Specific-cytokine associations with outcomes in knee osteoarthritis subgroups: breaking down disease heterogeneity with phenotyping.

BACKGROUND: Despite existing extensive literature, a comprehensive and clinically relevant classification system for osteoarthritis (OA) has yet to be established. In this study, we aimed to further characterize four knee OA (KOA) inflammatory phenotypes (KOIP) recently proposed by our group, by identifying the inflammatory factors associated with KOA severity and progression in a phenotype-specific manner. METHODS: We performed an analysis within each of the previously defined four KOIP groups, to assess the association between KOA severity and progression and a panel of 13 cytokines evaluated in the plasma and synovial fluid of our cohort's patients. The cohort included 168 symptomatic female KOA patients with persistent joint effusion. RESULTS: Overall, our analyses showed that associations with KOA outcomes were of higher magnitude within the KOIP groups than for the overall patient series (all p-values < 1.30e-16) and that several of the cytokines showed a KOIP-specific behaviour regarding their associations with KOA outcomes. CONCLUSION: Our study adds further evidence supporting KOA as a multifaceted syndrome composed of multiple phenotypes with differing pathophysiological pathways, providing an explanation for inconsistencies between previous studies focussed on the role of cytokines in OA and the lack of translational results to date. Our findings also highlight the potential clinical benefits of accurately phenotyping KOA patients, including improved patient stratification, tailored therapies, and the discovery of novel treatments.

THC exposure during adolescence increases impulsivity-like behavior in adulthood in a WIN 55,212-2 self-administration mouse model.

Background: Cannabis addiction is a chronically relapsing disorder lacking effective treatment. Regular cannabis consumption typically begins during adolescence, and this early cannabinoid exposure may increase the risk for drug addiction in adulthood. Objective: This study investigates the development of cannabis addiction-like behavior in adult mice after adolescent exposure to the main psychoactive component of cannabis, Δ9-tetrahydrocannabinol (THC). Methods: Adolescent male mice were exposed to 5 mg/kg of THC from postnatal days 37 to 57. Operant self-administration sessions of WIN 55,212-2 (12.5 µg/kg/infusion) were conducted for 10 days. Mice were tested for three addiction-like criteria (persistence of response, motivation, and compulsivity), two parameters related to craving (resistance to extinction and drug-seeking behavior), and two phenotypic vulnerability traits related to substance use disorders (impulsivity and reward sensitivity). Additionally, qPCR assays were performed to detect differentially expressed genes in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum, and hippocampus (HPC) of "addicted" and "non-addicted" mice. Results: Adolescent THC exposure did not modify WIN 55,212-2 reinforcement nor the development of cannabis addiction-like behavior. Inversely, THC pre-exposed mice displayed impulsive-like behavior in adulthood, which was more pronounced in mice that developed the addiction-like criteria. Moreover, downregulated drd2 and adora2a gene expression in NAc and HPC was revealed in THC pre-exposed mice, as well as a downregulation of drd2 expression in mPFC of vehicle pre-treated mice that developed addiction-like behaviors. Discussion: These findings suggest that adolescent THC exposure may promote impulsivity-like behavior in adulthood, associated with downregulated drd2 and adora2a expression in NAc and HPC.

A male mouse model of WIN 55,212-2 self-administration to study cannabinoid addiction.

We have established for the first time a mouse model of cannabinoid addiction using WIN 55,212-2 intravenous self-administration (0.0125 mg/kg/infusion) in C57Bl/6J mice. This model allows to evaluate the addiction criteria by grouping them into 1) persistence of response during a period of non-availability of the drug, 2) motivation for WIN 55,212-2 with a progressive ratio, and 3) compulsivity when the reward is associated with a punishment such as an electric foot-shock, in agreement with the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5). This model also allows to measure two parameters that have been related with the DSM-5 diagnostic criteria of craving, resistance to extinction and reinstatement, and two phenotypic traits suggested as predisposing factors, impulsivity and sensitivity to reward. We found that 35.6% of mice developed the criteria of cannabinoid addiction, allowing to differentiate between resilient and vulnerable mice. Therefore, we have established a novel and reliable model to study the neurobiological correlates underlying the resilience or vulnerability to develop cannabinoid addiction. This model included the chemogenetic inhibition of neuronal activity in the medial prefrontal cortex to the nucleus accumbens pathway to assess the neurobiological substrate of cannabinoid addiction. This model will shed light on the neurobiological substrate underlying cannabinoid addiction.

Hallazgo casual de un paraganglioma paraaórtico / An incidentally discovered paraaortic paraganglioma

Introducción: los paragangliomas son tumores neuroendocrinos derivados de células cromafi nes. Son entidadesmuy infrecuentes que se localizan típicamente en el cuello o en la base del cráneo. presentamos el caso de unparaganglioma paraaórtico, una ubicación inusual que cuenta con escasos reportes en la literatura. Caso clínico: mujer de 78 años que presenta una masa retroperitoneal hallada de forma casual durante el estudiopreoperatorio de una neoplasia ginecológica. ante la sospecha de un tumor del estroma gastrointestinal o unschawnnoma retroperitoneal, se indica su extirpación quirúrgica. Durante la operación se objetiva una masa muyvascularizada adherida a la cara anterior de la aorta, cuya resección provoca en la paciente un cuadro de crisishipertensiva y taquicardia asociadas a inestabilidad hemodinámica, que cede tras completar su exéresis. el estudioanatomopatológico posterior confi rma la sospecha diagnóstica intraoperatoria de paraganglioma paraaórtico. Discusión: los paragangliomas localizados en el abdomen suelen ser productores de catecolaminas y puedendesarrollar clínica adrenérgica de forma espontánea o inducida por fármacos, ejercicio o manipulación quirúrgica,como sucedió en nuestro caso. Un diagnóstico certero es clave para planificar un tratamiento adecuado quepermita reducir las posibles complicaciones en este tipo de pacientes.(AU)

Introduction: paragangliomas are neuroendocrine tumours derived from chromaffin cells. they are very rareentities that are typically located in the neck or at the base of the skull. We present the case of a para-aortic para-ganglioma, an unusual location that has few reports in the literature. Case report: a 78-year-old woman with a retroperitoneal mass found incidentally during the preoperative study fora gynecological neoplasm. Given the suspicion of a gastrointestinal stromal tumour or a retroperitoneal schawn-noma, surgical removal of it was indicated. Intraoperatively, a highly vascularized mass adhered to the anteriorface of the aorta was observed, whose resection caused a hypertensive crisis and tachycardia associated withhemodynamic instability, which subsided after completing the exeresis. the subsequent anatomopathologicalstudy confirmed the intraoperative diagnostic suspicion of paraaortic paraganglioma. Discussion: paragangliomas located in the abdomen are usually catecholamine producers and can develop adr-energic symptoms spontaneously or induced by drugs, exercise, or surgical manipulation, as occurred in our case.an accurate diagnosis is the key to planning an appropriate treatment that allows reducing possible complicationsin this type of patient.(au)

Metabolic and inflammatory profiles define phenotypes with clinical relevance in female knee osteoarthritis patients with joint effusion.

OBJECTIVES: Osteoarthritis has been the subject of abundant research in the last years with limited translation to the clinical practice, probably due to the disease's high heterogeneity. In this study, we aimed to identify different phenotypes in knee osteoarthritis (KOA) patients with joint effusion based on their metabolic and inflammatory profiles. METHODS: A non-supervised strategy based on statistical and machine learning methods was applied to 45 parameters measured on 168 female KOA patients with persistent joint effusion, consecutively recruited at our hospital after a monographic OA outpatient visit. Data comprised anthropometric and metabolic factors and a panel of systemic and local inflammatory markers. The resulting clusters were compared regarding their clinical, radiographic and ultrasound severity at baseline and their radiographic progression at two years. RESULTS: Our analyses identified four KOA inflammatory phenotypes (KOIP): a group characterized by metabolic syndrome, probably driven by body fat and obesity, and by high local and systemic inflammation (KOIP-1); a metabolically healthy phenotype with mild overall inflammation (KOIP-2); a non-metabolic phenotype with high inflammation levels (KOIP-3); and a metabolic phenotype with low inflammation and cardiovascular risk factors not associated with obesity (KOIP-4). Of interest, these groups exhibited differences regarding pain, functional disability and radiographic progression, pointing to a clinical relevance of the uncovered phenotypes. CONCLUSION: Our results support the existence of different KOA phenotypes with clinical relevance and differing pathways regarding their pathophysiology and disease evolution, which entails implications in patients' stratification, treatment tailoring and the search of novel and personalized therapies.

Evaluation of Non-Contact Device to Measure Body Temperature in Sheep.

Non-contact devices have been used in the measurement of body temperature in livestock production as a tool for testing disease in different species. However, there are few studies about the variation and correlations in body temperature between rectal temperature (RT) and non-contact devices such as non-contact infrared thermometers (NCIT) and thermal imaging/infrared thermography (IRT). The objective of this work was to evaluate the accuracy of non-contact devices to measure the body temperature in sheep, considering six body regions and the possibility of implementing these systems in herd management. The experiment was carried out at the experimental farm of the Catholic University of Valencia, located in the municipality of Massanassa in July of 2021, with 72 dry manchega ewes, and we compared the rectal temperature with two types of non-contact infrared devices for the assessment of body temperature in healthy sheep. Except for the temperature taken by NCIT at the muzzle, the correlation between RT vs. NCIT or IRT showed a low significance or was difficult to use for practical flock management purposes. In addition, the variability between devices was high, which implies that measurements should be interpreted with caution in warm climates and open pens, such as most sheep farms in the Spanish Mediterranean area. The use of infrared cameras devices to assess body temperature may have a promising future, but in order to be widely applied as a routine management method on farms, the system needs to become cheaper, simpler in terms of measurements and quicker in terms of analyzing results.

Remdesivir in Very Old Patients (≥80 Years) Hospitalized with COVID-19: Real World Data from the SEMI-COVID-19 Registry.

(1) Background: Large cohort studies of patients with COVID-19 treated with remdesivir have reported improved clinical outcomes, but data on older patients are scarce. Objective: This work aims to assess the potential benefit of remdesivir in unvaccinated very old patients hospitalized with COVID-19; (2) Methods: This is a retrospective analysis of patients ≥ 80 years hospitalized in Spain between 15 July and 31 December 2020 (SEMI-COVID-19 Registry). Differences in 30-day all-cause mortality were adjusted using a multivariable regression analysis. (3) Results: Of the 4331 patients admitted, 1312 (30.3%) were ≥80 years. Very old patients treated with remdesivir (n: 140, 10.7%) had a lower mortality rate than those not treated with remdesivir (OR (95% CI): 0.45 (0.29−0.69)). After multivariable adjustment by age, sex, and variables associated with lower mortality (place of COVID-19 acquisition; degree of dependence; comorbidities; dementia; duration of symptoms; admission qSOFA; chest X-ray; D-dimer; and treatment with corticosteroids, tocilizumab, beta-lactams, macrolides, and high-flow nasal canula oxygen), the use of remdesivir remained associated with a lower 30-day all-cause mortality rate (adjusted OR (95% CI): 0.40 (0.22−0.61) (p < 0.001)). (4) Conclusions: Remdesivir may reduce mortality in very old patients hospitalized with COVID-19.

Biomarker candidates for progression and clinical management of COVID-19 associated pneumonia at time of admission.

COVID-19 pathophysiology is currently not fully understood, reliable prognostic factors remain elusive, and few specific therapeutic strategies have been proposed. In this scenario, availability of biomarkers is a priority. MS-based Proteomics techniques were used to profile the proteome of 81 plasma samples extracted in four consecutive days from 23 hospitalized COVID-19 associated pneumonia patients. Samples from 10 subjects that reached a critical condition during their hospital stay and 10 matched non-severe controls were drawn before the administration of any COVID-19 specific treatment and used to identify potential biomarkers of COVID-19 prognosis. Additionally, we compared the proteome of five patients before and after glucocorticoids and tocilizumab treatment, to assess the changes induced by the therapy on our selected candidates. Forty-two proteins were differentially expressed between patients' evolution groups at 10% FDR. Twelve proteins showed lower levels in critical patients (fold-changes 1.20-3.58), of which OAS3 and COG5 found their expression increased after COVID-19 specific therapy. Most of the 30 proteins over-expressed in critical patients (fold-changes 1.17-4.43) were linked to inflammation, coagulation, lipids metabolism, complement or immunoglobulins, and a third of them decreased their expression after treatment. We propose a set of candidate proteins for biomarkers of COVID-19 prognosis at the time of hospital admission. The study design employed is distinctive from previous works and aimed to optimize the chances of the candidates to be validated in confirmatory studies and, eventually, to play a useful role in the clinical practice.

Psicodramatista en formación en su devenir quirón: sanadora herida / Psicodramatista em treinamento tornando-se um quíron: curandeiro ferido / Psychodramatist in training in her path of becoming a chiron: wounded healer

RESUMEN El tema del trabajo es la dinámica del proceso de transformación de una psicodramatista en formación, sus dificultades y los recursos puestos en juego para sortearlas. Desde el marco epistemológico y metodológico del enfoque clínico se diseñó un estudio de caso que involucra el análisis inductivo sobre 10 encuentros psicodramáticos coordinados por ella y una compañera, las 9 resonancias escritas por la propia psicodramatista en formación luego de cada encuentro, 10 supervisiones posteriores a cada encuentro y 3 entrevistas en profundidad. La teoría Jungiana sirve como base para la interpretación de la dinámica del proceso, permitiendo analizar el recorrido de la psicodramatista a través de la activación de ciertos arquetipos, su simbolización y su progresiva integración.

RESUMO O tema do trabalho é a dinâmica do processo de transformação de uma psicodramatista em formação, suas dificuldades e os recursos empregados para superá-las. A partir do referencial epistemológico e metodológico da abordagem clínica foi desenhado um estudo de caso que envolve a análise indutiva de 10 encontros psicodramáticos coordenados por ela e um parceiro, as 9 ressonâncias escritas pela própria psicodramatista em treinamento após cada encontro, 10 supervisões após cada reunião e 3 entrevistas em profundidade. A teoria junguiana serve de base para a interpretação da dinâmica do processo, permitindo analisar a trajetória do psicodramatista por meio da ativação de certos arquétipos, sua simbolização e sua integração progressiva.

ABSTRACT The subject of the work is the dynamics of the transformation process of a psychodramatist in training, her difficulties and the resources put into play to overcome them. From the epistemological and methodological framework of the clinical approach a case study was designed that involves the inductive analysis of 10 psychodramatic encounters coordinated by her and a partner, the 9 diary entries written by the psychodramatist herself in training after each encounter, 10 supervisions after each meeting and 3 in-depth interviews. Jungian theory serves as the basis for the interpretation of the dynamics of the process, allowing to analyze the path of the psychodramatist through the activation of certain archetypes, their symbolization and their progressive integration.

Neumonía en pacientes con demencia avanzada: enfoque terapéutico adoptado en un servicio de medicina interna de un hospital de media y larga estancia / Pneumonia in patients with advanced dementia: therapeutic approach adopted in an internal medicine service at a medium-to-long stay hospital

Introducción: La demencia es una enfermedad prevalente en las sociedades desarrolladas. La neumonía es la principal causa de muerte de los pacientes con demencia avanzada (DA). Numerosos expertos son partidarios de la adopción de un enfoque paliativo en estos enfermos. Objetivo: Conocer el tratamiento dispensado a pacientes con DA ingresados por neumonía en el Servicio de Medicina Interna de nuestro hospital. Metodología: Estudio retrospectivo con análisis de historias clínicas de 149 pacientes con DA que ingresan en nuestro servicio con neumonía del 1 de marzo de 2013 al 1 de junio de 2018. Resultados: Se incluyeron 149 sujetos. 147 (98 %) recibieron antibióticos i.v. 137 (91 %) sueroterapia i.v. Se realizaron 2,95 extracciones de sangre venosa por persona. A 22 (14 %) se les realizó al menos una gasometría arterial. 116 (77,8 %) portaron sonda urinaria. Se registraron 1,6 cambios de vía por persona. Se realizaron 10 sondajes nasogástricos (6,7). 64 fallecieron durante el ingreso (42,9 %). 35 (53,5 %) de ellos lo hicieron mientras recibían tratamientos encaminados a su curación. En tres la actitud fue puramente paliativa desde el principio. En 26 (40,6 %) la media de días que pasaron desde el primer día hasta la adopción de una estrategia puramente paliativa fue 13,3. De los 29 que fallecieron habiéndose adoptado dicho enfoque, 24 fueron sedados y fallecieron al cabo de 37,7 horas de media. En las últimas 48 horas de vida, 52 (81,2 %) presentaron síntomas y se realizaron numerosas pruebas o intervenciones. Conclusión: El enfoque terapéutico adoptado en nuestro servicio fue predominantemente curativo, medicalizado y alejado de una atención centrada en el paciente. (AU)

Introduction: Dementia is a prevalent disease in developed societies. Pneumonia is the leading cause of death in patients with advanced dementia (AD). Numerous experts are in favor of adopting a palliative approach in these patients. Objective: To analyze the treatment given to patients with AD admitted for pneumonia in the Internal Medicine Service of our hospital. Methodology: A retrospective study of the medical records of 149 patients with AD admitted for pneumonia in our service between 1/3/2013 and 1/6/2018. Results: A total of 149 patients were included; 147 (98 %) patients received intravenous antibiotics, 137 (91 %) received intravenous hydratation; 2.95 venous blood collections per person were performed; 22 (14 %) patients underwent at least one arterial gasometry; 116 (77.8 %) carried a urinary catheter; 1.6 changes of peripheral venous catheter were recorded per person; 10 (6.7 %) nasogastric tubes were placed; 64 (42.9 %) died during hospital stay; 35 (53.5 %) of them died while receiving treatments with curative intent. In 3 a purely palliative approach was selected from the beginning. In the remaining 26 patients the average number of days elapsed until a totally palliative approach was adopted was 13.3. Of the 29 patients who died with the latter approach, 24 were sedated and died after 37 hours on average. In the last 48 hours of life, 52 (81.2) presented symptoms and numerous tests or interventions were performed. Conclusion: The therapeutic approach adopted in our patients was predominantly curative, and still far removed from patient-centered care. (AU)

Inadequate use of antibiotics in the covid-19 era: effectiveness of antibiotic therapy.

BACKGROUND: Since December 2019, the COVID-19 pandemic has changed the concept of medicine. This work aims to analyze the use of antibiotics in patients admitted to the hospital due to SARS-CoV-2 infection. METHODS: This work analyzes the use and effectiveness of antibiotics in hospitalized patients with COVID-19 based on data from the SEMI-COVID-19 registry, an initiative to generate knowledge about this disease using data from electronic medical records. Our primary endpoint was all-cause in-hospital mortality according to antibiotic use. The secondary endpoint was the effect of macrolides on mortality. RESULTS: Of 13,932 patients, antibiotics were used in 12,238. The overall death rate was 20.7% and higher among those taking antibiotics (87.8%). Higher mortality was observed with use of all antibiotics (OR 1.40, 95% CI 1.21-1.62; p < .001) except macrolides, which had a higher survival rate (OR 0.70, 95% CI 0.64-0.76; p < .001). The decision to start antibiotics was influenced by presence of increased inflammatory markers and any kind of infiltrate on an x-ray. Patients receiving antibiotics required respiratory support and were transferred to intensive care units more often. CONCLUSIONS: Bacterial co-infection was uncommon among COVID-19 patients, yet use of antibiotics was high. There is insufficient evidence to support widespread use of empiric antibiotics in these patients. Most may not require empiric treatment and if they do, there is promising evidence regarding azithromycin as a potential COVID-19 treatment.

Risk Categories in COVID-19 Based on Degrees of Inflammation: Data on More Than 17,000 Patients from the Spanish SEMI-COVID-19 Registry.

(1) Background: The inflammation or cytokine storm that accompanies COVID-19 marks the prognosis. This study aimed to identify three risk categories based on inflammatory parameters on admission. (2) Methods: Retrospective cohort study of patients diagnosed with COVID-19, collected and followed-up from 1 March to 31 July 2020, from the nationwide Spanish SEMI-COVID-19 Registry. The three categories of low, intermediate, and high risk were determined by taking into consideration the terciles of the total lymphocyte count and the values of C-reactive protein, lactate dehydrogenase, ferritin, and D-dimer taken at the time of admission. (3) Results: A total of 17,122 patients were included in the study. The high-risk group was older (57.9 vs. 64.2 vs. 70.4 years; p < 0.001) and predominantly male (37.5% vs. 46.9% vs. 60.1%; p < 0.001). They had a higher degree of dependence in daily tasks prior to admission (moderate-severe dependency in 10.8% vs. 14.1% vs. 17%; p < 0.001), arterial hypertension (36.9% vs. 45.2% vs. 52.8%; p < 0.001), dyslipidemia (28.4% vs. 37% vs. 40.6%; p < 0.001), diabetes mellitus (11.9% vs. 17.1% vs. 20.5%; p < 0.001), ischemic heart disease (3.7% vs. 6.5% vs. 8.4%; p < 0.001), heart failure (3.4% vs. 5.2% vs. 7.6%; p < 0.001), liver disease (1.1% vs. 3% vs. 3.9%; p = 0.002), chronic renal failure (2.3% vs. 3.6% vs. 6.7%; p < 0.001), cancer (6.5% vs. 7.2% vs. 11.1%; p < 0.001), and chronic obstructive pulmonary disease (5.7% vs. 5.4% vs. 7.1%; p < 0.001). They presented more frequently with fever, dyspnea, and vomiting. These patients more frequently required high flow nasal cannula (3.1% vs. 4.4% vs. 9.7%; p < 0.001), non-invasive mechanical ventilation (0.9% vs. 3% vs. 6.3%; p < 0.001), invasive mechanical ventilation (0.6% vs. 2.7% vs. 8.7%; p < 0.001), and ICU admission (0.9% vs. 3.6% vs. 10.6%; p < 0.001), and had a higher percentage of in-hospital mortality (2.3% vs. 6.2% vs. 23.9%; p < 0.001). The three risk categories proved to be an independent risk factor in multivariate analyses. (4) Conclusion: The present study identifies three risk categories for the requirement of high flow nasal cannula, mechanical ventilation, ICU admission, and in-hospital mortality based on lymphopenia and inflammatory parameters.

Synovial fluid but not plasma interleukin-8 is associated with clinical severity and inflammatory markers in knee osteoarthritis women with joint effusion.

Several cytokines and adipokines are related to clinical severity and progression in knee osteoarthritis. The aim of this study was to evaluate the associations of IL-8 with clinical severity and with local and systemic adipokines and cytokines. This is a Cross-sectional study including 115 women with symptomatic primary knee osteoarthritis with ultrasound-confirmed joint effusion. Age, symptoms duration and body mass index were collected. Radiographic severity was evaluated according to Kellgren-Lawrence. Pain and disability were assessed by Lequesne and Knee injury and Osteoarthritis Outcome Score pain, symptoms and function scales. Three inflammatory markers and five adipokines were measured by ELISA in serum and synovial fluid. Partial correlation coefficient (PCC) and corresponding 95% confidence interval were used to evaluate association. Synovial fluid IL-8 was significantly associated with clinical severity scales. After controlling for potential confounders, associations measured by a Partial Correlation Coefficient (PCC) remained essentially unaltered for Lequesne (PCC = 0.237), KOOS pain (PCC = - 0.201) and KOOS symptoms (PCC = - 0.209), KOOS function (PCC = - 0.185), although the later did not reach statistical significance. Also in synovial fluid samples, associations were found between IL-8 and TNF (PCC = 0.334), IL6 (PCC = 0.461), osteopontin (PCC = 0.575), visfatin (PCC = 0.194) and resistin (PCC = 0.182), although significance was not achieved for the later after statistical control for confounders. None of these associations were detected in serum. In conclusion, IL-8 was associated with clinical severity, inflammatory markers and adipokines in synovial fluid, but not in blood. Although the reported associations are weak to moderate in magnitude, these findings reinforce the notion that local and not systemic inflammation is more relevant to clinical severity in knee OA women with joint effusion.

Derivación biliodigestiva guiada por ultrasonografía endoscópica en el paciente con adenocarcinoma de páncreas y obstrucción de la vía biliar estadio IV: reporte de caso / Biliodigestive shunt guided by endoscopic ultrasonography in patient with stage IV pancreatic adenocarcinoma and obstruction of the bile duct. A case report

Resumen La endosonografía endoscópica es una alternativa que sirve como guía para la realización de derivaciones biliodigestivas en los casos en los que la colangiopancreatografía retrógrada endoscópica (CPRE) ha fallado. Se han descrito técnicas como la coledocoduodenostomía o coledocoantrostomía guiadas por ultrasonografía endoscópica (USE). Se describe el caso de una paciente de 72 años con adenocarcinoma de páncreas, compromiso portal y de paredes duodenales, en quien se usó la CPRE para intentar una derivación paliativa y fue fallida, por lo cual se realizó la colocación de un stent metálico guiado por endosonografía endoscópica, con adecuada respuesta clínica al tratamiento. En conclusión, el procedimiento es seguro y la endosonografía es una vía alterna efectiva en los casos de CPRE fallidas para lograr derivaciones biliares en casos de obstrucción de la vía biliar de origen maligno.

Abstract Endoscopic endosonography is an alternative to guide biliodigestive shunting in cases where endoscopic retrograde cholangiopancreatography (ERCP) has failed. Techniques such as choledoduodenostomy or choledochoantrostomy guided by endoscopic ultrasonography have been described. This is the case of a 72-year-old patient with pancreatic adenocarcinoma, portal vein and duodenal wall involvement, in whom ERCP to try a palliative shunt failed. Therefore, a metal stent was placed using endoscopic endosonography, with adequate clinical response to the procedure and treatment. It is concluded that the procedure is safe and that endosonography is an effective alternative in cases of ERCP failure to achieve biliary bypass in cases of malignant biliary obstruction.

Severity Scores in COVID-19 Pneumonia: a Multicenter, Retrospective, Cohort Study.

BACKGROUND: Identification of patients on admission to hospital with coronavirus infectious disease 2019 (COVID-19) pneumonia who can develop poor outcomes has not yet been comprehensively assessed. OBJECTIVE: To compare severity scores used for community-acquired pneumonia to identify high-risk patients with COVID-19 pneumonia. DESIGN: PSI, CURB-65, qSOFA, and MuLBSTA, a new score for viral pneumonia, were calculated on admission to hospital to identify high-risk patients for in-hospital mortality, admission to an intensive care unit (ICU), or use of mechanical ventilation. Area under receiver operating characteristics curve (AUROC), sensitivity, and specificity for each score were determined and AUROC was compared among them. PARTICIPANTS: Patients with COVID-19 pneumonia included in the SEMI-COVID-19 Network. KEY RESULTS: We examined 10,238 patients with COVID-19. Mean age of patients was 66.6 years and 57.9% were males. The most common comorbidities were as follows: hypertension (49.2%), diabetes (18.8%), and chronic obstructive pulmonary disease (12.8%). Acute respiratory distress syndrome (34.7%) and acute kidney injury (13.9%) were the most common complications. In-hospital mortality was 20.9%. PSI and CURB-65 showed the highest AUROC (0.835 and 0.825, respectively). qSOFA and MuLBSTA had a lower AUROC (0.728 and 0.715, respectively). qSOFA was the most specific score (specificity 95.7%) albeit its sensitivity was only 26.2%. PSI had the highest sensitivity (84.1%) and a specificity of 72.2%. CONCLUSIONS: PSI and CURB-65, specific severity scores for pneumonia, were better than qSOFA and MuLBSTA at predicting mortality in patients with COVID-19 pneumonia. Additionally, qSOFA, the simplest score to perform, was the most specific albeit the least sensitive.

Cancer Research in the Time of COVID-19: A Colombian Narrative.

Cancer research is deficient in Colombia and efforts and resources diverted due to the COVID-19 pandemic could worsen the situation. We explore the impact of the pandemic on cancer research funding, output, and conduct. We sought information at national level and used the experience of an academic reference center to contrast the impact at institutional level. We searched databases and official documents of national governmental institutions, trial registries, hospital registries, and the Web of Science. We interviewed principal investigators (PIs) to retrieve information on the conduct of cancer research. A decline in resource availability and new proposals was observed at the national level with a shift to COVID-19 related research. However, at institutional level there was no decline in the number of cancer research proposals. The predominance of observational studies as opposed to the preponderance of clinical trials and basic science in high-income countries may be related to the lower impact at institutional level. Nevertheless, we found difficulties similar to previous reports for conducting research during the pandemic. PIs reported long recovery times and a great impact on research other than clinical trials, such as observational and qualitative studies. No significant impact on research output was observed. Alternatives to ensure research continuity such as telemedicine and remote data collection have scarcely been implemented given limited access and low technology literacy. In this middle-income setting the situation shows a notable dependency of international collaborations to develop research on COVID-19 and cancer and to overcome challenges for cancer research during the pandemic.

Synovial Adiponectin Was More Associated with Clinical Severity than Synovial Leptin in Women with Knee Osteoarthritis.

OBJECTIVE: Different adipokines have been reported to play a role in the development, progression, and severity of knee osteoarthritis, but this association may be mediated by obesity. The aim of this study was to evaluate separately the associations of leptin and adiponectin with clinical severity and inflammatory markers in nonobese and obese women with knee osteoarthritis. DESIGN: Cross-sectional study with systematic inclusion of 115 women with symptomatic primary knee osteoarthritis. Age, physical exercise, symptoms duration, and body mass index were collected. Radiographic severity was evaluated according to Kellgren-Lawrence scale. Pain and disability were assessed by WOMAC-total, -pain, -function subscales. Two adipokines (leptin and adiponectin) and 3 inflammatory markers (TNF-α, hsCRP, and IL-6) were measured by ELISA in synovial fluid and serum. RESULTS: Synovial fluid adiponectin was associated with WOMAC pain, function, and total and with synovial fluid IL-6 in nonobese female knee osteoarthritis after controlling by confounders (partial correlation coefficient [PCC] = 0.395, 0.387, 0.427, and 0.649, respectively). Synovial fluid and serum leptin were significantly associated with IL-6 (PCC = 0.354) after controlling by confounders but associations with clinical severity and the rest of inflammatory markers were mitigated after control. CONCLUSIONS: Adiponectin in synovial fluid was associated with clinical severity and local inflammatory markers in knee osteoarthritis women, while leptin relation was attenuated when controlled by confounders.

Decreased striatal adenosine A2A-dopamine D2 receptor heteromerization in schizophrenia.

According to the adenosine hypothesis of schizophrenia, the classically associated hyperdopaminergic state may be secondary to a loss of function of the adenosinergic system. Such a hypoadenosinergic state might either be due to a reduction of the extracellular levels of adenosine or alterations in the density of adenosine A2A receptors (A2ARs) or their degree of functional heteromerization with dopamine D2 receptors (D2R). In the present study, we provide preclinical and clinical evidences for this latter mechanism. Two animal models for the study of schizophrenia endophenotypes, namely the phencyclidine (PCP) mouse model and the A2AR knockout mice, were used to establish correlations between behavioural and molecular studies. In addition, a new AlphaLISA-based method was implemented to detect native A2AR-D2R heteromers in mouse and human brain. First, we observed a reduction of prepulse inhibition in A2AR knockout mice, similar to that observed in the PCP animal model of sensory gating impairment of schizophrenia, as well as a significant upregulation of striatal D2R without changes in A2AR expression in PCP-treated animals. In addition, PCP-treated animals showed a significant reduction of striatal A2AR-D2R heteromers, as demonstrated by the AlphaLISA-based method. A significant and pronounced reduction of A2AR-D2R heteromers was next demonstrated in postmortem caudate nucleus from schizophrenic subjects, even though both D2R and A2AR were upregulated. Finally, in PCP-treated animals, sub-chronic administration of haloperidol or clozapine counteracted the reduction of striatal A2AR-D2R heteromers. The degree of A2AR-D2R heteromer formation in schizophrenia might constitute a hallmark of the illness, which indeed should be further studied to establish possible correlations with chronic antipsychotic treatments.

Efficacy and safety of Nivolumab in older patients with pretreated lung cancer: A subgroup analysis of the Galician lung cancer group.

BACKGROUND: Nivolumab is an anti PD1 immunotherapy drug approved for advanced Non-Small Cell Lung Cancer (NSCLC) patients who previously received at least one prior line of treatment. Older patients are often not represented in clinical trials and drugs with acceptable safety profiles are necessary. We aim to report the efficacy and safety profile of Nivolumab in the real-world older subgroup of the Galician lung cancer group study. PATIENTS AND METHODS: We retrospectively reviewed 188 advanced NSCLC patients treated with at least one prior therapy. We collected data from patients who were ≥70 years old treated with Nivolumab in second or subsequent lines. Patient characteristics, treatment efficacy (overall survival, progression-free survival, and response rate), and safety profile were reported. RESULTS: Thirty-eight patients aged ≥70 years were included in the subgroup analysis. The median age was 74.5 years, a high percentage of patients were males (95%), most had a Performance Status of 1 (79%) and only 13% were non-smokers. The predominant histology was adenocarcinoma (53%), and 18% of patients received 2 or more lines. The median Progression-Free Survival was 7.53 months (CI 4.3-17.3, p = 0.15) and the median Overall Survival was 14.85 months (CI 10.5-20.7, p = 0.44). The objective response rate was 42%. No new adverse events were reported in comparison to a global population. CONCLUSIONS: The efficacy and safety profile of Nivolumab in advanced NSCLC patients treated with at least one prior therapy and age ≥70 years old can be overlapped to a global population. Further prospective trials are needed to define and confirm these results.

PD-(L)1 Inhibitors in Combination with Chemotherapy as First-Line Treatment for Non-Small-Cell Lung Cancer: A Pairwise Meta-Analysis.

The combination of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors with chemotherapy has emerged as a promising therapeutic option for advanced non-small-cell lung cancer (NSCLC). The aim of this meta-analysis was to evaluate the efficacy of the combined strategy in this setting. For this purpose, we performed a literature search of randomized controlled trials comparing PD-(L)1 inhibitors plus platinum-based chemotherapy versus chemotherapy alone in stage IV NSCLC patients. Seven clinical trials with 4562 patients were included. In the intention-to-treat wildtype population, PD-(L)1 inhibitor plus chemotherapy was significantly associated with improved progression-free survival (PFS) (Hazard ratio (HR) = 0.61, 95% confidence interval (CI): 0.57-0.65, p < 0.001) and overall survival (OS) (HR = 0.76, 95% CI: 0.67-0.86; p < 0.001) compared to chemotherapy. A significantly higher overall response rate (ORR) was also observed with the combined strategy (Odds ratio (OR) = 2.12, 95% CI: 1.70-2.63, p < 0.001). Furthermore, in all the analyzed subgroups, addition of PD-(L)1 inhibitors to chemotherapy significantly improved efficacy endpoints. Specifically, stratification according to PD-L1 expression revealed a benefit across all patients, regardless of their PFS status. In conclusion, PD-(L)1 blockade added to standard platinum-based chemotherapy significantly improved PFS, OS, and ORR in the up-front treatment of advanced NSCLC.