Liquid Biopsy in Alzheimer's Disease Patients Reveals Epigenetic Changes in the PRLHR Gene.

In recent years, new DNA methylation variants have been reported in genes biologically relevant to Alzheimer's disease (AD) in human brain tissue. However, this AD-specific epigenetic information remains brain-locked and unreachable during patients' lifetimes. In a previous methylome performed in the hippocampus of 26 AD patients and 12 controls, we found higher methylation levels in AD patients in the promoter region of PRLHR, a gene involved in energy balance regulation. Our aim was to further characterize PRLHR's role in AD and to evaluate if the liquid biopsy technique would provide life access to this brain information in a non-invasive way. First, we extended the methylation mapping of PRLHR and validated previous methylome results via bisulfite cloning sequencing. Next, we observed a positive correlation between PRLHR methylation levels and AD-related neuropathological changes and a decreased expression of PRLHR in AD hippocampus. Then, we managed to replicate the hippocampal methylation differences in plasma cfDNA from an additional cohort of 35 AD patients and 35 controls. The isolation of cfDNA from the plasma of AD patients may constitute a source of potential epigenetic biomarkers to aid AD clinical management.

Exploring the Disease-Associated Microglia State in Amyotrophic Lateral Sclerosis.

BACKGROUND: Neuroinflammation, and specifically microglia, plays an important but not-yet well-understood role in the pathophysiology of amyotrophic lateral sclerosis (ALS), constituting a potential therapeutic target for the disease. Recent studies have described the involvement of different microglial transcriptional patterns throughout neurodegenerative processes, identifying a new state of microglia: disease-associated microglia (DAM). The aim of this study is to investigate expression patterns of microglial-related genes in ALS spinal cord. METHODS: We analyzed mRNA expression levels via RT-qPCR of several microglia-related genes in their homeostatic and DAM state in postmortem tissue (anterior horn of the spinal cord) from 20 subjects with ALS-TDP43 and 19 controls donors from the Navarrabiomed Biobank. RESULTS: The expression levels of TREM2, MS4A, CD33, APOE and TYROBP were found to be elevated in the spinal cord from ALS subjects versus controls (p-value < 0.05). However, no statistically significant gene expression differences were observed for TMEM119, SPP1 and LPL. CONCLUSIONS: This study suggests that a DAM-mediated inflammatory response is present in ALS, and TREM2 plays a significant role in immune function of microglia. It also supports the role of C33 and MS4A in the physiopathology of ALS.

Association of Blood-Based DNA Methylation Markers With Late-Onset Alzheimer Disease: A Potential Diagnostic Approach.

BACKGROUND AND OBJECTIVES: There is an urgent need to identify novel noninvasive biomarkers for Alzheimer disease (AD) diagnosis. Recent advances in blood-based measurements of phosphorylated tau (pTau) species are promising but still insufficient to address clinical needs. Epigenetics has been shown to be helpful to better understand AD pathogenesis. Epigenetic biomarkers have been successfully implemented in other medical disciplines, such as oncology. The objective of this study was to explore the diagnostic accuracy of a blood-based DNA methylation marker panel as a noninvasive tool to identify patients with late-onset Alzheimer compared with age-matched controls. METHODS: A case-control study was performed. Blood DNA methylation levels at 46 cytosine-guanine sites (21 genes selected after a comprehensive literature search) were measured by bisulfite pyrosequencing in patients with "probable AD dementia" following National Institute on Aging and the Alzheimer's Association guidelines (2011) and age-matched and sex-matched controls recruited at Neurology Department-University Hospital of Navarre, Spain, selected by convenience sampling. Plasma pTau181 levels were determined by Simoa technology. Multivariable logistic regression analysis was performed to explore the optimal model to discriminate patients with AD from controls. Furthermore, we performed a stratified analysis by sex. RESULTS: The final study cohort consisted of 80 patients with AD (age: median [interquartile range] 79 [11] years; 58.8% female) and 100 cognitively healthy controls (age 77 [10] years; 58% female). A panel including DNA methylation levels at NXN, ABCA7, and HOXA3 genes and plasma pTau181 significantly improved (area under the receiver operating characteristic curve 0.93, 95% CI 0.89-0.97) the diagnostic performance of a single pTau181-based model, adjusted for age, sex, and APOE ɛ4 genotype. The sensitivity and specificity of this panel were 83.30% and 90.00%, respectively. After sex-stratified analysis, HOXA3 DNA methylation levels showed consistent association with AD. DISCUSSION: These results highlight the potential translational value of blood-based DNA methylation biomarkers for noninvasive diagnosis of AD. REGISTRATION INFORMATION: Research Ethics Committee of the University Hospital of Navarre (PI17/02218).

Outcomes of a multidisciplinary Diabetic Foot Day Unit.

OBJECTIVE: To analyse the main characteristics of patients and the health outcomes obtained and to evaluate the impact of peripheral artery disease (PAD) in patients treated in our multidisciplinary Diabetic Foot Unit. RESEARCH DESIGN AND METHODS: Observational prospective study. 273 patients from two different populations (with and without PAD - classified according to the presence of distal pulses) treated over a 14-month period in the multidisciplinary Diabetic Foot Unit were included. The data on patient characteristics and outcomes were analysed for the purpose of comparison. For the inference study, a comparison of medians with the non-parametric test for independent samples for the quantitative variables and a χ2 test for the comparison of proportions in qualitative variables were performed. RESULTS: Patients with PAD ulcers were older (60 (54-67) vs. 64 (75-81), p=0.000) and had a higher macrovascular burden (8.1% vs. 29% for ischaemic heart disease history, p=0.000; 6.7% vs. 18.1% for cerebrovascular disease history, p=0.004). Their Texas Score was higher (p=0.000) and their major amputation rate was higher (1.4% vs. 12.3%, p=0.001). They had less background of previous ulcers (52.6% vs. 26.8%, p=0.000), their episode duration was shorter (4 (0-10) vs. 0 (0-3) weeks, p=0.000), and their proportional need for antibiotic therapy was lower (64.4% vs. 51.4%, p=0.03). CONCLUSIONS: The differences found between ulcers with and without vascular involvement support the need for a different approach and for the inclusion of vascular surgeons on the team. The multidisciplinary care model for diabetic foot patients could be effective and improve health outcomes.

Profiling TREM2 expression in amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVES: There is growing evidence of the contribution of neuroinflammation, and in particular microglia, in the pathogenesis of amyotrophic lateral sclerosis (ALS). TREM2 gene plays a crucial role in shaping microglia in neurodegenerative conditions. To deepen the understanding of TREM2 in ALS and investigate the performance of TREM2 as a biomarker, we profiled TREM2 expression levels in spinal cord, cerebrospinal fluid and blood of patients with sporadic ALS. We also wanted to investigate whether the combined measurement of sTREM2 in fluids could improve the diagnostic yield of total and phosphorylated TDP-43 levels. METHODS: We performed a case-control study to profile overall and transcript-specific TREM2 mRNA levels by RT-qPCR and protein expression levels by Western-blot in postmortem specimens of spinal cord from ALS patients and controls. In parallel, we measured soluble TREM2 (sTREM2) protein levels and full length and phosphorylated TDP-43 (tTDP-43 and pTDP-43) by ELISA in CSF and serum from ALS patients vs healthy controls. Patients were prospectively recruited from an ALS unit of a tertiary hospital and fulfilled El Escorial revised criteria. After bivariate analysis, a logistic regression model was developed to identify adjusted estimates of the association of sTREM2 levels in CSF and serum with ALS status. RESULTS: Overall and transcript-specific TREM2 mRNA were upregulated in the spinal cord of ALS patients (n = 21) compared to controls (n = 19). Similar changes were observed in TREM2 protein levels (p < 0.01) in spinal cord of ALS patients vs healthy controls. We also detected significantly higher sTREM2 levels in CSF (p-value < 0.01) of ALS patients (n = 46) vs controls (n = 46) and serum (p-value < 0.001) of ALS patients (n = 100) vs controls (n = 100). In a logistic regression model, both CSF and serum sTREM2 remained independently associated with ALS status with OR = 3.41 (CI 95 %=1.34-8.66) (p-value < 0.05) and OR = 3.38 (CI 95 %: 1.86-6.16) (p-value < 0.001), respectively. We also observed that pTDP-43 levels in CSF is an independent predictor of ALS (p-value < 0.05). CONCLUSIONS: Our results support the role of TREM2 in ALS pathophysiology and demonstrates that the three TREM2 transcripts are deregulated in ALS in postmortem human specimens of spinal cord. We hypothesise about the possible influence of systemic-peripheral inflammation in the disease. Finally, we conclude that pTDP-43 levels in CSF could be a biomarker of ALS, and sTREM2 measurement in CSF and blood emerge as potential non-invasive biomarker in ALS.

Validation of the inverse method for the determination of the access flow with thermodilution.

INTRODUCTION: Thermodiluction is a widely used method for measuring vascular access flow (QA). Among the possibilities of TD, the reverse method (MI) can be beneficial in the execution time, without impact on the dialysis efficacy (Kt). However, it is not a sufficiently studied technique. METHOD: Transversal study of 117 arteriovenous fistulas (AVF). Two QA measurements were taken with the method described by the manufacturer (MR) and another with MI. MI is bases in the obtention of an inverted recirculation registry at the beginning of the session and a single subsequent recirculation measurement with the lines in normal position. In the concordance analysis, the Bland-Altman method and Cohen's Kappa index were used. RESULTS: Very good concordance between MR and MI was evidenced for QA below 700 ml/min, but it worsens as flow increases. The median variability between the MR measurements (intra-method variability) was 3.4% (-17.13). This value did not differ from the median variability generated between MR and MI (inter-method variability), which was 2% (-14, 12) (P = 0.287). The degree of agreement between the two to identify AVFs susceptible to intervention was very good (K = 0.834). The time spent using the MI was significantly shorter (P = 0.000) without evidence of variations in the Kt of the measurement sessions (P = 0.201). CONCLUSIONS: The thermodiluction MI is valid to determine the flow of the vascular access, especially in Qa lower than 700 ml/min, with great time savings, simplification of the procedure and without modifying the dialysis efficiency. The variability between the measurement by MR and MI is similar to that of MR. The concordance between methods in identifying potentially pathological AVFs is very good.

Validación del método inverso para la determinación del flujo de acceso con termodilución / Validation of the inverse method for the determination of the access flow with thermodilution

Introducción: La termodilución es un método ampliamente usado para la medición del flujo de acceso vascular (QA). Entre las posibilidades de la termodilución, el método inverso (MI) puede ser beneficioso en el tiempo de ejecución, sin repercusión en la eficacia dialítica (Kt). Sin embargo, no es una técnica lo suficientemente estudiada.MétodoEstudio transversal sobre 117 fístulas arteriovenosas. Se realizaron 2 mediciones de QA con el método descrito por el fabricante (MR) y otra con MI. El MI se basa en la obtención del registro de recirculación invertida al iniciar la sesión y una única medición posterior de recirculación con las líneas en posición normal. En el análisis de concordancia se utilizó el método Bland-Altman y el índice kappa de Cohen.ResultadosSe evidenció muy buena concordancia entre MR y MI para QA inferiores a 700ml/min, pero empeora a medida que aumenta el flujo. La variabilidad mediana entre las mediciones con MR (variabilidad intramétodo) fue del 3,4% (−17,13). Este valor no difirió de la variabilidad mediana generada entre MR y MI (variabilidad intermétodo), que fue del 2% (−14,12) (p=0,287). El grado de acuerdo entre ambos para identificar fístulas arteriovenosas susceptibles de intervención fue muy bueno (kappa=0,834). El tiempo empleado utilizando el MI fue significativamente menor (p=0,000), sin evidenciarse variaciones en el Kt de las sesiones de medida (p=0,201).ConclusionesEl MI de termodilución es válido para determinar el flujo del acceso vascular, especialmente en QA inferiores a 700ml/min, con gran ahorro de tiempo, simplificación del procedimiento y sin modificar la eficacia de diálisis. La variabilidad entre la medición por MR y MI es similar a la propia del MR. La concordancia entre métodos a la hora de identificar fístulas arteriovenosas potencialmente patológicas es muy buena. (AU)

Introduction: Thermodilution is a widely used method for measuring vascular access flow (QA). Among the possibilities of thermodilution, the reverse method (RM) can be beneficial in the execution time, without impact on the dialysis efficacy (Kt). However, it is not a sufficiently studied technique.MethodTransversal study of 117 arteriovenous fistulas. Two QA measurements were taken with the method described by the manufacturer (MR) and another with RM. RM is based on the obtention of an inverted recirculation registry at the beginning of the session and a single subsequent recirculation measurement with the lines in normal position. In the concordance analysis, the Bland-Altman method and Cohen's Kappa index were used.ResultsVery good concordance between MR and RM was evidenced for QA below 700ml/min, but it worsens as flow increases. The median variability between the MR measurements (intra-method variability) was 3.4% (−17.13). This value did not differ from the median variability generated between MR and RM (inter-method variability), which was 2% (−14,12) (P=.287). The degree of agreement between the 2 to identify arteriovenous fistulas susceptible to intervention was very good (Kappa=0.834). The time spent using the RM was significantly shorter (P=.000) without evidence of variations in the Kt of the measurement sessions (P=.201).ConclusionsThe thermodilution RM is valid to determine the flow of the vascular access, especially in QA lower than 700ml/min, with great time savings, simplification of the procedure and without modifying the dialysis efficiency. The variability between the measurement by MR and RM is similar to that of MR. The concordance between methods in identifying potentially pathological arteriovenous fistulas is very good. (AU)

Validation of the inverse method for the determination of the access flow with thermodilution. / Validación del método inverso para la determinación del flujo de acceso con termodilución.

INTRODUCTION: Thermodilution is a widely used method for measuring vascular access flow (QA). Among the possibilities of thermodilution, the reverse method (RM) can be beneficial in the execution time, without impact on the dialysis efficacy (Kt). However, it is not a sufficiently studied technique. METHOD: Transversal study of 117 arteriovenous fistulas. Two QA measurements were taken with the method described by the manufacturer (MR) and another with RM. RM is based on the obtention of an inverted recirculation registry at the beginning of the session and a single subsequent recirculation measurement with the lines in normal position. In the concordance analysis, the Bland-Altman method and Cohen's Kappa index were used. RESULTS: Very good concordance between MR and RM was evidenced for QA below 700ml/min, but it worsens as flow increases. The median variability between the MR measurements (intra-method variability) was 3.4% (-17.13). This value did not differ from the median variability generated between MR and RM (inter-method variability), which was 2% (-14,12) (P=.287). The degree of agreement between the 2 to identify arteriovenous fistulas susceptible to intervention was very good (Kappa=0.834). The time spent using the RM was significantly shorter (P=.000) without evidence of variations in the Kt of the measurement sessions (P=.201). CONCLUSIONS: The thermodilution RM is valid to determine the flow of the vascular access, especially in QA lower than 700ml/min, with great time savings, simplification of the procedure and without modifying the dialysis efficiency. The variability between the measurement by MR and RM is similar to that of MR. The concordance between methods in identifying potentially pathological arteriovenous fistulas is very good.

Characterization of the perioperative changes of exosomal immune-related cytokines induced by prostatectomy in early-stage prostate cancer patients.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) are relevant in prostate cancer microenvironment collaborating in tumor development. The main tumor marker used in this disease, prostate-specific antigen (PSA), does not provide information related to this tumor microenvironment. Cancer cells secrete exosomes carrying bioactive molecules contributing to MDSCs recruitment and induction. The aim of this study was to characterize the perioperative changes of exosomal cytokines relevant in MDSCs recruitment induced by prostatectomy in prostate cancer patients. METHODS: Blood was drawn from 26 early-stage prostate cancer patients before and after radical prostatectomy and from 16 healthy volunteers. Serum exosomes were separated by precipitation. Cytokines related with MDSC cell recruitment and activation CCL2, CXCL2, CXCL5, CXCL8, CXCL12, MIF, S100A9 and TGF-ß were measured in serum and serum-derived exosomes using immunometric assays. RESULTS: All cytokines were detected both in serum and exosomes, except for CXCL12, which was detected only in serum. Exosomes were enriched specially in MIF, TGF-ß and CXCL2. Presurgical MIF levels in exosomes correlated negatively with serum PSA. Also, presurgical TGF-ß decreased both in serum and exosomes as Gleason score rises. Patients presurgical exosomes had increased CCL2, CXCL5 and TGF-ß levels than exosomes from healthy controls. These differences were not observed when cytokines were analyzed in serum, except for TGF-ß. Cytokine levels of CCL2, CXCL5 decreased in patients' postsurgical exosomes, while TGF-ß further increased. On the contrary, S100A9 levels were lower in patients presurgical exosomes but increased after radical prostatectomy. CONCLUSIONS: Blood exosomal content in cytokines constitute an attractive source to evaluate MDSCs immunomodulators providing additional information related to tumor microenvironment in prostate cancer.

Performance comparison of two next-generation sequencing panels to detect actionable mutations in cell-free DNA in cancer patients.

Background Genomic alterations studies in cell-free DNA (cfDNA) have increasing clinical use in oncology. Next-generation sequencing (NGS) technology provides the most complete mutational analysis, but nowadays limited data are available related to the comparison of results reported by different platforms. Here we compare two NGS panels for cfDNA: Oncomine™ Pan-Cancer Cell-Free Assay (Thermo Fisher Scientific), suitable for clinical laboratories, and Guardant360® (GuardantHealth), with more genes targeted but only available in an outsourcing laboratory. Methods Peripheral blood was obtained from 16 advanced cancer patients in which Guardant360® (G360) was requested as part of their clinical assistance. Blood samples were sent to be analyzed with G360 panel, and an additional blood sample was drawn to obtain and analyze cfDNA with Oncomine™ Pan-Cancer (OM) panel in an Ion GeneStudio S5™ System. Results cfDNA analysis globally rendered 101 mutations. Regarding the 55/101 mutations claimed to be included by manufacturers in both panels, 17 mutations were reported only by G360, 10 only by OM and 28 by both. In those coincident cases, there was a high correlation between the variant allele fractions (VAFs) calculated with each panel (r = 0.979, p < 0.01). Regarding the six actionable mutations with an FDA-approved therapy reported by G360, one was missed with OM. Also, 12 mutations with clinical trials available were reported by G360 but not by OM. Conclusions In summary, G360 and OM can produce different mutational profile in the same sample, even in genes included in both panels, which is especially important if these mutations are potentially druggable.

Interaction of Phenyl-Substituted Diazaperylenium with Cucurbit[n]uril: Complex versus Supramolecular Polymer.

A phenyl-substituted diazaperylenediium dication (DAP) was synthesized that shows concentration-dependent aggregation in water. The host-guest complexation of DAP was studied with the macrocyclic host cucurbit[n]uril (n = 7, 8) in water. With CB[7], it forms a 1:2 complex by placing two aryl substituents inside the CB[7]; whereas, with CB[8], a supramolecular polymer is formed. The resulting complex and supramolecular polymer have been characterized by ITC (isothermal titration calorimetry), ESI-MS (electrospray ionization mass spectrometry), 1H NMR (proton nuclear magnetic resonance), 2D NOESY (two-dimensional nuclear Overhauser enhancement spectroscopy), and DOSY (diffusion-ordered spectroscopy) spectra.

Utility of recombinant human TSH stimulation test in the follow-up of patients with differentiated thyroid cancer depending on basal thyroglobulin results.

Background: Thyroglobulin (Tg) is fundamental for differentiated thyroid cancer (DTC) monitoring. Tg detection can be enhanced using recombinant human thyroid-stimulating hormone (TSH) (rhTSH). This study is aimed to evaluate the use of the rhTSH stimulation test when using a high-sensitivity Tg assay. Methods: We retrospectively studied 181 rhTSH tests from 114 patients with DTC and negative for antithyroglobulin antibodies (anti-TgAb). Image studies were performed in all cases. Serum Tg and anti-TgAb were measured using specific immunoassays. Results: rhTSH stimulation in patients with basal serum Tg (b-Tg) concentrations lower than 0.2 ng/mL always resulted in rhTSH-stimulated serum Tg (s-Tg) concentrations lower than 1.0 ng/mL and negative structural disease. In patients with b-Tg concentration between 0.2 and 1.0 ng/mL, s-Tg detected one patient (1/30) who showed biochemical incomplete response. Patients with negative images had lower s-Tg than those with nonspecific or abnormal findings (p<0.05). Receiver operating characteristic curve analysis of the s-Tg to detect altered images showed an area under the curve of 0.763 (p<0.05). With an s-Tg cutoff of 0.85 ng/mL, the sensitivity was 100%, decreasing to 96.15% with an s-Tg cutoff of 2 ng/mL. Conclusions: Patients with DTC with b-Tg concentrations equal or higher than 0.2 ng/mL can benefit from the rhTSH stimulation test.

Comparison of six commercial serum exosome isolation methods suitable for clinical laboratories. Effect in cytokine analysis.

Background Exosomes are nanovesicles released by cells that can be detected in blood. Exosomes contain several molecules, such as cytokines that have potential utility as disease biomarkers. The aim of the present work is to compare six different commercial kits suitable for the clinical laboratory in relation to the efficiency and purity of exosome isolation, and their effect in subsequent cytokines analysis. Methods Serum exosomes were obtained from 10 volunteers using six commercial kits: exoEasy, ExoQuick, Exo-spin, ME kit, ExoQuick Plus and Exo-Flow. Exosome concentrations and size distributions were quantified by nanoparticle tracking analysis. Exosome markers CD63, CD9 and TSG101 were determined by Western blot. ApoB and albumin were measured using nephelometry. S100A9, CXCL5 and CXCL12 were measured using a Luminex assay. Results The concentration of particles obtained between different kits varied by a factor of 100. There was no correlation in particle concentrations extracted between different kits, except between ExoQuick and Exo-Flow. The highest exosome purity was achieved with ExoQuick Plus and exoEasy, while the lowest were achieved with ME and ExoQuick. Albumin was present in all exosome extracts analyzed and ApoB in all except those extracted with Exo-Flow and ME. Cytokine detection varied depending on the purification kit used and there was no correlation in cytokine concentrations between samples obtained with different kits. Conclusions Both the sample and the type of commercial kit used affect the efficiency and purity of exosome isolation. In addition, the exosome purification method deeply affects the capability to detect and quantify cytokines.

The Dynamic Use of EGFR Mutation Analysis in Cell-Free DNA as a Follow-Up Biomarker during Different Treatment Lines in Non-Small-Cell Lung Cancer Patients.

Epidermal growth factor receptor (EGFR) mutational testing in advanced non-small-cell lung cancer (NSCLC) is usually performed in tumor tissue, although cfDNA (cell-free DNA) could be an alternative. We evaluated EGFR mutations in cfDNA as a complementary tool in patients, who had already known EGFR mutations in tumor tissue and were treated with either EGFR-tyrosine kinase inhibitors (TKIs) or chemotherapy. We obtained plasma samples from 21 advanced NSCLC patients with known EGFR tumor mutations, before and during therapy with EGFR-TKIs and/or chemotherapy. cfDNA was isolated and EGFR mutations were analyzed with the multiple targeted cobas EGFR Mutation Test v2. EGFR mutations were detected at baseline in cfDNA from 57% of patients. The semiquantitative index (SQI) significantly decreased from the baseline (median = 11, IQR = 9.5-13) to the best response (median = 0, IQR = 0-0, p < 0.01), followed by a significant increase at progression (median = 11, IQR = 11-15, p < 0.01) in patients treated with either EGFR-TKIs or chemotherapy. The SQI obtained with the cobas EGFR Mutation Test v2 did not correlate with the concentration in copies/mL determined by droplet digital PCR. Resistance mutation p.T790M was observed at progression in patients with either type of treatment. In conclusion, cfDNA multiple targeted EGFR mutation analysis is useful for treatment monitoring in tissue of EGFR-positive NSCLC patients independently of the drug received.

Paraparesia secundaria a metástasis vertebral como manifestación inicial de un carcinoma de pulmón: reporte de caso y revisión bibliográfica / Secondary paraparesia to vertebral metastasis as an initial manifestationof a lung carcinoma: case report and bibliographical review

Introducción: Las metástasis de la columna vertebral son la manifestación de una neoplasia sistémica. Se evidencia que la prevalencia de los tumores metastásicos de la columna es alta, siendo estos 40 veces más frecuentes que todos los tumores primarios óseos combinados. La historia natural de la columna vertebral metastásica es la compresión parcial o total de la médula espinal o de las raíces nerviosas conociéndose esto como síndrome de compresión medular. Un tercio de los casos que presentan este síndrome son la primera manifestación del tumor, especialmente en el cáncer de pulmón, con tendencia a metastatizar en un 13%. Caso Clínico: Se presenta el caso de un paciente masculino de 40 años de edad, sin antecedentes de interés, quien es ingre-sado por paraparesia asociada a incontinencia urinaria y fecal; dos días después del ingreso se le realizó una resonancia magnética con gadolinio la cual reportó lesión a nivel de T3 que comprimía y ensanchaba la vértebra por lo que se le diagnóstico síndrome de compresión medular. Se le realizó una laminectomia descompresiva y biopsia dando ésta el diagnóstico de carcinoma metastásico en columna vertebral, de probable origen pulmonar según estudio inmunohistoquímico. Conclusiones: El diagnóstico y tratamiento oportuno es fundamental para revertir la evolución natural de esta enfermedad, instaurándose el tratamiento dentro de las primeras 12 a 24 h evitando así una discapacidad neurológica signiicativa...(AU)

Liquid Biopsy: From Basic Research to Clinical Practice.

Liquid biopsy refers to the molecular analysis in biological fluids of nucleic acids, subcellular structures, especially exosomes, and, in the context of cancer, circulating tumor cells. In the last 10 years, there has been an intensive research in liquid biopsy to achieve a less invasive and more precise personalized medicine. Molecular assessment of these circulating biomarkers can complement or even surrogate tissue biopsy. Because of this research, liquid biopsy has been introduced in clinical practice, especially in oncology, prenatal screening, and transplantation. Here we review the biology, methodological approaches, and clinical applications of the main biomarkers involved in liquid biopsy.

Miastenia gravis: presentación de un caso enmascarado por proceso respiratorio agudo / Miastenia gravis: presentación of a case masked by acute respiratory

Describimos el caso clínico de paciente femenino de 21 años de edad quien presenta inicialmente síntomas de disartria, ptosis palpebral, disfagia y diplopía. Dos meses después el paciente presenta cuadro respiratorio infeccioso agudo, que se acompaña de insufiencia respiratoria lo cual motiva a que la paciente ingrese a la Unidad de Cuidados Intensivos del Hospital Regional "Teodoro Maldonado Carbo" mejorando su cuadro infeccioso y debido a las manifestaciones previas obligó una mejor investigación y su posterior diagnóstico...