Seven-Year Experience of Intramural Surgery in the Middle East: A Safety and Feasibility Analysis.

Background: Intramural surgery techniques, particularly esophageal peroral endoscopic myotomy (E-POEM), gastric peroral endoscopic myotomy (G-POEM), and peroral endoscopic myotomy for Zenker's (Z-POEM), have emerged as forefront minimally invasive endoscopic procedures. While several studies have reported on the outcomes in North America and Asia, evidence in the Middle East and North Africa remains limited. This study aims to evaluate the feasibility and safety of intramural surgery techniques within this region. Methods: This retrospective cohort study was conducted with approval from the institutional review board. All patients who underwent esophageal peroral endoscopic myotomy, gastric peroral endoscopic myotomy, and peroral endoscopic myotomy for Zenker's from January 2016 to August 2023 were included. Results: In total, 119 patients underwent intramural surgery procedures during this period. The esophageal peroral endoscopic myotomy group had 81 (68%) patients, the gastric peroral endoscopic myotomy had 34 (28.6%) patients, and the peroral endoscopic myotomy for Zenker's had 4 (3.4%) patients. The full cohort was 48.7% female, with a mean overall age of 40.5 years. The mean overall body mass index was 27.5 kg/m2. The chief complaint was dysphagia (n = 80, 67.2%). All cases were successfully completed endoscopically. During the first 30 days, the most common complications were nausea/vomiting requiring admission (n = 4, 4.76%) and pneumomediastinum (n = 2, 2.38%). At a follow-up of 19 months, there were four mortalities; the causes of death were cardiac arrest (three cases) and end-stage prostate cancer (one case). Conclusions: Intramural surgery techniques are safe and technically feasible with low complication rates. Our study suggests that clinical success in the Middle East and Northern Africa population is comparable to larger international series.

Opposing Actions of TLR2 and TLR4 in Adipocyte Differentiation and Mature-Onset Obesity.

Understanding the signaling cascades that govern adipocyte metabolism and differentiation is necessary for the development of therapies for obesity. Toll-like receptors (TLRs) are key mediators in adipogenesis, but their specific role is not completely understood. In this study, siRNA knockdown of Tlr2 in 3T3-L1 cells allowed them to differentiate more efficiently into adipocytes, whereas the opposite was observed for the knockdown of Tlr4. At the same time, we show that TLR2 knock-out mice spontaneously developed mature-onset obesity and insulin resistance. Besides a higher incidence of hyperplasia and hypertrophy in white adipose tissue (WAT), we found a significantly increased number of adipocyte precursor cells in TLR2-/- mice compared to TLR4-/- mice. Interestingly, genetic inactivation of Tlr4 in TLR2-/- mice reverted their increased adiposity, insulin resistance, and restored normal levels of adipocyte precursor cells. These findings provide evidence that TLR2 and TLR4 play opposing roles in WAT homeostasis and point to the existence of cross-regulation among TLR2 and TLR4 during adipocyte differentiation both in vitro and in vivo.

Redundant roles of the phosphatidate phosphatase family in triacylglycerol synthesis in human adipocytes.

AIMS/HYPOTHESIS: In mammals, the evolutionary conserved family of Mg(2+)-dependent phosphatidate phosphatases (PAP1), involved in phospholipid and triacylglycerol synthesis, consists of lipin-1, lipin-2 and lipin-3. While mutations in the murine Lpin1 gene cause lipodystrophy and its knockdown in mouse 3T3-L1 cells impairs adipogenesis, deleterious mutations of human LPIN1 do not affect adipose tissue distribution. However, reduced LPIN1 and PAP1 activity has been described in participants with type 2 diabetes. We aimed to characterise the roles of all lipin family members in human adipose tissue and adipogenesis. METHODS: The expression of the lipin family was analysed in adipose tissue in a cross-sectional study. Moreover, the effects of lipin small interfering RNA (siRNA)-mediated depletion on in vitro human adipogenesis were assessed. RESULTS: Adipose tissue gene expression of the lipin family is altered in type 2 diabetes. Depletion of every lipin family member in a human Simpson-Golabi-Behmel syndrome (SGBS) pre-adipocyte cell line, alters expression levels of adipogenic transcription factors and lipid biosynthesis genes in early stages of differentiation. Lipin-1 knockdown alone causes a 95% depletion of PAP1 activity. Despite the reduced PAP1 activity and alterations in early adipogenesis, lipin-silenced cells differentiate and accumulate neutral lipids. Even combinatorial knockdown of lipins shows mild effects on triacylglycerol accumulation in mature adipocytes. CONCLUSIONS/INTERPRETATION: Overall, our data support the hypothesis of alternative pathways for triacylglycerol synthesis in human adipocytes under conditions of repressed lipin expression. We propose that induction of alternative lipid phosphate phosphatases, along with the inhibition of lipid hydrolysis, contributes to the maintenance of triacylglycerol content to near normal levels.

Aplasia medular severa secundaria a triple terapia para virus hepatitis C: a propósito de un caso / Severe bone marrow aplasia due to triple therapy for hepatitis C virus infection: Apropos of a case

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[Primary esophageal melanoma]. / Melanoma esofagico primario.

Primary Esophageal Melanoma (PEM) is an extremely rare neoplasm, with less than 270 cases described. Although clinical presentation is similar to any other esophageal neoplasm, MEP's behavior is more aggressive and fatal in most cases. We report two new cases of MEP diagnosed through endoscopy and anatomical-pathological analysis of collected biopsies. Both samples were positive for HMB-45 and S100, so the presence of primary melanoma in other location was ruled out. The form of presentation as left miosis with no eyelid ptosis or enophthalmos should be highlighted in the first case, which was described by this early manifestation. Unfortunately, the neoplasm could not be excised when diagnosed because the thoracic artery was found to be affected through echoendoscopy. In the second case, in spite of the fact that the neoplastic extension was only local, and neoplasm was subject to transhiatal esophagectomy, the patient had multiple post-surgical complications and died nineteen days after the surgical procedure. Furthermore, bibliographic review is applied to diagnosis, treatment options, and prognosis of this exceptional neoplasm.

Melanoma esofágico primario / Primary esophageal melanoma

El melanoma esofágico primario (MEP) es una neoplasia extremadamente rara, con menos de 270 casos descritos. Aunque la presentación clínica es similar a cualquier otra neoplasia esofágica, su comportamiento es más agresivo y fatal en la mayoría de los casos. Presentamos dos nuevos casos de MEP diagnosticados mediante endoscopia y estudio anatomopatológico de las biopsias obtenidas, siendo en ambos casos las muestras positivas para HMB-45 y S100, descartando así mismo la presencia de melanoma primario en otra localización. En el primer caso merece destacar la forma de presentación como miosis izquierda sin ptosis palpebral ni enoftalmos, siendo el primer caso descrito con esta manifestación inicial, lamentablemente al momento del diagnóstico fue irresecable, demostrando así mismo por ecoendoscopia afectación de la aorta torácica. El segundo caso a pesar de ser una neoplasia sin extensión locorregional y sometido a esofaguectomía transhiatal presentó múltiples complicaciones postoperatorias falleciendo al decimo noveno día de la intervención. Así mismo se hace una revisión bibliográfica sobre diagnóstico, opciones de tratamiento y pronóstico de esta excepcional neoplasia.

Primary Esophageal Melanoma (PEM) is an extremely rare neoplasm, with less than 270 cases described. Although clinical presentation is similar to any other esophageal neoplasm, MEP's behavior is more aggressive and fatal in most cases. We report two new cases of MEP diagnosed through endoscopy and anatomical-pathological analysis of collected biopsies. Both samples were positive for HMB-45 and S100, so the presence of primary melanoma in other location was ruled out. The form of presentation as left miosis with no eyelid ptosis or enophthalmos should be highlighted in the first case, which was described by this early manifestation. Unfortunately, the neoplasm could not be excised when diagnosed because the thoracic artery was found to be affected through echoendoscopy. In the second case, in spite of the fact that the neoplastic extension was only local, and neoplasm was subject to transhiatal esophagectomy, the patient had multiple post-surgical complications and died nineteen days after the surgical procedure. Furthermore, bibliographic review is applied to diagnosis, treatment options, and prognosis of this exceptional neoplasm.