Mexiletine: Antiarrhythmic mechanisms, emerging clinical applications and mortality.

Mexiletine, a class Ib antiarrhythmic drug, exhibits its major antiarrhythmic effect via inhibition of the fast and late Na+ currents in myocardial tissues that are dependent on the opening of Na+ channels for their excitation. Through a comprehensive examination of mexiletine's therapeutic benefits and potential risks, we aim to provide valuable insights that reinforce its role as a vital therapeutic option for patients with ventricular arrhythmias, long QT syndrome, and other heart rhythm disorders. This review will highlight the current understandings of the antiarrhythmic effects and rationales for recent off-label use and address the mortality and proarrhythmic effects of mexiletine utilizing published basic and clinical studies over the past five decades.

Renal cell carcinoma in the pediatric population: A case report and review of the literature.

Renal cell carcinoma is a cancer thought to originate from renal epithelial cells. Commonly seen in patients older than 60 years of age, renal cell carcinoma presents as rare pathological entity seen in urological cancers among the pediatric population. A 17-year-old female patient presented with complaints of intermittency, dysuria, and gross hematuria. Radiological imaging was in favor of a left renal mass. Under general anesthesia, the left kidney was completely laparoscopically resected and sent to pathology, which along with correlating the age group of the patient and the morphology on pathological analysis, was suggestive of microphthalmia family translocation renal cell carcinoma.

Retrospective Comparison of Patients ≥ 80 Years With Atrial Fibrillation Prescribed Either an FDA-Approved Reduced or Full Dose Direct-Acting Oral Anticoagulant.

Direct-acting oral anticoagulants (DOACs) represent the standard for preventing stroke and systemic embolization (SSE) in patients with atrial fibrillation (AF). There is limited information for patients ≥ 80 years. We report a retrospective analysis of AF patients ≥ 80 years prescribed either a US Food and Drug Administration (FDA)-approved reduced (n = 514) or full dose (n = 199) DOAC (Dabigatran, Rivaroxaban, or Apixaban) between January 1st, 2011 (first DOAC commercially available) and May 31st, 2017. The following multivariable differences in baseline characteristics were identified: patients prescribed a reduced dose DOAC were older (p < 0.001), had worse renal function (p = 0.001), were more often prescribed aspirin (p = 0.004) or aspirin and clopidogrel (p < 0.001), and more often had new-onset AF (p = 0.001). SSE and central nervous system (CNS) bleed rates were low and not different (1.02 vs 0 %/yr and 1.45 vs 0.44 %/yr) for the reduced and full dose groups, respectively. For non-CNS bleeds, rates were 10.89 vs 4.15 %/yr (p < 0.001, univariable) for the reduced and full doses, respectively. The mortality rate was 6.24 vs 1.75 %/yr (p = 0.001, univariable) for the reduced and full doses. Unlike the non-CNS bleed rate, mortality rate differences remained significant when adjusted for baseline characteristics. Thus, DOACs in patients ≥ 80 with AF effectively reduce SSE with a low risk of CNS bleeding, independent of DOAC dose. The higher non-CNS bleed rate and not the mortality rate is explained by the higher risk baseline characteristics in the reduced DOAC dose group. Further investigation of the etiology of non-CNS bleeds and mortality is warranted.

Correlation between Fibroscan and laboratory tests in non-alcoholic fatty liver disease/non-alcoholic steatohepatitis patients for assessing liver fibrosis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of disease ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), through to advanced fibrosis and cirrhosis. Many patients with NAFLD remain undiagnosed and recognizing those at risk is very crucial. Although liver biopsy is the gold standard method for diagnosing and staging NAFLD, non-invasive imaging and lab modalities are also very promising in diagnosing these diseases. AIM: To explore some of these non-invasive modalities in this context and assess how they hold up in terms of making a diagnosis while avoiding an invasive procedure like a liver biopsy. METHODS: This study was conducted on NAFLD/NASH patients (n = 73) who underwent Fibroscan examinations at Saint George Hospital University Medical Center over 17 mo in order to assess liver fibrosis. Obtained Fibroscan results were correlated to laboratory tests and calculated aspartate transaminase (AST)/alanine transaminase (ALT) ratio, AST platelet ratio index (APRI) score and Fibrosis-4 score. RESULTS: A significant age difference was observed across fibrosis stages of investigated patients. The mean stiffness score was 9.48 ± 11.77 KPa. A significant negative correlation was observed between ALT, AST, Albumin, gamma-glutamyl transferase, cholesterol, LDL, HDL, triglycerides, and ALP when compared across fibrosis stages. On the other hand, a significant positive correlation was found between Bilirubin, PT INR, partial thromboplastin time, glucose, and Platelet count when compared across fibrosis stages, in addition to AST/ALT ratio, APRI, and Fib-4 scores. CONCLUSION: This study showed that Ultrasound alone is not efficient in the assessment of advancement of liver disease. Furthermore, the high positive relation between AST/ALT ratio, APRI and Fib-4 scores with fibrosis stages in NAFLD patients suggests that they could be used clinically in combination with Fibroscan to predict significant fibrosis and cirrhosis and to avoid liver biopsy.

Celiacomesenteric trunk associated with superior mesenteric artery aneurysm: A case report and review of literature.

In rare cases, the celiac artery and the superior mesenteric artery arise from a common origin known as a common celiacomesenteric trunk. Celiac trunk stenosis or occlusion has been reported to accompany this anatomical aberrancy. Even rarer, are aneurysms associated with this common celiacomesenteric trunk. In general, visceral artery aneurysms are uncommon. We hereby present a 39-year-old female patient with a 1-month history of mild diffuse abdominal pain, with an incidental finding of superior mesenteric artery aneurysm on abdominal ultrasound. Subsequent contrast-enhanced computed tomography revealed severe narrowing of the celiac trunk and saccular aneurysmal dilatation of the superior mesenteric artery. Coil embolization of the aneurysm was performed, while maintaining persistent flow in the superior mesenteric artery and celiacomesenteric trunk. Visceral artery aneurysms are increasingly being identified incidentally with improvement in imaging techniques. The question lies whether to treat these aneurysms or observe. No universal guidelines exist regarding that matter, but the decision to intervene is made based on aneurysm location, size, and patient characteristics.

Organic Nanoparticles as Drug Delivery Systems and Their Potential Role in the Treatment of Chronic Myeloid Leukemia.

Chronic myeloid leukemia is a myeloproliferative neoplasm that occurs more prominently in the older population, with a peak incidence at ages 45 to 85 years and a median age at diagnosis of 65 years. This disease comprises roughly 15% of all leukemias in adults. It is a clonal stem cell disorder of myeloid cells characterized by the presence of t(9;22) chromosomal translocation, also known as the Philadelphia chromosome, or its byproducts BCR-ABL fusion protein/messenger RNA, leading to the expression of a protein with enhanced tyrosine kinase activity. This fusion protein has become the main therapeutic target in chronic myeloid leukemia therapy, with imatinib displaying superior antileukemic effects, placing it at the forefront of current treatment protocols and displaying great efficacy. Alternatively, nanomedicine and employing nanoparticles as drug delivery systems may represent new approaches in future anticancer therapy. This review focuses primarily on the use of organic nanoparticles aimed at chronic myeloid leukemia therapy in both in vitro and in vivo settings, by going through a thorough survey of published literature. After a brief introduction on the pathogenesis of chronic myeloid leukemia, a description of conventional, first- and second-line, treatment modalities of chronic myeloid leukemia is presented. Finally, some of the general applications of nanostrategies in medicine are presented, with a detailed focus on organic nanocarriers and their constituents used in chronic myeloid leukemia treatment from the literature.

Analysis of gastric and duodenal biopsy results in patients presenting with dyspepsia: a cross-sectional study in a middle eastern population.

OBJECTIVE: Correa's cascade is a 'Model for Gastric Cancer Development' described by Peleyo Correa. The reversibility of Correa's cascade remains debatable. The literature contains insufficient data on the specific stage of the cascade during which Helicobacter pylori is detected, treated, and the effect on prognosis. Herein, we aim to determine the prevalence of various precancerous and cancerous gastric lesions in patients presenting with dyspepsia, the prevalence of gastritis and H. pylori infection, the prevalence of duodenal pathology in patients presenting with dyspepsia, identify the stage of H. pylori detection in relation to Correa's cascade, and investigate a possible relationship between H. pylori and celiac disease. DESIGN: Retrospective cross-sectional study conducted on a middle eastern population at a Lebanese tertiary hospital centre. 1428 patients presenting with dyspepsia underwent gastroscopy with gastric and duodenal biopsies. Variables include age, sex, presence/absence of H. pylori infection, and histopathological analysis of gastric and duodenal biopsies. RESULTS: Being above 40 years of age was associated with increased likelihood of exhibiting abnormal gastric biopsy result. Gastritis and metaplasia were detected more frequently than glandular atrophy (p<0.001) with gastritis being present the most (p<0.001). The presence of H. pylori and the gastric biopsy results were not associated with any of the duodenal biopsy results. CONCLUSION: The burden of H. pylori infection in patients with dyspepsia was high. H. pylori was detected at various precancerous lesions with varying significance. The prevalence of duodenal adenocarcinoma in dyspeptic patients is unexpectedly high. No association between gastric and duodenal pathologies was found.

Gas-Forming Liver Abscess versus Emphysematous Hepatitis: A Radiologic Diagnostic Dilemma-A Case Report and Review of the Literature.

A 38-year-old diabetic woman, with history of cholecystectomy and ventral hernia repair, was hospitalized due to sudden-onset abdominal pain and fever. Computed tomography revealed a mixed collection containing necrotic debris and emphysematous change in the left lobe of the liver mainly in segments II and III. These radiological findings suggested emphysematous hepatitis (EH). The patient's condition deteriorated rapidly, and she was rushed to the operating room for urgent exploratory laparotomy where debridement was performed. Intraoperatively the patient was found to have an abscess with incomplete capsule concurrent with hepatic necrosis suggesting the co-occurrence of abscess and EH. The patient survived and was discharged after 13 days. Relevant literature was reviewed, and to the best of our knowledge, EH is an extremely rare entity with limited data regarding its pathogenesis, causative organisms, and management. EH is a rapidly invasive disease process that can be fatal if appropriate therapeutic intervention is delayed. Initial presentations are usually subtle, thus high clinical and radiological suspicion is required for early diagnosis and management to decrease associated mortality and morbidity. We hence report the first successfully treated case of EH with review of the literature.

Inorganic Nanoparticles as Drug Delivery Systems and Their Potential Role in the Treatment of Chronic Myelogenous Leukaemia.

Chronic myeloid leukemia is a myeloproliferative disease where cells of myeloid linage display a t(9;22) chromosomal translocation leading to the formation of the BCR/ABL fusion gene and the continuous activation of tyrosine kinases. This malignancy has a peak incidence at 45 to 85 years, accounting for 15% of all leukemias in adults. Controlling the activity of tyrosine kinase became the main strategy in chronic myeloid leukemia treatment, with imatinib being placed at the forefront of current treatment protocols. New approaches in future anticancer therapy are emerging with nanomedicine being gradually implemented. Setting through a thorough survey of published literature, this review discusses the use of inorganic nanoparticles in chronic myeloid leukemia therapy. After an introduction on the basics of chronic myeloid leukemia, a description of the current treatment modalities of chronic myeloid leukemia and drug-resistance mechanisms is presented. This is followed by a general view on the applications of nanostrategies in medicine and then a detailed breakdown of inorganic nanocarriers and their uses in chronic myeloid leukemia treatment.

Adenoma Detection before and after the age of 50: a retrospective analysis of Lebanese outpatients.

BACKGROUND AND AIM: Colorectal cancer (CRC) has an increased impact on the Lebanese population's morbidity and mortality. This study evaluated the situation of adenoma detection in an outpatient clinic in Lebanon. PATIENTS AND METHODS: 918 patients underwent colonoscopy over a period of 24 months by a qualified physician. Biopsy results were divided into normal versus abnormal colonic tissue, which was further subdivided into number of polyps and cancer. RESULTS: Out of 918 individuals included, 82 cases of Crohn's colitis (8.93%) and 22 cases of ulcerative colitis (2.39%) were identified. A total of 42 cases of CRC (4.58%) and 188 cases of adenomatous polyps (20.48%) were identified. The data show that age >50 years and male gender significantly correlate with increased incidence of precancerous and cancerous polyps. Further exploring the results by age groups and gender, detection of adenomatous polyps in women aged 40-49 (8.33%) was significantly different from their female counterparts aged ≥50 years old (25.26%) (p<0.01). However, no statistical difference between detection of adenomas was found between men aged 40-49 (33.33%) and their male counterparts aged ≥50 years old (37.5%) (p=0.6). CONCLUSION: Within the limitations of this study, the incidence of CRC and adenomatous polyps falls in the high range compared with international studies. Furthermore, symptomatic male patients aged 40-49 appear to exhibit detection rates of adenomas similar to their counterparts aged ≥50 years old. Subjects younger than 50 years underwent diagnostic rather than screening colonoscopy, which introduces some selection bias. Nevertheless, these findings can serve as a basis for further studies.

Colonic Malakoplakia: A Rare Finding in a Healthy Male.

Malakoplakia is a rare chronic granulomatous disease that may affect many organs, including the lung, brain, adrenal glands, pancreas, bone, and the genitourinary tract. The gastrointestinal tract is the most common site of involvement outside of the urinary tract. Herein, we present a case of a 65-year-old male who presented with abdominal pain and unintentional weight loss. Physical examination findings were unremarkable, but colonoscopy revealed an isolated large, flat, soft, and pale lesion in the transverse colon. Histopathological examination of the lesion showed expansion of the lamina propria due to numerous lymphocytes, plasma cells, neutrophils, and polygonal cells. Von Kossa stain showed small intracytoplasmic basophilic granular inclusions, and these histiocyte cells showed numerous Michaelis-Gutmann bodies, findings considered as diagnostic features of colonic malakoplakia. This is a rare case of isolated malakoplakia of the transverse colon diagnosed on endoscopic specimens. The majority of reported cases have shown an association between systemic diseases and colorectal adenocarcinoma. In addition, most reported cases of colonic involvement have been in the rectum, sigmoid, and right colon.