Evaluation of pro-regenerative and anti-inflammatory effects of isolecanoric acid in the muscle: Potential treatment of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a devastating degenerative disease of skeletal muscles caused by loss of dystrophin, a key protein that maintains muscle integrity, which leads to progressive muscle degeneration aggravated by chronic inflammation, muscle stem cells' (MuSCs) reduced regenerative capacity and replacement of muscle with fibroadipose tissue. Previous research has shown that pharmacological GSK-3ß inhibition favors myogenic differentiation and plays an important role in modulating inflammatory processes. Isolecanoric acid (ILA) is a natural product isolated from a fungal culture displaying GSK-3ß inhibitory properties. The present study aimed to investigate the proregenerative and anti-inflammatory properties of this natural compound in the DMD context. Our results showed that ILA markedly promotes myogenic differentiation of myoblasts by increasing ß-Catenin signaling and boosting the myogenic potential of mouse and human stem cells. One important finding was that the GSK-3ß/ß-Catenin pathway is altered in dystrophic mice muscle and ILA enhances the myofiber formation of dystrophic MuSCs. Treatment with this natural compound improves muscle regeneration of dystrophic mice by, in turn, improving functional performance. Moreover, ILA ameliorates the inflammatory response in both muscle explants and the macrophages isolated from dystrophic mice to, thus, mitigate fibrosis after muscle damage. Overall, we show that ILA modulates both inflammation and muscle regeneration to, thus, contribute to improve the dystrophic phenotype.

Association between use of enhanced recovery after surgery protocols and postoperative complications after gastric surgery for cancer (POWER 4): a nationwide, prospective multicentre study / Asociación entre el uso de protocolos de recuperación intensificada y complicaciones postoperatorias tras cirugía gástrica por cáncer (POWER 4): estudio nacional, prospective multicéntrico

Introduction: The effectiveness of the Enhanced Recovery After Surgery (ERAS) protocols in gastric cancer surgery remains controversial. Methods: Multicentre prospective cohort study of adult patients undergoing surgery for gastric cancer. Adherence with 22 individual components of ERAS pathways were assessed in all patients, regardless of whether they were treated in a self-designed ERAS centre. Each centre had a three-month recruitment period between October 2019 and September 2020. The primary outcome was moderate-to-severe postoperative complications within 30 days after surgery. Secondary outcomes were overall postoperative complications, adherence to the ERAS pathway, 30 day-mortality and hospital length of stay (LOS). Results: A total of 743 patients in 72 Spanish hospitals were included, 211 of them (28.4 %) from self-declared ERAS centres. A total of 245 patients (33 %) experienced postoperative complications, graded as moderate-to-severe complications in 172 patients (23.1 %). There were no differences in the incidence of moderate-to-severe complications (22.3% vs. 23.5%; OR, 0.92 (95% CI, 0.59 to 1.41); P = 0.068), or overall postoperative complications between the self-declared ERAS and non-ERAS groups (33.6% vs. 32.7%; OR, 1.05 (95 % CI, 0.70 to 1.56); P = 0.825). The overall rate of adherence to the ERAS pathway was 52% [IQR 45 to 60]. There were no differences in postoperative outcomes between higher (Q1, > 60 %) and lower (Q4, ≤ 45 %) ERAS adherence quartiles. Conclusions: Neither the partial application of perioperative ERAS measures nor treatment in self-designated ERAS centres improved postoperative outcomes in patients undergoing gastric surgery for cancer. (AU)

Introducción: La efectividad de los protocolos de recuperación intensificada o ERAS en la cirugía del cáncer gástrico sigue siendo controvertida. Métodos: Estudio de cohortes prospectivo multicéntrico de pacientes intervenidos de cáncer gástrico. Se evaluó la adherencia a 22 elementos ERAS en todos los pacientes, independientemente de la existencia de un protocolo ERAS. Cada centro tuvo un período de reclutamiento de tres meses, con un seguimiento de 30 días. La medida de resultado primario fue el numero de complicaciones posoperatorias moderadas a graves. Las medidas de resultado secundarias fueron el número total de complicaciones, la adherencia a los elementos ERAS, la mortalidad y la estancia. Resultados: Se incluyeron 743 pacientes en 72 hospitales, 211 (28,4 %) en centros ERAS. 245 pacientes (33 %) experimentaron complicaciones posoperatorias, moderadas o graves en 172 (23,1 %). No hubo diferencias en la incidencia de complicaciones moderadas a graves (22,3 % vs. 23,5 %; OR, 0,92 (IC 95 %, 0,59 a 1,41); P = 0,068), o complicaciones posoperatorias totales entre los centros ERAS y no ERAS (33,6 % vs. 32,7 %; OR, 1,05 (IC 95 %, 0,70 a 1,56); P = 0,825). La adherencia a los elementos ERAS fue del 52% [IQR 45 a 60]. No hubo diferencias entre los cuartiles de cumplimiento ERAS más alto (Q1, > 60 %) y más bajo (Q4, ≤ 45 %). Conclusiones: Ni la aplicación parcial de medidas ERAS ni el tratamiento en centros ERAS mejoraron los resultados en pacientes sometidos a cirugía gástrica por cáncer. (AU)

Association between use of enhanced recovery after surgery protocols and postoperative complications after gastric surgery for cancer (POWER 4): a nationwide, prospective multicentre study.

INTRODUCTION: The effectiveness of the Enhanced Recovery After Surgery (ERAS) protocols in gastric cancer surgery remains controversial. METHODS: Multicentre prospective cohort study of adult patients undergoing surgery for gastric cancer. Adherence with 22 individual components of ERAS pathways were assessed in all patients, regardless of whether they were treated in a self-designed ERAS centre. Each centre had a three-month recruitment period between October 2019 and September 2020. The primary outcome was moderate-to-severe postoperative complications within 30 days after surgery. Secondary outcomes were overall postoperative complications, adherence to the ERAS pathway, 30 day-mortality and hospital length of stay (LOS). RESULTS: A total of 743 patients in 72 Spanish hospitals were included, 211 of them (28.4 %) from self-declared ERAS centres. A total of 245 patients (33 %) experienced postoperative complications, graded as moderate-to-severe complications in 172 patients (23.1 %). There were no differences in the incidence of moderate-to-severe complications (22.3% vs. 23.5%; OR, 0.92 (95% CI, 0.59 to 1.41); P = 0.068), or overall postoperative complications between the self-declared ERAS and non-ERAS groups (33.6% vs. 32.7%; OR, 1.05 (95 % CI, 0.70 to 1.56); P = 0.825). The overall rate of adherence to the ERAS pathway was 52% [IQR 45 to 60]. There were no differences in postoperative outcomes between higher (Q1, > 60 %) and lower (Q4, ≤ 45 %) ERAS adherence quartiles. CONCLUSIONS: Neither the partial application of perioperative ERAS measures nor treatment in self-designated ERAS centres improved postoperative outcomes in patients undergoing gastric surgery for cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03865810.

Expanding the utility of Marfey's analysis by using HPLC-SPE-NMR to determine the Cß configuration of threonine and isoleucine residues in natural peptides.

The determination of amino acid chirality in natural peptides is typically addressed by Marfey's analysis. This approach relies on the complete hydrolysis of the peptide followed by the reaction of the resulting amino acid pool with Marfey's reagent, a chiral derivatizing agent which turns amino acid enantiomers into diastereomeric pairs which can be resolved by conventional reversed-phase HPLC. However, for certain amino acids possessing a second chiral centre at Cß, the discrimination between the two possible epimers may still be challenging due to the lack of chromatographic resolution. Such is the case of isoleucine and threonine which can also be found in natural nonribosomal peptides as their allo-diastereomers. We describe a new approach based on the extension of Marfey's analysis using HPLC-SPE-NMR to sort out this challenge. Marfey's derivatives of these epimeric amino acids at Cß can be differentiated by their distinct NMR spectra. Thus, simple comparison of the NMR spectra of trapped HPLC peaks with the corresponding spectra of standards enables the unambiguous assignment of the absolute configuration at the second chiral centre in such cases. The general applicability of this approach is showcased for two model cyclic peptides bearing L-Ile and L-Thr.

Early Return to Intended Oncologic Therapy after implementation of an Enhanced Recovery After Surgery pathway for gastric cancer surgery.

PURPOSE: Time to initiation and completion of adjuvant therapy are critical to improve postoperative oncologic outcomes. This study aims to determine whether an Enhanced Recovery After Surgery (ERAS) pathway for gastric cancer surgery promotes early Return to Intended Oncologic Therapy (RIOT). METHODS: This is a before-after intervention study including patients with gastric adenocarcinoma who underwent surgery from January 2016 to January 2021. Two periods were denoted based upon the implementation date of our institutional ERAS pathway (June 2018). Our primary outcome was time to RIOT after surgery. Hodges-Lehmann analysis was used to estimate median differences of non-parametric outcomes. RESULTS: Seventy patients with gastric adenocarcinoma were included (35 in pre-ERAS period and 35 in post-ERAS period). Fourteen of the pre-ERAS and twenty-two patients of the post-ERAS period received adjuvant therapy. Time to RIOT was reduced in the post-ERAS period (median 39 days, IQR 31-49) by 12 days (95% CI 3-14 days, p = 0.01) compared to the pre-ERAS period (median 51 days, IQR 42-62). Length of hospital stay (LOS) was lower in the ERAS group (6 days, IQR 5-11 vs 10 days, IQR 8-13, p < 0.01). CONCLUSION: Our institutional ERAS pathway for gastric cancer surgery was associated with earlier RIOT and shorter LOS.

Primary Pure Pancreatic -Type Acinar Cell Carcinoma of the Stomach: A Rare Entity with a Difficult Diagnosis and Review of the Literature.

Acinar cell carcinoma is an uncommon tumour, representing only 1% to 2% of all exocrine pancreatic tumours. Pancreatic-type acinar cell carcinoma can occur in other organs, including the stomach, but it is extraordinarily rare. We report a case of a 51-year-old woman with a pancreatic-type pure acinar carcinoma of the stomach coexisting with a large cell B lymphoma synchronously, and a literature review of gastric carcinomas with pancreatic cell differentiation. At present there is a preoperative underdiagnosis of these tumours that could be minimized by including this entity in the differential diagnosis of gastric cancer and by performing immunohistochemical analysis with neuroendocrine markers and exocrine pancreatic enzymes.

Teleconsultation in General Surgery during COVID-19 pandemic, satisfaction survey and feasibility for future.

BACKGROUND: The COVID-19 pandemic has made us to respond to the needs of the community. Telemedicine has gained worldwide acceptance. We describe our experience with teleconsultation in surgical patients during the first wave of the COVID-19 pandemic and evaluate patient satisfaction and the feasibility of maintaining it as a future strategy in selected patients. METHODS: An observational, retrospective, single-site cohort study was carried out by reviewing electronic medical records and conducting a telephone survey. RESULTS: During this time, 1706 teleconsultations have been carried out: 59.5% of patients were rescheduled, 26.1% have been solved and of these 57.3% (255 patients) have been discharged; 12.19% were not contacted. The 73.6% considered that teleconsultation was able to fully or partially resolve the reason for their medical appointment; 61.6% were willing to continue with teleconsultation; 15.2% of the patients needed some kind of help or required a second call to speak with a family member, and 37.2% would prefer a face-to-face visit because of difficulties with the teleconsultation. The overall satisfaction was 8.7 out of 10. CONCLUSIONS: Telemedicine has demonstrated to be a useful tool even for surgical patients during COVID-19 pandemic. A high proportion of patients can be managed by telephone call. Patients reported a high degree of satisfaction. Teleconsultation is a feasible strategy not also during the current COVID-19 pandemic but also for future.

Primary thyroid tuberculosis: a case report.

Involvement of the thyroid gland by tuberculosis is very rare and is usually secondary to disseminated infection. Very few cases of primary thyroid tuberculosis have been described even in countries with a high incidence of this disease. We present the case of a Spanish patient operated for a suspicious thyroid nodule that was finally diagnosed as primary thyroid tuberculosis.

La afectación de la glándula tiroidea por tuberculosis es muy rara y generalmente es secundaria a una enfermedad ­diseminada. Se han descrito muy pocos casos de tuberculosis tiroidea primaria incluso en paises con alta incidencia de esta enfermedad. Presentamos el caso de una paciente española operada por un nódulo tiroideo sospechoso que fue finalmente diagnosticado como tuberculosis tiroidea primaria.

Laparoscopic Diagnosis of Peritoneal Tuberculosis.

Peritoneal tuberculosis is a rare form of tuberculosis, which involves parietal and visceral peritoneum, omentum, and intestinal mesentery. Its incidence is increasing in developed countries due to HIV infection and immigration. We present a case of peritoneal tuberculosis in a twenty two-year-old patient misdiagnosed with appendicitis. A laparoscopic surgery was performed showing multiple implants on serosal surfaces and adhesions. Laparoscopic appendectomy and peritoneal biopsies were performed. As peritoneal tuberculosis was suspected, an early antituberculous treatment was initiated. A pathological examination of the samples revealed epithelioid granulomas with a centrale caseous necrosis and acid-fast bacilli. Peritoneal tuberculosis is a challenging diagnosis that can mimic other pathologies and should be kept in mind to establish an early antituberculosis treatment avoiding the high morbidity and mortality associated with a late treatment initiation. In case of suspicion of peritoneal tuberculosis, laparoscopy with guided biopsies is useful for the establishment of a correct diagnosis.

Structural Elucidation of Antibiotic TKR2999, an Antifungal Lipodepsipeptide Isolated from the Fungus Foliophoma fallens.

An antifungal lipodepsipeptide was obtained from cultures of the fungus Foliophoma fallens CF-236885. Its structure, elucidated by HRMS and NMR spectroscopy, contained Gly, Thr, Asn, ß-Ala, Orn, Ala, two Ser residues, and 3-hydroxy-4-methylhexadecanoic acid. The absolute configuration of its amino acid residues was determined using Marfey's analysis and J-based configuration analysis helped to establish the relative configuration of the 3-hydroxy-4-methylhexadecanoic acid moiety. A literature search retrieved a patent describing antibiotic TKR2999 (1), whose non-disclosed structure was confirmed to be identical to that found for our compound, according to its physicochemical properties and NMR spectra. Compound 1 displayed potent antifungal activity against Aspergillus fumigatus and a panel of Candida strains.

Results of a survey on peri-operative nutritional support in pancreatic and biliary surgery in Spain.

INTRODUCTION: Introduction: a survey on peri-operative nutritional support in pancreatic and biliary surgery among Spanish hospitals in 2007 showed that few surgical groups followed the 2006 ESPEN guidelines. Ten years later we sent a questionnaire to check the current situation. Methods: a questionnaire with 21 items sent to 38 centers, related to fasting time before and after surgery, nutritional screening use and type, time and type of peri-operative nutritional support, and number of procedures. Results: thirty-four institutions responded. The median number of pancreatic resections (head/total) was 29.5 (95% CI: 23.0-35; range, 5-68) (total, 1002); of surgeries for biliary malignancies (non-pancreatic), 9.8 (95% CI: 7.3-12.4; range, 2-30); and of main biliary resections for benign conditions, 10.4 (95% CI: 7.6-13.3; range, 2-33). Before surgery, only 41.2% of the sites used nutritional support (< 50% used any nutritional screening procedure). The mean duration of preoperative fasting for solid foods was 9.3 h (range, 6-24 h); it was 6.6 h for liquids (range, 2-12). Following pancreatic surgery, 29.4% tried to use early oral feeding, but 88.2% of the surveyed teams used some nutritional support; 26.5% of respondents used TPN in 100% of cases. Different percentages of TPN and EN were used in the other centers. In malignant biliary surgery, 22.6% used TPN always, and EN in 19.3% of cases. Conclusions: TPN is the commonest nutrition approach after pancreatic head surgery. Only 29.4% of the units used early oral feeding, and 32.3% used EN; 22.6% used TPN regularly after surgery for malignant biliary tumours. The 2006 ESPEN guideline recommendations are not regularly followed 12 years after their publication in our country.

INTRODUCCIÓN: Introducción: realizamos una encuesta sobre soporte nutricional perioperatorio en cirugía pancreática y biliar en hospitales españoles en 2007, que mostró que pocos grupos quirúrgicos seguían las guías de ESPEN 2006. Diez años después enviamos un cuestionario para comprobar la situación actual. Métodos: treinta y ocho centros recibieron un cuestionario con 21 preguntas sobre tiempo de ayunas antes y después de la cirugía, cribado nutricional, duración y tipo de soporte nutricional perioperatorio, y número de procedimientos. Resultados: respondieron 34 grupos. La mediana de pancreatectomías (cabeza/total) fue de 29,5 (IC 95%: 23,0-35; rango, 5-68) (total, 1002), la de cirugías biliares malignas de 9,8 (IC 95%: 7,3-12,4; rango, 2-30) y la de resecciones biliares por patología benigna de 10,4 (IC 95%: 7,6-13,3; rango, 2-33). Solo el 41,2% de los grupos utilizaban soporte nutricional antes de la cirugía (< 50% habian efectuado un cribado nutricional). El tiempo medio de ayuno preoperatorio para sólidos fue de 9,3 h (rango, 6-24 h), y de 6,6 h para líquidos (rango, 2-12). Tras la pancreatectomía, el 29,4% habían intentado administrar una dieta oral precoz, pero el 88,2% de los grupos usaron algún tipo de soporte nutricional y el 26,5% usaron NP en el 100% de los casos. Los demás grupos usaron diferentes porcentajes de NP y NE en sus casos. En la cirugía biliar maligna, el 22,6% utilizaron NP siempre y NE en el 19,3% de los casos. Conclusiones: la NP es el soporte nutricional más utilizado tras la cirugía de cabeza pancreática. Solo el 29,4% de las unidades usan nutrición oral precoz y el 32,3% emplean la NE tras este tipo de cirugía. El 22,6% de las instituciones usan NP habitualmente tras la cirugía de tumores biliares malignos. Las guías ESPEN 2006 no se siguen de forma habitual en nuestro país tras más de 10 años desde su publicación.

Extending the Metabolite Diversity of the Endophyte Dimorphosporicola tragani.

Fungi are one of the most prolific sources of microbial secondary metabolites. The production of new metabolites can be achieved using multiple fermentation conditions and by adding small-molecule effectors, including epigenetic modifiers. In the framework of our Natural Product screening programme targeting the discovery of new antimicrobial compounds, we applied multiple fermentation conditions and adsorptive polymeric resins on a large collection of fungal endophytes, to increase and stimulate their fungal secondary metabolite production. During this work the endophytic fungus Dimorphosporicola tragani CF-090383 showed antimicrobial activity only when grown in presence of adsorptive polymeric resins. In addition, seven epigenetic modifiers were added to fermentations of this endophytic fungus, in an attempt to activate its cryptic pathways as well as to analyse the metabolites produced under these conditions. D. tragani was seen to produce three different mycotoxin dendrodolides when the epigenetic modifiers 5-azacytidine and valproic acid were added to the fermentations, and these compounds were further characterized. However, the fungus produced the fatty acid synthesis inhibitor cerulenin, a molecule not previously described to be produced by this fungal species, only when cultivated in presence of the XAD-16 resin. We have found that the addition of XAD-16 resin resulted in four-fold higher titers in the production of cerulenin when compared to the best production conditions described in literature for the original fungal producer strain, Cephalosporium caerulens KF-140 (=Sarocladium oryzae), in a zeolite-based fermentation, used as an ammonium ion-trapping agent. The production of cerulenin by this strain of D. tragani, represents an alternative source for the improved production of cerulenin with better yields.

Quiste de duplicación gástrica de epitelio respiratorio: una lesión infrecuente de difícil diagnóstico diferencial / Gastric duplication cyst with respiratory epithelium: An uncommon injury that has a difficult diferential diagnosis

No disponible

Carcinoma verrucoso esofágico: una rara entidad de difícil diagnóstico / Verrucous carcinoma of the esophagus: A rare entity with a difficult diagnosis

No disponible

Fungal endophytes from arid areas of Andalusia: high potential sources for antifungal and antitumoral agents.

Native plant communities from arid areas present distinctive characteristics to survive in extreme conditions. The large number of poorly studied endemic plants represents a unique potential source for the discovery of novel fungal symbionts as well as host-specific endophytes not yet described. The addition of adsorptive polymeric resins in fungal fermentations has been seen to promote the production of new secondary metabolites and is a tool used consistently to generate new compounds with potential biological activities. A total of 349 fungal strains isolated from 63 selected plant species from arid ecosystems located in the southeast of the Iberian Peninsula, were characterized morphologically as well as based on their ITS/28S ribosomal gene sequences. The fungal community isolated was distributed among 19 orders including Basidiomycetes and Ascomycetes, being Pleosporales the most abundant order. In total, 107 different genera were identified being Neocamarosporium the genus most frequently isolated from these plants, followed by Preussia and Alternaria. Strains were grown in four different media in presence and absence of selected resins to promote chemical diversity generation of new secondary metabolites. Fermentation extracts were evaluated, looking for new antifungal activities against plant and human fungal pathogens, as well as, cytotoxic activities against the human liver cancer cell line HepG2. From the 349 isolates tested, 126 (36%) exhibited significant bioactivities including 58 strains with exclusive antifungal properties and 33 strains with exclusive activity against the HepG2 hepatocellular carcinoma cell line. After LCMS analysis, 68 known bioactive secondary metabolites could be identified as produced by 96 strains, and 12 likely unknown compounds were found in a subset of 14 fungal endophytes. The chemical profiles of the differential expression of induced activities were compared. As proof of concept, ten active secondary metabolites only produced in the presence of resins were purified and identified. The structures of three of these compounds were new and herein are elucidated.

Non-geminal Aliphatic Dihalogenation Pattern in Dichlorinated Diaporthins from Hamigera fusca NRRL 35721.

Two new epimeric dihalogenated diaporthins, (9 R *)-8-methyl-9,11-dichlorodiaporthin (2) and (9 S *)-8-methyl-9,11-dichlorodiaporthin (3), have been isolated from the soil fungus Hamigera fusca NRRL 35721 alongside the known regioisomeric isocoumarin 8-methyl-11,11-dichlorodiaporthin (1). Their structures were elucidated by high-resolution mass spectrometry and NMR spectroscopy combined with molecular modeling. Compounds 1-3 are the first isocoumarins and the first halogenated metabolites ever reported from the Hamigera genus. The new compounds 2 and 3 display a non-geminal aliphatic dichlorination pattern unprecedented among known fungal dihalogenated aromatic polyketides. A bifunctional methyltransferase/aliphatic halogenase flavoenzyme is proposed to be involved in the biosynthesis of dichlorinated diaporthins 1-3. These metabolites are weakly cytotoxic.