Autoimmune hepatitis after COVID-19 infection.

We report the case of a 58-year-old male patient presenting with clinical and laboratory findings indicative of acute hepatitis. Abdominal ultrasound excluded biliary tract abnormalities. Two weeks prior, the patient had contracted COVID-19. Viral hepatitis was ruled out, and the presence of autoantibodies was confirmed. Liver biopsy findings were consistent with autoimmune hepatitis and grade 1 fibrosis. Initial treatment with budesonide was ineffective, leading to a switch to prednisone, with maintenance therapy comprising prednisone and azathioprine. COVID-19 infection may act as a trigger for the development of autoimmune hepatitis.

Novel approaches in the medical management of compensated cirrhosis.

INTRODUCTION: Classically, clinical practice guidelines and expert recommendations have focused on the management of decompensated cirrhotic patients, so we focused this review on improving care for compensated cirrhotic patients who are followed up in outpatient clinics. AREAS COVERED: We reviewed the current methods for establishing liver function, the diagnosis and management of advanced chronic liver disease and clinically significant portal hypertension as well as the prevention of its complications, with special attention to covert hepatic encephalopathy, we also paid attention to the extrahepatic complications of cirrhosis and the palliative care. All this from the perspective of evidence-based medicine and trying to empower precision medicine. The literature search was undertaken by PubMed with 'cirrhosis,' 'advanced chronic liver disease,' 'liver function,' 'portal hypertension,' 'covert hepatic encephalopathy,' 'minimal hepatic encephalopathy,' 'palliative care' as MeSH terms. EXPERT OPINION: We must offer compensated cirrhotic patients specific care and measures to prevent the progression of the disease and the appearance of its complications beyond the calculation of liver function and imaging screening for hepatocellular carcinoma that we perform every six months. Entities that have typically received little attention, such as covert hepatic encephalopathy, extrahepatic complications and symptoms of cirrhosis, and palliative care, must come to the spotlight.

Restorative Strategies for Bilateral Mutilated Hands in a Secondary Care Level: A Report of a Case in Mexico.

This case report aims to delineate the challenges and management strategies for a patient with bilateral mutilated hands within a secondary care level in Mexico, contributing to medical literature and potentially guiding future patient care. Mutilated hands represent a significant surgical and rehabilitative challenge due to the profound structural damage they cause, leading to considerable functional impairment and psychological distress. The complexity of these injuries necessitates a multidisciplinary approach, particularly in resource-constrained settings. We present a case of a 45-year-old male with no prior significant medical history who sustained bilateral mutilated hands from an industrial accident involving hot rollers. The patient underwent extensive surgical reconstruction and postoperative care, facing complications such as skin graft integration issues and infections, which required a multidisciplinary treatment approach.

Survival and prognostic factors in pediatric patients with medulloblastoma treated at a national pediatric hospital in Peru: a retrospective cohort.

OBJECTIVE: The objectives of this study were to determine the overall survival (OS) and event-free survival (EFS) rates of patients with medulloblastoma treated in a national pediatric hospital in Peru, as well as to identify demographic, clinical, imaging, postoperative, and histopathological characteristics and prognostic factors associated with OS and EFS. METHODS: The authors conducted a retrospective study analyzing information from the medical records of children with a diagnosis of medulloblastoma who underwent surgical treatment at the Instituto Nacional de Salud del Niño-San Borja, a public hospital in Lima, Peru, from 2015 to 2020. Clinical-epidemiological variables, degree of disease extension, risk stratification, extent of resection, postoperative complications, status of oncological treatment received, histological subtype, and neurological sequelae were taken into account. The Kaplan-Meier method and Cox regression analysis were used to estimate OS, EFS, and prognostic factors. RESULTS: Of the 57 children evaluated with complete medical records, only 22 children (38.6%) underwent complete oncological treatment. OS was 37% (95% CI 0.25-0.55) at 48 months. EFS was 44% (95% CI 0.31-0.61) at 23 months. High-risk stratification-meaning patients with ≥ 1.5 cm2 of residual postoperative tumor, those younger than 3 years, those with disseminated disease (HR 9.69, 95% CI 1.40-67.0, p = 0.02), and those who underwent subtotal resection (HR 3.78, 95% CI 1.09-13.2, p = 0.04)-was negatively associated with OS. Failure to receive complete oncological treatment was negatively associated with OS (HR 20.0, 95% CI 4.84-82.6, p < 0.001) and EFS (HR 7.82, 95% CI 2.47-24.7, p < 0.001). CONCLUSIONS: OS and EFS of patients with medulloblastoma in the author's milieu are below those reported in developed countries. Incomplete treatment and treatment abandonment in the authors' cohort were also high compared with high-income country statistics. Failure to complete oncological treatment was the most important factor associated with poor prognosis, both in terms of OS and EFS. High-risk patients and subtotal resection were negatively associated with OS. Interventions are needed to promote the completion of adjuvant oncological therapy for medulloblastoma in the disadvantaged Peruvian population.

Antiangiogenic Effect of Dopamine and Dopaminergic Agonists as an Adjuvant Therapeutic Option in the Treatment of Cancer, Endometriosis, and Osteoarthritis.

Dopamine (DA) and dopamine agonists (DA-Ag) have shown antiangiogenic potential through the vascular endothelial growth factor (VEGF) pathway. They inhibit VEGF and VEGF receptor 2 (VEGFR 2) functions through the dopamine receptor D2 (D2R), preventing important angiogenesis-related processes such as proliferation, migration, and vascular permeability. However, few studies have demonstrated the antiangiogenic mechanism and efficacy of DA and DA-Ag in diseases such as cancer, endometriosis, and osteoarthritis (OA). Therefore, the objective of this review was to describe the mechanisms of the antiangiogenic action of the DA-D2R/VEGF-VEGFR 2 system and to compile related findings from experimental studies and clinical trials on cancer, endometriosis, and OA. Advanced searches were performed in PubMed, Web of Science, SciFinder, ProQuest, EBSCO, Scopus, Science Direct, Google Scholar, PubChem, NCBI Bookshelf, DrugBank, livertox, and Clinical Trials. Articles explaining the antiangiogenic effect of DA and DA-Ag in research articles, meta-analyses, books, reviews, databases, and clinical trials were considered. DA and DA-Ag have an antiangiogenic effect that could reinforce the treatment of diseases that do not yet have a fully curative treatment, such as cancer, endometriosis, and OA. In addition, DA and DA-Ag could present advantages over other angiogenic inhibitors, such as monoclonal antibodies.

Giant cavernous malformation of the posterior fossa with lymphangiomatous phenotype, associated with orbital venolymphatic anomaly in an 11-month-old patient: case report and literature review.

The synchronous presentation of venolymphatic anomalies of the orbit and noncontiguous intracranial cavernous malformations is uncommon. Herein, we present a case of an 11-month-old female patient diagnosed with orbital venolymphatic anomaly associated with a large cavernous malformation in the posterior fossa, who underwent complete surgical resection of the latter. The immunohistochemical analysis was positive for podoplanin, a marker expressed by lymphatic endothelial cells, but not vascular endothelium. This exceptional finding suggests lymphatic involvement in the etiology of the lesion. In our review of the literature, we did not find similar cases in patients under 1 year of age.

Ectopic ACTH syndrome in a patient with Crohn's disease.

We present the case of a 62-year-old man with Crohn's disease who consulted for abdominal pain and lower limbs edema. The patient developed Cushing's syndrome due to ectopic secretion of ACTH. Diagnostic imaging tests showed multiple metastatic liver lesions and asymmetric thickening of the ileum, that was suspected as the primary tumor. This tumor produced destabilizing gastrointestinal bleeding and an urgent surgical resection was performed. The histopathological study of the resection specimen confirmed a grade 3 neuroendocrine tumor.

Arthroscopic Matrix-Assisted Autologous Chondrocyte Transplantation Versus Microfracture: A 6-Year Follow-up of a Prospective Randomized Trial.

BACKGROUND: Few randomized controlled trials with a midterm follow-up have compared matrix-assisted autologous chondrocyte transplantation (MACT) with microfracture (MFx) for knee cartilage lesions. PURPOSE: To compare the structural, clinical, and safety outcomes at midterm follow-up of MACT versus MFx for treating symptomatic knee cartilage lesions. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 48 patients aged between 18 and 50 years, with 1- to 4-cm2 International Cartilage Repair Society (ICRS) grade III to IV knee chondral lesions, were randomized in a 1:1 ratio to the MACT and MFx treatment groups. A sequential prospective evaluation was performed using magnetic resonance imaging (MRI) T2 mapping, the MOCART (magnetic resonance observation of cartilage repair tissue) score, second-look arthroscopic surgery, patient-reported outcome measures, the responder rate (based on achieving the minimal clinically important difference for the Knee injury and Osteoarthritis Outcome Score [KOOS] pain and KOOS Sport/Recreation), adverse events, and treatment failure (defined as a reoperation because of symptoms caused by the primary defect and the detachment or absence of >50% of the repaired tissue during revision surgery). RESULTS: Overall, 35 patients (18 MACT and 17 MFx) with a mean chondral lesion size of 1.8 ± 0.8 cm2 (range, 1-4 cm2) were followed up to a mean of 6 years postoperatively (range, 4-9 years). MACT demonstrated significantly better structural outcomes than MFx at 1 to 6 years postoperatively. At final follow-up, the MRI T2 mapping values of the repaired tissue were 37.7 ± 8.5 ms for MACT versus 46.4 ± 8.5 ms for MFx (P = .003), while the MOCART scores were 59.4 ± 17.3 and 42.4 ± 16.3, respectively (P = .006). More than 50% defect filling was seen in 95% of patients at 2 years and 82% at 6 years in the MACT group and in 67% at 2 years and 53% at 6 years in the MFx group. The second-look ICRS scores at 1 year were 10.7 ± 1.3 for MACT and 9.0 ± 1.8 for MFx (P = .001). Both groups showed significant clinical improvements at 6 years postoperatively compared with their preoperative status. Significant differences favoring the MACT group were observed at 2 years on the KOOS Activities of Daily Living (P = .043), at 4 years on all KOOS subscales (except Symptoms; P < .05) and the Tegner scale (P = .008), and at 6 years on the Tegner scale (P = .010). The responder rates at 6 years were 53% and 77% for MFx and MACT, respectively. There were no reported treatment failures after MACT; the failure rate was 8.3% in the MFx group. Neither group had serious adverse events related to treatment. CONCLUSION: Patients who underwent MACT had better structural outcomes than those who underwent MFx at 1 to 6 years postoperatively. Both groups of patients showed significant clinical improvements at final follow-up compared with their preoperative status. MACT showed superiority at 4 years for the majority of the KOOS subscales and for the Tegner scale at 4 to 6 years. The MACT group also had a higher responder rate and lower failure rate at final follow-up. REGISTRATION: NCT01947374 (ClinicalTrials.gov identifier).

Papel de los estudios microbiológicos en la necrosis pancreática / Role of the microbiological studies in pancreatic necrosis / Papel dos estudos microbiológicos na necrose pancreática

RESUMEN Introducción: la infección de la necrosis pancreática es la complicación local más grave de la pancreatitis aguda. Ocurre aproximadamente en un 35% de los pacientes y presenta una mortalidad cercana al 80%. Objetivo: identificar el espectro microbiológico de la necrosis pancreática infectada Métodos: realizamos un estudio longitudinal, descriptivo, prospectivo en la Unidad de cuidados intensivos del Hospital Universitario Carlos Manuel de Céspedes de la ciudad de Bayamo, Cuba, en el periodo comprendido desde enero de 2012 hasta diciembre de 2018.Fueron incluidos 71 pacientes con el diagnostico o sospecha de pancreatitis aguda necrotizante infectada que requirieron necrosectomía con toma de cultivo intraoperatorio. Resultados: del total de pacientes de la serie la mayoría fueron masculinos representando el 56,3 % de la muestra. la etiología más frecuentemente encontrada fue la litiasica con 38 pacientes (53,5%). Mientras que 52 pacientes (73,2%) presentaban más del 50% de la glándula pancreática con necrosis. En 63 pacientes se confirmó la presencia de infección de la necrosis. Con predominio de la infección monomicrobiana en 48 casos (76,2%).El germen más frecuentemente encontrado fue E. coli (47,9%).La mortalidad post-operatoria fue de 15 pacientes (21, 1%).De ellos 14 pacientes (93,3%) con infección luego de la necrosectomía. Conclusiones: predominó la infección monomicrobiana por E. coli. Los pacientes con confirmación de crecimiento bacteriano post necrosectomía presentaron mayor mortalidad.

ABSTRACT Introduction: infection of pancreatic necrosis is the most serious local complication of acute pancreatitis. It occurs in approximately 35% of patients and has a mortality rate close to 80%. Objective: to identify the microbiological spectrum of infected pancreatic necrosis Methods: we carried out a longitudinal, descriptive, prospective study in the intensive care unit of the Carlos Manuel de Céspedes University Hospital in the city of Bayamo, Cuba, in the period from January 2012 to December 2018. 71 patients with the diagnosis or suspicion of infected acute necrotizing pancreatitis that required necrosectomy with intraoperative culture taking. Results: of the total number of patients in the series, the majority were male, representing 56.3% of the sample. the most frequently found etiology was lithiasis with 38 patients (53.5%). While 52 patients (73.2%) had more than 50% of the pancreatic gland with necrosis. In 63 patients, the presence of necrosis infection was confirmed. With a predominance of monomicrobial infection in 48 cases (76.2%). The most frequent germ found was E. coli (47.9%). Post-operative mortality was 15 patients (21.1%). Of them 14 patients (93.3%) with infection after necrosectomy. Conclusions: monomicrobial infection by E. coli predominated. Patients with confirmed bacterial growth post necrosectomy had higher mortality.

RESUMO Introdução: a infecção da necrose pancreática é a complicação local mais grave da pancreatite aguda. Ocorre em aproximadamente 35% dos pacientes e tem mortalidade próxima a 80%. Objetivo: identificar o espectro microbiológico da necrose pancreática infectada Métodos: foi realizado um estudo longitudinal, descritivo e prospectivo na unidade de terapia intensiva do Hospital Universitário Carlos Manuel de Céspedes, nacidade de Bayamo, Cuba, no período de janeiro de 2012 a dezembro de 2018. 71 pacientes portadores de diagnóstico ou suspeita de pancreatite necrosante aguda infectada que exigiu necrosectomia com coleta de cultura intraoperatória. Resultados: do total de pacientes da série, a maioria era do sexo masculino, representando 56,3% da amostra. a etiologia mais encontrada foi a litíase com 38 pacientes (53,5%). En quanto 52 pacientes (73,2%) apresentavam mais de 50% da glândula pancreática com necrose. Em 63 pacientes, foi confirmada a presença de infecção de necrose. Com predomínio de infecção monomicrobiana em 48 casos (76,2%). O germe mais encontrado foi E. coli (47,9%). A mortalidade pós-operatória foi de 15 pacientes (21,1%). Destes 14 pacientes (93,3%) com infecção após necrosectomia. Conclusões: a infecção monomicrobiana por E. coli predominou. Pacientes com crescimento bacteriano confirmado após necrosectomia apresentaram maior mortalidade.

Tumor de estroma gastrointestinal: a propósito de un caso y revisión de la literatura / Gastrointestinal stromal tumor: report of a case and review of the literature / Tumor estromal gastrointestinal: relato de um caso e revisão da literatura

RESUMEN Introducción: los tumores del estroma gastrointestinal (GIST), son las neoplasias de origen mesenquimático más frecuentes del tracto digestivo, sin embargo, representan menos del 1% de todos estos tumores. Actualmente se denominan GIST a los tumores mesenquimales CD117 positivos, fusiformes o epitelioides, primarios del tracto gastrointestinal, epiplón, mesenterio y retroperitoneo. Presentación de caso: presentamos un paciente de 60 años de edad que fue ingresado en el servicio de Medicina Interna por anemia crónica y dispepsia. Al examen físico se constata en la palpación de abdomen un tumor en hipocondrio derecho y epigastrio, no mesurable, fijo, doloroso. Se realizan complementarios como ecografía abdominal, esófago gastroduedenoscopia, TAC abdominal y laparoscopia demostrándose la presencia de un tumor de la curvatura mayor gástrica de aproximadamente 20 cm con crecimiento exofitico. Se interviene quirúrgicamente, realizándose gastrectomía total, espelenctomia y esofagoyeyunostomia. Los resultados definitivos de anatomía patológica informan: tumor de pared gástrica, fusocelular del estroma gastrointestinal, de bajo potencial. Tamaño del tumor 25cm. Índice Mitótico de 1 mitosis por 50 HPF con Inmunohistoquímica positiva para CD117, CD34, cumplió tratamiento quimioterapia y presenta una evolución favorable. Discusión: los GIST son tumores cuya presencia de síntomas dependerá del tamaño y localización del tumor y puede variar desde formas asintomáticas a casos que se presenten como una emergencia quirúrgica por perforación gástrica o sangramiento digestivo. Conclusiones: el paciente fue intervenido quirúrgicamente encontrándose un tumor fusocelular del estroma gastrointestinal (GIST) de pared gástrica, de bajo potencial de malignidad, comportamiento agresivo.

ABSTRACT Introduction: the Gastrointestinal Stroma Tumors (GIST), the neoplasia from which those stem are those of highest mesenquimatic frequency of the digestive tract, However, it represents less than 1 % of all these tumors. At present, mesenquimales name the tumors GIST CD117 positive, fusiform or epithelioid, primary of the tract gastrointestinal, epiplón, mesentery and retro-peritoneum. Case presentation: we introduced a 60-year-old patient that went through admittance in the Internal Medicine service due to chronic anemia and dyspepsia. To the physical examination through palpationof the abdomen, a tumor in straight hypochondrium and epigastrium is verified, notmeasurable, It is fixed, painful. Complementary tests are also performed, like abdominal echography, esophagus gastroduedenoscopy abdominal CAT and laparoscopy, showing the presence of a tumor of the bigger gastric curvature of approximately 20 cm with exofitic growth. Surgery is performed, coming true total gastrectomy, splenectomy and esofagoyeyunostomy, which have proven to be definite of morbid anatomy, as the inform discloses: Tumor of gastricwall, gastrointestinal fusocellular stroma, of potential bass. Size of the tumor 25cm. Meiotic index of 1 mitosis for 50 HPF with positive Inmunohistochemical for CD117, CD34, treatment fulfilled chemotherapy and it presents a favorable evolution. Discussion: the GIST symptoms are depended of the tumor size and localization. They had some types of clinical presentation such as gastric perforation or haemorrage. Conclusion: in the OR we found a gastrointestinal fusocelullar tumor, at the gastric wall. With very aggressive behavior.

RESUMO Introdução: os tumores estromais gastrointestinais (GIST) são as neoplasias mais frequentes de origem mesenquimal do trato digestivo, porém representam menos de 1% de todos esses tumores. Atualmente, os GISTs são positivos para CD117, fusiformes ou epitelióides, tumores mesenquimais primários do trato gastrointestinal, omento, mesentério e retroperitônio. Apresentação do caso: apresentamos um paciente de 60 anos que deu entrada no serviço de Clínica Médica por anemia crônica e dispepsia. O exame físico revelou tumor doloroso, fixo e não mensurável em quadrante superior direito e epigástrio à palpação de abdome. Exames complementares como ultrassonografia abdominal, gastroduedenoscopia de esôfago, tomografia computadorizada de abdome e laparoscopia são realizados, demonstrando a presença de tumor da grande curvatura gástrica de aproximadamente 20 cm com crescimento exofítico. Foi realizada intervenção cirúrgica, realizando gastrectomia total, espelenctomia e esofagojejunostomia. Os resultados definitivo do laudo anatomopatológico: tumor da parede gástrica, fusocelular do estroma gastrointestinal, de baixo potencial. Tamanho do tumor: 25cm. Índice mitótico de 1 mitose por 50 HPF com imunoistoquímica positiva para CD117, CD34, foi submetido a tratamento quimioterápico e apresenta evolução favorável. Discussão: GISTs são tumores cuja presença de sintomas dependerá do tamanho e localização do tumor e podem variar desde formas assintomáticas até casos que se apresentam como emergência cirúrgica por perfuração gástrica ou sangramento digestivo. Conclusões: a paciente foi operada e encontrou tumor de células fusiformes do estroma gastrointestinal (GIST) da parede gástrica, com baixo potencial de malignidade e comportamento agressivo.

Deciphering the Mechanism of Action Involved in Enhanced Suicide Gene Colon Cancer Cell Killer Effect Mediated by Gef and Apoptin.

Despite the great advances in cancer treatment, colorectal cancer has emerged as the second highest cause of death from cancer worldwide. For this type of tumor, the use of suicide gene therapy could represent a novel therapy. We recently demonstrated that co-expression of gef and apoptin dramatically inhibits proliferation of the DLD-1 colon cell line. In the present manuscript, we try to establish the mechanism underlying the enhanced induction of apoptosis by triggering both gef and apoptin expression in colon tumor cells. Scanning microscopy reveals that simultaneous expression of gef and apoptin induces the apparition of many "pores" in the cytoplasmic membrane not detected in control cell lines. The formation of pores induced by the gef gene and accentuated by apoptin results in cell death by necrosis. Moreover, we observed the presence of apoptotic cells. Performing protein expression analysis using western blot, we revealed an activation of mitochondrial apoptosis (increased expression of Pp53, cytochrome c, Bax, and caspase 9) and also the involvement of the extrinsic pathway through caspase 8activation. In conclusion, in this manuscript we demonstrate for the first time that the extrinsic pathway of apoptosis and pore formation is also involved in the cell death caused by the co-expression of the gef and apoptin genes. Our results suggest that co-expression of gef and apoptin genes induces an increase in post-apoptotic necrotic cell death and could be a valuable tool in the design of new antitumor strategies focused on the enhancement of the immune response against cancer cell death.

Enhancement of Tumor Cell Death by Combining gef Gene Mediated Therapy and New 1,4-Benzoxazepin-2,6-Dichloropurine Derivatives in Breast Cancer Cells.

New treatment modalities are urgently needed to better manage advanced breast cancer. Combination therapies are usually more effective than monotherapy. In this context, the use of cyclic and acyclic O,N-acetals derivative compounds in combination with the suicide gef gene shown a potent anti-tumor activity and represent a new generation of anticancer agents. Here, we evaluate the use of the gef gene to promote and increase the anti-tumor effect of cyclic and acyclic O,N-acetals purine derivatives and elucidate their mechanisms of action. Among all compounds tested, those with a nitro group and a cyclic pattern structures (FC-30b2, FC-29c, and bozepinib) are the most benefited from the gef gene effect. These compounds, in combination with gef gene, were able to abolish tumor cell proliferation with a minimal dose leading to more effective and less toxic chemotherapy. The effect of this combined therapy is triggered by apoptosis induction which can be found deregulated in the later stage of breast cancer. Moreover, the combined therapy leads to an increase of cell post-apoptotic secondary necrosis that is able to promote the immunogenicity of cancer cells leading to a successful treatment. This data suggests that this novel combination therapy represents a promising candidate for breast cancer treatment.

Activating Transcription Factor 4 Modulates TGFß-Induced Aggressiveness in Triple-Negative Breast Cancer via SMAD2/3/4 and mTORC2 Signaling.

Purpose: On the basis of the identified stress-independent cellular functions of activating transcription factor 4 (ATF4), we reported enhanced ATF4 levels in MCF10A cells treated with TGFß1. ATF4 is overexpressed in patients with triple-negative breast cancer (TNBC), but its impact on patient survival and the underlying mechanisms remain unknown. We aimed to determine ATF4 effects on patients with breast cancer survival and TNBC aggressiveness, and the relationships between TGFß and ATF4. Defining the signaling pathways may help us identify a cell signaling-tailored gene signature.Experimental Design: Patient survival data were determined by Kaplan-Meier analysis. Relationship between TGFß and ATF4, their effects on aggressiveness (tumor proliferation, metastasis, and stemness), and the underlying pathways were analyzed in three TNBC cell lines and in vivo using patient-derived xenografts (PDX).Results: ATF4 overexpression correlated with TNBC patient survival decrease and a SMAD-dependent crosstalk between ATF4 and TGFß was identified. ATF4 expression inhibition reduced migration, invasiveness, mammosphere-forming efficiency, proliferation, epithelial-mesenchymal transition, and antiapoptotic and stemness marker levels. In PDX models, ATF4 silencing decreased metastases, tumor growth, and relapse after chemotherapy. ATF4 was shown to be active downstream of SMAD2/3/4 and mTORC2, regulating TGFß/SMAD and mTOR/RAC1-RHOA pathways independently of stress. We defined an eight-gene signature with prognostic potential, altered in 45% of 2,509 patients with breast cancer.Conclusions: ATF4 may represent a valuable prognostic biomarker and therapeutic target in patients with TNBC, and we identified a cell signaling pathway-based gene signature that may contribute to the development of combinatorial targeted therapies for breast cancer. Clin Cancer Res; 24(22); 5697-709. ©2018 AACR.

Mesenchymal stem cell's secretome promotes selective enrichment of cancer stem-like cells with specific cytogenetic profile.

Cancer stem cells (CSCs) are responsible for tumor initiation, metastasis and cancer recurrence, however the involvement of microenvironment is crucial. Here, we have analyzed how human mesenchymal stem cells (MSCs)-derived conditioned medium (CM) affect colon and melanoma CSCs enrichment and maintenance. Our results strongly suggest that the secretome of CM-MSCs selects and maintains subpopulations with high expression of CSCs markers and ALDH1 activity, low proliferation rates with G1 phase arrest, and notably retain in vivo these properties. Cytogenetic analyses indicated that CM-cultured cells contain alterations in chromosome 17 (17q25). Subsequent SKY-FISH analyses suggested that genes located in 17q25 might be involved in stem-cell maintenance. The characterization of secreted proteins present in CM-MSCs revealed that four cytokines and seven growth factors are directly linked to the CSCs enrichment reported in this study. Further analyses revealed that the combination of just IL6 and HGF is enough to provide cancer cells with better stemness properties. In conclusion, this study demonstrates how specific chromosomal alterations present in CSCs subpopulations might represent an advantage for their in vitro maintenance and in vivo stemness properties.

Bloodstream infections in cancer patients. Risk factors associated with mortality.

OBJECTIVE: The aim of this study was to evaluate the clinical characteristics and risk factors associated with mortality in cancer patients with bloodstream infections (BSI), analyzing multidrug resistant bacteria (MDR). METHODS: We conducted a prospective observational study at a cancer referral center from August 2016 to July 2017, which included all BSI. RESULTS: 4220 patients were tested with blood cultures; 496 were included. Mean age was 48 years. In 299 patients with solid tumors, secondary BSI and Central Line-Associated BSI (CLABSI) were the most common (55.9% and 31.8%, respectively). In 197 hematologic patients, primary and mucosal barrier injury (MBI) BSI were the main type (38.6%). Gram-negative were the most frequent bacteria (72.8%), with Escherichia coli occupying the first place (n=210, 42.3%), 48% were Extended-Spectrum Beta-Lactamase (ESBL) producers, and 1.8% were resistant to carbapenems. Mortality at day 30, was 22%, but reached 70% when patients did not receive an appropriate antimicrobial treatment. Multivariate analysis showed that progression or relapse of the oncologic disease, inappropriate antimicrobial treatment, and having resistant bacteria were independently associated with 30-day mortality. CONCLUSIONS: Emergence of MDR bacteria is an important healthcare problem worldwide. Patients with BSI, particularly those patients with MDR bacteria have a higher mortality risk.

Tumor de células de sertoli esclerosante. Reporte de un caso / Sclerosing sertoli cell tumor. Case report

RESUMEN El tumor esclerosante de células de Sertoli del testículo es una entidad patológica infrecuente, con todo, que solo se han descrito 22 casos en la literatura científica. Son descritos como tumores unilaterales que en su mayoría se presentan entre la tercera y sexta década de vida, siendo carentes de malignidad, sin embargo, en ninguno de los casos reportados se han realizado seguimientos por periodos prolongados. Se presenta un caso clínico cuyo objetivo es socializar el primer caso de tumor esclerosante de células de Sertoli (SSCT), diagnosticado por el departamento de patología de la Universidad industrial de Santander, que se registra en Colombia. Después de tres años de seguimiento clínico el paciente no presenta recidiva, así como tampoco otras lesiones tumorales. Se considera la orquiectomia el tratamiento curativo.(AU)

SUMMARY Sclerosing tumor of Sertoli cells of the testis is an infrequent pathological entity, only 22 cases have been described in the scientific literature. They are described as unilateral tumors that mostly occur between the third and sixth decade of life, being devoid of malignancy, however, in none of the cases have been followed for prolonged periods. We present a clinical case whose objective is to socialize the first case of Sertoli cell sclerosing tumor (SSCT), diagnosed by the pathology department of the industrial university of Santander, which is registered in Colombia. After three years of clinical follow-up, the patient does not present recurrence, as well as other tumor lesions. Orchiectomy is considered the curative treatment.(AU)

1-(Benzenesulfonyl)-1,5-dihydro-4,1-benzoxazepine as a new scaffold for the design of antitumor compounds.

AIM: Bozepinib is a potent and selective anticancer compound which chemical structure is made up of a benzofused seven-membered ring and a purine moiety. We previously demonstrated that the purine fragment does not exert antiproliferative effect per se. METHODOLOGY: A series of 1-(benzenesulfonyl)-4,1-benzoxazepine derivatives were synthesized in order to study the influence of the benzofused seven-membered ring in the biological activity of bozepinib by means of antiproliferative, cell cycle and apoptosis studies. RESULTS & CONCLUSION: Our results show that the methyleneoxy enamine sulfonyl function is essential in the antitumor activity of the structures and thus, it is a scaffold suitable for further modification with a view to obtain more potent antitumor compounds.

Antitumoral activity of 1,2-diaminocyclohexane derivatives in breast, colon and skin human cancer cells.

AIM: Cancer is among the leading causes of death worldwide. Medical interest has focused on macrocyclic polyamines because of their properties as antitumor agents. Results/Methodology: We have designed and synthesized a series of 1,2-diaminocyclohexane derivatives with notable in vitro antiproliferative activities against the MCF-7, HCT-116 and A375 cancer cell lines. Cell cycle and apoptosis analyses were also carried out. Our results show that all the compounds are potent cytotoxic agents, especially against the A375 cell line. CONCLUSION: The selective activity of the macrocyclic derivative against A375, via apoptosis, supposes a great advantage for future therapeutic use. This exemplifies the potential of 1,2-diaminocyclohexane derivatives to qualify as lead structures for future anticancer drug development due to their easy syntheses and noteworthy bioactivity.

Relationship of receptors of adipokines with hypertension and obesity. Murine model

Background: The aim of this paper is to investigated the contribution of adipose tissue thought the adipokines and kidney failure (KF) Methods: In male rats were fed with a standard lab diet (C) or a hypercaloric diet including 30% sucrose; obese group (Ob) and obese with kidney failure group (Ob/KF). We evaluated the changes of adipokines under conditions of obesity and KF, using 5/6 surgery to induce vascular injury. The anterior and media branches of the left kidney artery were tied together, leaving the posterior branch viable to enable the kidney to function. The right kidney was removed. Results: A 90% survival rate of the animals was achieved due to special care taken. Kidney function progressively decreased after surgery. Compared with the control group, in the other two groups (Ob and Ob/KF) the level of leptin increased and that of adiponectin decreased (p < 0.01). Post-surgery increases were observed in blood pressure, lipids, creatinine and insulin (p < 0.01). Conclusion: This model is proposed for the study pathophysiological mechanisms that lead to obesity and complications of kidney or cardiovascular function.

Introducción: El objetivo de este trabajo es investigar la contribución del tejido adiposo y las adipocinas y la insuficiencia renal (KF). Métodos: Ratas machos se alimentaron con una dieta estándar de laboratorio (C) o una dieta hipercalórica incluyendo 30% de sacarosa; Grupo obeso (Ob) y obeso con grupo de insuficiencia renal (Ob/KF). Se evaluaron los cambios de adipocinas en condiciones de obesidad y KF, utilizando cirugía 5/6 para inducir lesión vascular. Las ramas anterior y media de la arteria renal izquierda fueron unidas, dejando la rama posterior viable para permitir sobreviviencia y función renal. El riñón derecho fue removido. Resultados: Se logró una tasa de supervivencia del 90% de los animales debido a un cuidado especial. La función renal disminuyó progresivamente después de la cirugía. En comparación con el grupo control, en los otros dos grupos (Ob y Ob/KF) el nivel de leptina aumentó y el de adiponectina disminuyó (p < 0.01). Se observaron aumentos postquirúrgicos en la presión arterial, los lípidos, la creatinina y la insulina (p < 0.01). Conclusión: Este modelo se propone para el estudio de los mecanismos fisiopatológicos que conducen a la obesidad y las complicaciones de la función renal o cardiovascular.

5-Fluorouracil derivatives: a patent review (2012 - 2014).

INTRODUCTION: 5-Fluorouracil (5-FU)-based chemotherapy is the most widely prescribed treatment for gastrointestinal solid tumors, but there are several drawbacks such as toxicities, lack of selectivity and effectiveness as well as the development of resistance that need to be overcome. AREAS COVERED: In this review, the authors present the latest innovations in 5-FU derivatives or combinations with: i) other chemotherapeutic drugs; ii) novel targeted compounds; iii) radiotherapy; iv) mAbs; v) siRNA strategies; and vi) traditional Chinese medicine extracts. Moreover, advances to overcome or determine 5-FU adverse effects and effectiveness are described. Finally, the authors introduce the ongoing clinical trials and highlight the main challenges to be addressed in the future. EXPERT OPINION: Although in the past few years there has been a great advancement in the antitumor effectiveness and selectivity of 5-FU-based therapies, it is envisaged that future approaches using 'omics' technologies that could determine the tumor heterogeneity may help in identifying additional candidate genes, microRNAs or cytokines involved in both the path mechanisms of 5-FU-related toxicity and its therapeutic efficacy. Moreover, the development of novel targeted 5-FU derivatives or 5-FU-based therapies tailored to individual patients opens up new possibilities in the improvement of the quality of life and survival for those suffering from this devastating disease.