Age-stratified comorbid and pharmacologic analysis of patients with glioblastoma.

Background: Increased age is a strong and unfavorable prognostic factor for patients with glioblastoma (GBM). However, the relationships between stratified patient age, comorbidities, and medications have yet to be explored in GBM patient survival analyses. Objective: To evaluate co-morbid conditions, tumor-related symptoms, medication prescriptions, and subject age for patients with GBM and to establish potential targets for prospective studies. Methods: Electronic health records for 565 patients with IDHwt GBM were evaluated at a single center between January 1, 2000 and August 9, 2021 were retrospectively assessed. Data were stratified by MGMT promoter methylation status when available and were used to construct multivariable time-dependent cox models and intra-cohort hazards. Results: Younger (<65 years of age) but not older (≥65 years) GBM patients demonstrated a worse prognosis with movement related disabilities (P < 0.0001), gait/balance difficulty (P = 0.04) and weakness (P = 0.007), as well as psychiatric conditions, mental health disorders (P = 0.002) and anxiety (P = 0.001). In contrast, older but not younger GBM patients demonstrated a worse prognosis with epilepsy (P = 0.039). Both groups had worse survival with confusion/altered mental status (P = 0.023 vs < 0.000) and an improved survival with a Temozolomide prescription. Older but not younger GBM patients experienced an improved hazard with a prescription of ace-inhibitor medications (P = 0.048). Conclusion: Age-dependent novel associations between clinical symptoms and medications prescribed for co-morbid conditions were demonstrated in patients with GBM. The results of the current work support future mechanistic studies that investigate the negative relationship(s) between increased age, comorbidities, and drug therapies for differential clinical decision-making across the lifespan of patients with GBM.

Enhancing Kidney Transplant Outcomes: The Impact of Living Donor Programs.

INTRODUCTION: The protocol for deceased donor kidney transplants has been standardised. The procedure for a living donor has peculiarities derived from the differences in the graft. When a living kidney donor program is implemented, changes occur in both the profile of the kidney transplant candidate and in the postoperative treatments. AIMS: To discover whether a living donor program influences the functional outcomes of kidney grafts in a longstanding classical deceased donor kidney transplant program and to identify the factors associated with transplant outcomes. METHODS: Retrospective observational multicentre study. SAMPLE: Kidney transplant patients in two urology referral centres for renal transplant in Spain between 1994 and 2019. Groups: TV (living transplant): patients given kidney transplants from living donors (n = 150); TCpre11 (deceased transplant previous to 2011): patients given kidney transplants from deceased donors before the living donor program was implemented (n = 650); and TCpost11 (deceased transplant after 2011): patients given kidney transplants from deceased donors after the living donor program was implemented (n = 500). RESULTS: Mean age was 55.75 years (18-80 years), higher in TCpre11. There were 493 female patients (37.92%) and 1007 male patients (62.08%). Mean body mass index (BMI) was 26.69 kg/m2 (17.50-42.78 kg/m2), higher in TCpre11. Mean ischemia time was 17.97 h (6-29 h), higher in TCpost11. Median duration of urethral catheter: 8 days (6-98 days), higher in TCpost11. Median duration of double-J ureteral stent: 58 days (24-180 days), higher in TCpost11. Pretransplant UTIs: 17.77%, higher in TCpre11 (25.69%) than in TV (12%), higher in TV (12%) than TCpost11 (9.2%), and higher in TCpre11 (25.69%) than TCpost11 (9.2%). Acute renal rejection in 9.33% of TV, 14.77% of TCpre11, and 9.8% of TCpost11. Multivariate analysis: TCpost11 featured higher BMI, more smoking, and chronic renal failure progression time. Lower use of nonantibiotic prophylaxis to prevent recurrent urinary tract infections, increased duration of urethral catheters due to obstructive problems, and favoured deterioration of kidney function was observed in the deceased donor program. The living donor (LD) program had a strong influence on deceased donor transplants in the prelysis phase. Implementation of a LD program was associated with a decrease in the likelihood of acute rejection in TCpost11 and an increase in the tendency towards normal kidney function. CONCLUSIONS: Implementing living donor transplant programs affects functional outcomes in deceased donor transplants, reducing the probability of acute rejection and increasing the tendency towards normal kidney function. Preventing recurrent urinary tract infections with measures other than antibiotics, smoking cessation, delaying the removal of the double-J stent from the graft, and pre-emptive transplant (transplant prior to dialysis) are associated with improved renal function of the graft.

EGFR amplification and EGFRvIII predict and participate in TAT-Cx43266-283 antitumor response in preclinical glioblastoma models.

BACKGROUND: Glioblastoma (GBM) commonly displays epidermal growth factor receptor (EGFR) alterations (mainly amplification and EGFRvIII) and TAT-Cx43266-283 is a Src-inhibitory peptide with antitumor properties in preclinical GBM models. Given the link between EGFR and Src, the aim of this study was to explore the role of EGFR in the antitumor effects of TAT-Cx43266-283. METHODS: The effect of TAT-Cx43266-283, temozolomide (TMZ), and erlotinib (EGFR inhibitor) was studied in patient-derived GBM stem cells (GSCs) and murine neural stem cells (NSCs) with and without EGFR alterations, in vitro and in vivo. EGFR alterations were analyzed by western blot and fluorescence in situ hybridization in these cells, and compared with Src activity and survival in GBM samples from The Cancer Genome Atlas. RESULTS: The effect of TAT-Cx43266-283 correlated with EGFR alterations in a set of patient-derived GSCs and was stronger than that exerted by TMZ and erlotinib. In fact, TAT-Cx43266-283 only affected NSCs with EGFR alterations, but not healthy NSCs. EGFR alterations correlated with Src activity and poor survival in GBM patients. Finally, tumors generated from NSCs with EGFR alterations showed a decrease in growth, invasiveness, and vascularization after treatment with TAT-Cx43266-283, which enhanced the survival of immunocompetent mice. CONCLUSIONS: Clinically relevant EGFR alterations are predictors of TAT-Cx43266-283 response and part of its mechanism of action, even in TMZ- and erlotinib-resistant GSCs. TAT-Cx43266-283 targets NSCs with GBM-driver mutations, including EGFR alterations, in an immunocompetent GBM model in vivo, suggesting a promising effect on GBM recurrence. Together, this study represents an important step toward the clinical application of TAT-Cx43266-283.

Needs and Expectations of Long-Term Cancer Survivors: Multi-Centre Study Protocol.

Cancer is a social issue as its outreach affects not only mortality (it is the second cause of death in our environment) but also the costs due to morbidity and the distress it causes, as well as the losses and consequences in personal, family, work, and even social areas. This study is trying to find out the health needs of long-term cancer survivors and their perceptions and expectations of the care they received during their survival stage. For this, a joint, cross-sectional descriptive study with a qualitative and quantitative approach has been designed. For the qualitative approach, we have used different focus groups representing different geographical areas of the Spanish territory. For the qualitative approach, we have used a validated questionnaire. This study will provide a better knowledge of the quality of life of these patients, as well as their level of unmet and even unexpressed needs, in order to develop effective strategies and interventions that allow for the implementation of adapted care plans that include such unexpressed needs. This study will also allow for the creation and development of assessment methods for health results from the patient's perspective and experience. These issues require a multidisciplinary, complex approach. These survivors may require not well-known health services, as the number of these patients has grown recently, and their survival time is also longer. This research explores a wider and more thorough perspective of long-term cancer survivors' needs, experiences, and expectations to be achieved.

Sodium-glucose cotransporter 2 inhibition in primary and secondary glomerulonephritis.

BACKGROUND: The role of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the management glomerular/systemic autoimmune diseases with proteinuria in real-world clinical settings is unclear. METHODS: This is a retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-h proteinuria from SGLT2i initiation to 3, 6, 9 and 12 months. Secondary outcomes included percentage change in estimated glomerular filtration rate (eGFR), proteinuria reduction by type of disease and reduction of proteinuria ≥30% from SGLT2i initiation. RESULTS: Four-hundred and ninety-three patients with a median age of 55 years and background therapy with renin-angiotensin system blockers were included. Proteinuria from baseline changed by -35%, -41%, -45% and -48% at 3, 6, 9 and 12 months after SGLT2i initiation, while eGFR changed by -6%, -3%, -8% and -10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. A correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up. By mixed-effects logistic regression model, serum albumin at SGLT2i initiation emerged as a predictor of ≥30% proteinuria reduction (odds ratio for albumin <3.5 g/dL, 0.53; 95% CI 0.30-0.91; P = .02). A slower eGFR decline was observed in patients achieving a ≥30% proteinuria reduction: -3.7 versus -5.3 mL/min/1.73 m2/year (P = .001). The overall tolerance to SGLT2i was good. CONCLUSIONS: The use of SGLT2i was associated with a significant reduction of proteinuria. This percentage change is greater in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.

Schnurri-3 drives tumor growth and invasion in cancer cells expressing interleukin-13 receptor alpha 2.

Interleukin 13 receptor alpha 2 (IL13Rα2) is a relevant therapeutic target in glioblastoma (GBM) and other tumors associated with tumor growth and invasion. In a previous study, we demonstrated that protein tyrosine phosphatase 1B (PTP1B) is a key mediator of the IL-13/IL13Rα2 signaling pathway. PTP1B regulates cancer cell invasion through Src activation. However, PTP1B/Src downstream signaling mechanisms that modulate the invasion process remain unclear. In the present research, we have characterized the PTP1B interactome and the PTP1B-associated phosphoproteome after IL-13 treatment, in different cellular contexts, using proteomic strategies. PTP1B was associated with proteins involved in signal transduction, vesicle transport, and with multiple proteins from the NF-κB signaling pathway, including Tenascin-C (TNC). PTP1B participated with NF-κB in TNC-mediated proliferation and invasion. Analysis of the phosphorylation patterns obtained after PTP1B activation with IL-13 showed increased phosphorylation of the transcription factor Schnurri-3 (SHN3), a reported competitor of NF-κB. SHN3 silencing caused a potent inhibition in cell invasion and proliferation, associated with a down-regulation of the Wnt/ß-catenin pathway, an extensive decline of MMP9 expression and the subsequent inhibition of tumor growth and metastasis in mouse models. Regarding clinical value, high expression of SHN3 was associated with poor survival in GBM, showing a significant correlation with the classical and mesenchymal subtypes. In CRC, SHN3 expression showed a preferential association with the mesenchymal subtypes CMS4 and CRIS-B. Moreover, SHN3 expression strongly correlated with IL13Rα2 and MMP9-associated poor prognosis in different cancers. In conclusion, we have uncovered the participation of SNH3 in the IL-13/IL13Rα2/PTP1B pathway to promote tumor growth and invasion. These findings support a potential therapeutic value for SHN3.

On optimal temozolomide scheduling for slowly growing glioblastomas.

Background: Temozolomide (TMZ) is an oral alkylating agent active against gliomas with a favorable toxicity profile. It is part of the standard of care in the management of glioblastoma (GBM), and is commonly used in low-grade gliomas (LGG). In-silico mathematical models can potentially be used to personalize treatments and to accelerate the discovery of optimal drug delivery schemes. Methods: Agent-based mathematical models fed with either mouse or patient data were developed for the in-silico studies. The experimental test beds used to confirm the results were: mouse glioma models obtained by retroviral expression of EGFR-wt/EGFR-vIII in primary progenitors from p16/p19 ko mice and grown in-vitro and in-vivo in orthotopic allografts, and human GBM U251 cells immobilized in alginate microfibers. The patient data used to parametrize the model were obtained from the TCGA/TCIA databases and the TOG clinical study. Results: Slow-growth "virtual" murine GBMs benefited from increasing TMZ dose separation in-silico. In line with the simulation results, improved survival, reduced toxicity, lower expression of resistance factors, and reduction of the tumor mesenchymal component were observed in experimental models subject to long-cycle treatment, particularly in slowly growing tumors. Tissue analysis after long-cycle TMZ treatments revealed epigenetically driven changes in tumor phenotype, which could explain the reduction in GBM growth speed. In-silico trials provided support for implementation methods in human patients. Conclusions: In-silico simulations, in-vitro and in-vivo studies show that TMZ administration schedules with increased time between doses may reduce toxicity, delay the appearance of resistances and lead to survival benefits mediated by changes in the tumor phenotype in slowly-growing GBMs.

Conventional Machine Learning Methods Applied to the Automatic Diagnosis of Sleep Apnea.

The overnight polysomnography shows a range of drawbacks to diagnose obstructive sleep apnea (OSA) that have led to the search for artificial intelligence-based alternatives. Many classic machine learning methods have been already evaluated for this purpose. In this chapter, we show the main approaches found in the scientific literature along with the most used data to develop the models, useful and large easily available databases, and suitable methods to assess performances. In addition, a range of results from selected studies are presented as examples of these methods. Very high diagnostic performances are reported in these results regardless of the approaches taken. This leads us to conclude that conventional machine learning methods are useful techniques to develop new OSA diagnosis simplification proposals and to act as benchmark for other more recent methods such as deep learning.

Suppressor of fused associates with dissemination patterns in patients with glioma.

Gliomas are the most common brain tumors, which present poor prognosis, due, in part, to tumor cell migration and infiltration into distant brain areas. However, the underlying mechanisms causing such effects are unknown. Hedgehog (HH)-Gli axis is one of the signaling pathways involved, with a high number of molecular mediators. In this study, we investigated the association between HH-Gli intermediates and clinical parameters. We found that high levels of SuFu are associated with high dissemination patterns in patients with glioma. Therefore, we analyzed SuFu expression data in three glioma cohorts of surgical samples (N =1,759) and modified its expression in Glioblastoma Cancer Stem Cells (GB CSC) in vitro models. Our data reveal that SuFu overexpression increases cancer stemness properties together with a migratory phenotype. This work identifies SuFu as a new molecular player in glioma cell migration and a promising target to develop blocking agents to decrease GB dissemination.

Propuesta de un modelo de la ideación suicida en estudiantes de Medicina en Colombia: un estudio de simulación / Proposal for a Model of Suicidal Ideation in Medical Students in Colombia: A Simulation Study

RESUMEN La conducta suicida es un problema de salud pública mundial, y una población en la que se presentan altos índices de prevalencia es la de estudiantes de Medicina, especialmente en el componente de ideación. Diversos modelos han intentado explicarla, pero son pocos los estudios inferenciales en población colombiana. Los modelos de ecuaciones estructurales utilizados en ciencias sociales resultan apropiados para explicar este problema y su poder analítico permite realizar generalizaciones con cierto grado de precisión. Estos análisis requieren una gran cantidad de datos para una estimación robusta, lo que limita su utilidad cuando hay restricciones para acceder a los datos, como sucede actualmente a causa de la COVID-19, y una cuestión que destaca en estos modelos es la evaluación del ajuste. Mediante un conjunto de 1.200 datos simulados, se encontró un adecuado ajuste del modelo a los datos (x2 524) = 1.732, 300; p< 0, 001; CFI = 0,97; GFI0= 0,97; TLI = 0,97; RMSEA = 0,04 [0,042-0,046]; SRMR = 0,06) para los predictores depresión y carga percibida, cuyos análisis se realizaron en el programa JASP. Se discute el papel de la pertenencia frustrada, la conveniencia del instrumento para evaluarla y consideraciones de seguimiento, evaluación e intervención de la ideación suicida en estudiantes de Medicina. © 2020 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.

ABSTRACT Suicidal behavior is a global public health problem, and one population group with high prevalence rates is medical students, especially in the ideation component. Various models have tried to explain it, but there are few inferential studies in the Colombian population. The structural equation models used in controlled social sciences to explain this problem and their analytical power allow generalizations to be made with a certain degree of precision. These analyses require a large amount of data for robust estimation, which limits their usability when there are restrictions to access the data, as is the case today due to Covid-19, and a question that stands out in these models is the evaluation of the fit. Through a set of 1,200 simulated data, an appropriate model fit was found (x2 524) = 1.732, 300; p< 0, 001, CFI = 0.97, GFI = 0.97, TLI = 0.97, RMSEA = 0.04[0.042-0.046], SRMR = 0.06) for the predictors of depression and perceived burdensomeness, which were analyzed using the JASP pro-gram. The role of thwarted belongingness is discussed, as well as the appropriateness of the assessment instrument used to evaluate it an considerations regarding suicidal ideation monitoring, evaluation and intervention in medical students.

IDP-410: a Novel Therapeutic Peptide that Alters N-MYC Stability and Reduces Angiogenesis and Tumor Progression in Glioblastomas.

Glioblastomas (GBMs) are the most frequent and highly aggressive brain tumors, being resistant to all cytotoxic and molecularly targeted agents tested so far. There is, therefore, an urgent need to find novel therapeutic approaches and/or alternative targets to bring treatment options to patients. Here, we first show that GBMs express high levels of N-MYC protein, a transcription factor involved in normal brain development. A novel stapled peptide designed to specifically target N-MYC protein monomer, IDP-410, is able to impair the formation of N-MYC/MAX complex and reduce the stability of N-MYC itself. As a result, the viability of GBM cells is compromised. Moreover, the efficacy is found dependent on the levels of expression of N-MYC. Finally, we demonstrate that IDP-410 reduces GBM growth in vivo when administered systemically, both in subcutaneous and intracranial xenografts, reducing the vascularization of the tumors, highlighting a potential relationship between the function of N-MYC and the expression of mesenchymal/angiogenic genes. Overall, our results strengthen the view of N-MYC as a therapeutic target in GBM and strongly suggest that IDP-410 could be further developed to become a first-in-class inhibitor of N-MYC protein, affecting not only tumor cell proliferation and survival, but also the interplay between GBM cells and their microenvironment.

Blood-Brain Barrier Disruption: A Common Driver of Central Nervous System Diseases.

The brain is endowed with a unique cellular composition and organization, embedded within a vascular network and isolated from the circulating blood by a specialized frontier, the so-called blood-brain barrier (BBB), which is necessary for its proper function. Recent reports have shown that increments in the permeability of the blood vessels facilitates the entry of toxic components and immune cells to the brain parenchyma and alters the phenotype of the supporting astrocytes. All of these might contribute to the progression of different pathologies such as brain cancers or neurodegenerative diseases. Although it is well known that BBB breakdown occurs due to pericyte malfunctioning or to the lack of stability of the blood vessels, its participation in the diverse neural diseases needs further elucidation. This review summarizes what it is known about BBB structure and function and how its instability might trigger or promote neuronal degeneration and glioma progression, with a special focus on the role of pericytes as key modulators of the vasculature. Moreover, we will discuss some recent reports that highlights the participation of the BBB alterations in glioma growth. This pan-disease analysis might shed some light into these otherwise untreatable diseases and help to design better therapeutic approaches.

Lemmel's syndrome: an uncommon complication of periampullary duodenal diverticulum.

Lemmel's syndrome is an uncommon entity that causes obstructive jaundice due to a periampullary duodenal diverticulum in the absence of choledolithiasis or neoplasia. To date, there are few published cases and the etiopathogenesis remains unclear.

Lipidomic and Metabolomic Signature of Progression of Chronic Kidney Disease in Patients with Severe Obesity.

Severe obesity is a major risk for chronic kidney disease (CKD). Early detection and careful monitoring of renal function are critical for the prevention of CKD during obesity, since biopsies are not performed in patients with CKD and diagnosis is dependent on the assessment of clinical parameters. To explore whether distinct lipid and metabolic signatures in obesity may signify early stages of pathogenesis toward CKD, liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-high resolution accurate mass-mass spectrometry (GC-HRAM-MS) analyses were performed in the serum and the urine of severely obese patients with and without CKD. Moreover, the impact of bariatric surgery (BS) in lipid and metabolic signature was also studied, through LC-MS and GC-HRAM-MS analyses in the serum and urine of patients with severe obesity and CKD before and after undergoing BS. Regarding patients with severe obesity and CKD compared to severely obese patients without CKD, serum lipidome analysis revealed significant differences in lipid signature. Furthermore, serum metabolomics profile revealed significant changes in specific amino acids, with isoleucine and tyrosine, increased in CKD patients compared with patients without CKD. LC-MS and GC-HRAM-MS analysis in serum of patients with severe obesity and CKD after BS showed downregulation of levels of triglycerides (TGs) and diglycerides (DGs) as well as a decrease in branched-chain amino acid (BCAA), lysine, threonine, proline, and serine. In addition, BS removed most of the correlations in CKD patients against biochemical parameters related to kidney dysfunction. Concerning urine analysis, hippuric acid, valine and glutamine were significantly decreased in urine from CKD patients after surgery. Interestingly, bariatric surgery did not restore all the lipid species, some of them decreased, hence drawing attention to them as potential targets for early diagnosis or therapeutic intervention. Results obtained in this study would justify the use of comprehensive mass spectrometry-based lipidomics to measure other lipids aside from conventional lipid profiles and to validate possible early markers of risk of CKD in patients with severe obesity.

The Embryonic Key Pluripotent Factor NANOG Mediates Glioblastoma Cell Migration via the SDF1/CXCR4 Pathway.

NANOG is a key transcription factor required for maintaining pluripotency of embryonic stem cells. Elevated NANOG expression levels have been reported in many types of human cancers, including lung, oral, prostate, stomach, breast, and brain. Several studies reported the correlation between NANOG expression and tumor metastasis, revealing itself as a powerful biomarker of poor prognosis. However, how NANOG regulates tumor progression is still not known. We previously showed in medaka fish that Nanog regulates primordial germ cell migration through Cxcr4b, a chemokine receptor known for its ability to promote migration and metastasis in human cancers. Therefore, we investigated the role of human NANOG in CXCR4-mediated cancer cell migration. Of note, we found that NANOG regulatory elements in the CXCR4 promoter are functionally conserved in medaka fish and humans, suggesting an evolutionary conserved regulatory axis. Moreover, CXCR4 expression requires NANOG in human glioblastoma cells. In addition, transwell assays demonstrated that NANOG regulates cancer cell migration through the SDF1/CXCR4 pathway. Altogether, our results uncover NANOG-CXCR4 as a novel pathway controlling cellular migration and support Nanog as a potential therapeutic target in the treatment of Nanog-dependent tumor progression.

Pancreas-Kidney Transplantation: Do We Know the Frequency of Clinical Complications?

BACKGROUND: The objective of this study was to describe the most common medical complications in simultaneous pancreas-kidney recipients in our center. METHODS: Retrospective and descriptive study of complications observed in a series of 73 simultaneous pancreas-kidney transplant recipients, which included 54 men and 19 women with an average age of 40.6 years, between February 2009 and April 2019. The study assessed the incidence of cytopenia, viral infections, tumors, and graft rejection. Frequency tables were created for each complication in the analysis. RESULTS: Cytopenia was the most common complication, either by itself or associated with a different complication, and it was found in 23.3% of all patients. The most common infection was cytomegalovirus, which was in 55.6% of all 9 patients who presented infections in spite of universal prophylaxis with valganciclovir, followed by herpes virus (11.1%), papillomavirus (11.1%), and polyoma BK virus (22.2%). Regarding tumors, the number of patients who presented this complication was low; 2 gynecologic tumors were detected (cervical intracellular neoplasia and one ovarian tumor), and 1 case of skin tumor was also observed. There were 3 cases of acute rejection, which represents 4.1% of all patients. Rejection was cellular and steroid-sensitive except for 1 case that was humoral, with good response to treatment. CONCLUSIONS: In spite of the doses of immunosuppressive drugs received by these patients, the incidence of infections was low, and cytomegalovirus was the most common infection. As a consequence of the drugs administered, virtually all patients developed cytopenia. The number of tumors observed in this series was low in spite of the immunosuppressive treatment.

Renoprotective role of bariatric surgery in patients with established chronic kidney disease.

BACKGROUND: Bariatric surgery (BS) has been postulated as the most effective measure for weight reduction. Weight loss improves metabolic parameters and exerts changes in renal function that lead to the amelioration of absolute or relative glomerular hyperfiltration, a condition that may be renoprotective in the long term. However, few studies have demonstrated the influence of BS in patients with severe obesity and chronic kidney disease (CKD). Our objective was to analyse the evolution of renal function, adipose tissue-derived molecules and inflammatory parameters in patients with CKD after BS. METHODS: This is an observational and prospective study. Thirty patients were screened and 12 were included between January 2016 and January 2018 with a 24-month follow-up. Glomerular filtration rate (GFR) was determined by plasma iohexol clearance. Adipokines, cytokines, circulating hormones and fibrotic parameters were evaluated before and 12 months after BS using the Bioplex system. RESULTS: The mean age was 50.6 years and 58.3% were males. Seven patients had a body mass index >40 kg/m2 and 66.7% were diabetic. Twenty-four months following BS there was a significant decrease in body weight (36.4%). Proteinuria decreased by 63.7 ± 28.2%. Measured GFR significantly diminished from before surgery to Month 24 after surgery (94 ± 44 to 79 ± 44 mL/min, P = 0.03). There was a significant decrease in adipocyte-derived molecules (leptin and vifastin) as well as in pro-inflammatory cytokines [interleukin (IL)-1ß, tumour necrosis factor α, IL-6 and monocyte chemoattractant protein-1] and other circulating factors (vascular endothelial growth factor and transforming growth factor ß isoforms). CONCLUSIONS: BS is an effective option to prevent kidney damage in obese subjects with CKD due to the improvement of glomerular hyperfiltration, adipocyte cytokines metabolic and inflammatory parameters.

Netrin-1 in Glioblastoma Neovascularization: The New Partner in Crime?

Glioblastoma (GBM) is the most aggressive and common primary tumor of the central nervous system. It is characterized by having an infiltrating growth and by the presence of an excessive and aberrant vasculature. Some of the mechanisms that promote this neovascularization are angiogenesis and the transdifferentiation of tumor cells into endothelial cells or pericytes. In all these processes, the release of extracellular microvesicles by tumor cells plays an important role. Tumor cell-derived extracellular microvesicles contain pro-angiogenic molecules such as VEGF, which promote the formation of blood vessels and the recruitment of pericytes that reinforce these structures. The present study summarizes and discusses recent data from different investigations suggesting that Netrin-1, a highly versatile protein recently postulated as a non-canonical angiogenic ligand, could participate in the promotion of neovascularization processes in GBM. The relevance of determining the angiogenic signaling pathways associated with the interaction of Netrin-1 with its receptors is posed. Furthermore, we speculate that this molecule could form part of the microvesicles that favor abnormal tumor vasculature. Based on the studies presented, this review proposes Netrin-1 as a novel biomarker for GBM progression and vascularization.

SEGHI Study: Defining the Best Surveillance Strategy in Hodgkin Lymphoma after First-Line Treatment.

The optimal strategy for early surveillance after first complete response is unclear in Hodgkin lymphoma. Thus, we compared the various follow-up strategies in a multicenter study. All the included patients had a negative positron emission tomography/computed tomography at the end of induction therapy. From January 2007 to January 2018, we recruited 640 patients from 15 centers in Spain. Comparing the groups in which serial imaging were performed, the clinical/analytical follow-up group was exposed to significantly fewer imaging tests and less radiation. With a median follow-up of 127 months, progression-free survival at 60 months of the entire series was 88% and the overall survival was 97%. No significant differences in survival or progression-free survival were found among the various surveillance strategies. This study suggests that follow-up approaches with imaging in Hodgkin lymphoma provide no benefits for patient survival, and we believe that clinical/analytical surveillance for this group of patients could be the best course of action.

The Netrin-1-Neogenin-1 signaling axis controls neuroblastoma cell migration via integrin-ß1 and focal adhesion kinase activation.

Neuroblastoma is a highly metastatic tumor that emerges from neural crest cell progenitors. Focal Adhesion Kinase (FAK) is a regulator of cell migration that binds to the receptor Neogenin-1 and is upregulated in neuroblastoma. Here, we show that Netrin-1 ligand binding to Neogenin-1 leads to FAK autophosphorylation and integrin ß1 activation in a FAK dependent manner, thus promoting neuroblastoma cell migration. Moreover, Neogenin-1, which was detected in all tumor stages and was required for neuroblastoma cell migration, was found in a complex with integrin ß1, FAK, and Netrin-1. Importantly, Neogenin-1 promoted neuroblastoma metastases in an immunodeficient mouse model. Taken together, these data show that Neogenin-1 is a metastasis-promoting protein that associates with FAK, activates integrin ß1 and promotes neuroblastoma cell migration.