Aberrant ecotropic viral integration site-1 (EVI-1) and myocyte enhancer factor 2 C gene (MEF2C) in adult acute myeloid leukemia are associated with adverse t (9:22) & 11q23 rearrangements.

Acute myeloid leukemia (AML) shows multiple chromosomal translocations & point mutations which can be used to refine risk-adapted therapy in AML patients. Ecotropic viral integration site-1 (EVI-1) & myocyte enhancer factor 2 C gene (MEF2C) are key regulatory transcription factors in hematopoiesis and leukemogenesis & both drive immune escape. This prospective study involved 80 adult de novo AML patients recruited from Oncology Center, Mansoura University, between March 2019 and July 2021. The MEF2C and EVI1 expression were measured using a Taqman probe-based qPCR assay. The results revealed that EVI1 and MEF2C expression were significantly elevated in AML patients as compared to control subjects (p = 0.001. 0.007 respectively). Aberrant expressions of EVI1 and MEF2C showed a significant negative correlation with hemoglobin levels (p = 0.034, 0.025 respectively), & bone marrow blasts (p = 0.007, 0.002 respectively). 11q23 translocation was significantly associated with EVI1 and MEF2C (p = 0.004 and 0.02 respectively). Also, t (9;22) was significantly associated with EVI1 and MEF2C (p = 0.01 and 0.03 respectively), higher expression of EVI1 and MEF2C were significantly associated with inferior outcome after induction therapy (p = 0.001 and 0.018 respectively) and shorter overall survival (p = 0.001, 0.014 respectively). In conclusion, EVI1 & MEF2C were significantly expressed in AML cases. EVI1 & MEF2C overexpression were significantly associated with 11q23 rearrangements and t (9;22) and were indicators for poor outcome in adult AML patients; These results could be a step towards personalized therapy in those patients.

Sonographic reference values of nerve size in children: A systematic review and meta-analysis.

INTRODUCTION/AIMS: Nerve ultrasound is useful in the diagnosis and follow-up of peripheral nerve disorders in children. The aim of this study was to explore and analyze the current literature on nerve cross-sectional area (CSA) in healthy children, with the goal of presenting reference values and discussing their implications. METHODS: We performed a systematic review and meta-analysis of studies that reported ultrasound measurements of the upper or lower limb nerves in healthy children through a search of Web of Science, PubMed, Embase, and Scopus. RESULTS: Sixteen studies with measurements of 10 nerves covering a total of 5149 nerves measured in 823 healthy children (445 boys and 378 girls) were included. Mean nerve CSA increased with age in the median nerve at the middle and lower third of the upper arm, mid-forearm, and distal wrist crease, the ulnar nerve at the middle third of the upper arm and elbow, the radial nerve at the spiral groove, and the tibial nerve at the popliteal fossa. Growth charts for nerve CSA for different age groups were developed. DISCUSSION: This meta-analysis provides robust reference values for nerve CSA at different sites in children, and this can inform clinical practice and assist in identifying nerve enlargement. Moreover, it identifies the strength and quality of the current published data. We recommend future studies divide their samples into smaller age subgroups and standardize the anatomic site of measurement.

Factors associated with the laterality of Cardio-Embolic stroke.

OBJECTIVE: Understanding the lateralization factors, including the anatomic and hemodynamic mechanisms, is essential for diagnosing cardio-embolic stroke. This study aims to investigate the elements, for the first time together, that could affect the laterality of stroke. METHODS: We performed a monocentric retrospective case-control study based on prospective registries of acute ischemic stroke patients in the comprehensive stroke center of the RWTH University hospital of Aachen for three years (June 2018-June 2021). We enrolled 222 patients with cardioembolic stroke (136 left stroke and 86 right stroke) admitted for first-ever acute ischemic stroke with unilateral large vessel occlusion of the anterior circulation. The peak systolic velocity (PSV) asymmetry of middle cerebral artery (MCA) was assessed by doppler as well as internal carotid artery (ICA) angle, aortic arch (AA) branching pattern and anatomy were assessed by CT-Angiography. RESULTS: We found that the increasing left ICA angle (p = 0.047), presence of bovine type AA anatomy (p = 0.041) as well as slow PSV of the right MCA with a value of >15% than left (p = 0.005) were the predictors for left stroke lateralization, while the latter was an independent predictor for the left stroke (OR=3.341 [1.415-7.887]). Inter-Rater Reliability ranged from moderate to perfect agreement. CONCLUSION: The predictors for left stroke lateralization include the higher values of left ICA angle, presence of the bovine type AA and the slow right MCA PSV.

Fucoidan Ameliorates Hepatocellular Carcinoma Induced in Rats: Effect on miR143 and Inflammation.

Fucoidan is sulfated polysaccharide of brown seaweed. It offers various pharmacological actions like anti-inflammatory, anti-bacterial and anti-tumor activities. Therefore, we aimed to investigate the effect of targeting microRNA-143 and inflammatory pathway by Fucoidan on experimentally induced hepatocellular carcinoma (HCC) in rats. HCC is experimentally induced in Sprague Dawley by thioacetamide. Rats were treated with 100 mg/kg and 200 mg/kg Fucoidan. Hepatic sections were stained with hematoxylin/esosin for investigation of cell integrity. Moreover, hepatic sections were immunohistochemically stained with antibodies for ki67, TNF-α, and IL-1ß. Finally, hepatic tissues were investigated for expression of miR-143, NF-κB, TNF-α, and IL-1ß. We found that treating HCC with Fucoidan significantly reduced HCC-induced elevation in oxidative stress. Moreover, Fucoidan reduced HCC-induced in expression of miR-143, NF-κB, TNF-α, and IL-1ß. Finally, Fucoidan attenuated pseudohepatic lobules, broad fibrous septa and vacuolar to ballooning degeneration associated with reduction of immunostaining of ki67, TNF-α, and IL-1ß. Fucoidan elevated the survival of HCC rats and reduced their serum AFP. In addition, Fucoidan treatment revealed reduction in the expression of miR-143 associated with antioxidant and anti-inflammatory activities in HCC rats.

Clinical significance of the TNF-α receptors, TNFRSF2 and TNFRSF9, on cell migration molecules Fascin-1 and Versican in acute leukemia.

In human hematologic malignancies, some of the TNF receptor family members are up-regulated and have the ability to evoke reactions favoring tumor progression. Moreover, cell migration molecules, Fascin-1 and Versican are involved in proliferation, migration and invasion of cancer cells. They are linked to many human cancers. Therefore, we conducted this study to evaluate both the plasma and leukocytes concentrations of tumor necrosis factor receptor super family 2 (TNFRSF2), TNFRSF9, Fascin-1 and Versican in patients with acute leukemia, as well as to correlate these values with clinical features and treatment outcome. Therefore, forty-eight patients with acute myeloid leukemia (AML), thirty-two patients with acute lymphoblastic leukemia (ALL) and fifteen control subjects were included. TNFRSF2, TNFRSF9, Fascin-1 and Versican were measured in plasma and leukocytes of all subjects by enzyme-linked immunosorbent assay. We found that plasma TNFRSF9 was highly elevated in ALL and AML as compared with the control group. In addition, AML patients who failed to achieve complete remission showed a significant increase in leukocytes TNFRSF9 level. TNFRSF2 is significantly increased in plasma and leukocytes of ALL patients when compared with the control group and AML patients. Fascin-1 significantly increased in AML, but not in ALL cases. Plasma and leukocytes levels of Versican significantly increased in AML compared to both control and ALL subjects. Plasma Versican correlated with poor response to induction of chemotherapy in AML cases. In conclusion, TNFRSF2 and TNFRSF9 could act as a possible prognostic biomarkers for the outcomes of ALL patients and TNFRSF9 could be a potential target in AML. Versican may be used as a diagnostic biomarker and as a predictor of the response to chemotherapy in AML. In addition, plasma Fascin-1 is a potential biomarker for AML.

Galectin-3 and matrix metalloproteinase-9: Perspective in management of hepatocellular carcinoma.

AIM: Hepatocellular carcinoma (HCC) is the fifth most common cancer in men and the seventh in women. HCC varies widely in incidence through the world, with rising incidence in Egypt. This study aimed to estimate the serum levels of matrix metalloproteinase-9 (MMP-9) and its substrate galectin-3 in order to evaluate their diagnostic accuracy and their relation to HCC-related clinical features. METHODS: For this purpose, serum levels of these biochemical markers were assessed in 50 HCC patients, 30 cirrhotic patients in addition to 10 healthy subjects as a control group using enzyme linked immune-sorbent assay (ELISA). RESULTS: In the present study, circulating level of galectin-3, MMP-9 increased significantly in HCC as compared to the control group (P = 0.044 and 0.04, respectively). However, no significant difference was observed between cirrhotic and HCC patients (P = 0.231 and 0.193, respectively). Our study found that HCC patients with metastatic spread had a significant elevation of both serum galectin-3 and MMP-9 levels (P = 0.028 and <0.0001, respectively). In addition, galectin-3 level significantly increased in HCC patients with poor prognosis suffering from portal vein invasion (P = 0.014). Moreover, MMP-9 increased significantly with increasing stage of Barcelona-Clinic Liver Cancer Group diagnostic and treatment strategy (P = 0.01). CONCLUSION: MMP-9 and galectin-3 could be used as a guide for prognosis of HCC since they may play a role in HCC progression and metastasis. However, they are not useful markers for HCC diagnosis.

Clinical outcome of HCV-positive patients with diffuse large B-cell lymphoma treated with rituximab-based chemotherapy.

The influence of rituximab therapy on prognosis and hepatic toxicity (HT) in patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphoma (DLBCL) is unclear. Thus, we assessed HT and clinical outcome in patients with DLBCL and HCV infection who received rituximab-containing immunochemotherapy. We carried out a prospective analysis on a total of 280 HCV-positive patients with DLBCL, 200 of whom received chemotherapy plus rituximab (R-CHT), 80 received chemotherapy (CHT)-only. Survival outcomes and HT were compared according to rituximab administration. The median follow-up was 41 months. Addition of rituximab did not significantly affect prognosis (median progression-free survival, 40 vs 35 months, P = 0.26; median overall survival, 51 vs 43 months P = 0.09). Of 200 patients who received rituximab, 53 (26.5 %) had severe HT (grade 3-4), compared with 11 of 80 (13.75 %) patients who received rituximab-free regimens (P = 0.033). Among patients treated with rituximab, 50 patients (25 %) did not complete planned course of therapy, 14 patients because of hepatic toxicity and 36 patients because of progressive disease. Pretreatment liver function impairment was predictive of severe HT. These results raise concerns regarding the routine use of rituximab with chemotherapy in individuals with HCV-positive DLBCL. However, more studies are warranted before a definitive conclusion can be made.

Prevalence of tobacco smoking among health-care physicians in Bahrain.

BACKGROUND: There is a clear shift in smoking habits among the Middle Eastern population with a recent and alarming increase in the prevalence of waterpipe (shisha) smoking. This phenomenon has not yet been studied sufficiently across the physician population. Therefore, we set out to establish the smoking status of primary healthcare physicians in the kingdom of Bahrain. METHODS: A self-administered questionnaire was distributed to a random sample of 175 out of the total 320 primary care physicians. Descriptive analysis was performed on all data and associations between variables were tested using Fishers Exact t test with statistical significance set as P-value < 0.05. RESULTS: One hundred and fifty two physicians agreed to participate in the study. Sixty seven percent of physicians were females and the mean (SD) age was 45 (10) years. The majority of the physicians were married (93%) and of Bahraini nationality (76%). Ever-smokers were 11% of the population while current smokers corresponded to 8.6%. Waterpipe was the most common method of tobacco smoking followed by cigarettes. Among male physicians, the prevalence of current 'waterpipe only' smokers was 12%, followed by 4% and 2% corresponding to 'cigarette only' smokers and both, respectively. There were only three female smokers in the population, two 'waterpipe only' smokers and one cigar smoker. Of those who smoked waterpipe (n = 9; 6%), 33% smoked daily, 44% smoked weekly and 22% smoked at least once a month. Current smoking status was associated with male gender (P < 0.001) and showed a male to female smoking ratio of (10:1). CONCLUSION: Waterpipe smoking rates exceeded cigarette smoking among the population of physicians in Bahrain. Prevalence of smoking remains unacceptably high among male physicians. Assessment of physicians' knowledge of the harmful effects of waterpipe tobacco smoking is warranted to plan future interventions.

Cytotoxic effects of suramin against HepG2 cells through activation of intrinsic apoptotic pathway.

PURPOSE: To investigate the cytotoxic activity of suramin against HepG2 human HCC cell line. METHODS: HepG2 cells were treated with 15, 30 and 45 µM suramin. HepG2 cell proliferation was measured by MTT and lactate dehydrogenase (LDH) assays. Heparan sulfate proteoglycans (HSPGs), glucuronic acid and glucosamine levels were measured. Moreover, apoptosis was assessed by measuring caspase-8 and caspase-9 activities. The effect of suramin on HepG2 cells was compared with the same doses of a standard drug, cisplatin. RESULTS: Suramin blocked heparanase leading to dose-dependent increase in HSPGs and reduction in glucuronic acid and glucosamine levels. Suramin reduced HepG2 cells survival and showed cell cytotoxicity in a dose-dependent manner with LD50 45.04 µM, compared with cisplatin (LD50 28.9 µM) (p<0.05). Moreover, suramin was able to increase the activity of caspase-9 but not of caspase-8. CONCLUSION: Suramin possesses cytotoxic properties, which can be partially explained by its ability to inhibit heparanase and restore HSPGs. Suramin activates intrinsic apoptosis without affecting the extrinsic pathway.

Cardiac Arrest Following GoLytely Consumption: A Potential Trigger for Hypovolemic Shock.

This case report presents a rare but severe complication of polyethylene glycol (PEG) used for colonoscopic bowel preparation. A 71-year-old male developed cardiac arrest secondary to hypovolemic shock following consumption of GoLytely. Despite being hemodynamically stable prior to ingestion, the patient experienced extreme weakness, dizziness, and orthostatic hypotension post-consumption. Evaluation ruled out other causes of arrest. While serious complications from PEG are rare, this case underscores the importance of vigilance. Further investigation is warranted to elucidate the relationship between PEG use and cardiac events and to identify potential risk factors for adverse outcomes associated with bowel preparation regimens.

A Case of an Unusual Bleeder: Small Bowel Lymphoma.

This case report highlights an uncommon presentation of small bowel lymphoma as gastrointestinal bleeding in an 87-year-old female with a history of ulcerative colitis. Despite non-specific symptoms and negative findings on upper endoscopy and colonoscopy, ileoscopy revealed a distal ileal mass with a solitary non-bleeding ulcer, confirmed by biopsy as diffuse large B-cell lymphoma (DLBCL). The patient opted for palliative management. Small intestinal lymphomas, particularly DLBCL, pose diagnostic challenges due to their varied presentations. Timely detection is crucial for optimal outcomes, emphasizing the importance of prompt utilization of diagnostic methods in suspected cases.

An Anaphylactic Encounter With Ferric Gluconate Infusion: A Case Report.

Iron deficiency anemia (IDA) is a prevalent condition globally, often necessitating intravenous iron therapy. We present a case of a 71-year-old female with IDA who experienced a severe anaphylactic reaction shortly after commencing a sodium ferric gluconate complex infusion. Prompt cessation of the infusion and administration of epinephrine with steroids led to rapid recovery. This case underscores the importance of recognizing and managing rare yet potentially life-threatening hypersensitivity reactions to intravenous iron formulations, highlighting the need for vigilance among healthcare providers.

Microscopic Colitis Secondary to Leflunomide: A Case Report.

Microscopic colitis (MC) is characterized by chronic watery diarrhea that requires histological examination for diagnosis. Here, we present a case of a 63-year-old female with rheumatoid arthritis who developed persistent diarrhea following leflunomide initiation. Despite a normal colonoscopy, random colonic biopsies confirmed MC. Discontinuation of leflunomide led to symptom resolution, implicating it as the causative agent. Leflunomide-induced MC is exceedingly rare, with limited documented cases. Understanding its variability in presentation and timely recognition is crucial. This case underscores the importance of thorough medication history assessment and consideration of drug-induced colitis in patients presenting with unexplained diarrhea, facilitating prompt management and resolution.

Safety and Efficacy of Highly Selective 5-Hydroxytryptamine Receptor 4 Agonists for Diabetic and Idiopathic Gastroparesis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Gastroparesis significantly affects quality of life and healthcare expenditure. Effective treatment options are limited, and the utility of current prokinetic agents is inhibited by serious adverse effects. There exists an unmet need for prokinetic agents demonstrating both efficacy and an acceptable adverse effect profile. Highly selective 5-Hydroxytryptamine receptor 4 (5-HT4) agonists have exhibited clinical efficacy and safety in randomized controlled trials (RCTs). Consequently, we conducted a meta-analysis to comprehensively assess the safety and efficacy of these highly selective agents. Multiple databases, including PubMed, Scopus, and Embase, were systematically screened from inception until September 2023. Only RCTs evaluating the efficacy and safety of highly selective 5-HT4 agonists for gastroparesis were included. Key outcomes of interest included the pooled rates of Gastroparesis Cardinal Symptom Index (GCSI) scores, gastric emptying time (GET), and adverse event rates in each group. We adhered to standard meta-analysis methodology utilizing the random-effects model, with heterogeneity assessed by I2 statistics. Our analysis identified six RCTs, comprising 570 patients with diabetic (48%) or idiopathic (51%) gastroparesis, with mean ages of 46 and 45.9 years in the intervention and placebo groups, respectively. In the meta-analysis, highly selective 5-HT4 agonists demonstrated significantly superior pooled GCSI scores compared to placebo (mean difference: 4.283, (1.380, 7.186), p<0.05). Pooled GET was also significantly improved with 5-HT4 agonists compared to placebo (mean difference: 2.534, (1.695, 3.373), p<0.05). Although pooled rates of total adverse events were higher with 5-HT4 agonists (mean difference: 6.975, (1.042, 46.684), p<0.05), rates of specific adverse events such as diarrhea, abdominal pain, and headaches were comparable. In conclusion, this meta-analysis underscores a statistically significant improvement in GET and GCSI scores among patients receiving highly selective 5-HT4 agonists (Velusetrag, Felcisetrag, Prucalopride) for both diabetic and idiopathic gastroparesis. While the overall adverse effect profile is deemed acceptable, larger studies with extended follow-up periods are needed to investigate rare and/or serious adverse events. Moreover, future high-quality RCTs comparing the efficacy and safety of these novel agents with currently available agents are essential to further validate these findings.

Unraveling the Narrow Alley: A Case Report of Groove Pancreatitis.

Groove pancreatitis, a rare subtype of chronic pancreatitis, predominantly affects middle-aged men with a history of alcohol abuse. We present a unique case of a 31-year-old female with minimal alcohol consumption. Imaging revealed characteristic findings consistent with groove pancreatitis. Despite its rarity in young females, clinical suspicion led to the appropriate diagnosis and conservative management, resulting in symptomatic resolution. This case underscores the importance of recognizing atypical presentations of groove pancreatitis, emphasizing the necessity of tailored diagnostic approaches, and highlighting the efficacy of conservative management in achieving favorable outcomes, particularly in non-typical demographics.

The Hepatic Imposter: Solitary Necrotic Nodules Masquerading as Hepatic Metastasis.

Solitary necrotic nodules in the liver present a diagnostic challenge due to their rarity and resemblance to metastatic tumors. We report a case where imaging revealed multiple hepatic lesions suggestive of malignancy, prompting a needle biopsy. Histopathology confirmed necrosis without malignancy. Despite advancements in imaging modalities, distinguishing solitary necrotic nodules from metastases remains difficult. Recognition of characteristic imaging features and consideration of biopsy are crucial for accurate diagnosis and management. This case underscores the importance of thorough evaluation and differential diagnosis in liver lesions to prevent unnecessary surgical interventions and ensure appropriate clinical care.

Bigger Than a Hen's Egg: A Case of Bouveret Syndrome.

Bouveret syndrome, a rare complication of cholelithiasis resulting in gallstone ileus, presents diagnostic and therapeutic challenges due to its low incidence and nonspecific symptoms. We report a case of Bouveret syndrome in a middle-aged male without significant medical history, emphasizing the need for heightened clinical suspicion. Diagnostic imaging, including computed tomography and upper endoscopy, revealed gastric outlet obstruction and a cholecystoduodenal fistula. Treatment involved unsuccessful endoscopic lithotripsy followed by surgical intervention. This case underscores the importance of interdisciplinary collaboration for successful management. With no standardized approach, individualized treatment strategies, including endoscopic and surgical interventions, are crucial for favorable outcomes in Bouveret syndrome.

Duodenal Carcinosarcoma: An Apple-Core Lesion Causing Gastric Outlet Obstruction.

We present a case of a 58-year-old male with a rare duodenal carcinosarcoma causing gastric outlet obstruction. Despite its aggressive nature and poor prognosis, with only 12 documented cases in the literature, this report sheds light on the clinical presentation and challenges in diagnosis and treatment. Carcinosarcoma, characterized by both carcinomatous and sarcomatous elements, poses difficulties in management due to its diverse tissue characteristics. Surgical resection remains the primary treatment, although the prognosis remains grim, emphasizing the need for further research into advanced therapeutic strategies to improve patient outcomes. This case underscores the rarity and clinical complexities associated with duodenal carcinosarcomas.

Non-cirrhotic Ascites: A Case of Severe Alcoholic Hepatitis.

This case report presents a unique instance of ascites in acute alcoholic hepatitis (AH) occurring in a non-cirrhotic patient. Comprehensive diagnostic evaluation excluded alternative etiologies, pinpointing sinusoidal non-cirrhotic portal hypertension. Present therapeutic modalities for AH, including steroids and pentoxifylline, offer limited efficacy, necessitating ongoing investigation. Liver transplantation may be contemplated in refractory cases. This case underscores the intricate nature of AH presentations and the challenges in their management, emphasizing the imperative need for continued research to delineate optimal therapeutic strategies. Early intervention remains pivotal in addressing AH complications, underscoring the need for heightened clinical vigilance and proactive treatment approaches in such cases.

Chest Pain Redefined: Atypical Presentation of Superior Mesenteric Artery Syndrome.

Superior mesenteric artery (SMA) syndrome is a rare cause of small bowel obstruction characterized by duodenal compression due to the narrowing of the SMA-aorta angle. We present a case of a 43-year-old male with postprandial chest pain, severe weight loss, and a narrowed aortomesenteric angle evident on computed tomography. Conservative management, including hydration, positioning, and weight gain, was initiated, leading to symptom resolution. SMA syndrome diagnosis requires clinical suspicion and radiological confirmation. Understanding this syndrome's varied presentations, diagnostic challenges, and therapeutic approaches is crucial for prompt management, especially when atypical symptoms like chest pain manifest, as seen in our case.