Long non-coding RNA (lncRNA) as a new biomarker for hepatocellular carcinoma (HCC) progression and drug resistance

Hepatocellular carcinoma (HCC) is a primary malignant liver tumor that commonly occurs as a progression of chronic liver inflammation due to long-standing viral hepatitis infection, toxins, metabolic conditions, and congenital disorders. In 2018, HCC was the 4th leading cause of cancer-related deaths worldwide, accounting for approximately 780,000 deaths in total. HCC’s prognosis is directly correlated with early detection. Unfortunately, HCC has an asymptomatic pattern of growth in the early stages of the disease which makes early detection challenging. When HCC progresses to advanced stages, it leaves clinicians with limited therapeutic and curative options, leading to high rates of morbidity and mortality. In general, one major hurdle in treating advanced cancer is that cancer cells develop drug resistance. Research studies have elucidated the role of long non-coding RNAs (lncRNAs) in progression and drug resistance in various cancers such as bladder cancer, prostate cancer, and non-small cell lung cancer. Long non-coding RNAs (lncRNAs) are non-coding RNA segments that are \u3e200 nucleotides long that play various roles in biological processes regarding DNA, RNA, and protein regulation. In carcinogenesis, lncRNAs can promote growth and differentiation of cancer stem cell populations, promoting chemoresistance and tumor recurrence. The role of lncRNAs in the chemoresistance of HCC has not been well-studied. There is a need to uncover novel lncRNA biomarkers for both the early detection of HCC and to create drug strategies for clinicians when predicting chemoresistance. The goal of our review is three-fold. Firstly, we aim to describe HCC risk factors, the pathologic progression of HCC from benign pathologies such as viral hepatitis and non-alcoholic fatty liver disease (NAFLD), current diagnostic standards and challenges, and approved treatment options for HCC. Secondly, we aim to explain the molecular role of lncRNAs in cancer progression and drug resistance. Lastly, we aim to compile a comprehensive list of studied lncRNAs involved in HCC progression and drug resistance, their mechanisms of action, their binding partners, and the impact these lncRNAs had on metastatic potential and tumor proliferation. Additionally, we aim to include a list of proteins involved in HCC and their interactions with lncRNAs

Arrhythmogenic Right Ventricular Cardiomyopathy: Is Coxsackie the Criminal?

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by right ventricular dysfunction, which can precipitate sudden cardiac death in young adults. Case Presentation: A 22-year-old Hispanic male with PMH of hypertriglyceridemia and exertional syncopal episodes was brought to the ED after experiencing a sudden cardiac arrest while on the treadmill. On arrival, the patient was intubated and placed on a defibrillator which detected Vfib with torsade de pointes. On arrival to ED, initial ECG revealed 1-2 mm ST depressions in leads II, III, and aVF and incomplete RBBB. Chest XR showed water-bottle-shaped cardiac silhouette. Coronary angiography demonstrated patent coronary arteries. Subsequently, 2D echo was performed which showed severe enlargement of RV with EF of 30-35% and RV free wall akinesis. The only pertinent positives were Coxsackie A and B antibodies with titers as high as 1:1600 in Coxsackie A Ab. The patient met the 2010 Task Force Criteria for ARVC including 1 major criterion by 2D echo and 2 major criteria by ECG. The first major criteria met were regional RV akinesia and increased RV dimensions in end-diastole of PLAX RVOT \u3e32mm and/or PSAX RVOT \u3e36 mm. The second major criteria met were inverted T-waves in V1, V2, and V3 in the absence of complete RBBB. Lastly, the third major criterion met was the presence of VT of left bundle branch morphology with superior axis. Conclusion: This case highlights the uncertainty behind the pathogenesis of ARVC and the role that cardiotropic viruses such as Coxsackie play in the pathophysiology of this disease

A Puzzling Case of Glutamic Acid Decarboxylase 65 (GAD65) Neurologic Syndrome

Autoimmune encephalitis (AE) is a rare group of neurological disorders in which antibodies are directed against intracellular or surface antigens. The incidence of AE ranged from between 0.4-1.2 per 100,000 person-years between 1995 and 2015. A subset of these autoimmune encephalitides that target glutamic acid decarboxylase (GAD) are termed anti-GAD related neurological disorders. GAD is the rate-limiting enzyme involved in the synthesis of GABA from glutamate, and is expressed in neurons of the cerebral cortex, cerebellum, and hippocampus. In addition, it is found in the B-islets of the pancreas, epithelial cells of the fallopian tube, and spermatocytes of the testes. Antibodies directed against GAD have been linked to a group of autoimmune neurological syndromes such as stiff person syndrome (SPS), cerebellar ataxia (CA), limbic encephalitis, and temporal lobe epilepsy. In the following case report, a 62-year-old-male presented to the emergency department with dysphagia and drooling. On this admission, he had multiple neurological findings including right gaze palsy, diminish facial sensation on the right V1 branch, moderate left facial droop, and left leg dysmetria on Heel-Knee-Shin Test. We began the workup to determine the pathogenicity of the autoimmune response. We ordered several antibody titers from CSF and serum (anti-aquaporin4 IgG, anti-MOG IgG, anti-Ma 1 and 2, anti-amphiphysin, anti-gly5, anti- NMDAR, anti-VGKC). All antibodies were negative, and no oligoclonal bands were found on CSF analysis. Anti-GAD65 titers were elevated, giving us strong suspicion for anti-GAD immune-mediated neurologic disorders, which include stiff person syndrome (SPS), cerebellar ataxia (CA), limbic encephalitis, and temporal lobe epilepsy. From these disorders, cerebellar ataxia aligned with our patient’s clinical presentation. There were concerns that elevated anti-GAD65 antibodies could be due to underlying type 1 diabetes because B-islets in the pancreas also contain these antigens. Previous studies have demonstrated that highly elevated quantitative titer levels of anti-GAD65 (threshold \u3e10,000 units/mL) are associated with anti-GAD65 associated neurologic syndromes. This is particularly important because lower levels of anti-GAD65 help differentiate between an incidental finding of T1DM and these neurologic syndromes. However, similar studies demonstrate that even with low anti-GAD65 titers, 1-8% of patients still present with neurologic findings. Our case highlights the necessity for a systematic approach workup of autoimmune encephalitis. Currently, there are no established criteria for the diagnosis of these autoimmune neurologic syndromes, particularly in relation to GAD65 syndromes. Multiple in-vivo studies have shown limited evidence for the autoimmune pathogenicity of anti-GAD65 antibodies in stiff-person syndrome, cerebellar ataxia, limbic encephalitis, and temporal lobe epilepsy. This was evident in our management due to our patient’s limited clinical response to immunotherapy (IVIG and steroids). Our case report elucidates the need for scientific exploration into molecular mechanisms of anti-GAD65 neurologic syndromes

Retrospective Study Examining Obesity Hypoventilation Syndrome in COVID+ Patients

Purpose: Coronavirus disease 2019 (COVID-19) has affected millions of people all over the world with worse proven outcomes in those with certain comorbid conditions, such as diabetes, cardiovascular disease, and pulmonary complications. The Rio Grande Valley located in South Texas with a largely Hispanic population has been hit especially hard during this pandemic with over 3,200 virus-related deaths. This region’s high population of diabetic and obese patients is likely correlated with the especially high mortality rate. While it is understood the impact that obesity has on worsening health outcomes, further research is needed to better understand whether more adverse COVID-19 outcomes are correlated with an underdiagnosis of Obesity Hypoventilation Syndrome (OHS) amongst obese patients. Patients and Methods: Using an observational database from Valley Baptist Medical Center (VBMC) in Harlingen, TX, we gathered a list of COVID+ patients admitted between March 19, 2020 and September 25, 2020. COVID-19 was diagnosed based on World Health Organization (WHO) guidance. The official database is still a work-in-progress, as we are still working on manual data-entry for co-existing conditions and lab values for these patients. Once the database is completed, evaluation guidelines as listed in the American Journal of Respiratory and Critical Care Medicine will be used as a screening method to identify OHS in COVID+ patients. COVID-19 outcomes including hospitalization length, ICU transfer/admission, intubation count, in-hospital death will then be evaluated. Results: Of the 1114 patients with COVID-19+ included in our database, we have completed chart review on 112 patients. Once the database is completed, statistical analysis will be performed using Python to see if there is a higher percentage of adverse COVID-19+ outcomes in OHS-suspected patients compared to obese patients who don’t meet the criteria for OHS. Further analysis will also be done to compare these outcomes to the remaining admitted COVID+ patients. Conclusion: Database still in progress and no conclusion can be drawn at this time

Long non-coding RNA (lncRNA) as a new biomarker for hepatocellular carcinoma (HCC) drug resistance

Background: Hepatocellular carcinoma (HCC) is the 4th leading cause of cancer-related deaths worldwide and the 6th most common cancer worldwide. When HCC progresses to advanced stages, drug resistance becomes a major hurdle and leaves clinicians with limited therapeutic options. Long non-coding RNAs (lncRNAs) have shown to promote drug resistance in various cancers. The goal of our research is to explain the molecular role of lncRNAs in HCC drug resistance and compile a comprehensive list of studied lncRNAs involved in HCC drug resistance. Methods: To compile a list of lncRNA involved in HCC drug resistance we performed an advanced search on Lnc2Cancer, a database that provides experimentally supported associations between lncRNA and human cancer, using the following filters: “hepatocellular carcinoma”, “drug clinical application”, “lncRNA”, “all biological function”, and “all regulatory mechanism.” Results: We identified 12 lncRNAs that are involved in HCC drug resistance: Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT 1), Keap1 Regulation-Associated LncRNA (KRAL), Transcribed Ultra-conserved Region 338 (TUC338), Long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR), Linc-VLDLR, Highly Upregulated in Liver Cancer (HULC), HCC associated long non-coding RNA (HANR), LncRNA Regulator of AKT Signaling Associated with HCC and RCC (LncARSR), Taurine up-regulated gene 1 (TUG1), H19, NR2F1 Antisense RNA 1 (NR2F1-AS1), and HOX Transcript Antisense RNA (HOTAIR). Conclusions: Our review demonstrates that lncRNAs involved in HCC drug resistance participate in various mechanistic categories such as autophagy, epithelial-mesenchymal transition, and efflux pump upregulation. There is a need to uncover novel lncRNA biomarkers for both the early detection of HCC and to create drug strategies for clinicians when predicting chemoresistance

Bactrim, Spironolactone and Lisinopril. Stay Away! A Dangerous Cocktail for Hyperkalemia

Introduction: Hyperkalemia is a potentially life-threatening complication of several medications, particularly in situations of polypharmacy. Trimethoprim/sulfamethoxazole (TMP-SMX) is a first line antibiotic for outpatient treatment of MRSA for skin and soft tissue infections that can enhance the hyperkalemic effects of spironolactone and Angiotensin receptor inhibitors (ACEI). Case Presentation: A 53-year-old female with history of HTN, stage 3 CKD, CHF, hypercholesterolemia and DM II, chronic left foot ulcer presented to our local hospital with generalized malaise, severe lower extremity weakness and heaviness of 2 days duration. She normally uses a walker but has had increasing difficulty standing from a seated position. Her medications included: spironolactone, carvedilol, lisinopril, amlodipine, aspirin, atorvastatin, and insulin and had been started on TMP-SMX for the management of an infected chronic ulcer. Physical exam was significant for a blood pressure of 182/87 mm Hg, BMI of 52, lethargy, dry oral mucous membranes, and nonsignificant musculoskeletal examination. The laboratory results revealed significantly elevated potassium levels at 8.6 mmol/L; GFR of 31 and creatinine: 1.79 mg/dL. EKG revealed tall, peaked T-waves with widened QRS complexes in the precordial leads and a right BBB. TMP-SMX, spironolactone and lisinopril were discontinued, and the patient was started on a hyperkalemia treatment protocol. The patient improved rapidly over the next 3 days with resolution of the ECG changes, improved muscle strength and the potassium level was back to normal limits by the time of discharge. Conclusion: Clinicians and pharmacists should be aware of the enhanced hyperkalemic effects of TMP-SMX, spironolactone and lisinopril and should avoid this combination

In situ development and application of natural coatings on non-absorbable sutures to reduce incision site infections

Objective: The purpose of the study was the development of a suture line that has antibacterial properties and reduces the chance of wound infection thus facilitating the healing process. Method: Hydrolysed chitosan, turmeric powder and clove oil were used in different proportions to formulate antimicrobial coating for the polyethylene terephthalate (PET) and polyamide (Nylon 6) threads. The threads were coated using a lab-scale yarn sizing machine. Tensile, and knot strength of the coated sutures were measured. As was the antimicrobial action of Staphylococcus aureus strain ATCC29213. Results: The results show that coatings have slightly improved the tensile and knot strength properties of these sutures. The coated sutures also have satisfactory microbial inhibition against Staphylococcus aureus. Conclusion: The coating slightly improved the tensile strength of the sutures. However, the knot is the weakest part of the suture strand. All the formulations of the coating have shown satisfactory antimicrobial activity against Gram-positive Staphylococcus aureus bacteria. We conclude that application of natural coatings on non-absorbable sutures can be useful to reduce the incisions and wound site infections. </jats:sec