Circulating tumor DNA and its role in detection, prognosis and therapeutics of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is considered the fifth most prevalent cancer among all types of cancers and has the third most morbidity value. It has the most frequent duplication time and a high recurrence rate. Recently, the most unique technique used is liquid biopsies, which carry many markers; the most prominent is circulating tumor DNA (ctDNA). Varied methods are used to investigate ctDNA, including various forms of polymerase chain reaction (PCR) [emulsion PCR (ePCR), digital PCR (dPCR), and bead, emulsion, amplification, magnetic (BEAMing) PCR]. Hence ctDNA is being recognized as a potential biomarker that permits early cancer detection, treatment monitoring, and predictive data on tumor burden are subjective to therapy or surgery. Numerous ctDNA biomarkers have been investigated based on their alterations such as 1) single nucleotide variations (either insertion or deletion of a nucleotide) markers including TP53, KRAS, and CCND1; 2) copy number variations which include markers such as CDK6, EFGR, MYC and BRAF; 3) DNA methylation (RASSF1A, SEPT9, KMT2C and CCNA2); 4) homozygous mutation includes ctDNA markers as CDKN2A, AXIN1; and 5) gain or loss of function of the genes, particularly for HCC. Various researchers have conducted many studies and gotten fruitful results. Still, there are some drawbacks to ctDNA namely low quantity, fragment heterogeneity, less stability, limited mutant copies and standards, and differential sensitivity. However, plenty of investigations demonstrate ctDNA's significance as a polyvalent biomarker for cancer and can be viewed as a future diagnostic, prognostic and therapeutic agent. This article overviews many conditions in genetic changes linked to the onset and development of HCC, such as dysregulated signaling pathways, somatic mutations, single-nucleotide polymorphisms, and genomic instability. Additionally, efforts are also made to develop treatments for HCC that are molecularly targeted and to unravel some of the genetic pathways that facilitate its early identification.

Sclerotherapy in the Treatment of Hydroceles: A Comprehensive Review of the Efficacy, Types of Sclerosants, and Comparative Outcomes Against Hydrocelectomy.

While hydrocelectomy is the gold-standard for treating hydroceles, it poses an increased risk to patients and a greater burden to the healthcare system. Sclerotherapy is an alternative treatment for hydroceles that involves injecting a sclerosant into the hydrocele under ultrasound guidance. This literature review aimed to assess the types of sclerosants used and how sclerotherapy compares to hydrocelectomy. A literature search was conducted of MEDLINE and EMBASE using the terms "sclerotherapy" and "hydrocelectomy," which yielded 1058 studies, of which 29 met the inclusion criteria. Only studies published after 2000 were included to ensure the most recent information was reviewed. The results showed hydrocele sclerotherapy is done using a variety of sclerosants. The most used agents are polidocanol, phenol, and STS. Of these, phenol had the highest clinical success rate of 96.5%. There was evidence for the use of atypical agents, such as tetracycline antibiotics, which yielded cure rates up to 93%, and alcohol, which was found to be especially useful for treating multiseptated hydroceles. The results comparing sclerotherapy to hydrocelectomy indicated hydrocelectomy to be a more effective method in completely curing hydroceles. However, this came at the cost of more complications. Additionally, sclerotherapy was found to be more advantageous for secondary outcomes, such as healthcare costs and burden to patients. In conclusion, this review shows that while hydrocelectomy is more effective, sclerotherapy is a valuable alternative for treating hydroceles. Due to the lack of standardization among studies, a definitive conclusion cannot be made regarding which sclerosant is best to use.

Chorea-acanthocytosis.

A middle-aged Asian man had gait difficulty progressing over several years. His speech had gradually become slurred with involuntary tongue biting. He was the product of a consanguineous marriage with no other relevant family history. MR scan of brain showed bilateral caudate atrophy. Nerve conduction studies showed a predominantly sensory peripheral neuropathy. Serum creatine kinase was slightly elevated but electromyography showed no evidence of myopathy. Three consecutive peripheral blood films were negative for acanthocytes. Whole-genome sequencing confirmed a mutation in VPS13A gene, consistent with autosomal recessive chorea-acanthocytosis.

Efficacy and safety of antibody-drug conjugates in triple-negative and HER-2 positive breast cancer: A systematic review and meta-analysis of clinical trials.

Breast cancer (BC) is the 2nd most common cause of cancer-related deaths. Antibody-drug conjugates (ADCs) are monoclonal antibodies linked to cytotoxic agents and are directed towards a specific tumor protein. Therefore, they are more potent and can have relatively less toxicity. In this meta-analysis, we assessed the efficacy and safety of ADCs in breast cancer. We searched PubMed, Cochrane, Web of Science, and clinicaltrials.gov for relevant studies and included 7 randomized clinical trials (N = 5,302) and 7 non-randomized clinical trials (N = 658). R programming language software was used to conduct this meta-analysis. In 4 RCTs on HER-2 positive BC (N = 2,825), the pooled HR of PFS and OS was 0.72 (95% CI = 0.61-0.84, I2 = 71%) and 0.73 (95% CI = 0.64-0.84, I2 = 20%), respectively in favor of ADCs versus chemotherapy. In RCT on triple negative BC (N = 468), HR of PFS and OS were 0.55 (95%CI = 0.51-0.61) and 0.59 (95% CI = 0.54-0.66), respectively, in favor of saci-gov versus chemotherapy. In RCT on HER-2 positive residual invasive BC, HR of recurrence/death was 0.61 (95% CI = 0.54-0.69) in favor of ADC versus chemotherapy. In an RCT (N = 524), the HR of PFS and OS were 0.28 (95% CI = 0.22-0.37) and 0.55 (95%CI = 0.36-0.86), respectively, in favor of trastuzumab-deruxtecan (T-der) as compared to trastuzumab-emtansine (T-DM1). Anemia, rash, diarrhea, fatigue, hypertension, thrombocytopenia, and elevated aminotransferases were the common ≥grade 3 adverse events reported in 4%, 1%, 2%, 1%, 2%, 9%, and 3% of the patients, respectively. ADCs were more effective than single and double agent chemotherapy in patients with HER-2 positive or triple negative BC. Among ADCs, T-der was more effective than T-DM1.

Increasing statin prescription rates to prevent cardiovascular disease among high-risk populations: a quality improvement intervention centred on a novel interactive tool.

Statins are indicated for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). Our previous study of 1042 consecutive patient encounters at our large urban academic institution found that one in five patients were not prescribed an appropriate statin therapy. Only one-third of patients had follow-up cholesterol levels ordered to monitor treatment efficacy. In order to improve adherence to cholesterol guidelines at our institution, a quality improvement project was undertaken. We implemented interventions over a 4-month period to improve statin prescription rates: (a) development of an online interactive tool, (b) physician education on updated cholesterol guidelines and utilisation of the tool, (c) display of guideline summary in the workspace and (d) a documentation reminder in the electronic health record. We randomly selected encounter dates, from which 622 consecutive patient encounters were analysed. The primary outcome measures were prescription rates of statins, documentation of a 10-year ASCVD risk score and follow-up cholesterol levels ordered to monitor treatment efficacy. Out of the 622 patient encounters, 232 met statin indication. In this post-intervention group, statin prescription rates improved when compared with the pre-intervention group (90.5% vs 82.3%, p=0.006). Among patients who met statin indication solely via a 10-year ASCVD risk score ≥7.5%, there was an increase in documentation of the calculated 10-year ASCVD risk score (72.3% vs 57.8%; p=0.039) and in statin prescription rate (90.8% vs 67.6%; p<0.001). In addition, there was an increase in follow-up cholesterol levels ordered in all patients included in our study who met statin indication (64.1% vs 33.3%; p<0.001). Our quality improvement project showed higher rates of statin prescription, 10-year ASCVD risk score documentation and treatment monitoring after multiple interventions, centred on an easily accessible online interactive tool.

Betamethasone Dipropionate Derivatization, Biotransformation, Molecular Docking, and ADME Analysis as Glucocorticoid Receptor.

Betamethasone is an important glucocorticoids (GCs), frequently used to cure allergies (such as asthma and angioedema), Crohn's disease, skin diseases (such as dermatitis and psoriasis), systemic lupus erythematosus, rheumatic disorders, and leukemia. Present investigation deals to find potential agonist of glucocorticoid receptors after biotransformation of betamethasone dipropionate (1) and to carry out the molecular docking and ADME analyses. Biotransformation of 1 was carried out with Launaea capitata (dandy) roots and Musa acuminate (banana) leaves. M. acuminate furnished low-cost value-added products such as Sananone dipropionate (2) in 5% yields. Further, biocatalysis of Sananone dipropionate (2) with M. acuminate gave Sananone propionate (3) and Sananone (4) in 12% and 7% yields, respectively. However, Sananone (4) was obtained in 37% yields from Launaea capitata. Compound 5 was obtained in 11% yield after ß-elimination of propionic acid at C-17 during oxidation of compound 1. The structure elucidation of new compounds 2-5 was accomplished through combined use of X-ray diffraction and NMR (1D and 2D) studies. In addition to this, molecular docking and ADME analyses of all transformed products of 1 were also done. Compounds 1-5 showed -12.53 to -10.11 kcal/mol potential binding affinity with glucocorticoid receptor (GR) and good ADME profile. Moreover, all the compounds showed good oral bioavailability with the octanol/water partition coefficient in the range of 2.23 to 3.65, which indicated that compounds 1-5 were in significant agreement with the given criteria to be considered as drug-like.

A Rare Presentation of Infective Endocarditis Due to Serratia marcescens.

Serratia marcescens is an opportunistic organism that can commonly cause respiratory tract infections in immunocompromised individuals. It has also been shown to cause urinary tract infections and soft tissue infections. It has several virulence factors including fimbriae-like adhesions that allow for surface attachment and biofilm formation to increase the likelihood of infections in humans. However, it has rarely been shown to cause infective endocarditis but has an increased mortality compared to the usual microbial agents associated with it (Staphylococcus and Streptococcus). Therefore, a high index of suspicion is necessary to accurately diagnose and treat patients at risk. Most published cases of S. marcescens endocarditis show that almost all described patients had chronic medical conditions or cardiovascular abnormalities. Furthermore, treatment has become difficult as S. marcescens has been shown to exhibit antibacterial resistance with beta-lactamase production. Here, we present a complicated case of S. marcescens pneumonia and infective endocarditis with a good prognosis. Our patient had a rapid onset of complications (i.e. including joint infections, splenic abscesses, myositis, and septic arthritis), despite the initial benign presentation concerning for pneumonia. However, the patient had a favorable outcome due to the prompt work-up and treatment that was initiated. Therefore, S. marcescens bacteremia in a patient with risk factors should prompt further investigation with a thorough evaluation of source followed by immediate management. This case highlights the fastidious nature of S. marcescens. Further investigation needs to be done to elucidate the pathogenesis of the organism that can serve as a target for future therapeutic intervention.

Characteristics of warfarin under-prescription in older adults with atrial fibrillation.

BACKGROUND: The prevalence of atrial fibrillation (AF) and atrial flutter (AFl) increases with age. Under-prescription of anticoagulants in older adults can lead to increased morbidity and mortality. We analyzed warfarin prescription patterns in older adults. METHODS: In this observational single-center study, we analyzed 2179 consecutive patients with admission diagnosis of AF or AFl. Patients were divided into "older" (≥ 75 years old) and "younger" (<75 years old) groups. Prescription patterns of warfarin were analyzed. Patients discharged from the hospital on a non-warfarin anticoagulation were excluded. RESULTS: Of the 1988 patients analyzed, 46.9% were ≥75 years old, of which 50.8% were prescribed warfarin. There was no association between mean CHA2DS2-VASc score and warfarin prescription on discharge (OR = 1.06 (95% CI 0.93-1.21), p = 0.388) in the older group. After adjusting for hypertension, renal function, and Black race, warfarin prescription in older adults was independently associated with lower aspirin prescription rates (OR = 0.57 (95% CI 0.43-0.75), p < 0.001), lower body mass index (OR = 1.03 (95% CI 1.01-1.06), p = 0.018), and lower hemoglobin levels (OR = 1.11 (95% CI 1.04-1.19), p = 0.002). CONCLUSIONS: In our study, older adults (≥75 years old) with AF and AFl tended to have lower rates of warfarin prescription despite higher CHA2DS2-VASc score and higher risk of thromboembolic events. Anemia, lower body weight, and aspirin use were characteristics associated with warfarin under-prescription.

Micra™ Leadless Intracardiac Pacemaker Implantation: A Safer Option During the Coronavirus Disease 2019 Pandemic.

The Micra™ Transcatheter Pacing System (Medtronic, Minneapolis, MN, USA) is a fairly novel leadless intracardiac pacemaker implanted in the right ventricle via a femoral-vein transcatheter approach. Due to the less-invasive nature of the implantation procedure and its smaller size, patients receiving the Micra™ device tend to experience fewer complications, hospitalizations, and revisions when compared with those with transvenous pacemakers. Certain arrhythmias and conduction abnormalities, such as high-degree atrioventricular blocks, require urgent and timely pacemaker insertion-a necessity that has persisted even during the coronavirus disease 2019 (COVID-19) pandemic. Here, we present a case series of 10 patients with various conduction disease abnormalities who required right ventricle pacemaker implantation during the months of March to May 2020, which was the initial peak of the COVID-19 pandemic in New Jersey, including the enhanced precautions taken to avoid viral spread.

Factors Associated with Disparities in Appropriate Statin Therapy in an Outpatient Inner City Population.

Lipid-lowering therapies are essential for the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). The aim of this study is to identify discrepancies between cholesterol management guidelines and current practice with a focus on statin treatment in an underserved population based in a large single urban medical center. Among 1042 reviewed records, we identified 464 statin-eligible patients. Age was 61.0 ± 10.4 years and 53.9% were female. Most patients were black (47.2%), followed by Hispanic (45.7%) and white (5.0%). In total, 82.1% of patients were prescribed a statin. An appropriate statin was not prescribed in 32.4% of statin-eligible patients who qualified based only on a 10-year ASCVD risk of ≥7.5%. After adjustment for gender and health insurance status, appropriate statin treatment was independently associated with age >55 years (OR = 4.59 (95% CI 1.09-16.66), p = 0.026), hypertension (OR = 2.38 (95% CI 1.29-4.38), p = 0.005) and chronic kidney disease (OR = 3.95 (95% CI 1.42-14.30), p = 0.017). Factors independently associated with statin undertreatment were black race (OR = 0.42 (95% CI 0.23-0.77), p = 0.005) and statin-eligibility based solely on an elevated 10-year ASCVD risk (OR = 0.14 (95% CI 0.07-0.25), p < 0.001). Hispanic patients were more likely to be on appropriate statin therapy when compared to black patients (86.8% vs. 77.2%). Statin underprescription is seen in approximately one out of five eligible patients and is independently associated with black race, younger age, fewer comorbidities and eligibility via 10-year ASCVD risk only. Hispanic patients are more likely to be on appropriate statin therapy compared to black patients.

Purification and Characterization of an Extracellular T2 Family Ribonuclease (RNase) from Bacillus megaterium NRRL 3712.

BACKGROUND: Ribonucleases of T2 family are ubiquitous cellular components which have played several biological functions in molecular and pharmaceutical fields. OBJECTIVE: Therefore, a soluble and highly active RNase belonging to T2 family was screened from Bacillus megaterium NRRL 3712, and different cultivation strategies were applied to enhance the production of enzyme. METHOD: A high-level of an extracellular RNase and cell density was produced using optimal cultivation conditions. A monomeric enzyme with a molecular mass of 45 kDa, was purified to homogeneity using acetone precipitation and ion-exchange chromatography. RESULTS: Purified enzyme was optimally activity at 45°C and pH 7.0, and it displayed a half-life of 26 min at 64°C. It was quite stable up to 60 min at 40-50°C temperature and over a broad range of pH 4.5-8.0. It showed great substrate specificity with yeast RNA, poly (A), poly (G), poly (C), and poly (U). Kinetic parameters such as Km, Vmax, kcat and kcat Km -1 values against yeast RNA as substrate, were 71.67 µg mL-1, 7866.4 µmol mg-1min-1, 17669.4 sec-1, and 246.53, respectively. CONCLUSION: The article provides a valuable novel RNase which exhibited great resistance against various organic solvents, detergents and metal ions, whereas its activity was stimulated up to 142% by adding 5 mM EDTA. Hence, dictates its applicability as therapeutic agent and in various other biotechnological fields.

Assessment of biochemical and antioxidative status in patients suffering from dengue fever.

A multi-centred study was designed to collect dengue epidemiologic data from government and registered private hospitals/clinics and maintained archive of frozen specimens in bio-bank to be used for future dengue epidemic control program, and assess the epidemiology of dengue fever (DF) by evaluating biochemical and oxidative status of patients. ELISA IgM antibodies test was done to confirm DF. From August 2010 to December 2011, 101 confirmed blood samples of DF patients referred to pathology lab of Jinnah Hospital Lahore were subjected to the epidemiologic assessment by evaluating the biochemical and physiological indices and alterations of circulating antioxidants. Clinical features of DF patients and effect of fever on blood components and serum proteins of liver were recorded. The hospital stay in DF, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) showed significant difference. Significant increases in serum alanine amino transferase (ALT) (P=0.000), aspartate amino transferase (AST) (P=0.000), alkaline phosphatase (ALP) (P=0.000), malondialdehyde (MDA) along with significant decreases in total protein (TP) (P=0.000), reduced glutathione (GSH) (P=0.000), superoxide dismutase (SOD), catalase (CAT) (P=0.000), and sialic acid contents (P=0.016) were observed. A positive correlation existed between bound sialic acid levels, liver enzymes and circulating antioxidants (r=0.656, P=0.016). In the present study, alterations of circulating antioxidants in DF suggest that DF might be a metabolic response to an acute, self-limiting tropical viral infection, and a consequence of the viral inflammatory process.

Assessment of biochemical and antioxidative status in patients suffering from dengue fever / 华中科技大学学报（医学）（英德文版）

A multi-centred study was designed to collect dengue epidemiologic data from government and registered private hospitals/clinics and maintained archive of frozen specimens in bio-bank to be used for future dengue epidemic control program, and assess the epidemiology of dengue fever (DF) by evaluating biochemical and oxidative status of patients. ELISA IgM antibodies test was done to confirm DF. From August 2010 to December 2011, 101 confirmed blood samples of DF patients referred to pathology lab of Jinnah Hospital Lahore were subjected to the epidemiologic assessment by evaluating the biochemical and physiological indices and alterations of circulating antioxidants. Clinical features of DF patients and effect of fever on blood components and serum proteins of liver were recorded. The hospital stay in DF, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) showed significant difference. Significant increases in serum alanine amino transferase (ALT) (P=0.000), aspartate amino transferase (AST) (P=0.000), alkaline phosphatase (ALP) (P=0.000), malondialdehyde (MDA) along with significant decreases in total protein (TP) (P=0.000), reduced glutathione (GSH) (P=0.000), superoxide dismutase (SOD), catalase (CAT) (P=0.000), and sialic acid contents (P=0.016) were observed. A positive correlation existed between bound sialic acid levels, liver enzymes and circulating antioxidants (r=0.656, P=0.016). In the present study, alterations of circulating antioxidants in DF suggest that DF might be a metabolic response to an acute, self-limiting tropical viral infection, and a consequence of the viral inflammatory process.

Confusing presentation of chaetomium brain abscess.

We put forth the case of a young immunocompetent female who presented with fever and left basal ganglia bleed secondary to vasculitis. After 2 weeks of prednisolone therapy, she continued to deteriorate. MRI scan revealed enhancement of previous hematoma, pus was aspirated surgically and fungal culture grew Chaetomium.

New possibilities in hepatocellular carcinoma treatment.

Hepatocellular carcinoma diagnosis and treatment has witnessed many major changes and challenges in the past two decades. Increasing incidence of HCC has introduced new monitoring systems and increased the efficacy of screening tests, as well as prognosis of the disease, including the staging system, serological testing and diagnostic imaging. Moreover, surgical resection, liver transplantation and herbal therapy have improved treatment. The most encouraging specific serological marker for HCC is alpha fetoprotein (AFP), which, along with ultrasonography, has improved earlier detection of HCC. Most recently, circulating tumor cell measurement has emerged as a promising tool for the prognosis of HCC. Herbal drugs and herbal composite formula drugs are promising towards the prevention of invasion and proliferation of tumor cells. Chemotherapeutic agents, such as sorafenib, bevacizumab and erlotinib, which target growth factor receptors in signaling pathways, are also used as HCC treatments. Furthermore, radiotherapy is employed in the treatment of unresectable tumors. The present report provides an analysis of the above parameters in the management of HCC.

Novel bluetongue virus serotype from Kuwait.

Sheep and goats sampled in Kuwait during February 2010 were seropositive for bluetongue virus (BTV). BTV isolate KUW2010/02, from 1 of only 2 sheep that also tested positive for BTV by real-time reverse transcription-PCR, caused mild clinical signs in sheep. Nucleotide sequencing identified KUW2010/02 as a novel BTV serotype.