-of-fit test for the Burr X Weibull model. The modified goodness-of-fit statistics test is applied for the right censored real data set. Based on the censored maximum likelihood estimators on initial data, the modified goodness-of-fit test recovers the loss in information while the grouped data follows the chi-square distribution. The elements of the modified criteria tests are derived. A real data application is for validation under the uncensored scheme.

Physicians' knowledge and practice on death certification in the North West Bank, Palestine: across sectional study.

BACKGROUND: Mortality data are essential for many aspects of everyday public health practices at both national and international levels. Despite the current developments in various aspects of the medical field, the apparent inability of physicians to complete death notification forms (DNF) accurately is still worldwide concern. The aim of this study is to assess the physicians' knowledge and practice on completing the DNF. METHODS: A self-administered questionnaire was distributed to 200 physicians in governmental and non-governmental hospitals in the North West-Bank in Palestine. Furthermore, a case scenario was included in the questionnaire and physicians were asked to fill the cause of death section. The percentage of errors committed while completing the cause of death section were computed. A Chi square test was used to assess the association between physicians' characteristics and their responses. RESULTS: Only 40.6% of the participants completed the cause of death section correctly. The immediate and underlying causes of death were correctly identified by 48.7% and 71.3% of physicians, respectively. Almost one-fifth (17.3%) of physicians wrote the mechanism of death without reporting the underlying cause of death and 14.7% of them reported the sequence of events leading to death incorrectly. CONCLUSIONS: Physicians' knowledge and practice on completing the DNF is poor and insufficient, which may seriously affect the accuracy of mortality data. Complicated cases, problems in the current design of the DNFs and lack of training were the most common factors contributing to inaccuracy in death certification. We recommend offering periodical training workshops on completing the DNF to all physicians, and developing a manual on completing the DNFs with clear instructions and guidelines.

Stearidonic acid, a plant-based dietary fatty acid, enhances the chemosensitivity of canine lymphoid tumor cells.

Lymphoma is the most common hematopoietic tumor in dogs and humans, with similar pathogenesis and therapeutic responses. Anticancer drugs like vincristine (VCR) and doxorubicin (DOX) are often used in treating lymphoma. However, the cure rate is generally poor due to chemoresistance. Here, we sought to determine whether stearidonic acid (SDA), a plant-based dietary fatty acid, sensitizes chemoresistant canine lymphoid-tumor cells. GL-1 B-cell lymphoid-tumor cells were found to be highly sensitive to the antitumor-activity of VCR and DOX, while OSW T-cell and 17-71 B-cell lymphoid-tumor cells were moderately and fully resistant, respectively. SDA, at its non-toxic concentrations, significantly promoted the antitumor action of VCR and DOX in both OSW and 17-71 cells. SDA-mediated chemosensitization was associated with SDA inhibition of P-glycoprotein (P-gp) function. This was confirmed in HEK293 cells stably expressing P-gp as well as by increased binding-affinity of SDA to P-gp in P-gp docking analysis. SDA at its chemosensitizing concentrations did not affect the viability of healthy dog peripheral blood mononuclear cells, suggesting that SDA is non-toxic to normal dog peripheral blood leucocytes at its chemosensitizing concentrations. Our study identifies a novel dietary fatty acid that may be used as a dietary supplement in combination with chemotherapy to promote the antitumor efficacy of the chemotherapy drugs in dogs and possibly in humans with chemoresistant lymphoma.

A possible antineoplastic potential of selective, irreversible proteasome inhibitor, carfilzomib on chemically induced hepatocarcinogenesis in rats.

The antineoplastic effect of carfilzomib (CFZ) against chemically induced hepatocarcinogenesis was studied. A total of 60 male Wistar albino rats were divided into six groups with 10 animals in each group. Rats in group 1 (control group) were given dimethylsulphoxide (DMSO) (0.4 mL/kg i.p) twice a week for 3 weeks from week 8 to week 10. Animals in groups 2 and 3 were given CFZ (2 and 4 mg/kg i.p) twice a week from week 8 to week 10, respectively. Rats in group 4 were given diethylnitrosamine (DENA) at a dose of 0.01% in drinking water for 10 weeks and received a DMSO (0.4 mL/kg i.p) twice a week from week 8 to week 10. Animals in groups 5 and 6 were given DENA at a dose of 0.01% in drinking water for 10 weeks and treated with CFZ (2 and 4 mg/kg i.p) twice a week from week 8 to week 10, respectively. CFZ succeeded in suppressing the elevated serum tumor marker α-fetoprotein and carcinoembryonic antigen. The antineoplastic effect of CFZ was also accompanied by normalization of elevated hepatic tissue growth factors, matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1, and augmentation of hepatic endostatin and metallothionein. A histopathological examination of liver samples treated with CFZ after DENA intoxication correlated with the biochemical observation. Treatment with CFZ confers an antineoplastic activity against chemically induced hepatocarcinogenesis. These findings suggest that CFZ plays a pivotal role in the treatment of hepatocarcinogenesis.

The existence of a bidirectional link between ischemic heart disease and fibromyalgia.

STUDY OBJECTIVES: Fibromyalgia (FM) is one of the most common causes of chronic widespread musculoskeletal pain, but also sleep disturbances, cognitive and psychological disorders. It has been suggested that FM may have a correlation with cardiovascular events. In this study, we aimed to assess the association between FM and ischemic heart disease (IHD). METHODS: A population-based cross-sectional study was conducted utilizing data retrieved from the largest medical records database in Israel, Clalit Health Services. Patients were defined as having FM or IHD when there were at least two such documented diagnoses in their medical records. The occurrence of IHD was compared between FM and age- and sex-frequency-matched healthy controls. A logistic regression model was used to estimate this association following an adjustment for conventional cardiovascular risk factors and depression. RESULTS: An overall population of 18 598 FM patients and 36 985 age- and gender-matched controls were included in the study. The proportion of IHD amongst FM patients was increased in comparison to controls (9.2% and 6.2%, respectively; P  < 0.001). Furthermore, FM demonstrated an independent association with IHD on multivariate analysis (odds ratio [OR], 1.43; 95% confidence intervals [CI], 1.33-1.54; P  < 0.0001). Finally, IHD was also found to be independently associated with the diagnosis of FM (OR, 1.40; CI, 1.31-1.51; P  < 0.0001). CONCLUSION: Our data suggest a bidirectional link between FM and IHD even after the adjustment for conventional cardiovascular risk factors. These findings should be considered when treating patients with either FM or IHD, and their routine interactional screening may be of clinical importance.

Unravelling the Phytochemical Composition and Antioxidant Potential of Different Parts of Rumex vesicarius L.: A RP-HPLC-MS-MS/MS, Chemometrics, and Molecular Docking-Based Comparative Study.

Rumex vesicarius L. Polygonaceae is a wildly grown plant in Egypt, North Africa, and Asia with wide traditional uses. Several studies reported its biological activities and richness in phytochemicals. This research addresses a comprehensive metabolic profiling of the flowers, leaves, stems, and roots via RP-HPLC-QTOF-MS and MS/MS with chemometrics. A total of 60 metabolites were observed and grouped into phenolic acids, flavonoids, phenols, terpenes, amino acids, fatty acids, organic acids, and sugars. Principal component analysis and hierarchal cluster analysis showed the segregation of different parts. Moreover, the antioxidant capacity was determined via several methods and agreed with the previous results. Additionally, an in silico approach of molecular docking of the predominant bioactive metabolites was employed against two antioxidant targets, NADPH oxidase and human peroxiredoxin 5 enzyme (PDB ID: 2CDU and 1HD2) receptors, alongside ADME predictions. The molecular modelling revealed that most of the approached molecules were specifically binding with the tested enzymes, achieving high binding affinities. The results confirmed that R. vesicarius stems and roots are rich sources of bioactive antioxidant components. To our knowledge, this is the first comprehensive metabolic profiling of R. vesicarius giving a prospect of its relevance in the development of new naturally based antioxidants.

Effects of Cannabidiol, ∆9-Tetrahydrocannabinol, and WIN 55-212-22 on the Viability of Canine and Human Non-Hodgkin Lymphoma Cell Lines.

In our previous study, we demonstrated the impact of overexpression of CB1 and CB2 cannabinoid receptors and the inhibitory effect of endocannabinoids (2-arachidonoylglycerol (2-AG) and Anandamide (AEA)) on canine (Canis lupus familiaris) and human (Homo sapiens) non-Hodgkin lymphoma (NHL) cell lines' viability compared to cells treated with a vehicle. The purpose of this study was to demonstrate the anti-cancer effects of the phytocannabinoids, cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), and the synthetic cannabinoid WIN 55-212-22 (WIN) in canine and human lymphoma cell lines and to compare their inhibitory effect to that of endocannabinoids. We used malignant canine B-cell lymphoma (BCL) (1771 and CLB-L1) and T-cell lymphoma (TCL) (CL-1) cell lines, and human BCL cell line (RAMOS). Our cell viability assay results demonstrated, compared to the controls, a biphasic effect (concentration range from 0.5 µM to 50 µM) with a significant reduction in cancer viability for both phytocannabinoids and the synthetic cannabinoid. However, the decrease in cell viability in the TCL CL-1 line was limited to CBD. The results of the biochemical analysis using the 1771 BCL cell line revealed a significant increase in markers of oxidative stress, inflammation, and apoptosis, and a decrease in markers of mitochondrial function in cells treated with the exogenous cannabinoids compared to the control. Based on the IC50 values, CBD was the most potent phytocannabinoid in reducing lymphoma cell viability in 1771, Ramos, and CL-1. Previously, we demonstrated the endocannabinoid AEA to be more potent than 2-AG. Our study suggests that future studies should use CBD and AEA for further cannabinoid testing as they might reduce tumor burden in malignant NHL of canines and humans.

Comparative performance of liquid chromatography and spectrophotometry in determining metformin hydrochloride within pharmaceutical formulations.

The present study compared the performance of Ultra-high performance liquid chromatography (UHPLC) and UV-Vis spectrophotometry for the quantification of metformin hydrochloride in five commercially available metformin hydrochloride products with different strengths. The metformin hydrochloride was measured in the UHPLC with a mobile phase consisting of a mixture of 0.05 M phosphate buffer solution and methanol (35:65, v/v) with a pH of 3.6. Metformin hydrochloride was determined spectrophotometrically at 234 nm using a mixture of methanol and water as a blank. The methods' linearity for metformin hydrochloride was within the concentration range of (2.5-40 µg/ml) in both techniques. The validation process encompassed assessments of specificity, selectivity, linearity, accuracy, precision, the lower limit of quantification (LLOQ), the lower limit of detection (LLOD), robustness, and system suitability. For the UHPLC validation method, the repeatability and reproducibility (expressed as relative standard deviation) were less than 1.578 and 2.718 %, respectively. The LLOQ for metformin hydrochloride was 0.625 µg/ml, and the LLOD was 0.156 µg/ml. For the UV-Vis spectrophotometric validation method, the repeatability and reproducibility (stated as relative standard deviation) were less than 3.773 and 1.988 %, respectively. The percentage recovery results for the five brands of metformin hydrochloride tablets were (98-101 %) and (92-104 %) for the UHPLC and UV-Vis spectrophotometric methods, respectively. In conclusion, the described methodologies were successfully employed for the quantitative analysis of metformin hydrochloride in different pharmaceutical tablet products.

Prevalence of Cardiac Sarcoidosis in Middle-Aged Adults Diagnosed with High-Grade Atrioventricular Block.

INTRODUCTION: Atrioventricular block may be idiopathic or a secondary manifestation of an underlying systemic disease. Cardiac sarcoidosis is a significant underlying cause of high-grade atrioventricular block, posing diagnostic challenges and significant clinical implications. This study aimed to assess the prevalence and clinical characteristics of cardiac sarcoidosis among younger patients presenting with unexplained high-grade atrioventricular block. METHODS: We evaluated patients aged between 18 and 65 years presenting with unexplained high-grade atrioventricular block, who were systematically referred for cardiac magnetic resonance imaging, positron emission tomography-computed tomography, or both, prior to pacemaker implantation. Subjects with suspected cardiac sarcoidosis based on imaging findings were further referred for tissue biopsy. Cardiac sarcoidosis diagnosis was confirmed based on biopsy results. RESULTS: Overall, 30 patients with high-grade atrioventricular block were included in the analysis. The median age was 56.5 years (interquartile range 53-61.75, years). In 37%, cardiac magnetic resonance imaging, positron emission tomography-computed tomography, or both, were suggestive of cardiac sarcoidosis, and in 33% cardiac sarcoidosis was confirmed by tissue biopsy. Compared with idiopathic high-grade atrioventricular block patients, all cardiac sarcoidosis patients were males (100% vs 60%, P = .029), were more likely to present with heart failure symptoms (50% vs 10%, P = .047), had thicker inter-ventricular septum on echocardiography (12.2 ± 2.7 mm vs 9.45 ± 1.6 mm, P = .002), and were more likely to present with right ventricular dysfunction (33% vs 10%, P = .047). CONCLUSIONS: Cardiac sarcoidosis was confirmed in one-third of patients ≤ 65 years, who presented with unexplained high-grade atrioventricular block. Cardiac sarcoidosis should be highly suspected in such patients, particularly in males who present with heart failure symptoms or exhibit thicker inter-ventricular septum and right ventricular dysfunction on echocardiography.

Expect the Unexpected: A Rare Case of Isolated Superior Mesenteric Artery Vasculitis.

Vasculitis of the mesenteric vessels is considered rare and typically occurs as a part of systemic inflammation. Isolated mesenteric artery vasculitis without systemic involvement is rarely reported in the literature. Clinical presentation is usually nonspecific which can range from abdominal pain, nausea and vomiting to gangrene and intestinal perforation in severe cases. Recognizing mesenteric artery vasculitis as a potential cause of abdominal pain can be challenging, and delay in diagnosis can lead to significant mortality and morbidity. Herein, we present a case of a 19-year-old male who initially presented with abdominal pain. Later, isolated superior mesenteric artery (SMA) vasculitis was confirmed by CT angiography. Treatment with systemic steroids alone resulted in a marked improvement in the patient's symptoms as well as in radiographic findings.

Culture Media Supplemented With 10% Equine Serum Provided Chondroprotection in an In Vitro Co-Culture of Cartilage and Synovial Membrane.

No studies have evaluated the effect of culture in serum-free media (SF) vs. media supplemented with equine serum (ES) on co-culture of synovial membrane and cartilage tissue explants. The study objective was to evaluate the effects of equine serum supplementation on induced production of inflammatory and catabolic mediators from articular cartilage and synovial explants while in co-culture. Articular cartilage and synovial membrane explants were harvested from femoropatellar joints of five adult horses. Cartilage and synovial explants were harvested from the stifle of five horses, placed in co-culture, stimulated with IL-1ß (10 ng/ml) and maintained in culture for 3, 6 and 9 days in 10% ES or SF. At each time point, media was harvested for analysis of cellular viability (Lactate dehydrogenase) and elution of glycosaminoglycans (Dimethylene Blue Binding Assay). Tissue explants were harvested for histopathologic and gene expression analyses. No differences in cell viability were observed between SF and ES groups. SF culture produced an upregulation of TNF-α in synovial membrane and ADAMTS-4 and five in articular cartilage at 9 days of culture. ES produced an upregulation of aggrecan expression in cartilage at 9 days of culture. No differences in tissue viability were found between culture media, but SF media produced a higher glycosaminoglycan concentration in media at 3 days of culture. The addition of 10% ES produced a slight chondroprotective effect in an inflamed co-culture system. This effect should be considered when designing studies evaluating treatment of serum or plasma-based orthobiologic studies in vitro.

The Incidence and Outcomes of Venous Thromboembolisms in Patients Admitted with Different Gastrointestinal Malignancies.

Introduction: Venous thromboembolism (VTE) is associated with significant morbidity and mortality in cancer patients. Our study compares the mortality in hospitalized VTE patients among the four most common gastrointestinal (GI) malignancies which include esophageal, gastric, pancreatic, and colorectal cancer. Methods: A retrospective study was conducted utilizing the Nationwide Inpatient Sample database (NIS) from 2016 to 2019. Patients with VTE were identified using ICD-10 codes from all primary discharge diagnoses. Only deep venous thrombosis (DVT) and pulmonary embolism (PE) were considered. Patients with VTE were further divided into groups: esophageal cancer, gastric cancer, pancreatic cancer, and colorectal cancer, and compared with patients who did not have these malignancies. The adjusted odds ratio (aOR) was calculated using multivariate regression analysis. Results: Among 999,559 patients discharged with a VTE diagnosis, 25,775 (2.6%) had one of the four GI malignancies. Among patients with one of the four included GI malignancy diagnosis, 18,816 (73%) patients had PE and 6,959 (27%) patients had DVT. The study shows that adults admitted to the hospitals for VTE have higher mortality when compared to patients who did not have GI malignancies, with esophageal cancer having the highest inpatient mortality with an aOR of 2.701; 95% confidence interval (CI) 1.989-3.669, p value <0.000. For the remaining GI cancers, gastric cancer had an aOR 1.576; CI: 1.094-2.269, p value 0.015, and pancreatic cancer had an aOR of 1.736; 95% CI: 1.445-2.085, p value <0.000. Patients with colorectal cancer had no significant increase in the odds of mortality with aOR of 1.213; 95% CI: 0.988-1.489, p value 0.066. Conclusions: This study demonstrates that VTE in hospitalized patients with esophageal cancer is associated with greater mortality compared to other GI malignancies.

Augmentation of Docetaxel-Induced Cytotoxicity in Human PC-3 Androgen-Independent Prostate Cancer Cells by Combination With Four Natural Apoptosis-Inducing Anticancer Compounds.

Docetaxel (DTX) is the treatment of choice for metastatic castration-resistant prostate cancer. However, developing drug resistance is a significant challenge for achieving effective therapy. This study evaluated the anticancer and synergistic effects on DTX of four natural compounds (calebin A, 3'-hydroxypterostilbene, hispolon, and tetrahydrocurcumin) using PC-3 androgen-resistant human prostate cancer cells. We utilized the CellTiter-Glo® luminescent cell viability assay and human PC-3 androgen-independent prostate cancer cells to determine the antiproliferative effects of the four compounds alone and combined with DTX. Cytotoxicity to normal human prostate epithelial cells was tested in parallel using normal immortalized human prostate epithelial cells (RWPE-1). We used cell imaging and quantitative caspase-3 activity to determine whether these compounds induce apoptosis. We also measured the capacity of each drug to inhibit TNF-α-induced NF-kB using a colorimetric assay. Our results showed that all four natural compounds significantly augmented the toxicity of DTX to androgen-resistant PC-3 prostate cancer cells at IC50. Interestingly, when used alone, each of the four compounds had a higher cytotoxic activity to PC-3 than DTX. Mechanistically, these compounds induced apoptosis, which we confirmed by cell imaging and caspase-3 colorimetric assays. Further, when used either alone or combined with DTX, the four test compounds inhibited TNF-α-induced NF-kB production. More significantly, the cytotoxic effects on normal immortalized human prostate epithelial cells were minimal and non-significant, suggesting prostate cancer-specific effects. In conclusion, the combination of DTX with the four test compounds could effectively enhance the anti-prostate cancer activity of DTX. This combination has the added value of reducing the DTX effective concentration. We surmise that calebin A, 3'-hydroxypterostilbene, hispolon, and tetrahydrocurcumin were all excellent drug candidates that produced significant antiproliferative activity when used alone and synergistically enhanced the anticancer effect of DTX. Further in vivo studies using animal models of prostate cancer are needed to confirm our in vitro findings.

Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia.

Proprotein convertase subtilisin kexin type 9 (PCSK9) lowers the abundance of surface low-density lipoprotein (LDL) receptor through an undefined mechanism. The structure of human PCSK9 shows the subtilisin-like catalytic site blocked by the prodomain in a noncovalent complex and inaccessible to exogenous ligands, and that the C-terminal domain has a novel fold. Biosensor studies show that PCSK9 binds the extracellular domain of LDL receptor with K(d) = 170 nM at the neutral pH of plasma, but with a K(d) as low as 1 nM at the acidic pH of endosomes. The D374Y gain-of-function mutant, associated with hypercholesterolemia and early-onset cardiovascular disease, binds the receptor 25 times more tightly than wild-type PCSK9 at neutral pH and remains exclusively in a high-affinity complex at the acidic pH. PCSK9 may diminish LDL receptors by a mechanism that requires direct binding but not necessarily receptor proteolysis.

A Rare Case of Pulmonary Embolism in a Patient With Interrupted Inferior Vena Cava and Polysplenia.

Interrupted inferior vena cava (IVC) with azygos continuation is one of the anomalies of the inferior vena cava (AIVCs) where venous drainage of the lower extremities is accomplished through a dilated azygos system and is usually accompanied by other congenital malformations such as polysplenia. AIVCs are more common in patients younger than 40 presenting with deep venous thrombosis (DVT). However, pulmonary embolism (PE) in association with AIVCs remains underreported. In this article, we describe a rare case of a 23-year-old male who presented with syncope secondary to sub-massive pulmonary embolism in the setting of an interrupted vena cava draining directly into the azygous vein.

Clinical Characteristics and Outcomes of Decompensated Cirrhosis Patients Admitted to Hospitals With Acute Pulmonary Embolisms: A Nationwide Analysis.

INTRODUCTION: Cirrhosis is a significant cause of mortality and morbidity worldwide. Recent studies suggested that cirrhosis is associated with an increased risk of venous thromboembolism (VTE), which disproves the old belief that chronic liver disease coagulopathy is considered protective against VTE. We conducted a retrospective study which is to our knowledge the first of its kind to assess clinical characteristics and outcomes of decompensated cirrhosis (DC) patients admitted with acute pulmonary embolism (APE). METHODOLOGY: We used the National Inpatient Sample database for the years 2016-2019. All adults admitted to the hospitals with a primary diagnosis of APE were included. Patients less than 18 years old, missing race, gender, or age were excluded. Patients were divided into two groups, either having DC or not. A multivariate logistic regression model was built by using only variables associated with the outcome of interest on univariable regression analysis at P < 0.05. RESULTS: 142 million discharges were included in the NIS database between the years 2016 and 2019, of which 1,294,039 met the study inclusion criteria, 6,200 patients (0.5%) had DC. For adult patients admitted to the hospitals with APE, odds of inpatient all-cause mortality were higher in the DC group than in patients without DC; OR of 1.996 (95% CI, 1.691-2.356, P-value < 0.000). Also, vasopressor use, mechanical ventilation, and cardiac arrest were more likely to occur in the DC group, OR of 1.506 (95% CI, 1.254-1.809, P-value < 0.000), OR of 1.479 (95% CI, 1.026-2.132, P-value 0.036), OR of 1.362 (95% CI, 1.050-1.767, P-value 0.020), respectively. In addition, DC patients tend to have higher total hospital charges and longer hospital length of stay, coefficient of 14521 (95% CI, 6752-22289, P-value < 0.000), and a coefficient of 1.399 (95% CI, 0.848-1.950, P-value < 0.000), respectively. CONCLUSION: This study demonstrates that DC is a powerful predictor of worse hospital outcomes in patients admitted with APE. An imbalance between clotting factors and natural anticoagulants produced by the liver is believed to be the primary etiology of thrombosis in patients with DC. The burden of APE can be much more catastrophic in cirrhotic than in non-cirrhotic patients; therefore, those patients require closer monitoring and more aggressive treatment.

Aberrant Right Subclavian Artery Causing Dysphagia: A Case Report of Dysphagia Lusoria.

Dysphagia lusoria is a rare condition, with a prevalence of less than 1%, that occurs through secondary compression of the esophagus posteriorly by an aberrant right subclavian artery. It commonly presents with dysphagia to solids. Management is usually done with dietary modification; however, more severe and intractable cases may require surgical intervention. We describe this rare vascular anomaly in a 54-year-old female presenting with mechanical dysphagia.

The Impact of Cirrhosis on Outcomes of Patients Admitted With Diabetic Ketoacidosis: A Nationwide Study.

Introduction Diabetic ketoacidosis (DKA) is the most common acute hyperglycemic emergency in people with diabetes mellitus (DM). Cirrhosis is a consequence of chronic inflammation that is followed by hepatic fibrosis. It has been noted that cirrhosis is associated with an increased risk of developing type II DM due to altered glucose homeostasis. The prognostic value of DM in cirrhotic patients has been studied before and was found to be associated with lower survival. However, the risk of mortality and adverse events in cirrhotic patients admitted with DKA needs further evaluation. The aim of this study is to compare outcomes in patients with cirrhosis admitted to the hospital with DKA compared to non-cirrhotic patients. Methods The data for this study were extracted from the National Inpatient Sample (NIS) 2016-2019. The NIS was queried for all patients who had a discharge diagnosis of DKA. Patients with cirrhosis were identified and subclassified into compensated and decompensated cirrhosis using the International Classification of Diseases 10th revision, Clinical Modification (ICD-10-CM) codes. Patients without cirrhosis were the control group. ICD-10-CM codes that have been validated for cirrhosis were utilized. The primary outcome was in-hospital mortality. Secondary outcomes were hospital charges, length of stay (LOS), and in-hospital complications, including shock, mechanical ventilation, and acute kidney injury (AKI) requiring dialysis. Results We included 1,098,875 hospitalizations with a discharge diagnosis of DKA. Overall, 9,190 patients had compensated cirrhosis and 4,355 had decompensated cirrhosis. Cirrhotic patients had overall worse outcomes compared to non-cirrhotics. Decompensated cirrhotics had the highest mortality (11.26%; 95% confidence interval [CI]: 9.36% to 13.49%) compared to compensated cirrhotics (3.54%; 95% CI: 2.79% to 4.48%) and non-cirrhotics (2.15%; 95% CI: 1.89% to 2.43%). Similarly, decompensated cirrhotics also had the highest LOS, total charges, and in-hospital complications among the groups. On multivariate analysis, decompensated cirrhosis, rather than compensated cirrhosis, was an independent predictor of higher mortality (adjusted odds ratio [AOR]: 2.30; 95% CI: 1.81 to 2.92), LOS (regression coefficient: +1.82 days; 95% CI: +1.19 to +2.44 days), hospital charges (regression coefficient: +$28,497; 95% CI: +$18,107 to +$38,887), shock (AOR: 2.31; 95% CI: 1.68 to 3.18), mechanical ventilation (AOR: 1.91; 95% CI: 1.58 to 2.29), and AKI requiring dialysis (AOR: 2.31; 95% CI: 1.68 to 3.18). Conclusion This study showed that patients with decompensated liver cirrhosis who were admitted with DKA had the worst in-hospital outcomes. Additionally, only decompensated cirrhosis was an independent predictor of worse outcomes. Decompensated cirrhotics who develop DKA should be approached with more caution with a probable lower threshold for intensive care unit admission for a higher level management.

Pre-Diagnosis Aspirin Use Has No Effect on Overall Survival in Patients With Colorectal Cancer: A Study of a Multi-Racial Population.

Introduction Aspirin has been associated with a reduction in mortality in patients diagnosed with colorectal cancer (CRC). A possible mechanism for this is related to the programmed cell death 1 (PD-1) immune checkpoint pathway. Aspirin may have a synergistic effect with PD-1 inhibitors via inhibition of prostaglandin E2 (PGE2) production, which can reverse the ability of tumor cells to evade the immune system. This appears to be strongest in cancers that express PI3 kinase (PI3K) signaling activity, which aspirin downregulates. However, the benefit of pre-diagnosis aspirin use on CRC overall survival (OS) and cancer-specific survival is still controversial, and most studies have been performed in racially homogenous populations. Our study examines the effect of pre-diagnosis aspirin therapy on OS in a racially diverse group of patients with CRC. Methods This is a retrospective chart review of 782 patients diagnosed with CRC from January 2007 to December 2020. Kaplan-Meier curve was created to study the association of aspirin exposure compared to no exposure on OS. In addition, univariate and multivariate binary logistic regression analyses were done to investigate potential predictors of survival. Results Of the 782 patients with CRC, 55.1% were males, 22.2% whites, 58.5% Asians, and 17.7% Pacific-Islanders. Moreover, 38.4% of the patients had a history of aspirin use, 79% of them used it for more than one year. There were more patients with hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), and chronic kidney disease (CKD) among those with a history of aspirin use. There was no difference in one, three, and five-year OS among aspirin users compared to non-users, p-value = 0.63. Age, grade, and stage were potential predictors of worsened OS. However, treatment with chemotherapy and CKD were potential predictors of worsened OS on univariate analysis only. No significant association was noticed with gender, tumor location, or other associated comorbidities. Conclusion The effect of pre-diagnosis aspirin use on CRC survival is not clear. In this retrospective analysis of a racially diverse population of CRC patients, we found that aspirin use was not associated with improved OS. Therefore, physicians should be careful about using aspirin as adjuvant therapy in CRC patients until high-quality prospective data are available, given the potential associated complications.