Effect of Analgesic Low-Dose Ketamine Infusions on the Cardiovascular Response: A Retrospective Analysis.

BACKGROUND: Low-dose ketamine infusion (LDKI) has shown effectiveness for treating acute pain associated with surgical and nonsurgical (traumatic, neuropathic, and acute cancer-related) origin as an adjuvant to opioids. The increasing use of LDKI as an opioid-sparing agent in multimodal analgesia requires a better understanding of its effects on the cardiovascular response, a known dose-dependent side effect of ketamine administration. We investigated the cardiovascular response of acute pain patients treated with LDKI. OBJECTIVES: The aim of the present study was to evaluate the effect of LDKI in hemodynamic variables (blood pressure [BP] and heart rate [HR]) during LDKI analgesia for up to 48 hours of treatment in an acute pain setting. Secondary objectives were to evaluate psychomimetic effects. STUDY DESIGN: Retrospective unicentric cohort design. SETTING: The study was conducted at an academic university hospital. METHODS: We conducted a single-center retrospective cohort analysis of adult patients who underwent LDKI to treat surgical and nonsurgical acute pain. We obtained data from the Hospital San Vicente Fundación Health Documentation System database and evaluated the medical records of 318 patients with surgical and nonsurgical pain. Patients received a 0.1 mg/kg/h ketamine infusion as part of a multimodal analgesic plan. Baseline systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and HR values were compared with those measured after 24 and 48 hours of treatment. Pain level and psychomimetic effects were measured at 24 and 48 hours. Cardiovascular complications and treatment duration were also recorded. Patients with a history of psychiatric, cardiovascular, or cognitive disease were excluded from the study. This study was registered in the clinicaltrials.gov database (identifier: NCT03979105). RESULTS: No statistical differences in SBP, DBP, MAP, or HR were observed when baseline and post-LDKI treatment values were compared (P < 0.05). When comparing hemodynamic variables after exposure to LDKI in patients with and without hypertension, we did not observe statistically significant differences in mean HR, systolic arterial pressure, diastolic arterial pressure, or MAP values at 24 and 48 hours. The frequency of severe pain was reduced from 72% on day 0 to 4.4% on day 1 and 6.2% on day 2 post-LDKI. Observed psychomimetic effects were confusion 4.39%, hallucinations 2.51%, and nightmares 1.25%. No major cardiovascular events were observed. LIMITATIONS: This study was limited by its retrospective design, the lack of a comparative matching cohort, and the good general condition of the majority of patients included in the study. CONCLUSIONS: LDKI (0.1 mg/kg/h) was not associated with significant changes in baseline BP or HR. Our results suggest that as an adjuvant in multimodal analgesia for surgical and nonsurgical acute pain, LDKI has a low impact on the cardiovascular response. KEY WORDS: Ketamine, adverse effects, tachycardia, hypertension, postoperative pain, chronic postsurgical pain.

[Leukocytoclastic vasculitis as an adverse effect of propylthiouracil. A case report]. / Vasculitis leucocitoclástica como efecto adverso del propiltiouracilo. Reporte de un caso.

BACKGROUND: The most common cause of hyperthyroidism is Graves' disease. Propylthiouracil (PTU) is one of the drugs used to treat this disease. Leukocytoclastic vasculitis is described among dermatologic adverse effects of PTU. CASE REPORT: A 18-year-old woman, allergic to methimazole, developed a vasculitis associated to ANCAs with characteristics of leukocytoclastic vasculitis, associated to PTU treatment. She did not present systemic involvement. PTU treatment was suspended. Two months later, the skin lesions had almost completely resolved. CONCLUSIONS: Leukocytoclastic vasculitis should be considered in the spectrum of complications caused by the consumption of propylthiouracil. The lesions can manifest over time, from a few weeks to years after taking the drug. When there is no systemic involvement, propylthiouracil suspension is sufficient to cure the disease.

ANTECEDENTES: La causa más frecuente de hipertiroidismo es la enfermedad de Graves. El propiltiouracilo es uno de los medicamentos más prescritos para esta enfermedad. Uno de los efectos adversos dermatológicos del propiltiouracilo es la vasculitis leucocitoclástica. REPORTE DE CASO: Paciente femenina de 18 años, alérgica al metamizol, con vasculitis asociada a ANCAs, con características de vasculitis leucocitoclástica provocada por el consumo de propiltiouracilo. No se observó afectación sistémica. Dos meses después de suspender el propiltiouracilo desaparecieron casi por completo las lesiones en la piel. CONCLUSIONES: La vasculitis leucocitoclástica debe considerarse en el espectro de complicaciones provocadas por el consumo de propiltiouracilo. Las lesiones pueden manifestarse con el paso del tiempo, desde unas semanas hasta años después de consumir el fármaco. Cuando no existe afectación sistémica, la suspensión del propiltiouracilo es suficiente para detener la enfermedad.

Expedited gene delivery for osteochondral defect repair in a rabbit knee model: A one-year investigation.

Objective: To evaluate a single-step, gene-based procedure for repairing osteochondral lesions. Design: Osteochondral lesions were created in the patellar groove of skeletally mature rabbits. Autologous bone marrow aspirates were mixed with adenovirus vectors carrying cDNA encoding green fluorescent protein (Ad.GFP) or transforming growth factor-ß1 (Ad.TGF-ß1) and allowed to clot. The clotted marrow was press-fit into the defects. Animals receiving Ad.GFP were euthanized at 2 weeks and intra-articular expression of GFP examined by fluorescence microscopy. Animals receiving Ad.TGF-ß1 were euthanized at 3 months and 12 months; repair was compared to empty defects using histology and immunohistochemistry. Complementary in vitro experiments assessed transgene expression and chondrogenesis in marrow clots and fibrin gels. In a subsequent pilot study, repair at 3 months using a fibrin gel to encapsulate Ad.TGF-ß1 was evaluated. Results: At 2 weeks, GFP expression was seen at variable levels within the cartilaginous lesion. At 3 months, there was no statistically significant improvement (p > 0.05) in healing of lesions receiving Ad.TGF-ß1 and variability was high. At 12 months, there were still no significant difference (p > 0.05) between the empty defects and those receiving Ad.TGF-ß1 in the overall, cartilage, and bone scores. Variability was still high. In vitro experiments suggested that variability reflected variable transduction efficiency and chondrogenic activity of the marrow clots; using fibrin gels instead of marrow may address this issue but more research is needed. Conclusions: This approach to improving the repair of osteochondral lesions needs further refinement to reduce variability and provide a more robust outcome.

All About (NK Cell-Mediated) Death in Two Acts and an Unexpected Encore: Initiation, Execution and Activation of Adaptive Immunity.

NK cells are key mediators of immune cell-mediated cytotoxicity toward infected and transformed cells, being one of the main executors of cell death in the immune system. NK cells recognize target cells through an array of inhibitory and activating receptors for endogenous or exogenous pathogen-derived ligands, which together with adhesion molecules form a structure known as immunological synapse that regulates NK cell effector functions. The main and best characterized mechanisms involved in NK cell-mediated cytotoxicity are the granule exocytosis pathway (perforin/granzymes) and the expression of death ligands. These pathways are recognized as activators of different cell death programmes on the target cells leading to their destruction. However, most studies analyzing these pathways have used pure recombinant or native proteins instead of intact NK cells and, thus, extrapolation of the results to NK cell-mediated cell death might be difficult. Specially, since the activation of granule exocytosis and/or death ligands during NK cell-mediated elimination of target cells might be influenced by the stimulus received from target cells and other microenvironment components, which might affect the cell death pathways activated on target cells. Here we will review and discuss the available experimental evidence on how NK cells kill target cells, with a special focus on the different cell death modalities that have been found to be activated during NK cell-mediated cytotoxicity; including apoptosis and more inflammatory pathways like necroptosis and pyroptosis. In light of this new evidence, we will develop the new concept of cell death induced by NK cells as a new regulatory mechanism linking innate immune response with the activation of tumour adaptive T cell responses, which might be the initiating stimulus that trigger the cancer-immunity cycle. The use of the different cell death pathways and the modulation of the tumour cell molecular machinery regulating them might affect not only tumour cell elimination by NK cells but, in addition, the generation of T cell responses against the tumour that would contribute to efficient tumour elimination and generate cancer immune memory preventing potential recurrences.

Picrosirius Red Staining: Revisiting Its Application to the Qualitative and Quantitative Assessment of Collagen Type I and Type III in Tendon.

Collagen has a major role in the structural organization of tendons. Picrosirius red (PSR) staining viewed under polarized light microscopy is the standard method to evaluate the organization of collagen fibers in tissues. It is also used to distinguish between type I and type III collagen in tissue sections. However, accurate analysis and interpretation of PSR images are challenging because of technical factors and historical misconceptions. The aim of this study was to clarify whether collagen types I and III can be distinguished by PSR staining in rat Achilles tendons, using double immunohistochemistry as the positive control. Our findings showed that PSR staining viewed with polarized light microscopy was suitable for qualitative and quantitative assessment of total collagen but was not able to distinguish collagen types. We found it critical to use a polarizing microscope equipped with a rotating stage; tendon section orientation at 45° with respect to crossed polarizers was optimal for the qualitative and quantitative assessment of collagen organization. Immunohistochemistry was superior to PSR staining for detection of collagen type III. We also compared formalin and Bouin solution as fixatives. Both produced similar birefringence, but formalin-fixed tendons provided higher quality histological detail with both hematoxylin-eosin and immunostaining.

Clinical and epidemiological characteristics, morbidity and treatment based on the registry of acromegalic patients in Colombia: RAPACO.

AIMS: Describe the local characteristics, methodology and results of the registry of acromegalic patients in Colombia (RAPACO). METHODS: Multicenter, retrospective study based on the registry of acromegalic patients in Colombia: RAPACO. The data collected included: demographics, diagnosis, approximate time of disease evolution, data on weight, height, body mass index (BMI), neck circumference (NC) abdominal circumference (AC) hip circumference (HC) and waist/hip ratio (WHR); clinical and biochemical data at the time of diagnosis, etiology, immunohistochemistry of the tumor and information related to types of treatment. Descriptive analytics were employed. RESULTS: A total of 201 patients (60% females) with an average age at registration of 49.5 ± 14.6 years and an average time of evolution of the disease of 6.96 ± 4.5 years. Average weight was 75.1 Kg ± 12.98, with an average BMI of 28.11 ± 4.33. The most frequent symptoms mentioned at the time of diagnosis were extremity enlargement and headache. The most frequent comorbidity was arterial hypertension in 50.3% of the cases. 78.6% of cases were caused by macroadenoma. 80.1% received surgical treatment, 77.6% were under medical treatment, of which 95.7% were receiving somatostatin analogues. 26.4% of patients were treated with radiation therapy. Of the patients who received any type of clinical treatment, only 2.5% reported biochemical control at registration. CONCLUSION: It is important to recognize the local epidemiological, clinical, biochemical and treatment characteristics in order to assist in further understanding this pathology to implement local measures to improve both the quality of life as well as the prognosis of the patients diagnosed.

Características clínicas y sociodemográficas de una población adulta con tumores neuroendocrinos

Introducción: Los tumores neuroendocrinos representan un grupo de neoplasias de baja incidencia que derivan de células neuroendocrinas distribuidas en todo el cuerpo en especial sistema respiratorio y gastrointestinal. Objetivo: Determinar las características clínicas y sociodemográficas de una población adulta con padecimiento de tumores neuroendocrinos. Materiales y métodos: Estudio descriptivo transversal, se evaluaron 91 historias clínicas con diagnóstico de tumores neuroendocrinos confirmados por patología entre los años 2013 a 2020. Análisis realizado en Microsoft Excel 2013 y EpiInfo 7.2. Resultados: La media de edad fue 60 años, con predominio en hombres (57%). Los principales antecedentes fueron el tabaquismo (35%), hipertensión arterial (22%) y EPOC (9%). Los principales síntomas fueron el dolor abdominal (43%), pérdida de peso (31%) y tos (26%). Según el origen, fueron más frecuentes los de intestino anterior (75%), predominando los de tracto respiratorio (39,5%). En el 21,9%, el origen fue desconocido. Teniendo en cuenta la clasificación 2019 de la OMS, predominaron los carcinomas neuroendocrinos (56%), de los cuales el más frecuente fue el carcinoma de células pequeñas. Entre los bien diferenciados (44%), fueron más frecuentes los de bajo grado (58%) seguido grado intermedio (24%) y bajo grado (17%). Las metástasis se registraron en 37% de los casos con afectación principalmente hepática (49%), ganglios (21%) y sistema nervioso central (9%). La muerte se presentó en el 24% de los casos. Conclusiones: Los resultados del presente estudio concuerdan con lo reportado a nivel mundial, resaltando el predominio de los tumores de origen pulmonar, como también clínica semejante según los órganos afectados.

Introduction: Neuroendocrine tumors represent a group of low-incidence neoplasms derived from neuroendocrine cells distributed throughout the body, especially the respiratory and gastrointestinal systems. Objective: To determine the clinical and sociodemographic characteristics of an adult population with neuroendocrine tumors. Materials and methods: In a descriptive cross-sectional study, 91 medical records with a diagnosis of neuroendocrine tumors confirmed by pathology were evaluated between the years 2013 and 2020. Analysis carried out in Microsoft Excel 2013 and EpiInfo 7.2. Results: The mean age was 60 years, with a predominance in men (57%). The main antecedents were smoking (35%), arterial hypertension (22%), and COPD (9%). The main symptoms were abdominal pain (43%), weight loss (31%), and cough (26%). According to the origin, those of the foregut were more frequent (75%), predominantly those of the respiratory tract (39.5%). In 21.9%, the origin was unknown. Taking into account 2019 WHO classification, neuroendocrine carcinomas predominated (56%), of which the most frequent was small cell carcinoma. Among the well-differentiated (44%), low-grade (58%) followed by intermediate grade (24%) and low-grade (17%). Metastases were registered in 37% of the cases with mainly liver involvement (49%), lymph nodes (21%), and central nervous system (9%). Death occurred in 24% of cases. Conclusions: The results of the present study coincide with those reported worldwide, highlighting the predominance of tumors of pulmonary origin, as well as similar clinical symptoms according to the affected organs

[Levels of 25 hydroxy vitamin D of serum and broncho-alveolar lavage in patients with pulmonary tuberculosis]. / Concentraciones de 25 hidroxi vitamina D séricas y en lavado bronco-alveolar en pacientes con tuberculosis pulmonar.

BACKGROUND: Alteration of vitamin D is a risk factor for tuberculosis (TB). AIM: To evaluate the pulmonary and serum levels of 25-hydroxy vitamin D (25OHD) in patients with and without pulmonary TB. METHODS: Two-stage study: the first part was retrospective cross-sectional and the second prospective. Those > 18 years of age who underwent fiberoptic bronchoscopy for suspected pulmonary TB and in whom the infection was confirmed were included. Patients with another type of infection without TB and non-infectious diseases were taken as controls for the first stage and infectious controls without TB in the prospective phase. The measurement of 25OHD was performed by ELFA (enzyme-linked fluorescence assay). The Kruskal-Wallis test was used to evaluate association, considering a value of p < 0.05 to be significant. The data were processed with the SPSS version 23 program. RESULTS: The total sample was 77 patients (35 in the first stage and 42 in the second). The characteristics between the groups were homogeneous. Serum (second phase) and broncho-alveolar lavage (first and second phase) levels of 25OHD were lower in TB patients compared to controls and were independent of serum calcium level (serum: 22.4 ng/mL vs 33 ng/mL, p = 0.006 and broncho-alveolar lavage: 9.7 ng/mL vs 12.2 ng/mL; p = 0.012). CONCLUSIONS: There was a significant difference between the levels of 25OHD in both serum and broncho-alveolar lavage in patients with pulmonary TB in relation to their controls.

Off-label use of second-generation antipsychotics in borderline personality disorder: a comparative real-world study among oral and long-acting injectables in Spain.

The aim of the present study was to evaluate the use of oral vs. long-acting injectables (LAIs) antipsychotics, as well as, to compare the effectiveness of different LAI antipsychotics [aripiprazole-1-month, paliperidone-1-month (PP1M), paliperidone-3-month (PP3M) and risperidone long-acting injectable (RLAI)] in patients diagnosed with borderline personality disorder (BPD), by evaluating the following clinical outcomes: (1) the number of hospital admissions; (2) the number of documented suicidal behaviour/attempts; and (3) the use of concomitant treatments, including benzodiazepines, oral antipsychotics and biperiden. We included a total of 116 patients diagnosed with BPD and treated with antipsychotic medication: 50 using a LAI antipsychotic formulation and 66 using the equivalent main oral antipsychotic. Patients treated with LAIs showed a decreased ratio of visits to emergency compared with the oral treatment group, and between LAIs, PP3M vs. aripiprazole-1-month group. Furthermore, patients treated with LAIs used lower number and dose of concomitant antipsychotics compared with patients treated with oral antipsychotics. Moreover, PP1M and PP3M used lower daily dose of diazepam equivalents compared with the aripiprazole-1-month and RLAI treatment groups. In conclusion, the use of LAIs may play a role in the management of BPD.

Evaluation of Risk Factors Associated to Prescription of Benzodiazepines and its Patterns in a Cohort of Patients from Mental Health: A Real World Study in Spain.

Purpose: we aimed 1) to evaluate the risk factors associated to the benzodiazepines intake; 2) to assess the impact about the use of long acting injectables antipsychotics (LAIs); 3) to assess the risk in severe and affective disorders and 4) to identify the prescription patterns of use in mental health in a cohort of patients from Spain. Methods: 735 outpatients from Mental Health were included. Demographic and clinical data were collected. In order to compare the use of benzodiazepines we calculated the daily dose equivalents (mg/day) to diazepam as standard. Results: The most commonly prescribed benzodiazepine was clonazepam (33%) and the mean daily dose of diazepam equivalents was 24.9 mg. It was higher in affective disorders (40.35 ± 3.36) and lower in patients using LAIs antipsychotics (17.50 ± 1.39; p = 0.001). Multivariate analysis showed that to be women (OR = 1.559, 95% CI = 1.059-2.295, p = 0.024), the use of drugs (OR = 1.671, 95% CI = 1.127-2.477, p = 0.011) and suffering any affective disorder (OR = 1.542, 95% CI = 1.355-1.826, p = 0.040) increased the risk of benzodiazepine intake. In contrast, the use of LAIs antipsychotics significantly reduced it versus oral antipsychotics (OR = 5.226, 95% CI = 3.185-8.575, p = 0.001). Conclusions: benzodiazepines are widely prescribed, mainly clonazepam followed by lorazepam and diazepam. Most of patients used at least one benzodiazepine and the mean daily intake was 25 mg diazepam equivalents. Therefore, benzodiazepines are extensively prescribed and used at higher doses than desirable. These, findings could be useful for clinicians and their practice.

A multicenter investigation of the hemodynamic effects of induction agents for trauma rapid sequence intubation.

BACKGROUND: Several options exist for induction agents during rapid sequence intubation (RSI) in trauma patients, including etomidate, ketamine, and propofol. These drugs have reported variable hemodynamic effects (hypotension with propofol and sympathomimetic effects with ketamine) that could affect trauma resuscitations. The purpose of this study was to compare the hemodynamic effects of these three induction agents during emergency department RSI in adult trauma. We hypothesized that these drugs would display a differing hemodynamic profile during RSI. METHODS: We performed a retrospective (2014-2019), multicenter trial of adult (≥18 years) trauma patients admitted to eight ACS-verified Level I trauma centers who underwent emergency department RSI. Variables collected included systolic blood pressure (SBP) and pulse before and after RSI. The primary outcomes were change in heart rate and SBP before and after RSI. RESULTS: There were 2,092 patients who met criteria, 85% received etomidate (E), 8% ketamine (K), and 7% propofol (P). Before RSI, the ketamine group had a lower SBP (E, 135 vs. K, 125 vs. P, 135 mm Hg, p = 0.04) but there was no difference in pulse (E, 104 vs. K, 107 vs. P, 105 bpm, p = 0.45). After RSI, there were no differences in SBP (E, 135 vs. K, 130 vs. P, 133 mm Hg, p = 0.34) or pulse (E, 106 vs. K, 110 vs. P, 104 bpm, p = 0.08). There was no difference in the average change of SBP (E, 0.2 vs. K, 5.2 vs. P, -1.8 mm Hg, p = 0.4) or pulse (E, 1.7 vs. K, 3.5 bpm vs. P, -0.96, p = 0.24) during RSI. CONCLUSION: Contrary to our hypothesis, there was no difference in the hemodynamic effect for etomidate versus ketamine versus propofol during RSI in trauma patients. LEVEL OF EVIDENCE: Therapeutic, Level IV.

Concentraciones de 25 hidroxi vitamina D séricas y en lavado bronco-alveolar en pacientes con tuberculosis pulmonar / Levels of 25 hydroxy vitamin D of serum and broncho-alveolar lavage in patients with pulmonary tuberculosis

INTRODUCCIÓN: La alteración de la vitamina D es un factor de riesgo para enfermar de tuberculosis (TBC). OBJETIVO: Evaluar la concentración pulmonar y sérica del compuesto 25-hidroxi-vitamina D (25OHD) en pacientes con y sin TBC pulmonar. METODOLOGÍA: Estudio de dos etapas: la primera parte fue de corte transversal, retrospectiva, y la segunda prospectiva. Se incluyeron > 18 años a los que se les realizó fibrobroncoscopia por sospecha de TBC pulmonar y en quienes se confirmó la infección. Se tomaron como controles a pacientes con otro tipo de infección no TBC, y enfermedades no infecciosas para la primera etapa y controles infecciosos sin TBC en la fase prospectiva. La medición de 25OHD se realizó mediante ELFA (ensayo de fluorescencia ligado a enzima). Se empleó la prueba de Kruskal-Wallis para evaluar asociación considerando significativo un valor de p < 0,05. Los datos se procesaron con el programa SPSS versión 23. RESULTADOS: La muestra total fue de 77 pacientes (35 en la primera etapa y 42 en la segunda). Las características entre los grupos fueron homogéneas. Las concentraciones en suero (segunda fase) como en el lavado bronco-alveolar (primera y segunda fase) de 25OHD fueron más bajas en pacientes con TBC comparado con los controles e independientes de la concentración de calcio sérico (suero: 22,4 ng/mL vs 33 ng/mL, p = 0,006 y lavado bronco-alveolar: 9,7 ng/mL vs 12,2 ng/mL; p = 0,012). CONCLUSIONES: Hubo una diferencia significativa entre las concentraciones de 25OHD, tanto en suero como en lavado bronco-alveolar, en pacientes con TBC pulmonar con relación a sus controles.

BACKGROUND: Alteration of vitamin D is a risk factor for tuberculosis (TB). AIM: To evaluate the pulmonary and serum levels of 25-hydroxy vitamin D (25OHD) in patients with and without pulmonary TB. METHODS: Two-stage study: the first part was retrospective cross-sectional and the second prospective. Those > 18 years of age who underwent fiberoptic bronchoscopy for suspected pulmonary TB and in whom the infection was confirmed were included. Patients with another type of infection without TB and non-infectious diseases were taken as controls for the first stage and infectious controls without TB in the prospective phase. The measurement of 25OHD was performed by ELFA (enzyme-linked fluorescence assay). The Kruskal-Wallis test was used to evaluate association, considering a value of p < 0.05 to be significant. The data were processed with the SPSS version 23 program. RESULTS: The total sample was 77 patients (35 in the first stage and 42 in the second). The characteristics between the groups were homogeneous. Serum (second phase) and broncho-alveolar lavage (first and second phase) levels of 25OHD were lower in TB patients compared to controls and were independent of serum calcium level (serum: 22.4 ng/mL vs 33 ng/mL, p = 0.006 and broncho-alveolar lavage: 9.7 ng/mL vs 12.2 ng/mL; p = 0.012). CONCLUSIONS: There was a significant difference between the levels of 25OHD in both serum and broncho-alveolar lavage in patients with pulmonary TB in relation to their controls.

Evaluation of long-acting injectable antipsychotics with the corresponding oral formulation in a cohort of patients with schizophrenia: a real-world study in Spain.

To date, only a few studies compared some long-acting injectables (LAIs) antipsychotics showing similar symptom improvement, relapse rates and adherence to treatment. We evaluated the use of LAIs antipsychotics [aripiprazole-1-month (A1M); paliperidone-1-month and 3-month (PP1M and PP3M) and biweekly (2w)-LAIs] and their corresponding oral formulations through (1) the number of hospital re-admissions, (2) the number of documented suicidal behaviour/attempts and (3) the use of concomitant benzodiazepines, oral antipsychotics and biperiden. A total of 277 patients, ≥18 years old, were included if were treated with the corresponding oral or LAI antipsychotic during at least 12 months and were previously diagnosed with schizophrenia. Our results showed that LAIs associated significantly lower suicidal behaviour, reduced the number of hospital admissions, lower diazepam and haloperidol equivalents and mean daily dose of biperiden intake versus oral antipsychotics. Furthermore, significant differences were found between LAIs. Specifically, PP3M was associated to lower hospital admissions versus A1M; PP1M and PP3M lower doses of diazepam equivalents versus 2w-LAIs and finally, PP1M lower antipsychotic intake versus 2w-LAIs. In conclusion, LAIs improved clinical outcomes by reducing the need for concomitant treatments and hospital admissions over oral antipsychotics. PP1M and PP3M showed better outcomes versus A1M and biweekly LAIs.

Niveles de vitamina D en pacientes con tratamiento anticonvulsivante para epilepsia que asistieron a la consulta externa de un hospital de tercer nivel de Colombia / Vitamin D levels in patients receiving anticonvulsant treatment for epilepsy in an outpatient clinic in Colombia

RESUMEN INTRODUCCIÓN: La vitamina D actúa en múltiples tejidos y procesos fisiológicos. El objetivo del estudio fue determinar los niveles de vitamina D en pacientes con epilepsia tratados con anticonvulsivantes. MATERIAL Y MÉTODOS: Estudio observacional, descriptivo, de corte transversal en pacientes con diagnóstico de epilepsia que asistieron al servicio de consulta externa de un hospital de tercer nivel de atención de Neiva, Colombia, entre marzo y octubre de 2018. Se midieron los niveles séricos de vitamina D, paratohormona, albúmina y calcio. RESULTADOS: Una muestra de 90 pacientes. La mediana de edad fue de 36,5 (rango 18-81 años), 46 (51,1%) presentaron niveles bajos de vitamina D (38,8% en rango de insuficiencia y 12,2% rango de deficiencia). Se documentó asociación entre el sexo femenino y niveles insuficientes y deficientes de vitamina D, el no realizar ejercicio con niveles insuficientes de vitamina D, la exposición diaria al sol menor de 15 minutos y el no realizar caminata con niveles deficientes de vitamina D. El déficit de vitamina D se asoció con incremento de los niveles de paratohormona, mediana 103,9 pg/ml (rango 30,7-182,9 pg/ml, P <0,01). No se encontraron diferencias entre los niveles de vitamina D y el uso de monoterapia, politerapia, ni con la utilización fármacos inductores enzimáticos. CONCLUSIONES: En pacientes con terapia anticonvulsivante es frecuente encontrar niveles insuficientes/ deficientes de vitamina D aunque no se encontró asociación con el uso de monoterapia, politerapia o inductores enzimáticos hepáticos.

SUMMARY INTRODUCTION: Vitamin D acts in many tissues and different physiological processes. The objective was to determine vitamin D levels in patients with epilepsy treated with anticonvulsants. MATERIALS AND METHOD: Observational, descriptive, cross-section study in consecutive patients with epilepsy who attended the Neurology outpatient service of a university hospital in Neiva, Colombia, between March and October 31, 2018. We obtained serum levels of vitamin D, parathormone, albumin and calcium. RESULTS: There were 90 patients with a median age of 36.5 (range 18-81 years), 46 (51.1%) had low levels of vitamin D (38.8% in the range of insufficiency and 12.2% with deficiency). Females had more insufficient and deficient levels of vitamin D; not exercising was associated with insufficient levels of vitamin D, daily exposure to the sun under 15 minutes and not walking, with deficient levels of vitamin D. Vitamin D deficiency was associated with an increase in parathyroid hormone levels, median 103.9 pg / ml (range 30.7 - 182.9 pg / ml, P <0.01). No difference was found between vitamin D levels and the use of monotherapy, polytherapy, or the use of enzyme-inducing drugs. CONCLUSIONS: In epileptic patients with anticonvulsants it is common to find insufficient / deficient levels of vitamin D although we found no association with the use of monotherapy, polytherapy or hepatic enzyme inducers.

Long-Acting Injectable Antipsychotics: Analysis of Prescription Patterns and Patient Characteristics in Mental Health from a Spanish Real-World Study.

BACKGROUND AND OBJECTIVE: Long-acting injectable antipsychotics (LAIs) have been widely studied in schizophrenia and evidence suggests that they could be also used for the treatment of bipolar and schizoaffective disorders. Nonetheless, there are no studies evaluating their role in other psychiatric disorders. We aimed to evaluate the use of the newest monthly and 3-monthly LAIs-aripiprazole once monthly, paliperidone 1- and 3-monthly (PP1M, PP3M)-against the 2-weekly LAIs, using the following clinical outcomes: (1) the number of hospital re-admissions, (2) the number of documented suicidal behaviors/attempts, and (3) the use of concomitant treatments, including benzodiazepines, oral antipsychotics, and biperiden. METHODS: A total of 431 patients were included who were treated with the corresponding LAI over at least 12 months and were previously diagnosed with a psychiatric disorder. Statistical analyses were performed using an ANCOVA model, Student's t test, and the Pearson's r test. RESULTS: Our results showed significantly decreased re-admissions using PP3M versus the bi-weekly LAIs and aripiprazole once monthly, while no significant differences were found in suicidal behavior. Furthermore, we found a significantly lower intake of benzodiazepines in PP1M and PP3M groups versus the bi-weekly and aripiprazole once-monthly groups. In addition, patients treated with PP1M and PP3M used a significantly lower dose of haloperidol equivalents versus the bi-weekly LAIs group. Finally, significantly higher doses of biperiden were used by the bi-weekly LAIs group. CONCLUSION: In conclusion, paliperidone LAIs reduced hospital re-admissions and, as aripiprazole once monthly, lowered concomitant psychiatric medication versus the bi-weekly LAIs. Further research and analysis of subgroups are needed; however, these findings might be useful for clinicians.

Perfil hormonal, metabólico y hematológico en adultos con el Virus de Inmunodeficiencia Humana / Hormonal, metabolic and hematological profile in adults with the Human Immunodeficiency Virus

Resumen Introducción: Son escasos los datos del impacto de la infección por el virus de inmunodeficiencia humana (VIH) a nivel hormonal, metabólico y hematológico en pacientes hospitalizados en Colombia. Objetivo: Describir el perfil hormonal, metabólico y hematológico de los pacientes con VIH hospitalizados en una institución de tercer nivel. Material y método: Estudio observacional de corte transversal, donde se incluyeron variables sociodemográficas, clínicas, hormonales, metabólicas y hematológicas de pacientes con VIH entre el 2013 y 2014. Resultados: Se incluyeron 52 pacientes, 34 hombres, con media de edad 39,7 años (Ds 12,6, Min: 21 Max: 79). 23% habían cursado con tuberculosis, 13% con toxoplasmosis cerebral. 26 pacientes tenían historia de consumo de tóxicos: cigarrillo (58%), alcohol (27%) y sustancias alucinógenas (15%). 14% de los pacientes recibían terapia antirretroviral al ingreso, los esquemas contenían principalmente inhibidores de proteasa. Otros medicamentos usados fueron: trimetoprim-sulfametoxazol (27.2%) y antituberculosos (15%). Las principales causas de hospitalización fueron toxoplasmosis cerebral (31%) y tuberculosis (15%). 52% de la población presentó síndrome de desgaste. El tiempo de diagnóstico del VIH fue <1 de un año en el 48% de la población. 79% de los pacientes tenía recuento de CD4 <200cel/mm3 (Ds 199, Min: 3 Max: 641). En el perfil hormonal, 58% (29 pacientes) presentaron alteración del eje tiroideo, de los cuales 14 presentaron perfil de hipotiroidismo central. 55,8% de los hombres presentaron hiperprolactinemia. El perfil metabólico se caracterizó por hipertrigliceridemia (44%) y HDL bajas (81%). La alteración electrolítica de mayor frecuencia fue hiponatremia (37%). Conclusiones: En la población de pacientes hospitalizados con VIH, se encontraron alteraciones endocrinas que sugieren compromiso glandular primario hipofisiario y adrenal; alteraciones lipídicas y electrolíticas en gran medida relacionadas con enfermedad avanzada.

Abstract Introduction: Data on the impact of human immunodeficiency virus (HIV) infection on a hormonal, metabolic and haematological level in patients hospitalized in Colombia are scarce. Objective: To describe the hormonal, metabolic and haematological profile of HIV patients hospitalized in a third level institution. Material and method: Cross-sectional observational study, which included sociodemographic, clinical, hormonal, metabolic and hematological variables of patients with HIV between 2013 and 2014. Results: We included 52 patients, 34 men, with an average age of 40 years (SD 12.6, Min: 21 Max: 79). 23% had tuberculosis, 13% had cerebral toxoplasmosis. 26 patients had a history of toxic consumption: cigarette (58%), alcohol (27%) and hallucinogenic substances (15%). 14% of the patients received antiretroviral therapy at admission, mainly with protease inhibitors. Other medications used were: trimethoprim-sulfamethoxazole (27.2%) and antituberculous drugs (15%). The main causes of hospitalization were cerebral toxoplasmosis (31%) and tuberculosis (15%). 52% of the population had Wasting syndrome. The time of diagnosis of HIV was <1 year in 48% of the population. 79% of the patients had a CD4 count <200 cell/mm3 (SD 199, Min: 3 Max: 641). In the hormonal profile, 58% (29 patients) presented alteration of the thyroid axis, of which 14 session profile of central hypothyroidism. 55.8% of men had hyperprolactinemia. The metabolic profile was characterized by hypertriglyceridemia (44%) and low HDL (81%). The most frequent electrolyte alteration was hyponatremia (37%). Conclusions: In the population of patients hospitalized with HIV, endocrine alterations were found suggesting primary glandular, pituitary and adrenal involvement, with lipid and electrolyte alterations largely related to advanced disease.

Phosphodiesterase PDE2 activity, increased by isoprenaline, does not reduce ß-adrenoceptor-mediated chronotropic and inotropic effects in rat heart.

Myocardial PDE2 activity increases in terminal human heart failure and after isoprenaline infusion in rat heart. PDE2 inhibitors do not potentiate the murine sinoatrial tachycardia produced by noradrenaline. We investigated whether isoprenaline infusion induces PDE2 to decrease the chronotropic and inotropic effects of catecholamines in rat heart. Sprague-Dawley rats were infused with isoprenaline (2.4 mg kg-1 day-1) for 3 days. We used spontaneously beating right atria, paced right ventricular strips and left ventricular papillary muscles. The effects of the PDE2 inhibitors EHNA (10 µM) and Bay 60-7550 (0.1-1 µM) were investigated on the cardiostimulation produced by noradrenaline (ICI118551 50 nM present to block ß2-adrenoceptors) and adrenaline (CGP20712A 300 nM present to block ß1-adrenoceptors). Hydrolysis of cAMP by PDE2 was measured by radioenzyme assay. Bay 60-7550 but not EHNA increased sinoatrial beating. A stable tachycardia elicited by noradrenaline (10 nM) or adrenaline (1 µM) was not increased by the PDE2 inhibitors. Isoprenaline infusion increased the hydrolytic PDE2 activity threefold in left ventricle, reduced the chronotropic and inotropic effects and potency of noradrenaline and abolished the effects of adrenaline. The potency of the catecholamines was not increased by the PDE2 inhibitors. Neither EHNA nor Bay 60-7550 potentiated the effects of the catecholamines. Rat PDE2 decreased basal sinoatrial beating but did not reduce the sinoatrial tachycardia or increases of ventricular force mediated through ß1- and ß2-adrenoceptors. The ß-adrenoceptor desensitization induced by the isoprenaline infusion was not reversed by the PDE2 inhibitors despite the increased hydrolysis of cAMP by PDE2.

Challenges in the diagnosis and management of acromegaly: a focus on comorbidities.

INTRODUCTION: Acromegaly is a rare, insidious disease resulting from the overproduction of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), and is associated with a range of comorbidities. The extent of associated complications and mortality risk is related to length of exposure to the excess GH and IGF-1, thus early diagnosis and treatment is imperative. Unfortunately, acromegaly is often diagnosed late, when patients already have a wide range of comorbidities. The presence of comorbid conditions contributes significantly to patient morbidity/mortality and impaired quality of life. METHODS: We conducted a retrospective literature review for information relating to the diagnosis of acromegaly, and its associated comorbidities using PubMed. The main aim of this review is to highlight the issues of comorbidities in acromegaly, and to reinforce the importance of early diagnosis and treatment. FINDINGS AND CONCLUSIONS: Successful management of acromegaly goes beyond treating the disease itself, since many patients are diagnosed late in disease evolution, they present with a range of comorbid conditions, such as cardiovascular disease, diabetes, hypertension, and sleep apnea. It is important that patients are screened carefully at diagnosis (and thereafter), for common associated complications, and that biochemical control does not become the only treatment goal. Mortality and morbidities in acromegaly can be reduced successfully if patients are treated using a multimodal approach with comprehensive comorbidity management.

Inhibitors of phosphodiesterases PDE2, PDE3, and PDE4 do not increase the sinoatrial tachycardia of noradrenaline and prostaglandin PGE1 in mice.

Phosphodiesterases PDE2, PDE3, and PDE4 are expressed in murine sinoatrial cells. PDE3 and/or PDE4 reduce heart rate but apparently do not influence the tachycardia mediated through sinoatrial ß1- and ß2-adrenoceptors despite the high content of sinoatrial cAMP. The function of PDE2 is, however, uncertain. Prostaglandin PGE1 elicits sinoatrial tachycardia through EP receptors, but the control by phosphodiesterases is unknown. We investigated on spontaneously beating right atria of mice the effects of the PDE2 inhibitors Bay 60-7550 and EHNA on basal beating and the tachycardia produced by noradrenaline (3 nM) and PGE1 (1 µM). Bay 60-7550 (1 µM), but not EHNA (10 µM), increased basal sinoatrial beating. EHNA also failed to produce tachycardia in the presence of the adenosine deaminase inhibitor 2'-deoxycoformycin (10 µM), remaining inconclusive whether PDE2 reduces basal sinoatrial beating. Rolipram (10 µM) and cilostamide (300 nM) caused moderate tachycardia. The tachycardia evoked by Bay 60-7550 was similar in the absence and presence of rolipram. Noradrenaline elicited stable tachycardia that was not increased by Bay 60-7550. A stable tachycardia caused by PGE1 was not increased by the inhibitors of PDE2, PDE3, and PDE4. Unlike PDE3 and PDE4 which reduce murine basal sinoatrial beating, a possible effect of PDE2 needs further research. The stable tachycardia produced by noradrenaline and PGE1, together with the lack potentiation by the inhibitors of PDE2, PDE3, and PDE4, suggests that cAMP generated at the receptor compartments is hardly hydrolyzed by these phophodiesterases. Evidence from human volunteers is consistent with this proposal.