Molecular mechanism of empagliflozin cardioprotection in 5-fluorouracil (5-FU)-induced cardiotoxicity via modulation of SGLT2 and TNFα/TLR/NF-κB signaling pathway in rats.

One of the commoly used chemotherapeutic agents is 5-Fluorouracil (5-FU). Unfortunately, the clinical administration of 5-FU is complicated with serious cardiotoxic effects and the safe use becomes an urgent task in cardio-oncology. Till now, there are no studies discussed the role of empagliflozin (EMP) against 5-FU cardiotoxicity. Thus, we investigated this effect and the involved mechanisms in 5-FU induced heart injury. Forty male rats of Wistar albino species were used and divided randomly into four groups. Group I is the control group, group II is EMP given group, group III is 5-FU cardiotoxic group and group IV is 5-FU plus EMP group. 5-FU (150 mg/kg) was administered as a single intraperitoneal (i.p.) dose on 1st day to induce cardiotoxicity with or without EMP (30 mg/kg/d) orally for 5 days. The dose of 5-FU is relevant to the human toxic dose. Our data showed that 5-FU given group caused cardiotoxicity with significant increase of serum cardiac enzymes, toll like receptors, enhancement of nuclear factor kappa B (NF-κB), interleukin1ß (IL1ß), IL6, myeloid-differentiation-factor 88 (MYD88), heart weight, malondialdehyde (MDA), tumor-necrosis-factor-alpha (TNFα), sodium glucose co-transporter 2 (SGLT2), P53 and caspase3 expression with clear histopathological features of cardiotoxicity. Moreover, there is a significant decrease in reduced glutathione (GSH) and total antioxidant capacity (TAC). Interestingly, co-administration of EMP could ameliorate 5-FU induced biochemical and histopathological changes. This effect may be due to modulation of SGLT2, decreasing inflammation, oxidative stress and apoptosis with downregulation of an essential inflammatory cascade that mediates 5-FU cardiotoxicity; TNFα/TLR/NF-κB. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00204-1.

Transient Descending Colocolonic Intussusception Due to a Large Fecaloma in an Adult.

Intussusception typically occurs in infants and children, with adults representing 5% of cases. A 53-year-old African American woman presented with lower abdominal pain and tenderness. Computed tomography of the abdomen and pelvis demonstrated a 3.5 cm colocolonic intussusception in the descending colon. Emergent colonoscopy found solid stool in the mid descending colon. Water-soluble rectal enema showed a filling defect in the mid descending colon. Repeat colonoscopy demonstrated presence of a large fecaloma in left colon. Laxatives were initiated, and abdominal pain subsided. To our knowledge, this is the first report of colocolonic intussusception secondary to fecaloma.

Diagnosis of Splenic Lymphoma by Endoscopic Ultrasound Guided Fine Needle Aspiration: A Case Report and Review of the Literature.

Introduction. Splenic tumor is usually found as an incidental finding on CT of abdomen. Traditionally, ultrasound (US) or computed tomography (CT) guided biopsies were employed for the purpose of sampling; however they have been reported to have a complication rate of 5.3%. Endoscopic ultrasound-fine needle aspiration (EUS-FNA) has been recently utilized for the purpose of sampling splenic tumors. In literature there are 7 reported instances where splenic lymphoma was diagnosed using EUS-FNA. We present a case of follicular B cell lymphoma of the spleen diagnosed using EUS-FNA. Case Report. 58-year-old female presented to her primary care physician for left upper quadrant abdominal pain for one week. Physical exam was significant for left upper quadrant tenderness. Her laboratory tests were within normal limits. She underwent CT scan of abdomen which revealed approximately 5 cm × 5 cm mass in spleen. EUS-FNA of the spleen revealed a large hypoechoic, heterogeneous, well-demarcated mass measuring 54.7 mm × 43.0 mm. Fine needle aspiration was performed, and the sample was submitted for cytology and flow cytometry. Flow cytometry revealed a lambda monotypic population of B cells displaying dim CD19 and CD10. Diagnosis of B cell non-Hodgkin low grade follicular lymphoma was made. Conclusion. Endoscopic ultrasound with fine needle aspiration is a very rare but safe, reliable method of diagnosis of splenic lymphomas.

Endoscopic Appearance of Oropharyngeal and Upper GI Kaposi's Sarcoma in an Immunocompromised Patient.

Introduction. Kaposi's sarcoma (KS) usually manifests as a cutaneous disease but GI manifestation is often rare. It is associated with human herpes virus-8 (HHV-8) and seen in immunocompromised patients. In the USA, use of highly active antiretroviral therapy (HAART) has drastically reduced incidence of KS in HIV patients. Case Presentation. A 65-year-old male with human immunodeficiency virus (HIV) was admitted to the intensive care unit (ICU) with cardiopulmonary arrest secondary to hyperkalemia of 7.5 meq/L. Following placement of orogastric and endotracheal tube (ETT), a significant amount of blood was noticed in the ETT. Hemoglobin trended down from 9.6 mg/dL to 6.7 mg/dL over five days. Stool guaiac was positive. Esophagogastroduodenoscopy (EGD) was performed and revealed multiple large hypervascularized violaceous submucosal nodular lesions with stigmata of bleeding seen on the soft palate and pharynx and within the cricopharyngeal area close to the vocal cords. Biopsy of the soft palate lesions showed proliferation of neoplastic spindle shaped cells arranged in bundles with slit-like capillary spaces containing erythrocytes consistent with Kaposi's sarcoma. Biopsy was positive for HHV-8. Colonoscopy was unremarkable. There were no cutaneous manifestations of the disease. Conclusion. GI involvement of Kaposi's sarcoma must be considered in immunocompromised patients and can be confirmed by endoscopic methods.

Diagnosis of Pseudomyxoma peritonei via endoscopic ultrasound guided fine needle aspiration: a case report and review of literature.

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a rare condition caused by mucinous adenocarcinoma cancerous cells that produce abundance of mucin or gelatinous ascites. This cancer can cause tissue fibrosis and can impair normal organ function. Diagnosis can involve multiple imaging modalities including CT scan. There have been few cases of endoscopic ultrasound (EUS) being used as a means for diagnosis of this condition. Here we report a second case of PMP with a previous history of appendectomy diagnosed with EUS guided fine needle aspiration (FNA) biopsy. CASE STUDY: A 66-year-old male with a history of an appendectomy presented with intermittent abdominal pain for two years and weight loss of 40 pounds over two months. EGD and colonoscopy performed at an outside hospital was unremarkable. CT abdomen revealed perigastric ascities and lesions of the liver. ESR was elevated at 75. At our facility, EUS was performed revealing a peri-gastric and omental mass measuring 36.6 mm × 25.5 mm. FNA performed of both mass and ascetic fluid revealed low grade mucinous adenocarcinoma with mucinous deposits in the peritoneum consistent with PMP. CONCLUSIONS: Endoscopic ultrasound guided FNA, although very rarely used, can be a reliable and safe technique in diagnosis of PMP.