Identification of a pathogenic mutation in ARPP21 in patients with amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVE: Between 5% and 10% of amyotrophic lateral sclerosis (ALS) cases have a family history of the disease, 30% of which do not have an identifiable underlying genetic cause after a comprehensive study of the known ALS-related genes. Based on a significantly increased incidence of ALS in a small geographical region from Spain, the aim of this work was to identify novel ALS-related genes in ALS cases with negative genetic testing. METHODS: We detected an increased incidence of both sporadic and, especially, familial ALS cases in a small region from Spain compared with available demographic and epidemiological data. We performed whole genome sequencing in a group of 12 patients with ALS (5 of them familial) from this unique area. We expanded the study to include affected family members and additional cases from a wider surrounding region. RESULTS: We identified a shared missense mutation (c.1586C>T; p.Pro529Leu) in the cyclic AMP regulated phosphoprotein 21 (ARPP21) gene that encodes an RNA-binding protein, in a total of 10 patients with ALS from 7 unrelated families. No mutations were found in other ALS-causing genes. CONCLUSIONS: While previous studies have dismissed a causal role of ARPP21 in ALS, our results strongly support ARPP21 as a novel ALS-causing gene.

Assessment of brain-derived extracellular vesicle enrichment for blood biomarker analysis in age-related neurodegenerative diseases: An international overview.

INTRODUCTION: Brain-derived extracellular vesicles (BEVs) in blood allows for minimally-invasive investigations of central nervous system (CNS) -specific markers of age-related neurodegenerative diseases (NDDs). Polymer-based EV- and immunoprecipitation (IP)-based BEV-enrichment protocols from blood have gained popularity. We systematically investigated protocol consistency across studies, and determined CNS-specificity of proteins associated with these protocols. METHODS: NDD articles investigating BEVs in blood using polymer-based and/or IP-based BEV enrichment protocols were systematically identified, and protocols compared. Proteins used for BEV-enrichment and/or post-enrichment were assessed for CNS- and brain-cell-type-specificity, extracellular domains (ECD+), and presence in EV-databases. RESULTS: A total of 82.1% of studies used polymer-based (ExoQuick) EV-enrichment, and 92.3% used L1CAM for IP-based BEV-enrichment. Centrifugation times differed across studies. A total of 26.8% of 82 proteins systematically identified were CNS-specific: 50% ECD+, 77.3% were listed in EV-databases. CONCLUSIONS: We identified protocol steps requiring standardization, and recommend additional CNS-specific proteins that can be used for BEV-enrichment or as BEV-biomarkers. HIGHLIGHTS: Across NDDs, we identified protocols commonly used for EV/BEV enrichment from blood. We identified protocol steps showing variability that require harmonization. We assessed CNS-specificity of proteins used for BEV-enrichment or found in BEV cargo. CNS-specific EV proteins with ECD+ or without were identified. We recommend evaluation of blood-BEV enrichment using these additional ECD+ proteins.

Proteomic comparison between non-purified cerebrospinal fluid and cerebrospinal fluid-derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia.

Dementia is a leading cause of death worldwide, with increasing prevalence as global life expectancy increases. The most common neurodegenerative disorders are Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). With this study, we took an in-depth look at the proteome of the (non-purified) cerebrospinal fluid (CSF) and the CSF-derived extracellular vesicles (EVs) of AD, PD, PD-MCI (Parkinson's disease with mild cognitive impairment), PDD and DLB patients analysed by label-free mass spectrometry. This has led to the discovery of differentially expressed proteins that may be helpful for differential diagnosis. We observed a greater number of differentially expressed proteins in CSF-derived EV samples (N = 276) compared to non-purified CSF (N = 169), with minimal overlap between both datasets. This finding suggests that CSF-derived EV samples may be more suitable for the discovery phase of a biomarker study, due to the removal of more abundant proteins, resulting in a narrower dynamic range. As disease-specific markers, we selected a total of 39 biomarker candidates identified in non-purified CSF, and 37 biomarker candidates across the different diseases under investigation in the CSF-derived EV data. After further exploration and validation of these proteins, they can be used to further differentiate between the included dementias and may offer new avenues for research into more disease-specific pharmacological therapeutics.

Assessment of brain-derived extracellular vesicle enrichment for blood biomarker analysis in age-related neurodegenerative diseases: An international overview.

INTRODUCTION: Brain-derived extracellular vesicles (BEVs) in blood allows for minimally- invasive investigations of CNS-specific markers of age-related neurodegenerative diseases (NDDs). Polymer-based EV- and immunoprecipitation (IP)-based BEV-enrichment protocols from blood have gained popularity. We systematically investigated protocol consistency across studies, and determined CNS-specificity of proteins associated with these protocols. METHODS: NDD articles investigating BEVs in blood using polymer-based and/or IP-based BEV enrichment protocols were systematically identified, and protocols compared. Proteins used for BEV-enrichment and/or post-enrichment were assessed for CNS- and brain-cell-type- specificity; extracellular domains (ECD+); and presence in EV-databases. RESULTS: 82.1% of studies used polymer-based (ExoQuick) EV-enrichment, and 92.3% used L1CAM for IP-based BEV-enrichment. Centrifugation times differed across studies. 26.8% of 82 proteins systematically identified were CNS-specific: 50% ECD+, 77.3% were listed in EV- databases. DISCUSSION: We identified protocol steps requiring standardization, and recommend additional CNS-specific proteins that can be used for BEV-enrichment or as BEV-biomarkers.

Basal forebrain atrophy along the Alzheimer's disease continuum in adults with Down syndrome.

BACKGROUND: Basal forebrain (BF) degeneration occurs in Down syndrome (DS)-associated Alzheimer's disease (AD). However, the dynamics of BF atrophy with age and disease progression, its impact on cognition, and its relationship with AD biomarkers have not been studied in DS. METHODS: We included 234 adults with DS (150 asymptomatic, 38 prodromal AD, and 46 AD dementia) and 147 euploid controls. BF volumes were extracted from T-weighted magnetic resonance images using a stereotactic atlas in SPM12. We assessed BF volume changes with age and along the clinical AD continuum and their relationship to cognitive performance, cerebrospinal fluid (CSF) and plasma amyloid/tau/neurodegeneration biomarkers, and hippocampal volume. RESULTS: In DS, BF volumes decreased with age and along the clinical AD continuum and significantly correlated with amyloid, tau, and neurofilament light chain changes in CSF and plasma, hippocampal volume, and cognitive performance. DISCUSSION: BF atrophy is a potentially valuable neuroimaging biomarker of AD-related cholinergic neurodegeneration in DS.

Association of biological sex with clinical outcomes and biomarkers of Alzheimer's disease in adults with Down syndrome.

The study of sex differences in Alzheimer's disease is increasingly recognized as a key priority in research and clinical development. People with Down syndrome represent the largest population with a genetic link to Alzheimer's disease (>90% in the 7th decade). Yet, sex differences in Alzheimer's disease manifestations have not been fully investigated in these individuals, who are key candidates for preventive clinical trials. In this double-centre, cross-sectional study of 628 adults with Down syndrome [46% female, 44.4 (34.6; 50.7) years], we compared Alzheimer's disease prevalence, as well as cognitive outcomes and AT(N) biomarkers across age and sex. Participants were recruited from a population-based health plan in Barcelona, Spain, and from a convenience sample recruited via services for people with intellectual disabilities in England and Scotland. They underwent assessment with the Cambridge Cognitive Examination for Older Adults with Down Syndrome, modified cued recall test and determinations of brain amyloidosis (CSF amyloid-ß 42 / 40 and amyloid-PET), tau pathology (CSF and plasma phosphorylated-tau181) and neurodegeneration biomarkers (CSF and plasma neurofilament light, total-tau, fluorodeoxyglucose-PET and MRI). We used within-group locally estimated scatterplot smoothing models to compare the trajectory of biomarker changes with age in females versus males, as well as by apolipoprotein ɛ4 carriership. Our work revealed similar prevalence, age at diagnosis and Cambridge Cognitive Examination for Older Adults with Down Syndrome scores by sex, but males showed lower modified cued recall test scores from age 45 compared with females. AT(N) biomarkers were comparable in males and females. When considering apolipoprotein ɛ4, female ɛ4 carriers showed a 3-year earlier age at diagnosis compared with female non-carriers (50.5 versus 53.2 years, P = 0.01). This difference was not seen in males (52.2 versus 52.5 years, P = 0.76). Our exploratory analyses considering sex, apolipoprotein ɛ4 and biomarkers showed that female ɛ4 carriers tended to exhibit lower CSF amyloid-ß 42/amyloid-ß 40 ratios and lower hippocampal volume compared with females without this allele, in line with the clinical difference. This work showed that biological sex did not influence clinical and biomarker profiles of Alzheimer's disease in adults with Down syndrome. Consideration of apolipoprotein ɛ4 haplotype, particularly in females, may be important for clinical research and clinical trials that consider this population. Accounting for, reporting and publishing sex-stratified data, even when no sex differences are found, is central to helping advance precision medicine.

Epidemiological characteristics and real-world treatment outcomes of hepatitis C among HIV/HCV co-infected patients in Myanmar: A prospective cohort study.

Background and Aims: In Myanmar, public sector treatment programs for hepatitis C virus (HCV) infection were nonexistent until June 2017. WHO highlights the importance of simplification of HCV service delivery through task-shifting among health workers and decentralization to the primary health care level. Between November 2016 and November 2017, a study was conducted to describe the epidemiological data and real-world outcomes of treating HIV/HCV coinfected patients with generic direct acting antiviral (DAA) based regimens in the three HIV clinics run by nonspecialist medical doctors in Myanmar. Methods: HCV co-infection among people living with HIV (PLHIV) from two clinics in Yangon city and one clinic in Dawei city was screened by rapid diagnostic tests and confirmed by testing for viral RNA. Nonspecialist medical doctors prescribed sofosbuvir and daclatasvir based regimens (with or without ribavirin) for 12 or 24 weeks based on the HCV genotype and liver fibrosis status. Sustained virologic response at 12 weeks after treatment (SVR12) was assessed to determine cure. Results: About 6.5% (1417/21,777) of PLHIV were co-infected with HCV. Of 864 patients enrolled in the study, 50.8% reported history of substance use, 27% history of invasive medical procedures and 25.6% history of incarceration. Data on treatment outcomes were collected from 267 patients of which 257 (96.3%) achieved SVR12, 7 (2.6%) failed treatment, 2 (0.7%) died and 1 (0.4%) became loss to follow-up. Conclusion: The study results support the integration of hepatitis C diagnosis and treatment with DAA-based regimens into existing HIV clinics run by nonspecialist medical doctors in a resource-limited setting. Epidemiological data on HIV/HCV co-infection call for comprehensive HCV care services among key populations like drug users and prisoners in Yangon and Dawei.

Amyloid precursor protein 𝛽CTF accumulates in synapses in sporadic and genetic forms of Alzheimer's disease.

AIMS: Amyloid precursor protein (APP) 𝛽-C-terminal fragment (𝛽CTF) may have a neurotoxic role in Alzheimer's disease (AD). 𝛽CTF accumulates in the brains of patients with sporadic (SAD) and genetic forms of AD. Synapses degenerate early during the pathogenesis of AD. We studied whether the 𝛽CTF accumulates in synapses in SAD, autosomal dominant AD (ADAD) and Down syndrome (DS). METHODS: We used array tomography to determine APP at synapses in human AD tissue. We measured 𝛽CTF, A𝛽40, A𝛽42 and phosphorylated tau181 (p-tau181) concentrations in brain homogenates and synaptosomes of frontal and temporal cortex of SAD, ADAD, DS and controls. RESULTS: APP colocalised with pre- and post-synaptic markers in human AD brains. APP 𝛽CTF was enriched in AD synaptosomes. CONCLUSIONS: We demonstrate that 𝛽CTF accumulates in synapses in SAD, ADAD and DS. This finding might suggest a role for 𝛽CTF in synapse degeneration. Therapies aimed at mitigating 𝛽CTF accumulation could be potentially beneficial in AD.

Enrichment of Astrocyte-Derived Extracellular Vesicles from Human Plasma.

Extracellular vesicles (EVs) are biological nanoparticles secreted by all cells for cellular communication and waste elimination. They participate in a vast range of functions by acting on and transferring their cargos to other cells in physiological and pathological conditions. Given their presence in biofluids, EVs represent an excellent resource for studying disease processes and can be considered a liquid biopsy for biomarker discovery. An attractive aspect of EV analysis is that they can be selected based on markers of their cell of origin, thus reflecting the environment of a specific tissue in their cargo. However, one of the major handicaps related to EV isolation methods is the lack of methodological consensuses and standardized protocols. Astrocytes are glial cells with essential roles in the brain. In neurodegenerative diseases, astrocyte reactivity may lead to altered EV cargo and aberrant cellular communication, facilitating/enhancing disease progression. Thus, analysis of astrocyte EVs may lead to the discovery of biomarkers and potential disease targets. This protocol describes a 2-step method of enrichment of astrocyte-derived EVs (ADEVs) from human plasma. First, EVs are enriched from defibrinated plasma via polymer-based precipitation. This is followed by enrichment of ADEVs through ACSA-1-based immunocapture with magnetic micro-beads, where resuspended EVs are loaded onto a column placed in a magnetic field. Magnetically labeled ACSA-1+ EVs are retained within the column, while other EVs flow through. Once the column is removed from the magnet, ADEVs are eluted and are ready for storage and analysis. To validate the enrichment of astrocyte markers, glial fibrillary acidic protein (GFAP), or other specific astrocytic markers of intracellular origin, can be measured in the eluate and compared with the flow-through. This protocol proposes an easy, time-efficient method to enrich ADEVs from plasma that can be used as a platform to examine astrocyte-relevant markers.

Association of Alzheimer Disease With Life Expectancy in People With Down Syndrome.

Importance: People with Down syndrome have a high risk of developing Alzheimer disease dementia. However, penetrance and age at onset are considered variable, and the association of this disease with life expectancy remains unclear because of underreporting in death certificates. Objective: To assess whether the variability in symptom onset of Alzheimer disease in Down syndrome is similar to autosomal dominant Alzheimer disease and to assess its association with mortality. Design, Setting, and Participants: This study combines a meta-analysis with the assessment of mortality data from US death certificates (n = 77 347 case records with a International Classification of Diseases code for Down syndrome between 1968 to 2019; 37 900 [49%] female) and from a longitudinal cohort study (n = 889 individuals; 46% female; 3.2 [2.1] years of follow-up) from the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI). Main Outcomes and Measures: A meta-analysis was conducted to investigate the age at onset, age at death, and duration of Alzheimer disease dementia in Down syndrome. PubMed/Medline, Embase, Web of Science, and CINAHL were searched for research reports, and OpenGray was used for gray literature. Studies with data about the age at onset or diagnosis, age at death, and disease duration were included. Pooled estimates with corresponding 95% CIs were calculated using random-effects meta-analysis. The variability in disease onset was compared with that of autosomal dominant Alzheimer disease. Based on these estimates, a hypothetical distribution of age at death was constructed, assuming fully penetrant Alzheimer disease. These results were compared with real-world mortality data. Results: In this meta-analysis, the estimate of age at onset was 53.8 years (95% CI, 53.1-54.5 years; n = 2695); the estimate of age at death, 58.4 years (95% CI, 57.2-59.7 years; n = 324); and the estimate of disease duration, 4.6 years (95% CI, 3.7-5.5 years; n = 226). Coefficients of variation and 95% prediction intervals of age at onset were comparable with those reported in autosomal dominant Alzheimer disease. US mortality data revealed an increase in life expectancy in Down syndrome (median [IQR], 1 [0.3-16] years in 1968 to 57 [49-61] years in 2019), but with clear ceiling effects in the highest percentiles of age at death in the last decades (90th percentile: 1990, age 63 years; 2019, age 65 years). The mortality data matched the limits projected by a distribution assuming fully penetrant Alzheimer disease in up to 80% of deaths (corresponding to the highest percentiles). This contrasts with dementia mentioned in 30% of death certificates but is in agreement with the mortality data in DABNI (78.9%). Important racial disparities persisted in 2019, being more pronounced in the lower percentiles (10th percentile: Black individuals, 1 year; White individuals, 30 years) than in the higher percentiles (90th percentile: Black individuals, 64 years; White individuals, 66 years). Conclusions and Relevance: These findings suggest that the mortality data and the consistent age at onset were compatible with fully penetrant Alzheimer disease. Lifespan in persons with Down syndrome will not increase until disease-modifying treatments for Alzheimer disease are available.

Evaluation of an augmented reality platform for austere surgical telementoring: a randomized controlled crossover study in cricothyroidotomies.

Telementoring platforms can help transfer surgical expertise remotely. However, most telementoring platforms are not designed to assist in austere, pre-hospital settings. This paper evaluates the system for telementoring with augmented reality (STAR), a portable and self-contained telementoring platform based on an augmented reality head-mounted display (ARHMD). The system is designed to assist in austere scenarios: a stabilized first-person view of the operating field is sent to a remote expert, who creates surgical instructions that a local first responder wearing the ARHMD can visualize as three-dimensional models projected onto the patient's body. Our hypothesis evaluated whether remote guidance with STAR could lead to performing a surgical procedure better, as opposed to remote audio-only guidance. Remote expert surgeons guided first responders through training cricothyroidotomies in a simulated austere scenario, and on-site surgeons evaluated the participants using standardized evaluation tools. The evaluation comprehended completion time and technique performance of specific cricothyroidotomy steps. The analyses were also performed considering the participants' years of experience as first responders, and their experience performing cricothyroidotomies. A linear mixed model analysis showed that using STAR was associated with higher procedural and non-procedural scores, and overall better performance. Additionally, a binary logistic regression analysis showed that using STAR was associated to safer and more successful executions of cricothyroidotomies. This work demonstrates that remote mentors can use STAR to provide first responders with guidance and surgical knowledge, and represents a first step towards the adoption of ARHMDs to convey clinical expertise remotely in austere scenarios.

Telementoring in Leg Fasciotomies via Mixed-Reality: Clinical Evaluation of the STAR Platform.

INTRODUCTION: Point-of-injury (POI) care requires immediate specialized assistance but delays and expertise lapses can lead to complications. In such scenarios, telementoring can benefit health practitioners by transmitting guidance from remote specialists. However, current telementoring systems are not appropriate for POI care. This article clinically evaluates our System for Telementoring with Augmented Reality (STAR), a novel telementoring system based on an augmented reality head-mounted display. The system is portable, self-contained, and displays virtual surgical guidance onto the operating field. These capabilities can facilitate telementoring in POI scenarios while mitigating limitations of conventional telementoring systems. METHODS: Twenty participants performed leg fasciotomies on cadaveric specimens under either one of two experimental conditions: telementoring using STAR; or without telementoring but reviewing the procedure beforehand. An expert surgeon evaluated the participants' performance in terms of completion time, number of errors, and procedure-related scores. Additional metrics included a self-reported confidence score and postexperiment questionnaires. RESULTS: STAR effectively delivered surgical guidance to nonspecialist health practitioners: participants using STAR performed fewer errors and obtained higher procedure-related scores. CONCLUSIONS: This work validates STAR as a viable surgical telementoring platform, which could be further explored to aid in scenarios where life-saving care must be delivered in a prehospital setting.

Desordenes musculoesqueléticos en trabajadores de mantenimiento de alcantarillado en una empresa de servicios públicos de Colombia y su relación con características sociodemográficas, laborales y condiciones médicas generales, Medellín 2016 / Musculoskeletal disorders in sewer maintenance workers in an utility of Colombia and its relationship to sociodemographic characteristics, employment and general medical conditions, Medellin 2016

Introducción: trabajadores que realizan mantenimiento en alcantarillados se exponen a riesgos disergonomicos que pueden desencadenar patologías osteomusculares. Métodos: estudio descriptivo, con fuente primaria de información, previa obtención de consentimiento informado a un censo de trabajadores (43) que realizan labores de mantenimiento en una empresa de servicios públicos de Colombia. Se exploraron variables socio-demográficas, económicas, de salud y laborales. El riesgo ergonómico fue evaluado con el cuestionario RULA. Se realizaron análisis descriptivos y de asociación, con una confianza del 95% y error del 5%. Resultados: trabajadores con 43 años (±12 años), 44,2% eran oficiales de mantenimiento de aguas, con peso normal y sobre peso, prevalencia de diabetes 5,1%, artrosis y lesión de tejidos blandos 12,5%, fumadores activos un 12,8% y 37,2% con dolor en miembros superiores. El 86,0% realizaba labores que requieren cambios urgentes, 25,6% con diagnóstico de síndrome del manguito de rotadores y 7,0% manguito de rotadores y epicondilitis lateral y/o medial de codo. Aumento de desórdenes musculo esqueléticos con el aumento del tiempo de labor, haber tenido cirugía de hombro o antecedentes de accidentes en hombro y mayor edad. Conclusiones: se evidencia la necesidad de adelantar acciones preventivas y correctivas en la población de estudio, características como el tiempo en su oficio, la labor que se desempeña y la edad, se asocian con mayor riesgo de desórdenes musculoesqueléticos

Introduction: workers who perform maintenance in sewage systems are exposed to disergonomic risks that can trigger osteomuscular diseases. Methods: a descriptive study, with a primary source of information, after obtaining informed consent to a census of workers (43) who perform maintenance tasks in a public utility company in Colombia. Socio-demographic, economic, health and labor variables were explored. The ergonomic risk was evaluated with the RULA questionnaire. Descriptive and association analyzes were performed, with 95% confidence and 5% error. Results: of te workers aged 43 (± 12 years), 44.2% were water maintenance officers, with normal weight and overweight, prevalence of diabetes 5.1%, osteoarthritis and soft tissue injury 12.5%, active smokers 12.8% and 37.2% with pain in upper limbs. 86.0% performed tasks requiring urgent changes, 25.6% with a diagnosis of rotator cuff and 7.0% rotator cuff and lateral and/or medial elbow epicondylitis. The increase of musculoskeletal disorders with increased labor time, was associated to having had shoulder surgery or a history of shoulder accidents and older age. Conclusions: there is evidence of the need to carry out preventive and corrective actions in the study population, characteristics such as time in office, the work performed and age, are associated with increased risk of musculoskeletal disorders

Aterectomía rotacional para manejo de expansión inadecuada de stent (stentablacion) / Rotational atherectomy for the management of inadequate stent expansion (stent ablation)

Resumen El uso de la aterectomía rotacional para la ablación de parte de un stent metálico ha sido muy limitado. Reportamos el caso de una paciente de 40 años de edad, con inadecuada expansión del stent a pesar de la dilatación con balón de alta presión, debido a una placa severamente calcificada. La paciente es tratada con éxito con ablación del stent.

Abstract The use of rotational atherectomy for the ablation of part of a metallic stent has been very limited. We report the case of a 40 year-old female patient with an inadequate expansion of the stent despite the dilation with a high-pressure balloon, due to severely calcified plaque. Patient is successfully treated with stent ablation.

Prueba de vasorreactividad con iloprost en hipertensión arterial pulmonar / Proof of vasoreactivity with iloprost in pulmonary arterial hypertension

Resumen Introducción: la detección de vasorreactividad pulmonar en hipertensión pulmonar es importante para determinar el beneficio del tratamiento con calcioantagonistas a largo plazo. En los últimos años se ha utilizado el iloprost como alternativa para la realización de la prueba con buenos resultados, por lo que es importante evaluar su respuesta en pacientes con esta enfermedad. Métodos: estudio cuasiexperimental no controlado con diseño de antes y después para evaluar la respuesta a un vasodilatador inhalado en pacientes remitidos al laboratorio de hemodinamia para pruebas de reactividad pulmonar. Se analizó una muestra no probabilística por conveniencia con la cohorte descrita. Se les realizó cateterismo derecho con medición de parámetros hemodinámicos y se evaluó la respuesta a la administración de 10 mcg de iloprost inhalado. Se consideró positiva la prueba si la presión arterial pulmonar media disminuía > 10 mmHg hasta < 40 mmHg, con aumento del gasto cardiaco o sin cambios en éste. Resultados: se incluyeron 30 pacientes; el promedio de edad fue de 55.5 ± 12 años, el 76.7% fueron mujeres y la fracción de eyección del ventrículo izquierdo fue de 52 ± 10%. La prueba se consideró positiva en 16.7% de los casos, sin complicaciones relacionadas al uso del medicamento. Se observó aumento no significativo del gasto cardiaco, con descenso importante en la resistencia vascular sistémica (1279 ± 438 vs 1110± 379, p=0.000004), resistencia vascular pulmonar (483 ± 210 vs 383 ± 185, p=0.000002), presión arterial pulmonar (47 ± 6 vs 39 ± 7, p=0.000002) y presión en cuña de la arteria pulmonar (16 ± 5 vs 15 ± 4, p<0.00009). Conclusión: el uso de iloprost inhalado en dosis de 10 mcg, en pacientes con hipertensión pulmonar llevados a cateterismo cardiaco derecho es una alternativa para identificar vasorreactividad, con baja tasa de eventos adversos. (Acta Med Colomb 2016; 40: 229-234).

Abstract Introduction: the detection of pulmonary vasoreactivity in pulmonary hypertension is important to determine the benefit of treatment with long-term calcium antagonists. In recent years, iloprost has been used as an alternative to perform the test with good results, so it is important to evaluate its response in patients with this disease. Methods: a quasi-experimental, uncontrolled study with before and after design to evaluate the response to an inhaled vasodilator in patients referred to the hemodynamic laboratory for pulmonary reactivity tests. A non-probabilistic sample was analyzed for convenience with the described cohort. Right catheterization was performed with measurements of hemodynamic parameters and the response to administration of 10 mcg of inhaled iloprost was performed in these patients. The test was considered positive if mean pulmonary artery pressure decreased >10 mmHg to <40 mmHg, with or without cardiac output increase. Results: 30 patients were included; mean age was 55.5 ± 12 years, 76.7% were women and the left ventricular ejection fraction was 52 ± 10%. The test was considered positive in 16.7% of cases, without complications related to the use of the drug. There was significant increase in cardiac output with an important decrease in systemic vascular resistance (1279 ± 438 vs 1110 ± 379, p = 0.000004), pulmonary vascular resistance (483 ± 210 vs 383 ± 185, p = 0.000002), blood pressure (47 ± 6 vs 39 ± 7, p = 0.000002), and wedge pressure of the pulmonary artery (16 ± 5 vs. 15 ± 4, p <0.00009). Conclusion: The use of inhaled iloprost in doses of 10 mcg in patients with pulmonary hypertension taken to right cardiac catheterization is an alternative to identify vasoreactivity with low rate of adverse events. (Acta Med Colomb 2016; 40: 229-234).

Dimensional changes of hard and soft tissues in post-extraction sites: evaluation of two biomaterials / Cambios dimensionales de los tejidos duros y blandos en sitios post-exodoncia: evaluación de dos biomateriales

ABSTRACT Introduction: the techniques for alveolar ridge preservation with different biomaterials show better healing processes and modify the patterns of alveolar bone resorption. The goal of this study was to evaluate the clinical, radiographic, and histological changes of tissues in post-extraction sites after 90 and 180 days by using two biomaterials for alveolar ridge preservation. Materials: descriptive study involving the extraction of twenty-seven uni- and biradicular teeth comparing two biomaterials randomly distributed. Group A received resorbable synthetic hydroxyapatite (OsseoU) and Group B received mineralized freeze-dried allogeneic bone (Tissue Bank®). Quantitative and qualitative measurements were made 180 days post-extraction. The statistical analysis was conducted with the Shapiro-Wilks, Levine, and Student t tests. Results: comparing the two biomaterials on day 180 yielded no statistically significant differences in terms of the "height" variable. The "width" variable yields a p = 0.010 value, suggesting statistically significant differences, since Group A is 0.789 ± 0.276 times better (3.72 ± 0.76) than group B (2.93 ± 0.55). The radiographic evaluation did not yield differences between both groups (p = 0.711). Conclusion: this study shows the dimensional changes of post-extraction sites in both groups, with a clinical difference in ridge width, and no radiographic or histological differences, neither statistically significant changes in terms of alveolar ridge height. Resorbable synthetic hydroxyapatite (OsseoU) is then a biomaterial as effective as mineralized freeze-dried allogeneic bone (Tissue Bank®).

RESUMEN. Introducción: las técnicas de preservación del reborde alveolar con diferentes biomateriales demuestran un mejor proceso de cicatrización que si no se lleva a cabo ningún procedimiento y modifican los patrones de reabsorción del hueso alveolar. El objetivo del presente estudio consistió en evaluar los cambios clínicos, radiográficos e histológicos de los tejidos en sitios post-exodoncia a los 90 y 180 días, utilizando dos biomateriales para la preservación del reborde. Materiales: estudio descriptivo en el que se hacen las exodoncias de veintisiete dientes uni- y birradiculares y se comparan dos biomateriales diferentes repartidos aleatoriamente. El grupo A recibió hidroxiapatita sintética reabsorbible (OsseoU) y el grupo B recibió hueso alogénico mineralizado, secado por congelación (Tissue Bank®). Se hicieron mediciones cuantitativas y cualitativas a los 180 días. El análisis estadístico se realizó con pruebas de Shapiro-Wilks, Levine y t-Student. Resultados: al comparar los dos biomateriales a los 180 días, se observa que en la variable "altura" no existen diferencias estadísticamente significativas. En la variable "amplitud" se establece un valor p = 0,010, lo cual indica que hay diferencias estadísticamente significativas, siendo 0,789 ± 0,276 mejor el grupo A (3,72 ± 0,76) comparado con el grupo B (2,93 ± 0,55). En la evaluación radiográfica no se reportan diferencias entre los dos grupos (p = 0,711). Conclusión: este estudio demuestra cambios dimensionales de los sitios post-exodoncia en ambos grupos, con diferencia clínica en la amplitud de reborde, y sin diferencias radiográficas ni histológicas, ni cambios estadísticamente significativos en cuanto a la altura del reborde. La hidroxiapatita sintética reabsorbible (OsseoU) es entonces un biomaterial igual de efectivo que el hueso alogénico mineralizado, secado por congelación (Tissue Bank®). Palabras claves: técnicas de preservación de reborde, hidroxiapatita sintética, hueso alogénico mineralizado, secado por congelación.

Anomalías de las arterias coronarias / Coronary arteries abnormalities / As anormalidades das artérias coronárias

El dolor torácico no relacionado con trauma es una causa importante de consulta en los servicios de urgencias, con frecuencia alrededor del 10 %, y es secundario al síndrome coronario agudo. La mayoría de las veces está relacionado con la formación de un trombo por ulceración o ruptura de una placa aterosclerótica. En algunos casos es secundario a causas raras como las anomalías del origen de las arterias coronarias. Presentamos el caso de un paciente con origen anómalo del tronco de la arteria coronaria izquierda, que ingresó con cuadro clínico sugestivo de síndrome coronario agudo sin elevación del segmento ST. Se discuten sus principales aspectos, el significado clínico y las opciones terapéuticas.

Chest pain not related with injury is an important cause of visit to emergency departments; it accounts for 10 % of such visits and is caused by acute coronary syndrome. In most cases it is related to thrombus formation secondary to ulceration or rupture of an atherosclerotic plaque. Sometimes it is secondary to rare causes such as the presence of congenital coronary artery anomalies. We report the case of a patient with anomalous origin of the left main coronary artery, who was admitted to the hospital with a clinical picture suggestive of acute coronary syndrome without ST segment elevation. Its main aspects, clinical significance and therapeutic options are discussed.

das principais causas de consulta a serviços de emergência, muitas vezes em torno de 10 por cento e é secundária à síndrome coronariana aguda. A maior parte das vezes está relacionada com a formação de um trombo por ulceração ou ruptura de uma placa aterosclerótica. Em alguns casos, é secundária a causas raras como as anomalias da origem das artérias coronárias. Apresentamos o caso de um paciente com origem anômala da artéria coronária esquerda do tronco, que ingressou com um quadro clínico sugestivo de síndromes coronarianas agudas sem elevação do segmento ST . Se discutem os principais aspectos, o significado clínico e opções de tratamento.

Eficacia y seguridad del acceso radial y femoral en pacientes con síndrome coronario agudo llevados a intervencionismo coronario Redial - Registro de intervención por vía radial / Efficacy and safety of radial and femoral access in patients with acute coronary syndrome undergoing coronary intervention Redial - Registration of intervention by radial access

Introducción: el acceso transradial ha surgido como una alternativa atractiva a la vía femoral para realizar coronariografías e intervenciones coronarias. Describimos nuestra experiencia, y comparamos el acceso radial con una cohorte de acceso femoral en un periodo de tiempo. Objetivo: identificar las complicaciones vasculares relacionadas con la coronariografía en pacientes de la unidad de dolor torácico de una institución de alta complejidad de la ciudad de Medellín. Materiales y métodos: estudio epidemiológico observacional, analítico, de una cohorte retrospectiva de pacientes mayores de 18 años que ingresaron a la unidad de dolor torácico del hospital Universitario San Vicente Fundación con diagnóstico de síndrome coronario agudo con y sin elevación del ST, y a los cuales se les realizó coronariografía por acceso radial y femoral. Resultados: se evaluaron 675 pacientes, de los cuales 59.6% (n=402) se les realizó acceso femoral y 40.4% (n=273) acceso radial con diferencias, en relación al sexo y aspectos personales como el tabaquismo y la enfermedad renal crónica. Respecto a las complicaciones según el tipo de acceso, se hallaron diferencias significativas en la presencia de hematoma femoral (OR= 5.6; IC 95%: 1.28; 24.63) y el espasmo radial (p<0.05). Conclusión: los accesos radial y femoral son seguros y efectivos, sin embargo la disminución significativa de las complicaciones vasculares puede ser una razón para preferir el acceso radial como técnica de elección en la mayoría de estos pacientes. (Acta Med Colomb 2015; 40: 209-217).

Introduction: the transradial access has emerged as an attractive alternative to the femoral access for coronary angiography and coronary interventions. We describe our experience, and compare the radial access with a cohort of femoral access in a time period. Objective: to identify vascular complications related to coronary angiography in patients of the chest pain unit of a high complexity institution of the city of Medellin. Materials and Methods: epidemiological, observational, analytical study of a retrospective cohort of patients over 18 years admitted to the chest pain unit of the University Hospital San Vicente Foundation with diagnosis of acute coronary syndrome with and without ST elevation in which coronary angiography by radial and femoral access was performed. Results: 675 patients were evaluated. 59.6% (n = 402) underwent femoral access, and 40.4% (n = 273) radial access with differences in relation to sex and personal aspects such as smoking and chronic kidney disease. Regarding complications according to the type of access, significant differences were found in regard to the presence of femoral hematoma (OR = 5.6; 95% CI: 1.28; 24.63) and radial artery spasm (p <0.05). Conclusion: the radial and femoral accesses are safe and effective; however, the significant decrease in vascular complications may be a reason to prefer the radial access as technique of choice in most of these patients. (Acta Med Colomb 2015; 40: 209-217).

Evaluación del complejo ganglionar celular mediante tomografía de coherencia óptica en pacientes con hipertensión ocular / Ganglion cell complex evaluation with optical coherence tomography in patients with ocular hypertension

Objetivos: determinar el espesor del complejo ganglionar celular (CGC) mediante tomografía de coherencia óptica de dominio de Fourier (FD-OCT) en pacientes con diagnóstico de hipertensión ocular previa clasificación del riesgo de conversión a glaucoma utilizando la regla STAR (Scoring Tool For Assessing Risk). Materiales y Métodos: mediante la revisión de historias clínicas, se seleccionaron pacientes con diagnóstico previo de hipertensión ocular (HTO). A cada paciente se le realizó una valoración oftalmológica completa, medición del espesor del CGC mediante OCT y calculo del STAR. Los datos obtenidos se relacionaron con variables demográficas, presión intraocular, paquimetría central y perimetría computarizada. Resultados: se analizaron 106 ojos de 53 pacientes con HTO. La PIO promedio fue de 23.55 ± 0.69 mmHg. La regla STAR fue aplicada en 96 ojos. El 65.6% (63 ojos) se categorizó en alto riesgo de conversión a glaucoma en los próximos cinco años. Los pacientes de este grupo presentaron un espesor del CGC significativamente menor que el de los otros grupos. El valor promedio del espesor del complejo ganglionar superior e inferior fue de 83 ± 4.5 micras y 82.09 ± 4.98 micras respectivamente. Conclusión: los pacientes clasificados en el grupo de alto riesgo STAR tienen espesores del CGC significativamente menores. La disminución del espesor del CGC se correlacionó positivamente con las anormalidades registradas en la perimetría computarizada.

Objective: to determine the thickness of the ganglion cell complex (GCC) by Fourier domain optical coherence tomography (FDOCT) in patients diagnosed with ocular hypertension who were classified with the STAR rule (Scoring Tool for Assessing Risk) to determine the risk of conversion to glaucoma. Methods: patients with ocular hypertension previously diagnosed were selected from medical records. Each patient underwent a complete ophthalmic evaluation, measurement of the thickness of the CGC by FD-OCT (Nidek RS-3000) and calculation of the STAR. Data recorded was related to demographic variables, intraocular pressure, central corneal thickness and computerized perimetry. Results: 106 eyes of 53 patients with ocular hypertension were analyzed. The average intraocular presure was 23.55 ± 0.69 mmHg. The STAR rule was applied in 96 eyes. 65.6% (63 eyes) were categorized into high risk of conversion to glaucoma in the next five years. Patients in this group had a significantly lower thickness of the CGC than the other groups. The average value of the thickness of the upper and lower CGC was 83 ± 4.5 microns and 82.09 ± 4.98 microns respectively. Conclusion: patients classified in the STAR high risk group have a signifi cantly lower thickness of the CGC. The thinning of the CGC was positively correlated with abnormalities recorded in the computerized perimetry.

Revisión con aguja de ampollas filtrantes fallidas ¿Es realmente útil?: estudio de serie de casos / Needling of failed glaucoma blebs. Are they really useful? case series

Objetivo: evaluar si la revisión con aguja (needling) de ampollas filtrantes fallidas con la aplicación de 5-Fluorouracilo es eficaz a mediano plazo para disminuir la presión intraocular y evaluar la seguridad del procedimiento. Diseño: serie de casos, retrospectivo. Materiales y Métodos: se incluyeron 25 ojos de 19 pacientes entre enero 2007 a Julio 2013 con ampollas filtrantes fallidas en quienes se realizó revisión con aguja de sus ampollas filtrantes con la subsecuente aplicación de 5-Fluorouracilo subconjuntival y seguimiento superior a 6 meses. El procedimiento se realizó en lámpara de hendidura durante la consulta. El éxito del procedimiento fue definido en términos del porcentaje de disminución de la presión intraocular basado en la presión inicial antes del procedimiento con o sin el uso de medicaciones hipotensores. Resultados: la disminución de la PIO inmediatamente después del needling fue del 55.9% (13 mmHg), con reducciones de la PIO al seguimiento al primer corte de (40%), segundo (42%) y tercero de (27%) a los 14 meses. A todos los pacientes se les realizó suturolisis durante el procedimiento y aplicación de 2,4 dosis promedio de 5 mg de 5-FU subconjuntival inferior inter diarias. El seguimiento promedio fue de 14.5 meses, tiempo durante el cual se repitió la revisión en 13 ojos 2.2 veces. La medicación preoperatoria disminuyó de 3.1 a 1.6 medicamentos después del procedimiento. No se identificó ninguna utilidad del needling en el POP inmediato en 3 ojos (12%) por fibrosis marcada. Un paciente (4%) presentó desprendimiento coroideo como complicación al procedimiento. Conclusiones: la revisión con aguja de ampollas filtrantes con la aplicación de 5-Fluorouracilo subconjuntival es una alternativa muy útil en el rescate de ampollas filtrantes disfuncionales al mantener una disminución de la presión intraocular del 26 % durante 14 meses de seguimiento. Es un procedimiento sencillo y seguro que ayuda a disminuir la necesidad del uso de medicamentos y a dilatar el tiempo de re-intervenciones.

Purpose: to assess the efficacy and security of bleb needling with adjunctive 5-Fluorouracil in glaucomatous patients with late failed filtering blebs. Materials and Methods: a retrospective case series of 25 eyes of 19 patients was considered. All patients underwent needle bleb revision with adjuvant 5-Fluorouracil performed at the slit lamp, during an office visit. Postneedling intraocular pressure (IOP) with or without antiglaucoma medications was followed for 14 months. Results: There was a 56 % (13 mm Hg) reduction of IOP immediately after the procedure, The mean interval between filtering surgery and bleb revision was 14.5 months. Mean IOP was 23.0 ± 4.80 mmHg before surgery and 16.6 ± 3.7 mmHg at last postoperative follow-up. The mean follow-up was 14 months (6-48 months). The procedure was repeated in 13 eyes, 2.2 times. Cumulative rates of IOP reduction at 3, 6, and 14 months were 40%, 42%, and 27%, respectively. The mean number of antiglaucoma medications was reduced from 3.1 preoperatively to 1.6. Failure of the procedure was present in 3 yes and a choroidal effusion was present in one case. Conclusion: slit-lamp needle revision in office is a simple and effective method for treating flat filtering blebs without significant complications.