Toxic-Induced Encephalopathy Following Chemsex in a Young HIV-Positive Male: A Complex Case of Acute Cognitive Impairment with Anterograde Amnesia and Behavioral Alterations.

BACKGROUND: A broadened clinical spectrum of concomitant complications emerges among the escalating incidence of substance use, particularly within the 'chemsex' context. This case exemplifies the profound neurotoxic repercussions and neurological risk of chemsex in a young HIV-positive male and addresses the multifaceted challenges of such evolving paradigms in substance utilization. CLINICAL FINDING: After consuming cannabis, poppers, methamphetamine, and cocaine, a 28-year-old HIV-positive male exhibited significant neurological and cognitive impairment. The initial presentation included dysarthria and profound anterograde amnesia. Laboratory findings showed leukocytosis with a PCR of 3 mg/dl - elevated cerebrospinal fluid protein levels with no cells. Urine toxicology returned positive for cannabis and amphetamines. A brain CT scan revealed bilateral and symmetrical hippocampi and pale globes hypodensity, indicative of toxic-metabolic encephalopathy. MRI further identified lesions in the globus pallidus, cerebellum, and hippocampi. Following the detection of toxic encephalopathy, Initial neuropsychological was performed screening using the Montreal Cognitive Assessment (MoCA), which highlighted immediate memory deficits. An in-depth neuropsychological assessment conducted 3 weeks later included the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV), the Rey Auditory Verbal Learning Test (RAVLT), and tests for visuospatial skills, motor functions, and memory recall. The evaluations revealed pronounced anterograde amnesia, persistent long-term memory inconsistencies, and notable executive function challenges, detailed in Table 1. CONCLUSIONS: The detailed analysis of this case underpins the severe neurological consequences that can manifest from heavy substance use. Comprehensive diagnostic evaluations, including neuroimaging and neuropsychological assessments, are crucial in elucidating the full spectrum of substance-induced cognitive impairments. There is an urgent need for enhanced public awareness and preventative measures, especially in the context of chemsex, to bring forth multifaceted health, social, and government implications that modern society must adeptly navigate.

SARS-CoV-2 testing, positivity, and factors associated with COVID-19 among people with HIV across Europe in the multinational EuroSIDA cohort.

BACKGROUND: Although people with HIV might be at risk of severe outcomes from infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; coronavirus 2019 [COVID-19]), regional and temporal differences in SARS-CoV-2 testing in people with HIV across Europe have not been previously described. METHODS: We described the proportions of testing, positive test results, and hospitalizations due to COVID-19 between 1 January 2020 and 31 December 2021 in the EuroSIDA cohort and the factors associated with being tested for SARS-CoV-2 and with ever testing positive. RESULTS: Of 9012 participants, 2270 (25.2%, 95% confidence interval [CI] 24.3-26.1) had a SARS-CoV-2 polymerase chain reaction test during the study period (range: 38.3% in Northern to 14.6% in Central-Eastern Europe). People from Northern Europe, women, those aged <40 years, those with CD4 cell count <350 cells/mm3 , and those with previous cardiovascular disease or malignancy were significantly more likely to have been tested, as were people with HIV in 2021 compared with those in 2020. Overall, 390 people with HIV (4.3%, 95% CI 3.9-4.8) tested positive (range: 2.6% in Northern to 7.1% in Southern Europe), and the odds of testing positive were higher in all regions than in Northern Europe and in 2021 than in 2020. In total, 64 people with HIV (0.7%, 95% CI 0.6-0.9) were hospitalized, of whom 12 died. Compared with 2020, the odds of positive testing decreased in all regions in 2021, and the associations with cardiovascular disease, malignancy, and use of tenofovir disoproxil fumarate disappeared in 2021. Among study participants, 58.9% received a COVID-19 vaccine (range: 72.0% in Southern to 14.8% in Eastern Europe). CONCLUSIONS: We observed large heterogeneity in SARS-CoV-2 testing and positivity and a low proportion of hospital admissions and deaths across the regions of Europe.

[Translated article] Immobilisation with compression bandage vs. antebraquial splint in distal radius fractures operated by open reduction and locking plate. Randomised clinical trial.

INTRODUCTION: Currently, there is a lack of prospective studies to unify criteria about type and time for postoperative immobilisation in surgical distal radius fractures. The aim of this study is to compare functional and radiological results in two groups of distal radius fractures treated with internal fixation with locking plate, and immobilised with antebrachial splint or compression bandage for 3 weeks. MATERIAL AND METHOD: A randomised clinical trial was carried out with two parallel groups with 3, 6, and 12 weeks of follow-up. Main and secondary functional variables were measured, such as pain on VAS scale, values on PRWE, DASH and MRS scale, range of motion in flexion-extension, complications, etc. In addition, some radiological variables were measured at preoperative period and one week after surgery, such as union time, dorsal displacement, shortening, ulnar variance, etc. RESULTS: A total of 62 patients were evaluated: 27 immobilised with bandage and 35 with splint. Analysis of the results obtained showed significant differences in both groups for almost all radiological variables from pre to postoperative period, and for all functional variables from 3 to 12 weeks after surgery. No significant differences were found between the two groups for any of the radiological and functional variables evaluated (VAS 3-12 weeks: p=.584; PWRE 3-12 weeks: p=.248; flexion range of motion 3-12 weeks: p=.959; extension range of motion: p=.50; union time: p=.89). CONCLUSIONS: We do not find clinical or radiological differences between immobilisation with antebrachial splint or compression bandage for distal radius fractures operated with locking plate. A greater number of patients and follow-up are necessary to extrapolate the results to the general population and to establish criteria for good postoperative management of these fractures.

Immobilization with compression bandage vs antebraquial splint in distal radius fractures operated by open reduction and locking plate. Randomized clinical trial. / Inmovilización con vendaje compresivo vs férula antebraquial en fracturas de radio distal intervenidas mediante reducción abierta y placa bloqueada. Ensayo clínico aleatorizado.

INTRODUCTION: Currently, there is a lack of prospective studies to unify criteria about type and time for postoperative immobilization in surgical distal radius fractures. The aim of this study is to compare functional and radiological results in two groups of distal radius fractures treated with internal fixation with locking plate, and immobilized with antebrachial splint or compression bandage for 3weeks. MATERIAL AND METHOD: A randomized clinical trial was carried out with two parallel groups with 3, 6, and 12weeks of follow-up. Main and secondary functional variables were measured, such as pain on VAS scale, values on PRWE, DASH and MRS scale, range of motion in flexion-extension, complications, etc. In addition, some radiological variables were measured at preoperative period and one week after surgery, such as union time, dorsal displacement, shortening, ulnar variance, etc. RESULTS: A total of 62 patients were evaluated: 27 immobilized with bandage and 35 with splint. Analysis of the results obtained showed significant differences in both groups for almost all radiological variables from pre to postoperative period, and for all functional variables from 3 to 12weeks after surgery. No significant differences were found between the two groups for any of the radiological and functional variables evaluated (VAS 3-12weeks: P=.584; PWRE 3-12weeks: P=.248; flexion range of motion 3-12weeks: P=.959; extension range of motion: P=.50; union time: P=.89). CONCLUSIONS: We do not find clinical or radiological differences between immobilization with antebrachial splint or compression bandage for distal radius fractures operated with locking plate. A greater number of patients and follow-up are necessary to extrapolate the results to the general population and to establish criteria for good postoperative management of these fractures.

Predictors of poor health-related quality of life among people living with HIV aged ≥60 years in the PISCIS cohort: Findings from the Vive+ project.

INTRODUCTION: Advancements in and accessibility to effective antiretroviral therapy has improved the life expectancy of people living with HIV, increasing the proportion of people living with HIV reaching older age (≥60 years), making this population's health-related quality of life (HRQoL) more relevant. Our aim was to identify the determinants of poor HRQoL in people living with HIV aged ≥60 years and compare them with those of their younger counterparts. METHODS: We used data from the 'Vive+' study, a cross-sectional survey conducted between October 2019 and March 2020, nested within the PISCIS cohort of people living with HIV in Catalonia and the Balearic Islands, Spain. We used the 12-item short-form survey (SF-12), divided into a physical component summary (PCS) and a mental component summary (MCS), to evaluate HRQoL. We used the least absolute shrinkage and selection operator for variable selection and used multivariable regression models to identify predictors. RESULTS: Of the 1060 people living with HIV (78.6% males) who participated in the study, 209 (19.7%) were aged ≥60 years. When comparing older people living with HIV (≥60 years) and their younger counterparts, older people exhibited a worse PCS (median 51.3 [interquartile range {IQR} 46.0-58.1] vs. 46.43 [IQR 42.5-52.7], p < 0.001) but a similar MCS (median 56.0 [IQR 49.34-64.7] vs. 57.0 [IQR 48.9-66.3], p = 0.476). In the multivariable analysis, cognitive function correlated with a PCS (ß correlation factor [ß] -0.18, p = 0.014), and depressive symptoms and satisfaction with social role correlated with an MCS (ß 0.61 and ß -0.97, respectively, p < 0.001) in people living with HIV aged ≥60 years. CONCLUSION: Depressive symptoms, poor cognitive function, and lower satisfaction with social roles predict poorer HRQoL in older people living with HIV. These factors need to be considered when designing targeted interventions.

Diferencias clínicas entre los pacientes con dolor crónico primario y secundario atendidos por una unidad multidisciplinar de dolor crónico infantil / Clinical differences in a multidisciplinary pediatric pain unit between primary and secondary chronic pain

Introducción: El dolor crónico afecta a un porcentaje significativo de la población pediátrica en los países desarrollados, y puede tener una causa médica bien definida en el dolor crónico secundario (DCS), o desconocida en el dolor crónico primario (DCP). En España, hasta el momento, no existe información acerca de las diferencias clínicas de los pacientes atendidos en unidades multidisciplinarias. Métodos: Análisis retrospectivo de las historias clínicas de los pacientes atendidos en 2018 por la Unidad de Dolor Crónico Infantil del Hospital Universitario La Paz. Resultados: Se incluyeron los 92 pacientes atendidos, con edades comprendidas entre 2 y 19 años, y una edad media de 12,4 (SD=4,1) años, mayoritariamente de sexo femenino (55%) y una duración media del dolor de 11,3 (SD=10,4) meses. Los resultados de comparar pacientes con DCP (n=31) y DCS (n=61) mostraron que ambos grupos presentaban dolor medio con una gran intensidad (x=5,9; SD=2,2; rango=0-10), con duración y repercusión funcional similares, aunque el DCP se asoció menos a descriptores de tipo neuropático que el DCS (p=0,040) y era más extenso en su localización (p<0,001). Ambos grupos recibieron similar tratamiento basado en rehabilitación, psicoterapia, técnicas invasivas y tratamiento con medicación analgésica, aunque los pacientes del grupo DCP recibieron menos medicaciones analgésicas (gabapentinoides y opiáceos) que el DCS (p=0,011). Conclusión: Los pacientes con DCP o DCS, aunque tengan un perfil clínico similar, presentan diferencias en el número y tipo de analgésicos empleados, lo que avalaría la importancia del diagnóstico de la causa para adecuar el tratamiento farmacológico subsiguiente.(AU)

Introduction: Chronic pain affects an important part of the pediatric population in developed countries. secondary chronic pain (SCP) can have a well-defined medical cause, but primary chronic pain (PCP) can have an unknown etiology. In Spain, there is as yet no information on the clinical differences between patients treated in multidisciplinary units. Methods: Retrospective analysis of the clinical records of patients seen in 2018 at the Children's Chronic Pain Unit in University La Paz Hospital. Results: A total of 92 patients were included (age between 3 and 19 years), with a mean age of 12.4 (SD=4.1) years, mostly female (55%), with a mean duration of pain of 11.3 (SD=10.4) months. A comparison of patients with PCP (n=31) and SCP (n=61) showed that both groups, on average, presented intense pain (X=5.9; SD=2.2; range=0-10), with similar duration and functional repercussions, although PCP was less likely to be associated with neuropathic descriptors than SCP (p=.040), and was more extensive (p<.001). Both groups received similar treatment, based on rehabilitation, psychotherapy, invasive techniques and analgesic medication, although patients in the PCP group received less analgesic medication (gabapentinoids and opioids) than the SCP (p=.011). Conclusion: Patients treated in a multidisciplinary Child Pain Unit for PCP or SCP present a very similar clinical profile, though with differences in the number and type of analgesic drugs used. This shows the importance of etiologic diagnosis for adequate pharmacological treatment.(AU)

Clinical differences in a multidisciplinary pediatric pain unit between primary and secondary chronic pain.

INTRODUCTION: Chronic pain affects an important part of the pediatric population in developed countries. secondary chronic pain (SCP) can have a well-defined medical cause, but primary chronic pain (PCP) can have an unknown etiology. In Spain, there is as yet no information on the clinical differences between patients treated in multidisciplinary units. METHODS: Retrospective analysis of the clinical records of patients seen in 2018 at the Children's Chronic Pain Unit in University La Paz Hospital. RESULTS: A total of 92 patients were included, (age between 3 and 19 years), with a mean age of 12.4 (SD = 4.1) years, mostly female (55%), with a mean duration of pain of 11.3 (SD = 10.4) months. A comparison of patients with PCP (n = 31) and SCP (n = 61) showed that both groups, on average, presented intense pain (X = 5.9; SD = 2.2; range = 0-10), with similar duration and functional repercussions, although PCP was less likely to be associated with neuropathic descriptors than SCP (p = 0.040), and was more extensive (p < 0.001). Both groups received similar treatment, based on rehabilitation, psychotherapy, invasive techniques and analgesic medication, although patients in the PCP group received less analgesic medication (gabapentinoids and opioids) than the SCP (p = 0.011). CONCLUSION: Patients treated in a multidisciplinary Child Pain Unit for PCP or SCP present a very similar clinical profile, though with differences in the number and type of analgesic drugs used. This shows the importance of etiologic diagnosis for adequate pharmacological treatment.

Fetal cardiac and neonatal cerebral hemodynamics and oxygen metabolism in transposition of the great arteries.

OBJECTIVES: Hemodynamic abnormalities and brain development disorders have been reported previously in fetuses and infants with transposition of the great arteries and intact ventricular septum (TGA-IVS). A ventricular septal defect (VSD) is thought to be an additional risk factor for adverse neurodevelopment, but literature describing this population is sparse. The objectives of this study were to assess fetal cardiac hemodynamics throughout pregnancy, to monitor cerebral hemodynamics and oxygen metabolism in neonates, and to compare these data between patients with TGA-IVS, those with TGA-VSD and age-matched controls. METHODS: Cardiac hemodynamics were assessed in TGA-IVS and TGA-VSD fetuses and compared with healthy controls matched for gestational age (GA) during three periods: ≤ 22 + 5 weeks (GA1), 27 + 0 to 32 + 5 weeks (GA2) and ≥ 34 + 5 weeks (GA3). Left (LVO), right (RVO) and combined (CVO) ventricular outputs, ductus arteriosus flow (DAF, sum of ante- and retrograde flow in systole and diastole), diastolic DAF, transpulmonary flow (TPF) and foramen ovale diameter were measured. Aortic (AoF) and main pulmonary artery (MPAF) flows were derived as a percentage of CVO. Fetal middle cerebral artery and umbilical artery (UA) pulsatility indices (PI) were measured and the cerebroplacental ratio (CPR) was derived. Bedside optical brain monitoring was used to measure cerebral hemoglobin oxygen saturation (SO2 ) and an index of microvascular cerebral blood flow (CBFi ), along with peripheral arterial oxygen saturation (SpO2 ), in TGA-IVS and TGA-VSD neonates. Using hemoglobin (Hb) concentration measurements, these parameters were used to derive cerebral oxygen delivery and extraction fraction (OEF), as well as an index of cerebral oxygen metabolism (CMRO2i ). These data were acquired in the early preoperative period (within 3 days after birth and following balloon atrial septostomy) and compared with those of age-matched healthy controls, and repeat measurements were collected before discharge when vital signs were stable. RESULTS: LVO was increased in both TGA groups compared with controls throughout pregnancy. Compared with controls, TPF was increased and diastolic DAF was decreased in TGA-IVS fetuses throughout pregnancy, but only during GA1 and GA2 in TGA-VSD fetuses. Compared with controls, DAF was decreased in TGA-IVS fetuses throughout pregnancy and in TGA-VSD fetuses at GA2 and GA3. At GA2, AoF was higher in TGA-IVS and TGA-VSD fetuses than in controls, while MPAF was lower. At GA3, RVO and CVO were higher in the TGA-IVS group than in the TGA-VSD group. In addition, UA-PI was lower at GA2 and CPR higher at GA3 in TGA-VSD fetuses compared with TGA-IVS fetuses. Within 3 days after birth, SpO2 and SO2 were lower in both TGA groups than in controls, while Hb, cerebral OEF and CMRO2i were higher. Preoperative SpO2 was also lower in TGA-VSD neonates than in those with TGA-IVS. From preoperative to predischarge periods, SpO2 and OEF increased in both TGA groups, but CBFi and CMRO2i increased only in the TGA-VSD group. During the predischarge period, SO2 was higher in TGA-IVS than in TGA-VSD neonates, while CBFi was lower. CONCLUSIONS: Fetal cardiac and neonatal cerebral hemodynamic/metabolic differences were observed in both TGA groups compared with controls. Compared to those with TGA-IVS, fetuses with TGA-VSD had lower RVO and CVO in late gestation. A higher level of preoperative hypoxemia was observed in the TGA-VSD group. Postsurgical cerebral adaptive mechanisms probably differ between TGA groups. Patients with TGA-VSD have a specific physiology that warrants further study to improve neonatal care and neurodevelopmental outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Risk scores' performance and their impact on operative decision-making in left-sided endocarditis: a cohort study.

The accuracy of contemporary risk scores in predicting perioperative mortality in infective endocarditis (IE) remains controversial. The aim is to evaluate the performance of existent mortality risk scores for cardiovascular surgery in IE and the impact on operability at high-risk thresholds. A single-center retrospective review of adult patients diagnosed with acute left-sided IE undergoing surgery from May 2014 to August 2019 (n = 142) was done. Individualized risk calculation was obtained according to the available mortality risk scores: EuroScore I and II, PALSUSE, Risk-E, Costa, De Feo-Cotrufo, AEPEI, STS-risk, STS-IE, APORTEI, and ICE-PCS scores. A cross-validation analysis was performed on the score with the best area under the curve (AUC). The 30-day survival was 96.5% (95%CI 91-98%). The score with worse area under the curve (AUC = 0.6) was the STS-IE score, while the higher was for the RISK-E score (AUC = 0.89). The AUC of the majority of risk scores suggested acceptable performance; however, statistically significant differences in expected versus observed mortalities were common. The cross-validation analysis showed that a large number of survivors (> 75%) would not have been operated if arbitrary high-risk threshold estimates had been used to deny surgery. The observed mortality in our cohort is significantly lower than is predicted by contemporary risk scores. Despite the reasonable numeric performance of the analyzed scores, their utility in judging the operability of a given patient remains questionable, as demonstrated in the cross-validation analysis. Future guidelines may advise that denial of surgery should only follow a highly experienced Endocarditis Team evaluation.

Capacity Building in Sub-Saharan Africa as Part of the INTENSE-TBM Project During the COVID-19 Pandemic.

Tuberculous meningitis (TBM) is the most severe and disabling form of tuberculosis (TB), with at least 100,000 cases per year and a mortality rate of up to 50% in individuals co-infected with human immunodeficiency virus type 1 (HIV-1). To evaluate the efficacy and safety of an intensified anti-tubercular regimen and an anti-inflammatory treatment, the INTENSE-TBM project includes a phase III randomised clinical trial (TBM-RCT) in four countries in sub-Saharan Africa (SSA). Within this framework, we designed a comprehensive capacity-building work package ensuring all centres had, or would acquire, the ability to conduct the TBM-RCT and developing a network of skilled researchers, clinical centres and microbiology laboratories. Here, we describe these activities, identify strengths/challenges and share tools adaptable to other projects, particularly in low- and lower-middle income countries with heterogeneous settings and during the coronavirus disease 2019 (COVID-19) pandemic. Despite major challenges, TBM-RCT initiation was achieved in all sites, promoting enhanced local healthcare systems and encouraging further clinical research in SSA. In terms of certified trainings, the achievement levels were 95% (124/131) for good clinical practice, 91% (39/43) for good clinical laboratory practice and 91% (48/53) for infection prevention and control. Platform-based research, developed as part of capacity-building activities for specific projects, may be a valuable tool in fighting future infectious diseases and in developing high-level research in Africa.

The INTENSE-TBM project aimed to design a comprehensive work-package on capacity building, ensuring all centres would acquire the ability to conduct a phase III randomised clinical trial on TBM in sub-Saharan Africa, to reduce tuberculous meningitis mortality and morbidity in patients with/without HIV-1 co-infection. Therefore, the INTENSE-TBM project is an example of how an international clinical research consortium can provide opportunities to enhance local capacity building and promote centres without previous experience in clinical research. This article provides practical approaches for implementing effective capacity-building programmes. We highlight how to overcome limitations imposed by the COVID-19 pandemic to successfully complete clinics, laboratory set-ups and personnel training, so as to optimise resources and empower African institutions on a local level. At the same time, our experience shows how capacity-building programmes can deliver long-lasting impact that extends beyond the original aims of the project (e.g. HIV and TB), and support local health systems in fighting other infectious disease (e.g. COVID-19). Research projects in low- and lower-middle income countries with heterogeneous settings could stand to benefit the most.

HIV and SARS-CoV-2 Co-infection: Epidemiological, Clinical Features, and Future Implications for Clinical Care and Public Health for People Living with HIV (PLWH) and HIV Most-at-Risk Groups.

PURPOSE OF REVIEW: The purpose of this review is to use the currently available clinical and epidemiological data, to identify key aspects to improve both the clinical management and public health response to SARS-CoV-2/HIV co-infection among HIV vulnerable populations and people living with HIV (PLWH). RECENT FINDINGS: While at the beginning of the COVID-19 pandemic, the lack of robust information on SARS-CoV-2/HIV co-infection, prevented a clear picture of the synergies between them, currently available data strongly support the importance of common structural factors on both the acquisition and clinical impact of these infections and the relevance of age, comorbidities, and detectable HIV viral load as associated worse prognostic factors among PLWH. Although more information is needed to better understand the biological, clinical, and epidemiological relationship between both infections, a syndemic approach to prevent SARS-CoV-2 among HIV high-risk groups and PLWH, targeting these populations for SARS-CoV-2 vaccines and protocolizing early identification of PLWH with worse COVID-19 prognosis factors, is crucial strategies to decrease the overall impact of SARS-CoV-2 /HIV co-infection.

Infective endocarditis in children and adolescents: a different profile with clinical implications.

BACKGROUND: Our aim was to compare pediatric infective endocarditis (IE) with the clinical profile and outcomes of IE in adults. METHODS: Prospective multicenter registry in 31 Spanish hospitals including all patients with a diagnosis of IE from 2008 to 2020. RESULTS: A total of 5590 patients were included, 49 were <18 years (0.1%). Congenital heart disease (CHD) was present in 31 children and adolescents (63.2%). Right-sided location was more common in children/adolescents than in adults (46.9% vs. 6.3%, P < 0.001). Pediatric pulmonary IE was more frequent in patients with CHD (48.4%) than in those without (5.6%), P = 0.004. Staphylococcus aureus etiology tended to be more common in pediatric patients (32.7%) than in adults (22.3%), P = 0.082. Heart failure was less common in pediatric patients than in adults, due to the lower rate of heart failure in children/adolescents with CHD (9.6%) with respect to those without CHD (44.4%), P = 0.005. Inhospital mortality was high in both children, and adolescents and adults (16.3% vs. 25.9%; P = 0.126). CONCLUSIONS: Most IE cases in children and adolescents are seen in patients with CHD that have a more common right-sided location and a lower prevalence of heart failure than patients without CHD. IE in children and adolescents without CHD has a more similar profile to IE in adults. IMPACT: Infective endocarditis (IE) in children and adolescents is often seen in patients with congenital heart disease (CHD). Right-sided location is the most common in patients with CHD and heart failure is less common as a complication compared with patients without CHD. Infective endocarditis (IE) in children/adolescents without CHD has a more similar profile to IE in adults. In children/adolescents without CHD, locations were similar to adults, including a predominance of left-sided IE. Acute heart failure was the most frequent complication, seen mainly in adults, and in children/adolescents without CHD.

Proposing a sustainable urban 3D model to minimize the potential risk associated with green infrastructure by applying engineering tools.

The goal of this study is to estimate the potential risk of exposure to urban green infrastructure by calculating and improving of AIROT index, adding meteorological factors as wind direction and updating the index to be more accurate for smaller urban green areas. To achieve this objective, BIM methodology has been applied by creating a 3D BIM model from the reality capture of a street with LiDAR. The BIM model contains the parametric data needed to apply AIROT index and it allows to map results in a graphic environmental sustainability study. The importance of location of green infrastructure is one of main conclusions obtained in order to minimize aerobiological risks in future new buildings or even in maintenance tasks of urban green infrastructure. A valuable result obtained from the developed methodology are walk simulations in the 3D model with the aim to identify high risk of potential exposure of urban green infrastructure with allergenic interest for allergic patients in order to supply health itineraries of pedestrians in a proposal of Smart City.

Effects of maintenance dredging on the macrofauna of the water column in a turbid estuary.

Many human activities in or near aquatic habitats generate alterations in their environmental conditions, which could affect the organisms that inhabit them. Maintenance dredging of navigation channels in order to allow large ships access to inland ports is one such source of disturbance. In this study, by taking multiple approaches (immediate-, short- and medium term), we analysed the effects of a maintenance dredging operation on physiochemical variables and the early life stages of fish and other macrofauna groups present in two zones of the Guadalquivir estuary with different salinity ranges (poly- and mesohaline). Most physiochemical variables were homogenized in the water column immediately after the water mass passed by the dredger, including sediment resuspension. However, this process seemed to be transient as no significant increments in the depth-averaged levels of turbidity were observed in the short- and medium-terms. Instead, metal concentrations of Cr, Fe and Zn increased in the polyhaline station. Even so, these perturbations did not appear to be severe enough to influence the macrofauna. Still, organisms can suffer direct mechanical impacts of the trailer suction. Hyperbenthic species, like Pomatoshcistus spp. or decapods, tended to decrease slightly, while pelagic species such as Engraulis encrasicolus or mysids did not, indicating that benthic organisms are usually more susceptible to high entrainment. Nonetheless, the possible effects of this disturbance were of the same order or less than those of natural ones; therefore, organisms of the macrofauna could be well adapted to cope with them.

[Pilot study of a new tool to optimise dopaminergic treatment in Parkinson's disease: the OPTIMIPARK questionnaire]. / Estudio piloto de una nueva herramienta para optimizar el tratamiento dopaminérgico en la enfermedad de Parkinson: el cuestionario OPTIMIPARK.

INTRODUCTION: Dopaminergic therapy is effective in Parkinson's disease (PD), but should be adjusted as neurodegeneration progresses. AIMS: The aim of this study was to develop a questionnaire (OPTIMIPARK) to assess the patient's dopaminergic status and assist the clinician in adjusting treatment. PATIENTS AND METHODS: The preliminary, self-administered version of OPTIMIPARK includes nine items that take into account motor and non-motor complications as well as disability. Each item is given a score between 0 and 2, and an overall score from 0 to 18 is obtained. Thirty patients completed the OPTIMIPARK questionnaire and an ad hoc questionnaire about it in a single-centre, observational pilot study. Feasibility, acceptability and preliminary agreement with clinical criteria were analysed. RESULTS: Thirty patients with PD (68.5 ± 7.5 years; range: 43-80 years) in Hoehn and Yahr stage I-III completed OPTIMIPARK (mean total score: 6.7 ± 4; range: 0-14) and the ad hoc questionnaire. Clinical decisions were classified as: 'no change', 'adjustments to conventional treatment' and 'surgical or continuous infusion therapy'. The total OPTIMIPARK scores (mean ± standard deviation) for each option were: 1.4 ± 1 (range: 0-3); 7 ± 2.8 (range: 2-11); and 10.8 ± 1.8 (range: 9-14). The 3/4 cut-off point classified 95.5% of patients as 'no change' versus 'adjustment to conventional treatment', and the 9/10 cut-off point discriminated 78.3% of patients from 'adjustment to conventional treatment' versus 'surgical or continuous infusion therapy', with a concordance (kappa and Lin coefficients) of 0.81. CONCLUSIONS: Although still pending a validation study, OPTIMIPARK may be a viable and useful questionnaire for clinical decision-making in the therapeutic adjustment of PD patients and the identification of candidates for advanced therapies.

TITLE: Estudio piloto de una nueva herramienta para optimizar el tratamiento dopaminérgico en la enfermedad de Parkinson: el cuestionario OPTIMIPARK.Introducción. La terapia dopaminérgica es eficaz en la enfermedad de Parkinson (EP), si bien debe ajustarse conforme progresa la neurodegeneración. Objetivos. Desarrollar un cuestionario (OPTIMIPARK) para valorar el estado dopaminérgico del paciente y ayudar al clínico en el ajuste del tratamiento. Pacientes y métodos. La versión preliminar, autoadministrada, de OPTIMIPARK incluye nueve ítems que tienen en cuenta complicaciones motoras y no motoras, así como la discapacidad. Cada ítem se valora de 0 a 2, y se obtiene una puntuación global de 0 a 18. Treinta pacientes contestaron el cuestionario OPTIMIPARK y un cuestionario ad hoc sobre éste en un estudio piloto unicéntrico y observacional. Se analizaron la viabilidad, la aceptabilidad y la concordancia preliminar con los criterios clínicos. Resultados. Treinta pacientes con EP (68,5 ± 7,5 años; rango: 43-80 años) en estadio de Hoehn and Yahr I-III completaron el OPTIMIPARK (media de la puntuación total: 6,7 ± 4; rango: 0-14) y el cuestionario ad hoc. Las decisiones clínicas se clasificaron como: 'sin cambios', 'ajustes en el tratamiento convencional' y 'terapia quirúrgica o de infusión continua'. Las puntuaciones totales de OPTIMIPARK (media ± desviación estándar) para cada opción fueron: 1,4 ± 1 (rango: 0-3); 7 ± 2,8 (rango: 2-11); y 10,8 ± 1,8 (rango: 9-14). El punto de corte 3/4 clasificó al 95,5% de los pacientes 'sin cambios' frente a 'ajustes del tratamiento convencional', y el corte 9/10 discriminó al 78,3% de los pacientes de 'ajuste del tratamiento convencional' frente a 'terapia quirúrgica o de infusión continua', con concordancia (coeficientes kappa y Lin) de 0,81. Conclusiones. Pendiente del estudio de validación, OPTIMIPARK puede ser un cuestionario viable y útil para la toma de decisiones clínicas en el ajuste terapéutico de pacientes con EP y la identificación de candidatos para terapias avanzadas.

Predicting Tumor Killing and T-Cell Activation by T-Cell Bispecific Antibodies as a Function of Target Expression: Combining In Vitro Experiments with Systems Modeling.

Targeted T-cell redirection is a promising field in cancer immunotherapy. T-cell bispecific antibodies (TCB) are novel antibody constructs capable of binding simultaneously to T cells and tumor cells, allowing cross-linking and the formation of immunologic synapses. This in turn results in T-cell activation, expansion, and tumor killing. TCB activity depends on system-related properties such as tumor target antigen expression as well as antibody properties such as binding affinities to target and T cells. Here, we developed a systems model integrating in vitro data to elucidate further the mechanism of action and to quantify the cytotoxic effects as the relationship between targeted antigen expression and corresponding TCB activity. In the proposed model, we capture relevant processes, linking immune synapse formation to T-cell activation, expansion, and tumor killing for TCBs in vitro to differentiate the effect between tumor cells expressing high or low levels of the tumor antigen. We used cibisatamab, a TCB binding to carcinoembryonic antigen (CEA), to target different tumor cell lines with high and low CEA expression in vitro We developed a model to capture and predict our observations, as a learn-and-confirm cycle. Although full tumor killing and substantial T-cell activation was observed in high expressing tumor cells, the model correctly predicted partial tumor killing and minimal T-cell activation in low expressing tumor cells when exposed to cibisatamab. Furthermore, the model successfully predicted cytotoxicity across a wide range of tumor cell lines, spanning from very low to high CEA expression.

A new health care index predicts short term mortality for TB and HIV co-infected people.

BACKGROUND: Using 2004-2007 TB:HIV Study data from Europe and Latin America, we previously generated a health care index (HCI) for TB and HIV co-infected people. With improvements in diagnostic and management practices, we have now updated the HCI with new data.METHODS: We evaluated nine aspects of health care in Cox proportional hazards models on time from TB diagnosis to death. Kaplan-Meier methods were used to estimate the probability of death by HCI quartile.RESULTS: Of 1396 eligible individuals (72% male, 59% from Eastern Europe), 269 died within 12 months. Use of rifamycin/isoniazid/pyrazinamide-based treatment (HR 0.67, 95% CI 0.50-0.89), TB drug susceptibility testing (DST) and number of active TB drugs (DST + <3 drugs (HR 1.09, 95% CI 0.80-1.48), DST + ≥3 drugs (HR 0.49, 95% CI 0.35-0.70) vs. no DST), recent HIV-RNA measurement (HR 0.64, 95% CI 0.50-0.82) and combination antiretroviral therapy use (HR 0.72, 95% CI 0.53-0.97) were associated with mortality. These factors contributed respectively 5, -1, 8, 5 and 4 to the HCI. Lower HCI was associated with an increased probability of death; 30% (95% CI 26-35) vs. 9% (95% CI 6-13) in the lowest vs. the highest quartile.CONCLUSION: We found five potentially modifiable health care components that were associated with mortality among TB-HIV positive individuals. Validation of our HCI in other TB cohorts could enhance our findings.