Search

Resumen Introduccion La reconstruccion esofagica es un proceso quirurgico tecnicamente muy complejo, gravado por una importante morbilidad. Clasicamente se han utilizado la gastroplastia y la coloplastia, aunque la yeyunoplastia ya fue descrita por Roux en 1907. Parece demostrado que la plastia de yeyuno libre es una muy buena opcion en el tratamiento de la enfermedad del esofago cervical, pero no esta tan claro el papel de la yeyunoplastia supercharged en la reconstruccion del esofago toracico. El objetivo de este estudio es el analisis de las reconstrucciones esofagicas realizadas en nuestra unidad y que precisaron de un injerto de yeyuno. Metodos Estudio retrospectivo de las reconstrucciones esofagicas realizadas con yeyunoplastias en nuestra unidad entre enero de 2011 y diciembre de 2019. Se analizan datos epidemiologicos, indicaciones, tecnica quirurgica y morbimortalidad. Resultados Se realizaron 67 procedimientos quirurgicos de reconstruccion esofagica compleja de los que 10 fueron yeyunoplastias: 5 yeyunos libres en esofago cervical y 5 supercharged en esofago toracico con abordaje transesternal. La morbilidad, mortalidad, estancia media y tiempo de retirada de la alimentacion enteral fueron menores en los yeyunos libres que en los supercharged. Conclusiones En nuestro grupo la yeyunoplastia supercharged es la ultima opcion para la reconstruccion del esofago toracico; el acceso por esternotomia media nos permite un excelente abordaje del mediastino anterior y los vasos mamarios internos. El yeyuno libre seria la primera eleccion —con indemnidad del resto de esofago— en la reconstruccion del esofago cervical.

Resumen Objetivo Describir la experiencia del abordaje robotico en la cirugia de la acalasia en un centro de tercer nivel. Material y metodos Se analizaron los pacientes con acalasia intervenidos mediante cirugia robotica entre mayo de 2010 y abril de 2019. Las variables a estudio se recogieron en una base de datos prospectiva y se realizo un analisis descriptivo. Resultados Se incluyeron 45 pacientes (55,6% varones) con edad media de 44 anos. El sintoma principal al diagnostico fue la disfagia. Diecinueve pacientes (42,2%) habian recibido tratamiento endoscopico previo a la cirugia, mayoritariamente dilatacion neumatica (84,2%). La tecnica quirurgica empleada fue la miotomia de Heller asociada a funduplicatura tipo Toupet, con un tiempo operatorio medio de 211 minutos. La estancia media fue 5 dias. Se produjeron 2 perforaciones postoperatorias (4,4%). La mortalidad peroperatoria fue del 0%. El seguimiento medio fue de 64 meses. A 3 y 5 anos se evidencio una importante disminucion del Eckardt score y el estudio manometrico mostro una disminucion de la presion del esfinter esofagico inferior en reposo media del 58% y del 70%, respectivamente, con persistencia de hipomotilidad del cuerpo esofagico. En dos pacientes (5,4%) se diagnostico reflujo gastroesofagico patologico y 4 (10,8%) presentaron recurrencia de los sintomas, requiriendo dilataciones neumaticas endoscopicas. En 2 casos las dilataciones no fueron efectivas por lo que se planteo la realizacion de una miotomia endoscopica. Conclusiones Segun nuestra experiencia, la cirugia robotica constituye un procedimiento seguro y efectivo para el tratamiento de la acalasia.

This study aimed to describe the feasibility of the online adaptive radiation therapy (oART) method developed at the Hospital Quirónsalud Barcelona for prostate cancer, using a standard C-arm linear accelerator (linac) and without the support of artificial intelligence.The first 18 patients treated at the Hospital Quirónsalud Barcelona with the developed oART method were included. An ultrahypofractionated radiation therapy scheme consisting of 7 × 6.1 Gy was used. Patients were treated on 2 conventional Varian C-arm linacs. For each patient, a reference plan based on a planning computed tomography (pCT) scan was generated using the Eclipse system. On each treatment session, the pCT scan was rigidly registered with the daily cone beam computed tomography (CT) scan. The pCT-based target (prostate) and organs at risk were mapped onto the cone beam CT images and manually adapted to take into account the anatomy of the day. The reference plan was then copied to the cone beam CT scan, and a full reoptimization was done for the current anatomy (adapted plan). For each treatment session, the unaltered reference plan was recomputed on the daily cone beam CT scan by mimicking the soft-tissue alignment performed per our standard procedure (nonadapted plan). Over the 126 adapted sessions from the 18 patients, a dosimetric comparison of adapted against nonadapted plans was done.A significant difference in the target coverage was found between the adapted and nonadapted plans (97.1 vs 90.4; P.001) in favor of adapting. Without online adaptation, the optimal coverage of the prostate was not attained in 35% of fractions. Adapting allows for the improvement of the target coverage with compliance of all organ-at-risk dose constraints in all treatment fractions.The oART technique described in this study is technically feasible with a C-arm linac. To our knowledge, this is the first clinical experience with oART for prostate cancer including full replanning and delivered with a C-arm linac without artificial intelligence capability.

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread globally, it became evident that the SARS-CoV-2 virus infects multiple organs including the brain. Several clinical studies revealed that patients with COVID-19 infection experience an array of neurological signs ranging in severity from headaches to life-threatening strokes. Although the exact mechanism by which the SARS-CoV-2 virus directly impacts the brain is not fully understood, several theories have been suggested including direct and indirect pathways induced by the virus. One possible theory is the invasion of SARS-CoV-2 to the brain occurs either through the bloodstream or via the nerve endings which is considered to be the direct route. Such findings are based on studies reporting the presence of viral material in the cerebrospinal fluid and brain cells. Nevertheless, the indirect mechanisms, including blood-clotting abnormalities and prolonged activation of the immune system, can result in further tissue and organ damages seen during the course of the disease. This overview attempts to give a thorough insight into SARS-CoV-2 coronavirus neurological infection and highlights the possible mechanisms leading to the neurological manifestations observed in infected patients.

Purpose Individuals with obesity frequently regain weigh after endoscopic bariatric therapies (EBT) unless they adhere to healthy habits. The objective was to create and validate a short, self-administered questionnaire (EMOVE) to assess healthy dietary and physical activity (PA) habits’ adherence to be used in clinical practice. Materials and Methods In this prospective, unicentric study, 463 patients completed the short, Spanish EMOVE questionnaire, to be validated following the Medical Outcome Trust Criteria. Conceptual and measurement model, reliability (internal consistency and test–retest [subgroup of 93 patients]), construct validity, responsiveness, interpretability, and burden were evaluated. Patients enrolled from January 2017 through August 2018 and auto-filled the EMOVE at baseline and at 3, 6, and 12 months. Results Patients submitted to intragastric ballon for 6 and 12 months or POSE were 82.7% women with a mean age of 42.7 years, and a mean BMI of 37.1 kg/m2. Four factors were extracted with exploratory factor analysis related to intake frequency, portions and proportions, time and place of eating, and physical activity. EMOVE showed adequate internal consistency (α = 0.73), very good test–retest (r = 0.91, CI: 0.86–0.94; p r = 0.24, CI: 0.11–0.37, p r = 0.44, CI 0.30–0.58; p p p Conclusion The EMOVE is a useful tool in Spanish language to easily assess the level of adherence to healthy dietary and PA habits to be used routinely in clinical practice. Graphical abstract

Objective Multiple sclerosis (MS) is a degenerative disease of the central nervous system that can lead to lifelong disabilities. There is a significant increase in the global incidence of the disease. In Saudi Arabia (SA), the western region has the greatest number of MS cases. However, there is a lack of studies and research to assess public knowledge in the region. Thus, we aim to assess the public's knowledge of MS in Jeddah, SA. Methodology We conducted a cross-sectional study surveying 468 participants from the general population of Jeddah. A validated MS knowledge questionnaire (MSKQ-25) was used. Results Most participants were female 347 (74.1%) with a mean age of 35.73 ± 14.71 standard deviation (SD). MS was found in 14 (3%) of the participants. The average score of the (MSKQ) was 7.42 SD ± 4.568 versus the average score of people with MS with a mean of 13.92 SD ± 3.33 and a p value > 0.001. No significant variation was found in knowledge between gender and age groups, but there was a significant correlation between the educational level and the knowledge level. Conclusion The mean knowledge score was below average, which indicates poor knowledge of MS. Since the western region has the highest number of MS cases in SA, the level of understanding needs to increase. This can be improved by conducting educational programs using various types of media.

Introduction This study aimed to determine associations between health warning label content and motivation to quit waterpipe smoking by gender and smoking location. Methods Convenience samples of university students in three Eastern Mediterranean countries - Egypt (n=442), Jordan (n=535) and Palestine (n=487) - completed an online survey assessing health warning labels. Multinomial logit regression models were conducted to determine the association between different variables, particularly gender and smoking location, with motivation to quit. Results In Palestine, female smokers were more motivated to quit waterpipe smoking when seeing textual warning labels related to children (T2) and pregnancy (T6) [T2: 1.8 (95% CI: 1.1-2.8), T6: 2.7 (95% CI: 1.6-4.3)] compared to males. Similar results were found in Jordan [T2: 1.6 (95% CI: 1.0-2.6), T6: 1.8 (95% CI: 1.1-3.0)]. As for the smoking location, home-only smokers in Palestine were more likely to quit in response to the following warnings: waterpipe smoking is addictive T1: 2.3 (95% CI: 1.4-3.7), harmful for children T2: 2.3 (95% CI: 1.4-4.1), harmful for the baby during pregnancy T6: 2.4 (95% CI: 1.3-4.3), and to believe that quitting reduces the health risks T9: 1.8 (95% CI: 1.0-3.1). These results were not found in Jordan nor Egypt. Smokers reported that the most noticeable location of a HWL on a waterpipe device is the mouthpiece. Conclusions A better understanding of motivation to quit and its association with various warnings and smoking location could guide countries on which warnings to require in legislation and where best to require them particularly in relation to location.

Gastric and small intestine are the most common gastrointestinal stromal tumors (GISTs). There are few studies of patients who underwent surgical treatment with disparate findings. We aimed to evaluate the differences between groups and the risk factors for recurrence and mortality. A retrospective study of 96 gastric and 60 small intestine GIST was performed between 1995 and 2015. Both groups were compared in terms of clinicopathologic features, morbidity, recurrence, and mortality. Statistical analysis was performed with SPSS®. Eighty-one gastric GISTs and 56 small intestine GISTs underwent surgical treatment. Gastrointestinal bleeding was the most common cause of emergency surgery being more frequent in gastric GIST (P = 0.009); however, emergency surgery was indicated more frequently in the small intestinal GIST (P = 0.004) and was mostly due to perforation (P = 0.009). With a median follow-up of 66.9 (39.7–94.8) months, 28 (20.4%) patients had recurrence. A mitotic index > 5 (P ≤ 0.001) and the intestinal location (P = 0.012) were significantly associated to recurrence. Tumor size > 15 cm (P = 0.001) and an age of ≥ 75 years (P = 0.014) were associated to mortality. On univariate analysis, higher mean values of Ki-67 were associated to higher mortality (P = 0.0032). Small intestine GIST presented lower disease-free survival (DFS) than that of gastric GIST (65.7% vs 90.8%) with P = 0.003. The overall survival (OS) of gastric and small intestine GIST was 74.7% and 71.6%, respectively (P = 0.68). Small intestine GIST received emergency surgery more frequently showing lower DFS and same OS than that of gastric GIST. We found that Ki-67 could be a prognostic factor. Further studies are necessary to assess whether Ki-67 is a prognostic risk factor for GISTs.

The coronavirus pandemic has required those that are most vulnerable to protect themselves as best they can. This includes vulnerable states, among which are the island states of the Pacific, where...

Resumen Introduccion El quilotorax es una complicacion poco frecuente en las esofagectomias pero que se asocia a un aumento de la mortalidad posquirurgica. Se han descrito diversos factores que pueden incrementar su aparicion y el tratamiento del mismo es controvertido, siendo la linfografia con embolizacion percutanea del conducto toracico uno de los usados por varios grupos. Material y metodo Estudio retrospectivo de los pacientes a los que se les realizo una esofagectomia por cancer de esofago o de la union esofagogastrica a Siewert I/II entre enero del 2010 y abril del 2019, y desarrollaron un quilotorax como complicacion. Se analizan datos epidemiologicos, el tipo de cirugia, la morbilidad y el tratamiento. Resultados Se realizaron 274 esofagectomias por cancer en el periodo comprendido. Trece pacientes (4,7%) fueron diagnosticados de quilotorax en el postoperatorio; 3 se resolvieron con tratamiento conservador. En los 10 pacientes restantes se realizo linfografia con puncion de la cisterna de Pecquet y embolizacion del conducto toracico, con resolucion del quilotorax en 9. Un paciente (10%) presento una fistula biliar despues del procedimiento. Conclusiones La linfografia con puncion de la cisterna de Pecquet y embolizacion del conducto toracico es una tecnica con baja morbilidad y buenos resultados en la resolucion del quilotorax postesofagectomia.

Introduction Chylothorax is a rare complication in esophagectomies that is associated with increased postoperative mortality. Several factors have been described that may favor its appearance. Its treatment is controversial, and lymphography with percutaneous embolization of the thoracic duct is used by several groups. Material and method Our retrospective study included patients who underwent esophagectomy for cancer of the esophagus or the esophagogastric junction (Siewert I/II) between January 2010 and April 2019 and developed chylothorax as a complication. Epidemiological data, type of surgery, morbidity and treatment were analyzed. Results 274 cancer-related esophagectomies were performed in the study period. Thirteen patients (4.7%) were diagnosed with chylothorax in the postoperative period; 3 were resolved with conservative treatment. In the remaining 10 patients, lymphography was performed with aspiration of the cisterna chyli and thoracic duct embolization, which resolved the chylothorax in 9. One patient (10%) presented a biliary fistula after the procedure. Conclusions Lymphography with aspiration of the cisterna chyli and thoracic duct embolization is a technique with low morbidity that provides good results for the resolution of chylothorax after esophagectomy.

The significance of molecular analysis of peritoneal fluid in staging laparoscopy of oesophagogastric junction (EGJ) and gastric cancer is still controversial. METHODS: A retrospective analysis of prospective data collection of all patients diagnosed with locally advanced gastric neoplasia or Siewert II-III EGJ cancer from July 2009 to October 2019 who underwent staging peritoneal lavage prior to neoadjuvant treatment was performed. Cytology studies and molecular analysis of peritoneal lavage were performed by real-time reverse transcriptase polymerase chain reaction (RT_PCR) of carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) as tumor makers. RESULTS: 168 patients were operated. Citology and molecular analysis were performed in 138 patients. Macroscopic carcinomatosis (P+) was evidenced in 12.3% (17 patients). Of the remaining 87.7% (121 patients), 9.9% (12 patients) had positive cytology. In 21% (29 patients) disseminated macroscopic or microscopic disease (P + or Cyt+) was identified. 11.6% (16 patients) were P0Cyt- but RT-PCR+. Of these, 9 responded to chemotherapy before salvage surgery. The sensitivity of cytology and molecular analysis was 0.70 and 0.76, respectively (p = 0.67). The survival of Cyt-RT_PCR + vs. Cyt + RT_PCR + patients was similar (p = 0.1). However, there were no differences in the survival curves between Cyt-RT_PCR- patients vs Cyt-RT_PCR + patients who underwent salvage surgery (p = 0.69). CONCLUSION: Molecular analysis showed a sensitivity of 76%. In our study, the survival of P0 Cyt-RT_PCR + patients responding to chemotherapy and undergoing surgery was similar to that of P0 Cyt-RT_PCR- patients but less disease free survival.

Resumen El tumor de celulas granulares es una entidad muy infrecuente (0,03%) y con un manejo terapeutico controvertido debido a su escasa incidencia y a su comportamiento habitualmente benigno (98%). Su localizacion en el tracto digestivo es inusual (3-11%), y el esofago es el organo mas frecuentemente afectado, con unos 400 casos publicados. Sin embargo, la incidencia en el esofago cervical es anecdotica (20 casos publicados). Presentamos un paciente con un tumor de celulas granulares esofagico que invadia traquea, tiroides y partes blandas, realizandose una reseccion en bloque de esofago cervical, dos anillos traqueales, tiroides y musculatura pretiroidea. Para la reconstruccion digestiva se empleo un injerto de yeyuno libre con anastomosis microvascular y reconstruccion traqueal mediante anastomosis termino-terminal. La importancia del caso es doble: aportar mayor casuistica y describir una tecnica quirurgica altamente compleja nunca indicada en este tipo de tumores debido a su caracter raramente agresivo.

Purpose: The study examines the prevalence of Bulimia nervosa in students at King Abdulaziz University in Saudi Arabia.Bulimia nervosaisan eating disorder characterized by consumption of large amounts of food by an individual followed by an attempt such as self-induced vomiting, long periods of exercising, and diuretics to avoid gaining weight. Patients and Method: The study adopted a cross-sectional survey among King Abdulaziz University students in Saudi Arabia. A sample of 499 comprising 357 females and 142 males was randomly selectedparticipants—the age of the sample population aged between 20 to over 55 years. The participants filled questionnaires about eating behavior, smoking, body image, and psychiatrist disorders. The height and weight of the sample population were taken, and their BMI was established. Results: Based on our statistics, the prevalence of bulimia nervosa among the male was 0.3%, and that of the female was 1.4%. Extra observation revealed that those with mild or severe disorders were equally susceptible to depression and mood swing problems. The prevalence of Bulimia nervosa based on ages showed 80/50000 at 10 -30 years and 145/50000 at 31 – 80 years. The clinically prescribed healing period was idealized to be one year. Conclusion:The results show a comparatively high rate of BN among young people aged between 20 and 25, as reflected among King Abdulaziz University students in Saudi Arabia. Therefore, there is a need to increase public awareness about BN and other eating disorders in Saudi Arabia.

Pancreatic cancer (PC) is one the deadliest cancers worldwide. It is characterized by elevated mortality rates because of the lack of effective diagnostic methods, the dense stroma that shields the tumor from effective drug penetration, and the emergence of chemoresistance. Recent research has elucidated the role of PC-derived exosomes in driving and fueling PC progression, metastasis, and chemoresistance by transporting key molecules from tumor cells to recipient cells in the tumor microenvironment (TME). In this review, we delineate some of the key exosomal molecules involved in immune suppression and reprogramming of the TME, the establishment of metastatic niches, and drug resistance. We also explore the potential of exosomes as both diagnostic tools for early PC detection and management and as therapeutic targets.

The synthesis and pharmacological activity of a new series of 4-alkyl-1-oxa-4,9-diazaspiro[5.5]undecane derivatives as potent dual ligands for the σ1 receptor (σ1R) and the μ-opioid receptor (MOR) are reported. A lead optimization program over the initial 4-aryl analogues provided 4-alkyl derivatives with the desired functionality and good selectivity and ADME profiles. Compound 14u (EST73502) showed MOR agonism and σ1R antagonism and a potent analgesic activity, comparable to the MOR agonist oxycodone in animal models of acute and chronic pain after single and repeated administration. Contrary to oxycodone, 14u produces analgesic activity with reduced opioid-induced relevant adverse events, like intestinal transit inhibition and naloxone-precipitated behavioral signs of opiate withdrawal. These results provide evidence that dual MOR agonism and σ1R antagonism may be a useful strategy for obtaining potent and safer analgesics and were the basis for the selection of 14u as a clinical candidate for the treatment of pain.

Since 1999, the COCH gene encoding cochlin, has been linked to the autosomal dominant non-syndromic hearing loss, DFNA9, with or without vestibular abnormalities. The hearing impairment associated with the variants affecting gene function has been attributed to a dominant-negative effect. Mutant cochlin was seen to accumulate intracellularly, with the formation of aggregates both inside and outside the cells, in contrast to the wild-type cochlin that is normally secreted. While additional recessive variants in the COCH gene (DFNB110) have recently been reported, the mechanism of the loss-of-function (LOF) effect of the COCH gene product remains unknown. In this study, we used COS7 cell lines to investigate the consequences of a novel homozygous frameshift variant on RNA transcription, and on cochlin translation. Our results indicate a LOF effect of the variant and a major decrease in cochlin translation. This data have a dramatic impact on the accuracy of genetic counseling for both heterozygote and homozygote carriers of LOF variants in COCH.

Summary: This study assesses the efficacy of 2 different potentiated ionophores (monensin and narasin) and a chemical (nicarbazin, a shuttle) in program with narasin to control coccidiosis in challenged male broilers through the evaluation of performance and macroscopic lesions of internal organs. A total of 4,400 broiler chicks were housed in 44 floor pens of 100 birds each; birds of the first group were fed a narasin/nicarbazin (NN)–containing diet from 0 to 27 D of age followed by narasin diet until market age, and those of group 2 were fed a monensin/nicarbazin diet followed by narasin ration for the same trial periods. The coccidia challenge was performed at day 1 by the inclusion of a proven Eimeria-infected litter in the bedding of all floor pens followed by an oral challenge using a commercial cocci vaccine at 7 D of age with a concentration of 11 times the vaccine dose. Although results showed that NN and monensin/nicarbazin treatments both demonstrated efficacy at reducing coccidian lesions, NN significantly increased BW and reduced feed conversion ratio (P < 0.05) at 27 (1,405 vs. 1284 g and 1.458 vs. 1.566, respectively) and at 33 D of age (2,178 vs. 2,026 g and 1.549 vs. 1.642, respectively). Weight and weight percentages of the ready-to-cook carcass and carcass cutup parts were significantly improved by NN. Narasin/nicarbazin inclusion in diet for 0 to 27 D followed by narasin until market weight was a successful strategy because, in addition to preventing and controlling coccidiosis, it improved performance of broiler chickens.

Mutations in more than 150 genes are responsible for inherited hearing loss, with thousands of different, severe causal alleles that vary among populations. The Israeli Jewish population includes communities of diverse geographic origins, revealing a wide range of deafness-associated variants and enabling clinical characterization of the associated phenotypes. Our goal was to identify the genetic causes of inherited hearing loss in this population, and to determine relationships among genotype, phenotype, and ethnicity. Genomic DNA samples from informative relatives of 88 multiplex families, all of self-identified Jewish ancestry, with either non-syndromic or syndromic hearing loss, were sequenced for known and candidate deafness genes using the HEar-Seq gene panel. The genetic causes of hearing loss were identified for 60% of the families. One gene was encountered for the first time in human hearing loss: ATOH1 (Atonal), a basic helix-loop-helix transcription factor responsible for autosomal dominant progressive hearing loss in a five-generation family. Our results demonstrate that genomic sequencing with a gene panel dedicated to hearing loss is effective for genetic diagnoses in a diverse population. Comprehensive sequencing enables well-informed genetic counseling and clinical management by medical geneticists, otolaryngologists, audiologists, and speech therapists and can be integrated into newborn screening for deafness.

Objectiu múltiple; SRS; Fantasma virtual Objetivo múltiple; SRS; Fantasma virtual Multiple‐target; SRS; Virtual phantom The aim of this study was to benchmark the accuracy of the VIrtual Phantom Epid dose Reconstruction (VIPER) software for pre-treatment dosimetric verification of multiple-target stereotactic radiosurgery (SRS). VIPER is an EPID-based method to reconstruct a 3D dose distribution in a virtual phantom from in-air portal images. Validation of the VIPER dose calculation was assessed using several MLC-defined fields for a 6 MV photon beam. Central axis percent depth doses (PDDs) and output factors were measured with an ionization chamber in a water tank, while dose planes at a depth of 10 cm in a solid flat phantom were acquired with radiochromic films. The accuracy of VIPER for multiple-target SRS plan verification was benchmarked against Monte Carlo simulations. Eighteen multiple-target SRS plans designed with the Eclipse treatment planning system were mapped to a cylindrical water phantom. For each plan, the 3D dose distribution reconstructed by VIPER within the phantom was compared with the Monte Carlo simulation, using a 3D gamma analysis. Dose differences (VIPER vs. measurements) generally within 2% were found for the MLC-defined fields, while film dosimetry revealed gamma passing rates (GPRs) ≥95% for a 3%/1 mm criteria. For the 18 multiple-target SRS plans, average 3D GPRs greater than 93% and 98% for the 3%/2 mm and 5%/2 mm criteria, respectively. Our results validate the use of VIPER as a dosimetric verification tool for pre-treatment QA of single-isocenter multiple-target SRS plans. The method requires no setup time on the linac and results in an accurate 3D characterization of the delivered dose.

Recent breakthroughs in immunotherapy have revolutionized treatment for many types of cancer, but unfortunately trials of these therapies have failed to provide meaningful life-prolonging benefit for brain tumor patients, potentially due to abundant immunosuppressive myeloid cells in the tumor. Our ultimate goal is to reprogram immunosuppressive tumor associated myeloid cells to an antitumor state to enable effective immunotherapy. Towards this goal, we have deeply characterized the immune microenvironment of more than 50 primary high and low grade gliomas using high-throughput single-cell RNA-sequencing to reveal recurrent myeloid cell states and immunosuppressive programs across IDH1 wild-type and mutant tumors. We have also established a brain tumor organoid model from primary patient tissue that maintains all of the tumor microenvironment, including myeloid and other immune cells. We utilize the this model to functionally test data-driven reprogramming strategies and understand how they impact the states of tumor and immune cells in the ex vivo human tumor microenvironment.

We describe a case of Sjögren's syndrome-associated trigeminal neuropathy with mandibular nerve enhancement at the foramen ovale and Gasserian ganglion (Meckel's cave) in a patient with a prior history of breast cancer. We also explore the differential diagnosis of trigeminal neuropathy associated with mandibular nerve involvement at the foramen ovale and exclude other diseases such as Sjögren's syndrome or perineurial invasion as a result of various carcinomas. We emphasize the importance of an investigative triad of searching for a local head-and-neck malignancy that may metastasize by perineural spread or invasion, excluding a distant malignancy or paraneoplastic phenomenon and ruling out an autoimmune etiology such as Sjögren's syndrome. In the process, we briefly outline the basic immunopathologic processes.

Background: Diabetes self-management education (DSME) is an essential component of lifestyle management needed for diabetes care. Despite ranking second in the world in the prevalence of diabetes, there is no reported intervention addressing diabetes self-care in the Arab world This pilot-study tested the effect of culturally-tailored education targeting diabetes self-care on glycaemia and cardiovascular risk factors of Lebanese with type 2 diabetes (T2DM). Methods: A sample of 27 adults (Age: 61±10yrs, 59% males, HbA1c:8.98±1.38%) with T2DM was recruited from primary health care centers in Beirut. Participants received culturally tailored, multidisciplinary education. Scales assessing self-care, social support, fatalism, and diabetes knowledge, as well as anthropometric measures, and blood samples were collected at baseline, 3-months and 6-months post- intervention. Results: Diabetes self-care (Diet, Self-Monitoring Blood Glucose and foot care) improved after 6 months, which was reflected in a significant drop in glycemic level (HbA1c:-0.5%; FPG: -38 mg/dl), and cholesterol/HDL ratio (4.45±1.39 vs. 4.06±1.29). Waist circumference decreased at 6 months compared to 3 months (p

Summary This experiment was conducted to assess a protocol combining 20% excess dietary methionine above the modern breeder pullet's requirement and AviPro MGF vaccine in controlling Mycoplasma gallispeticum (MG) infection. In a complete randomized design, a total of 276 6-wk-old breeder pullets, of the Ross 308 strain were allocated into 4 treatments, each with 3 floor pen replicates of 23 birds/pen: 1) nonvaccinated with adequate methionine (NVAM), 2) nonvaccinated with 20% excess methionine (NVEM), 3) Vaccinated with adequate methionine (VAM), 4) Vaccinated with 20% excess methionine (VEM). Vaccination with AviPro MGF at 6 wk of age was performed via drinking water. Results indicated that the rate of depictable growth and tracheal colonization of MGF vaccine strain is 6 wk postvaccination. Sera Elisa titers showed that an 8-wk-postvaccination period was required for the vaccine to stimulate the humoral immunity response against MG. The 20% excess methionine numerically increased the IgG titer against MG in comparison to other groups, yet this increase was not enough to generate protective titer count. Furthermore, the addition of 20% excess methionine above the recommended levels hindered the tracheal colonization rate and log10 values of AviPro MGF vaccine colony forming units from 5.9/mL of tracheal swab suspension in VAM group to 0.82/mL of tracheal swab suspension in VEM group (P ˂ 0.05). In conclusion, the 20% excess methionine above the modern requirements reduced the tracheal colonization of F-strain MG. Further research is needed to confirm the ability of excess dietary methionine to enhance the adaptive and acquired immunity of broiler breeder pullets.

Gastric cancer (GC) remains the third leading cause of cancer-related death despite several improvements in targeted therapy. There is therefore an urgent need to investigate new treatment strategies, including the identification of novel biomarkers for patient stratification. In this study, we evaluated the effect of FDA-approved kinase inhibitors on GC. Through a combination of cell growth, migration and invasion assays, we identified dasatinib as an efficient inhibitor of GC proliferation. Mass-spectrometry-based selectivity profiling and subsequent knockdown experiments identified members of the SRC family of kinases including SRC, FRK, LYN and YES, as well as other kinases such as DDR1, ABL2, SIK2, RIPK2, EPHA2, and EPHB2 as dasatinib targets. The expression levels of the identified kinases were investigated on RNA and protein level in 200 classified tumor samples from patients, who had undergone gastrectomy, but had received no treatment. Levels of FRK, DDR1 and SRC expression on both mRNA and protein level were significantly higher in metastatic patient samples regardless of the tumor stage, while expression levels of SIK2 correlated with tumor size. Collectively, our data suggest dasatinib for treatment of GC based on its unique property, inhibiting a small number of key kinases (SRC, FRK, DDR1 and SIK2), highly expressed in GC patients.

Background:The most important goal in endoscopic pituitary surgery is bloodless field with better visualization under hemodynamic stability and good analgesia to improve the outcome, the current study was performed to evaluate the intraoperative anesthetic and postoperative analgesic effects of bilateral sphenopalatine ganglion block(SPGB)as adjuvant to general anesthesia in endoscopic transsphenoidal resection of pituitary adenoma. Patients and methods:thirty patients(ASA I-II)aged 22–55 years, randomly assigned into two equal groups. After stabilization of general anesthesia, the patients received bilateral sphenopalatine ganglion block with 2ml of either2% lidocaine: 1:200000 epinephrine(SPGB group)or sterile normal saline(control group). Mean arterial blood pressure was maintained at 60–70mmHg by using nitroglycerine. Intraoperative MAP and heart rate, Nitroglycerine and propranolol consumption, blood loss, average category scale, emergence time were recorded. Also, pre and postoperative plasma B-endorphin, VAS and time of first request for analgesia, total dose of meperidine consumption in the first 24hours postoperatively, patient’s satisfaction and post-operative complication were recorded. Results: Sphenopalatine ganglion block group showed decrease in blood loss(P

Introduction\ud \ud Patients with cancer who develop small bowel obstruction are at high risk of malnutrition and morbidity following compromise of gastrointestinal tract continuity. This study aimed to characterise current management and outcomes following malignant small bowel obstruction.\ud \ud \ud \ud Methods\ud \ud A prospective, multicentre cohort study of patients with small bowel obstruction who presented to UK hospitals between 16th January and 13th March 2017. Patients who presented with small bowel obstruction due to primary tumours of the intestine (excluding left-sided colonic tumours) or disseminated intra-abdominal malignancy were included. Outcomes included 30-day mortality and in-hospital complications. Cox-proportional hazards models were used to generate adjusted effects estimates, which are presented as hazard ratios (HR) alongside the corresponding 95% confidence interval (95% CI). The threshold for statistical significance was set at the level of P ≤ 0.05 a-priori.\ud \ud \ud \ud Results\ud \ud 205 patients with malignant small bowel obstruction presented to emergency surgery services during the study period. Of these patients, 50 had obstruction due to right sided colon cancer, 143 due to disseminated intraabdominal malignancy, 10 had primary tumours of the small bowel and 2 patients had gastrointestinal stromal tumours. In total 100 out of 205 patients underwent a surgical intervention for obstruction. 30-day in-hospital mortality rate was 11.3% for those with primary tumours and 19.6% for those with disseminated malignancy. Severe risk of malnutrition was an independent predictor for poor mortality in this cohort (adjusted HR 16.18, 95% CI 1.86 to 140.84, p = 0.012). Patients with right-sided colon cancer had high rates of morbidity.\ud \ud \ud \ud Conclusions\ud \ud Mortality rates were high in patients with disseminated malignancy and in those with right sided colon cancer. Further research should identify optimal management strategy to reduce morbidity for these patient groups.

Background: Neuraxial analgesia is the gold standard for conducting painless labor either by epidural route or combined spinal epidural. Aim of Study: This study is to evaluate the effect of adding neostigmine to levobupivacaine for epidural labor analgesia on mother and neonate. Patient and Methods: After approval from local ethical committee and obtaining written informed consent this pro-spective randomized double-blind study was conducted on 60 laboring mothers, aged between 21 to 38 years, ASA I & II, single pregnancy, gestational age >!37 weeks in active cervical dilatation (!95cm) subjected to normal labor by epidural analgesia. Parturient were randomly divided into two groups: Group L (n=30): Received 15ml of 0.125% levobupivacaine. Group N (n=30): Received 15ml of 0.125% levobupivacaine + 6mic/kg neostigmine. Onset of sensory block, duration of analgesia, maternal hemodynamics, motor block and total dose of levobupivacaine were recorded. Maternal outcome in the form of (duration of labor, mode of delivery), Apgar score at (1 and 5min) and side effects were also recorded. Results: There was faster onset of sensory block and prolonged duration of analgesia with neostigmine group compared with other group. No significant difference between both groups as regard hemodynamics. No motor blockade in both groups. There was significant reduction in the total dose of levobupivacaine with neostigmine group. There was shorter duration of labor with neostigmine group. No significant difference as regard mode of delivery, Apgar score and com-plications between the two groups. Conclusion: Neostigmine can be utilized as a safe adjuvant with levobupivacaine to provide a better quality of analgesia and reduce dose of local anesthetic during management of labor pain. Also it's safe for both mother and fetus.

Background: Breast cancer is women's most common malignancy and has steadily increased incidence over the past decade. Despite recent breast cancer surgery advances, this procedure is often associated with postoperative pain, nausea, and vomiting, contributing not only to increased patient discomfort, but also to extended hospital stays and associated costs. A significant risk factor for the development of chronic pain following breast surgery is acute postoperative pain due to insufficient or ineffective pain control.Aim of Study: Assess the effectiveness of ultrasound guided PECS block to thoracic epidural blockage in breast cancer surgery to minimize postoperative pain, analgesic requirements and complications.Patients and Methods: After Ethical Committee at Al-Zahraa University Hospital accepted, 50 female patients, age from 42-67 years, were included in the study with ASA physical status I-II patients scheduled for unilateral modified radical mastectomy and axillary lymph node dissection, randomly blind assigned, split two different groups of 25 patients in each, Thoracic epidural block (TEB group); patients were received a single shot of 15ml of 0.25% bupivacaine between T4 and T5 vertebrae. PECS group: Ultrasound-guided PECS block, the patients were received 0.25% of 10ml bupi-vacaine injected at fiscal plain between the pectoral s major and minor muscles (PECS I) also 0.25% of 20ml of pectoral-minor injection above the Serratus anterior muscle (PECS II). Primary outcome in the form of post-operative visual analogue scale (VAS) to assess pain in density. Secondary outcome in the form heart rate (HR), mean blood pressure (MBP) intra operative fentanyl consumption and, first request of analgesia, total amount of pethidine/24 hrs. were recorded and other any post-operative complication were assessed.Results: The patients of TEB group, the mean heart rate and the mean MAP were highly significant decrease than PECS group. Intra operative fentanyl consumption as statis-tically significant decrease in PECS group compared with TEB group. VAS pain scores was high statistically significant decrease immediately and at 4 hrs. post-operative in PECS group than TEB group. The time for the first request for pethidine was highly significantly longer in the PECS group than in TEB group. Amount of pethidine at 24 hrs. was high significant lower in PECS group in comparison with TEB group. Complications recorded as hypotension and bradycardia post-operative nausea and vomiting (PONV) occurrence in TEB group.Conclusion: PECS blocks provided superior post-operative analgesia, low pain scores and less total pethidine consumption in the early postoperative period and maintained hemodynamic stability compared to TEB.

Objectives To compare clinical features, laboratory data and fetal-maternal outcomes between 1000 women with obstetric APS (OAPS) and 640 with aPL-related obstetric complications not fulfilling Sydney criteria (non-criteria OAPS, NC-OAPS). Methods This was a retrospective and prospective multicentre study from the European Registry on Obstetric Antiphospholipid Syndrome. Results A total of 1650 women with 5251 episodes, 3601 of which were historical and 1650 latest episodes, were included. Altogether, 1000 cases (OAPS group) fulfilled the Sydney classification criteria and 650 (NC-OAPS group) did not. Ten NC-OAPS cases were excluded for presenting thrombosis during follow-up. All cases were classified as category I (triple positivity or double positivity for aPL) or category II (simple positivity). Overall, aPL laboratory categories showed significant differences: 29.20% in OAPS vs 17.96% in NC-OAPS (P < 0.0001) for category I, and 70.8% in OAPS vs 82% in NC-OAPS (P < 0.0001) for category II. Significant differences were observed when current obstetric complications were compared (P < 0.001). However, major differences between groups were not observed in treatment rates, livebirths and thrombotic complications. In the NC-OAPS group, 176/640 (27.5%) did not fulfil Sydney clinical criteria (subgroup A), 175/640 (27.34%) had a low titre and/or non-persistent aPL positivity but did meet the clinical criteria (subgroup B) and 289/640 (45.15%) had a high aPL titre but did not fulfil Sydney clinical criteria (subgroup C). Conclusion Significant clinical and laboratory differences were found between groups. Fetal-maternal outcomes were similar in both groups when treated. These results suggest that we could improve our clinical practice with better understanding of NC-OAPS patients.

Resumen La cirugia minimamente invasiva permite el tratamiento de los tumores de la union esofagogastrica en condiciones de seguridad, reduciendo las complicaciones respiratorias y parietales y mejorando la recuperacion postoperatoria, manteniendo ademas los principios de la cirugia oncologica que permitan obtener unos resultados optimos de efectividad a largo plazo. Para ello, es necesario un volumen de actividad suficiente y avanzar en la curva de aprendizaje de forma tutelada, para poder garantizar una reseccion R0 y una linfadenectomia adecuada. La minima invasion no puede ser un objetivo en si misma. En caso de gastrectomia total, el riesgo de afectacion del margen proximal obliga a verificarlo mediante biopsia intraoperatoria, sin descartar la cirugia abierta de entrada. Por su parte, la esofagectomia minimamente invasiva se ha ido imponiendo progresivamente. Su principal dificultad, la anastomosis intratoracica, puede realizarse mediante una sutura laterolateral mecanica o manualmente asistida por robot, gracias a la vision tridimensional y a la versatilidad del instrumental.

Minimally invasive surgery provides for the treatment of esophagogastric junction tumors under safe conditions, reducing respiratory and abdominal wall complications. Recovery is improved, while maintaining the oncological principles of surgery to obtain an optimal long-term outcome. It is important to have a sufficient volume of activity to progress along the learning curve with close expert supervision in order to guarantee R0 resection and adequate lymphadenectomy. Minimal invasiveness ought not become an objective in itself. Should total gastrectomy be performed, the risk of a positive proximal margin makes intraoperative biopsy compulsory, without ruling out a primary open approach. Meanwhile, minimally invasive esophagectomy has been gaining ground. Its main difficulty, the intrathoracic anastomosis, can be safely carried out either with a mechanical side-to-side suture or a robot-assisted manual suture, thanks to the 3-D vision and versatility of the instruments.

Cartilage is a specialized tissue that has a relatively homogenous endogenous cell population but a diverse extracellular matrix (ECM) with depth-dependent mechanical properties. Cartilage repair remains an elusive clinical goal, with biological interventions preferred to arthroplasty in younger patients. Osteochondral transplantation (OCT) has emerged for the treatment of cartilage defects and osteoarthritis. Fresh allografts stored at 4 °C for periods of time have been utilized, though matrix and cell viability loss remained an issue. To address this, several studies have developed media formulations to maintain cartilage explants in vitro. One promising factor for these applications is sprifermin, a human-recombinant fibroblast growth factor-18 which stimulates chondrocyte proliferation and matrix synthesis and is in clinical trials for osteoarthritis treatment. We hypothesized that addition of sprifermin during storage would maintain the unique depth-dependent mechanical profile of cartilage explants, a feature of cartilage not often evaluated. In this study, cartilage explants were maintained for up to 6 weeks with or without a weekly 24-hour exposure to sprifermin (100 ng/ml) and the compressive modulus was assessed. Results showed that sprifermin treated samples maintained their depth-dependent mechanical profile through 3 weeks, whereas untreated samples lost their mechanical integrity over 1 week of culture. Sprifermin also affected ECM balance by maintaining levels of extracellular collagen and suppression of matrix metalloproteinase production. These findings support the use of sprifermin as a medium additive for OCT allografts during in vitro storage, and present a potential mechanism where sprifermin may impact a functional characteristic of cartilage in repair strategies.

Aquaporins (AQPs) are hydrophobic integral trans-membrane channel proteins implicated in cellular proliferation and water transport in various cancers. They compose a family of 13 different isoforms (25–34 kDa) in mammals that have been identified to date. These AQPs exhibit a unique pattern of tissue expression. Though they can be found in most tissues, they are mostly active in endothelial and epithelial tissues. In this review, the AQPs associated with female-specific cancers are comprehensively explored and their significant features are analysed. Recent findings revealing their role in female-specific carcinogenesis, especially cervical, ovarian, uterine/endometrial, and breast, will be also discussed.

Therapeutic inhibition of hypoxia inducible factor-1α (HIF-1α) action has emerged as a potential approach for managing several diseases including breast cancer (BC). Genistein has been found to exert anti-malignant activity. However, its mechanisms of action remain unknown. Studies indicate that it could act by downregulating HIF-1α. Based on these findings, we investigated whether genistein could reduce HIF-1α in BC cell lines. Furthermore, we performed molecular docking studies to characterize the sites of interaction between genistein and HIF-1α. In the present investigation, we prove, for the first time, that genistein downregulates HIF-1α in BC cells. Molecular docking analysis also revealed that genistein binds to the FIH-1 binding site of HIF-1α protein. These findings thus indicate that genistein and/or HIF-1α antagonists could be a potential treatment for BC.

The ability to describe routes was assessed in participants with intellectual disability (ID) and participants without ID matched on chronological age (CA) or on mental age (MA). In two experiments, participants learned a route through a virtual environment until they reached a learning criterion. They were then asked to externalize their spatial knowledge in a verbal description task, a landmark recognition task, or a map completion task. Results revealed that participants with ID mainly described the route as a succession of actions (“turn left”), and participants in the CA group prescribed actions referring to a landmark (“turn left at the swing”). Yet, results from the other tasks showed that people with ID had good landmark knowledge of the environment.

Conventional cancer treatments such as chemotherapy and radiation therapy have reached their therapeutic potential, leaving a gap for developing more effective cancer therapeutics. Cancer cells evade the immune system using various mechanisms of immune tolerance, underlying the potential impact of immunotherapy in the treatment of cancer. Immunotherapy includes several approaches such as activating the immune system in a cytokine-dependent manner, manipulating the feedback mechanisms involved in the immune response, enhancing the immune response via lymphocyte expansion and using cancer vaccines to elicit long-lasting, robust responses. These techniques can be used as monotherapies or combination therapies. The present review describes the immune-based mechanisms involved in tumor cell proliferation and maintenance and the rationale underlying various treatment methods. In addition, the present review provides insight into the potential of immunotherapy used alone or in combination with various types of therapeutics.

Acral peeling skin syndrome (APSS) is a heterogenous group of genodermatoses, manifested by peeling of palmo-plantar skin and occasionally associated with erythema and epidermal thickening. A subset of APSS is caused by mutations in protease inhibitor encoding genes, resulting in unopposed protease activity and desmosomal degradation and/or mis-localization, leading to enhanced epidermal desquamation. We investigated two Arab-Muslim siblings with mild keratoderma and prominent APSS since infancy. Genetic analysis disclosed a homozygous mutation in SERPINB7, c.796C > T, which is the founder mutation in Nagashima type palmo-plantar keratosis (NPPK). Although not previously formally reported, APSS was found in other patients with NPPK. We hypothesized that loss of SERPINB7 function might contribute to the peeling phenotype through impairment of keratinocyte adhesion, similar to other protease inhibitor mutations that cause APSS. Mis-localization of desmosomal components was observed in a patient plantar biopsy compared with a biopsy from an age- and gender-matched healthy control. Silencing of SERPINB7 in normal human epidermal keratinocytes led to increased cell sheet fragmentation upon mechanical stress. Immunostaining showed reduced expression of desmoglein 1 and desmocollin 1. This study shows that in addition to stratum corneum perturbation, loss of SERPINB7 disrupts desmosomal components, which could lead to desquamation, manifested by skin peeling.