Clinical features and prognosis of malignant small bowel tumors: Experience from a university hospital in Chile.

BACKGROUND: Small bowel tumors (SBT) are infrequent and represent a small proportion of digestive neoplasms. There is scarce information about SBT in Latin America. AIM: To describe the epidemiology, clinical characteristics, diagnostic methods, and survival of malignant SBTs. METHODS: Retrospective observational study of adult patients with histopathological diagnosis of SBT between 2007 and 2021 in a university hospital in Chile. RESULTS: A total of 104 patients [51.9% men; mean age 57 years] with SBT. Histological type: neuroendocrine tumor (NET) (43.7%, n=38), gastrointestinal stromal tumors (GIST) (21.8%, n=19), lymphoma (17.2%, n=15) and adenocarcinoma (AC) (11.5%, n=10). GIST was more frequent in duodenum (50%; n=12) and NET in the ileum (65.8%; n=25). Metastasis was observed in 17 cases, most commonly from colon and melanoma. Nausea and vomiting were significantly more often observed in AC (p=0.035), as well as gastrointestinal bleeding in GIST (p=0.007). The most common diagnostic tools were CT and CT enteroclysis with an elevated diagnostic yield (86% and 94% respectively). The 5-year survival of GIST, NET, lymphoma and AC were 94.7% (95%CI: 68.1-99.2), 82.2% (95%CI: 57.6-93.3), 40.0% (95%CI: 16.5-82.8) and 25.9% (95%CI: 4.5-55.7%), respectively. NET (HR 6.1; 95%CI: 2.1-17.2) and GIST (HR 24.4; 95%CI: 3.0-19.8) were independently associated with higher survival compared to AC, adjusted for age and sex. CONCLUSIONS: Malignant SBT are rare conditions and NETs are the most common histological subtype. Clinical presentation at diagnosis, location or complications may suggest a more probable diagnosis. GIST and NET are associated with better survival compared to other malignant subtypes.

Risk factors for major complications after surgical treatment of primary ileocecal Crohn's disease. A multicentric Latin American experience.

INTRODUCTION: Complications after ileocecal resection for Crohn's disease (CD) are frequent. The aim of this study was to analyze risk factors for postoperative complications after these procedures. MATERIALS AND METHODS: We conducted a retrospective analysis of patients treated surgically for Crohn's disease limited to the ileocecal region during an 8-year period at 10 medical centers specialized in inflammatory bowel disease (IBD) in Latin America. Patients were allocated into 2 groups: those who presented major postoperative complications (Clavien-Dindo > II), the "postoperative complication" (POC) group; and those who did not, the "no postoperative complication" (NPOC) group. Preoperative characteristics and intraoperative variables were analyzed to identify possible factors for POC. RESULTS: In total, 337 patients were included, with 51 (15.13%) in the POC cohort. Smoking was more prevalent among the POC patients (31.37 vs. 17.83; P = .026), who presented more preoperative anemia (33.33 vs. 17.48%; P = .009), required more urgent care (37.25 vs. 22.38; P = .023), and had lower albumin levels. Complicated disease was associated with higher postoperative morbidity. POC patients had a longer operative time (188.77 vs. 143.86 min; P = .005), more intraoperative complications (17.65 vs. 4.55%; P < .001), and lower rates of primary anastomosis. In the multivariate analysis, both smoking and intraoperative complications were independently associated with the occurrence of major postoperative complications. CONCLUSION: This study shows that risk factors for complications after primary ileocecal resections for Crohn's disease in Latin America are similar to those reported elsewhere. Future efforts in the region should be aimed at improving these outcomes by controlling some of the identified factors.

¿Ha disminuido la colectomía por crisis de colitis ulcerosa?

Background: Treatment for moderate-severe active ulcerative colitis (UC) includes steroids, biologic therapy and total colectomy. Aim: To describe the features of patients with moderate to severe active UC, their hospital evolution and need for colectomy. Material and Methods: Non-concurrent cohort study of all patients admitted to our institution with a diagnosis of moderate or severe UC crisis between January 2008 and May 2019. Truelove Witts (TW) criteria were used to categorize disease severity. Twelve-month colectomy-free survival was estimated with Kaplan-Meier survival analysis. Results: One hundred-twenty patients aged 16 to 89 (median 35) years had 160 admissions for acute moderate to severe UC. Median admission per patient was 1 (1-3), and median hospital stay was six days (1-49). Cytomegalovirus and Clostridioides difficile were found in 17.5 and 14.2% of crises, respectively. Corticosteroids were used in all crises and biologic therapy in 6.9% of them. Emergency or elective colectomies were performed in 18.3 and 6.7% of patients, respectively. The need for emergency total colectomy decreased from 24.6 to 7.8% (Risk ratio 3.16, p < 0.01) between de first and second half of the study period. Kaplan-Meier analysis for long term colectomy-free survival in both periods confirmed this decrease (p < 0.01). Conclusions: Medical treatment for moderate to severe UC crises had a 86.3% success and a small percentage required emergency total colectomy. Emergency surgery decreased in the last decade.

Enzyme-Loaded Gel Core Nanostructured Lipid Carriers to Improve Treatment of Lysosomal Storage Diseases: Formulation and In Vitro Cellular Studies of Elosulfase Alfa-Loaded Systems.

Mucopolysaccharidosis IVA (Morquio A) is a rare inherited metabolic disease caused by deficiency of the lysosomal enzyme N-acetylgalatosamine-6-sulfate-sulfatase (GALNS). Until now, treatments employed included hematopoietic stem cell transplantation and enzyme replacement therapy (ERT); the latter being the most commonly used to treat mucopolysaccharidoses, but with serious disadvantages due to rapid degradation and clearance. The purpose of this study was to develop and evaluate the potential of nanostructured lipid carriers (NLCs) by encapsulating elosulfase alfa and preserving its enzyme activity, leading to enhancement of its biological effect in chondrocyte cells. A pegylated elosulfase alfa-loaded NLC was characterized in terms of size, ζ potential, structural lipid composition (DSC and XRD), morphology (TEM microscopy), and stability in human plasma. The final formulation was freeze-dried by selecting the appropriate cryoprotective agent. Viability assays confirmed that NLCs were non-cytotoxic to human fibroblasts. Imaging techniques (confocal and TEM) were used to assess the cellular uptake of NLCs loaded with elosulfase alfa. This study provides evidence that the encapsulated drug exhibits enzyme activity inside the cells. Overall, this study provides a new approach regarding NLCs as a promising delivery system for the encapsulation of elosulfase alfa or other enzymes and the preservation of its activity and stability to be used in enzymatic replacement therapy (ERT).

Congenital neurogenic muscular atrophy in megaconial myopathy due to a mutation in CHKB gene.

Choline kinase beta gene (CHKB) mutations have been identified in Megaconial Congenital Muscular Dystrophy (MDCMC) patients, a very rare inborn error of metabolism with 21 cases reported worldwide. We report the case of a Spanish boy of Caucasian origin who presented a generalized congenital muscular hypotonia, more intense at lower limb muscles, mildly elevated creatine kinase (CK), serum aspartate transaminase (AST) and lactate. Electromyography (EMG) showed neurogenic potentials in the proximal muscles. Histological studies of a muscle biopsy showed neurogenic atrophy with enlarged mitochondria in the periphery of the fibers, and complex I deficiency. Finally, genetic analysis showed the presence of a homozygous mutation in the gene for choline kinase beta (CHKB: NM_005198.4:c.810T>A, p.Tyr270(∗)). We describe here the second Spanish patient whit mutation in CHKB gene, who despite having the same mutation, presented an atypical aspect: congenital neurogenic muscular atrophy progressing to a combined neuropathic and myopathic phenotype (mixed pattern).

Intraspecific differentiation of Chilean isolates of the entomopathogenic fungi Metarhizium anisopliae var. anisopliae as revealed by RAPD, SSR and ITS markers

The genus Metarhizium consists of a diverse group of asexual entomopathogenic fungi, which have a wide geographical distribution. The Chilean National Agricultural Research Institute (Instituto de Investigaciones Agropecuarias - INIA, Quilamapu Chile) has collected about 350 isolates of Metarhizium anisopliae var. anisopliae from central and southern Chile. These isolates have been partially characterized using morphological traits such as conidia size and shape, colony color, growth pattern and the efficiency of the isolates in controlling specific pests. However, further characterization with molecular markers could detect differences in DNA which could help to better understand the genetic diversity and structure of Chilean populations of this fungus. We analyzed approximately 10 percent of the INIA collection (39 isolates selected at random) collected from different geographical origins using the polymerase chain reaction (PCR)-random amplified polymorphic DNA (RAPD) method, simple sequences repeat (SSR or microsatellites) analysis and the PCR-restriction fragment length polymorphism (RFLP) assay of internal transcribed spacer (ITS)-rDNA sequences. The RAPD data revealed high genetic diversity in this fungus and an average of 41 percent of similarity while SSR analysis detected 45.2 percent similarity and the ITS markers 70.2 percent similarity. For the three molecular markers, this diversity was not associated with the geographical origin of these isolates.