Influence of the flow split ratio on the position of the main atrial vortex: Implications for stasis on the left atrial appendage.

BACKGROUND: Despite the recent advances in computational fluid dynamics (CFD) techniques applied to blood flow within the left atrium (LA), the relationship between atrial geometry, flow patterns, and blood stasis within the left atrial appendage (LAA) remains unclear. A better understanding of this relationship would have important clinical implications, as thrombi originating in the LAA are a common cause of stroke in patients with atrial fibrillation (AF). AIM: To identify the most representative atrial flow patterns on a patient-specific basis and study their influence on LAA blood stasis by varying the flow split ratio and some common atrial modeling assumptions. METHODS: Three recent techniques were applied to nine patient-specific computational fluid dynamics (CFD) models of patients with AF: a kinematic atrial model to isolate the influence of wall motion because of AF, projection on a universal LAA coordinate system, and quantification of stagnant blood volume (SBV). RESULTS: We identified three different atrial flow patterns based on the position of the center of the main circulatory flow. The results also illustrate how atrial flow patterns are highly affected by the flow split ratio, increasing the SBV within the LAA. As the flow split ratio is determined by the patient's lying position, the results suggest that the most frequent position adopted while sleeping may have implications for the medium- and long-term risks of stroke.

Preoperative EUS vs. PET-CT Evaluation of Response to Neoadjuvant Therapy for Esophagogastric Cancer and Its Correlation with Survival.

BACKGROUND: The objective of our study was to investigate whether Endoscopic Ultrasonography (EUS) and Positron Emission Tomography-Computed Tomography (PET-CT) restaging can predict survival in upper gastrointestinal tract adenocarcinomas and to assess their accuracy when compared to pathology. METHODS: We conducted a retrospective study on all patients who underwent EUS for staging of gastric or esophago-gastric junction adenocarcinoma between 2010 and 2021. EUS and PET-CT were performed, and preoperative TNM restaging was conducted using both procedures within 21 days prior to surgery. Disease-free survival (DFS) and overall survival (OS) were evaluated. RESULTS: A total of 185 patients (74.7% male) were included in the study. The accuracy of EUS for distinguishing between T1-T2 and T3-T4 tumors after neoadjuvant therapy was 66.7% (95% CI: 50.3-77.8%), and for N staging, the accuracy was 70.8% (95% CI: 51.8-81.8%). Regarding PET-CT, the accuracy for N positivity was 60.4% (95% CI: 46.3-73%). Kaplan-Meier analysis revealed a significant correlation between positive lymph nodes on restaging EUS and PET-CT with DFS. Multivariate COX regression analysis identified N restaging with EUS and PET-CT, as well as the Charlson comorbidity index, as correlated factors with DFS. Positive lymph nodes on EUS and PET-CT were predictors of OS. In multivariate Cox regression analysis, the independent risk factors for OS were found to be the Charlson comorbidity index, T response by EUS, and male sex. CONCLUSION: Both EUS and PET-CT are valuable tools for determining the preoperative stage of esophago-gastric cancer. Both techniques can predict survival, with preoperative N staging and response to neoadjuvant therapy assessed by EUS being the main predictors.

Vascular anatomy of the breast and its implications in the breast-sharing reconstruction technique.

The most frequently described breast-sharing procedure consists in a pedicled technique where the transferred lower breast pole is based on the lower perforators of the internal mammary (IM) artery. The current article investigates the vascular supply of the breast and its surgical implications in breast-sharing reconstruction. Contrast-enhanced magnetic resonance images of 55 patients (110 breasts) were retrospectively examined. A total of 473 branches of the IM, lateral thoracic (LT) and anterior intercostal (AI) arteries with a diameter greater than 0.5 mm were traced throughout their course in the breast. Distinct connections between the vessels were equally recorded. Although any vessel could vascularise any quadrant in the individual patient, blood supply to the lower quadrants came fundamentally from the AI arteries (76.2% of all the perforators). Lower IM branches (4th-5th) were seen to reach both lower quadrants in only 6.4% of the breasts, whereas LT branches did in 15.5%. In 86.4% of the breasts, at least a distinct AI perforator was seen to perfuse both lower quadrants. Well-defined connections between the IM and the LT arteries were observed in 41.8% of the breasts, always at or above the nipple-areola level. Other connections were far less common. Our study strongly indicates that the breast-sharing technique based on 4th-5th contralateral branches of the IM or LT arteries is unreliable in most patients. Given the unpredictable vascularization pattern in the lower breast pole, a preoperative imaging study is mandatory when the use of the contralateral breast is considered. Due to its accuracy, availability, and anatomical reliability, contrast-enhanced magnetic resonance is the best technique in the preoperative evaluation of the breast-sharing reconstruction.

Telemedicine for neurological diseases: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The aim was to systematically review the effectiveness and safety of telemedicine combined with usual care (in-person visits) compared to usual care for the therapeutic management and follow-up assessment of neurological diseases. METHODS: The electronic databases MEDLINE, Embase, Web of Science and Cochrane Central Register of Controlled Trials were searched (June 2021). Randomized controlled trials (RCTs) on patients of any age with neurological diseases were considered. Two reviewers screened and abstracted data in duplicate and independently and assessed risk of bias using the Cochrane risk-of-bias tool for randomized trials (RoB 2). When possible, pooled effect estimates were calculated. RESULTS: Of a total of 3018 records initially retrieved, 25 RCTs (n = 2335) were included: 11 (n = 804) on stroke, four (n = 520) on Parkinson's disease, three (n = 110) on multiple sclerosis, two (n = 320) on epilepsy, one (n = 63) on dementia, one (n = 23) on spina bifida, one (n = 40) on migraine, one (n = 22) on cerebral palsy and one (n = 433) on brain damage. Types of telemedicine assessed were online visits (11 studies), tele-rehabilitation (seven studies), telephone calls (three), smartphone apps (two) and online computer software (two). The evidence was quite limited except for stroke. Compared to usual care alone, telemedicine plus usual care was found to improve depressive symptoms, functional status, motor function, executive function, generic quality of life, healthcare utilization and healthy lifestyle in patients in post-stroke follow-up. CONCLUSIONS: Well-designed and executed RCTs are needed to confirm our findings on stroke and to have more scientific evidence available for the other neurological diseases.

Adelgazamiento cortical y área tumoral. ¿Predictores de fractura patológica en encondromas de falanges de manos? / Cortical thinning and tumoral area. Predictors of pathological fracture in enchondromas of phalanges of the hand?

Introducción y objetivo: Los encondromas son los tumores primarios más comunes en las falanges de las manos. Cuando son descubiertos en pacientes asintomáticos, el cirujano debe decidir entre tratamiento quirúrgico o actitud expectante. Hasta la fecha, no se dispone de indicadores radiológicos establecidos que determinen el riesgo de fractura patológica. Pretendemos conocer la utilidad de dos parámetros de radiografía simple, adelgazamiento cortical y área ósea ocupada por tumor, como predictores de fractura patológica. Material y método: Estudio retrospectivo, observacional y analítico, de casos y controles, realizado entre 2003 y 2017 con 18 pacientes operados por encondromas en falanges de manos, 9 de ellos asintomáticos (grupo A, control), y otros 9 con fractura patológica como debut (grupo B, casos). Con el objetivo de identificar los parámetros radiológicos asociados con fractura, analizamos sus radiografías preoperatorias anteroposteriores y laterales. Cuantificamos el área de hueso ocupada por tumor y el grado de adelgazamiento cortical en ambos grupos. Resultados: No encontramos diferencias significativas respecto al área de hueso ocupada por tumor (p > 0.1). Sin embargo, en el grupo B evidenciamos, de manera estadísticamente significativa, un mayor grado de adelgazamiento cortical (p < 0.1).La probabilidad de desarrollar fractura patológica se incrementa en falanges con mayor adelgazamiento cortical, tanto en radiografías anteroposteriores [Odds Ratio (OR) 16, Intervalo de Confianza (IC) 90% 1.97-130.24] (p=0.01) como en laterales (OR 7, IC 90% 1.21-40.62) (p=0.03). Conclusiones: De nuestro estudio deducimos la asociación positiva entre adelgazamiento cortical y desarrollo de fractura patológica en falanges de manos afectadas por encondromas. (AU)

Background and objective: Enchondromas are the most common primary tumors involving phalanges of the hand. When they are identified in asymptomatic patients, surgeons must decide between surgery or watchful waiting. Till the date, there is no established radiological parameter for determining the risk of pathological fracture.Our study aims to determine the utility of two radiographic indicators, amount of cortical thinning and bone area occupied by tumor, as predictors of pathological fracture. Methods: Retrospective, observational and analytic, case-control study, conducted between 2003 and 2017. Eighteen patients with enchondromas of phalanges of the hand were operated on; 9 of them were asymptomatic (control, group A), and in the other 9 cases (group B), pathological fracture was the first presenting symptom of disease. In order to identify radiological parameters associated with pathological fracture, we analyzed their anteroposterior and lateral preoperative radiographs. We measured the bone area occupied by tumor, and the amount of cortical thinning, in both groups.Results: There was no statistically significant difference between the two groups with respect to bone area occupied by tumor (p > 0.1). Nevertheless, the amount of cortical thinning was significantly higher in group B (p < 0.1).The probability of developing a pathological fracture was increased in bones with greater cortical thinning. This was observed in anteroposterior radiographs [Odds Ratio (OR) 16, Confidence Interval (CI) 90% 1.97-130.24] (p=0.01) and in lateral radiographs (OR 7, CI 90% 1.21-40.62) (p=0.03). Conclusions: Our study suggests a positive association between cortical thinning and development of pathological fracture in hand phalanges affected by enchondromas. (AU)

Trigeminal trophic syndrome: An unusual nasal ulceration. A case report and review of the literature.

Trigeminal trophic syndrome is a rare condition characterized by self-inflicted persistent facial ulceration. It is believed to be consequent to central or peripheral insult to trigeminal nerve, which may have taken place even years before the ulcer development. The aggression to the nerve pathway causes dysesthesias in the trigeminal dermatomes that induce a self-mutilating behavior, with repetitive pinching or scratching in order to mitigate the altered sensation. Due to associated skin anesthesia, the patient does not interrupt manipulation of the affected area despite severe skin necrosis. Ulceration typically occurs in the ala nasi and may resemble other more common cutaneous diseases, such as tumors or infections. Given that this condition is not included in our daily clinical practice, the risk is that of a diagnostic delay with devastating functional and esthetic facial consequences. We present the case of a patient with a history of meningioma resection who developed this syndrome and we have reviewed the published literature to provide an update on the etiopathogenesis, diagnosis and treatment of this rare condition.

Evaluation of the Efficiency of European Health Systems Using Fuzzy Data Envelopment Analysis.

Many studies that assess efficiency in health systems are based on output mean values. That approach ignores the representativeness of the average statistic, which can become a serious problem in estimation. To solve this question, this research contributes in three different ways: the first aim is to evaluate the technical efficiency in the management of European health systems considering a set of DEA (Data Envelopment Analysis) and FDEA (Fuzzy Data Envelopment Analysis) models. A second goal is to assess the bias in the estimation of efficiency when applying the conventional DEA. The third objective is the evaluation of the statistical relationship between the bias in the efficiency estimation and the macroeconomic variables (income inequality and economic freedom). The main results show positive correlations between DEA and FDEA scores. Notwithstanding traditional DEA models overestimate efficiency scores. Furthermore, the size of the bias is positively related to income inequality and negative with economic freedom in the countries evaluated.

Colgajo fasciocutáneo pudendo bilateral para cobertura de tronco del pene: nuevo diseño e indicación / Bilateral pudendal thigh flap for penile shaft coverage: new indication and design

La Gangrena de Fournier es una forma poco frecuente de fascitis necrotizante que puede llegar a ser fatal si no es tratada adecuadamente. Las áreas habitualmente afectadas son el periné y los genitales externos y con frecuencia requieren amplios desbridamientos quirúrgicos que pueden dejar defectos de cobertura extensos.La reconstrucción del tronco del pene requiere una reparación libre de tensión que permita mantener la capacidad eréctil del tejido y evite la formación de una cicatriz retráctil. La viabilidad de la técnica empleada, su resultado estético y el grosor del pene reconstruido son otros factores a tener en cuenta. Las principales opciones para proporcionar cobertura son los colgajos pediculados locales y los injertos de piel de espesor parcial o total.El colgajo fasciocutáneo pudendo se emplea comúnmente en la cirugía reparadora de periné y vagina pero, de acuerdo con lo observado en la literatura, apenas existen 2 casos descritos de su uso en reconstrucción del tronco del pene, con variaciones respecto al diseño tradicional del colgajo. Describimos una secuela de Gangrena de Fournier en la que logramos con éxito la cobertura del tronco del pene gracias a una novedosa modificación en el diseño del colgajo fasciocutáneo pudendo. (AU)

Fournier ́s Gangrene is an uncommon form of necrotizing fasciitis, which can be fatal if inadequately treated. Perineum and external genitalia are the most commonly affected areas. Urgent radical surgical debridement is often required, which results in extensive soft tissue damage.Reparation of penis shaft must be tension-free, preserving erectile capacity, and avoiding retractile scar formation. Viability of the technique, aesthetic outcome, and thickness of the reconstructed penis should be also beard in mind. Local pedicled flaps, and split or full-thickness skin grafts are the main options for providing coverage.The pudendal thigh fasciocutaneous flap is one of the workhorse flaps of choice for perineal and vaginal reconstructive surgery but, to the best of our knowledge, it has only been used for penile shaft reconstruction in 2 single case studies, in which modifications to the classical design were performed. We report the case of a sequel of Fournier's Gangrene, in which penile shaft coverage was successfully accomplished with an innovative modification in the design of the pudendal thigh fasciocutaneous flap. (AU)

Comparative Efficacy of Active Group Music Intervention versus Group Music Listening in Alzheimer's Disease.

BACKGROUND: Music interventions are promising therapies for the management of symptoms in Alzheimer's disease (AD). Globally, music interventions can be classified as active or receptive depending on the participation of the subjects. Active and receptive music tasks engage different brain areas that might result in distinctive clinical effects. This study aims to compare the clinical effects of two types of music interventions and a control activity. METHODS: Ninety AD patients from six nursing homes participated in the study. Nursing homes were randomly and blindly assigned to receive either active music intervention, receptive music intervention, or the usual care. Effects on cognition, behaviour, daily living activities, and motor function were assessed. RESULTS: Active music intervention improved cognition, behaviour, and functional state in a higher extent than both receptive music intervention and usual care. The effect size of active music intervention for cognitive deficits and behavioural symptoms was large (η2 = 0.62 and 0.61, respectively), while for functional state, it was small-to-medium sized (η2 = 0.18). Receptive music intervention had a stabilizing effect on behavioural symptoms compared to control intervention (mean change from baseline ± standard deviation = -0.76 ± 3.66 and 3.35 ± 3.29, respectively). In the active music intervention, the percentage of patients who showed improvement in cognitive deficits (85.7), behavioural symptoms (92.9), and functional state (46.4) was higher than in both receptive listening (11.8, 42.9, and 14.3, respectively) and control group (6.3, 12.2, and 17.1, respectively). CONCLUSIONS: Active music intervention is useful to improve symptoms of AD and should be prescribed as a complement to the usual treatment.

[Active surveillance for patients with localized prostate cáncer. Adherence and protocol drop analysis.] / La vigilancia activa en pacientes con cáncer de próstata localizado. Análisis de adherencia y salida del protocolo.

OBJECTIVE: VA is currently considered the treatment of choice for patients with low and very low risk prostate cancer. We analyzed the evolution of this treatment strategy in our series and adherence to the protocol. MATERIAL AND METHODS: Ambispective study of patients in VA in our center between 2014- 2019. 237 meet inclusion criteria, of which 142 (60%) have a minimum of 12 months of follow- up. Mean age: 68.5 (4678), median PSA 6.37 ng / ml (1-33). 229 (96.6%) are ISUP 1 and 8 (3.4%) ISUP 2. Objectives are proposed to assess our adherence to the protocol. Descriptive statistics are used to communicate the results. RESULTS: According to the classification by risk groups of the NCCN, 145 (61.2%), 49 (20.7%) and 42 (17.7%) were very low risk, low risk and favorable intermediate risk patients, respectively. The median of follow-up is 14 months (0-66). Of the patients with a minimum follow-up of 12 months, 107 (75.4%) were re-biopsied. 80 (33.8%) leave the protocol in these 5 years, 31.3% (25) by their own decision, 55% (44) due to medical criteria, and 11.3% (9) go to WW. After 5 years of follow-up, 99.2% of patients are still alive, 0.8% died of specific non-cancer causes. Of the objectives to assess adherence, 8 are achieved, 1 partially and 1 is not evaluable. CONCLUSIONS: VA in our center is already the treatment of choice for very low-risk patients, with a constant increase from year to year. Adherence to the protocol has been favorable during the period of time studied.

OBJETIVO: La VA se ha convertido en uno de los tratamientos de elección del CP localizado de bajo y muy bajo riesgo. Analizamos la evolución de esta estrategia de tratamiento en nuestra serie, así como la adherencia al protocolo.MATERIAL Y MÉTODOS: Estudio ambispectivo de los pacientes incluidos en VA en nuestro centro entre los años 2014-2019. 237 pacientes cumplen los criterios de inclusión en VA, de los cuales 142 (60%) tienen un seguimiento mínimo de 12 meses. Edad media: 68,5(46-78), mediana PSA 6,37 ng/ml (1-33). 229 pacientes (96,6%) son ISUP 1 y 8 (3,4%) ISUP 2. Se proponen unos objetivos para valorar nuestra adherencia al protocolo. Se utiliza estadística descriptiva y contraste de hipótesis para comunicar los resultados.RESULTADOS Y DISCUSIÓN: Atendiendo a la clasificación por grupos de riesgo de la NCCN, 145 (61,2%), 49 (20,7%) y 42 (17,7%) eran pacientes muy bajo riesgo, bajo riesgo y riesgo intermedio favorable respectivamente. El tiempo (mediana) de permanencia en el programa es de 14 meses (0-66). De los pacientes con un seguimiento mínimo de 12 meses, 107 (75,4%) son re ­ biopsiados. 80 pacientes (33,8%) salen del protocolo en estos 5 años, 31,3% (25) por decisión propia, 55% (44) por criterios médicos, y 11,3% (9) pasan a WW. Tras 5 años de seguimiento, el 99,2% de los pacientes continúan vivos, el 0,8% falleció por causas no cáncer específicas. De los objetivos para evaluar la adherencia, 8 de ellos se alcanzan, 1 parcialmente y 1 no es evaluable. CONCLUSIONES: La VA en nuestro centro constituye actualmente el tratamiento de elección para los pacientes con muy bajo riesgo. La adherencia al protocolo ha sido favorable durante el periodo de tiempo estudiado.

The presence of both HLA-DRB1*04:01 and HLA-B*15:01 increases the susceptibility to cranial and extracranial giant cell arteritis.

OBJECTIVES: To determine if patients with the predominant extracranial large-vessel-vasculitis (LVV) pattern of giant cell arteritis (GCA) have a distinctive HLA-B association, different from that reported in biopsy-proven cranial GCA patients. In a further step we assessed if the combination of HLA-B and HLA-DRB1 alleles confers an increased risk for GCA susceptibility, either for the cranial and extracranial LVV phenotypes. METHODS: A total of 184 patients with biopsy-proven cranial GCA, 105 with LVV-GCA and 486 healthy controls were included in our study. We compared HLA-B phenotype frequencies between the three groups. RESULTS: HLA-B*15 phenotype was significantly increased in patients with classic cranial GCA compared to controls (14.7% versus 5.8%, respectively; p<0.01; OR [95% CI] =2.81 [1.54-5.11]). It was mainly due to the HLA-B*15:01 allele (12.5% versus 4.0%, respectively; p<0.01; OR [95% CI] =3.51 [1.77-6.99]) and remained statistically significant after Bonferroni correction. Similar HLA-B*15 association was observed in patients with the LVV-GCA (11.4% versus 5.8%, p=0.04, OR [95% CI] =2.11 [1.04-4.30]). This association was also mainly due to the HLA-B*15:01 allele (10.5% versus 4.0%, respectively; p=0.0054; OR [95% CI] =2.88 [1.19-6.59]). Noteworthy, the presence of HLA-B*15:01 together with HLA-DRB1*04:01 led to an increased risk of developing both cranial and extracranial LVV-GCA. CONCLUSIONS: Susceptibility to GCA is strongly related to the HLA region, regardless of the clinical phenotype of expression of the disease.

Co-Design Process of a Virtual Community of Practice for the Empowerment of People with Ischemic Heart Disease.

INTRODUCTION: Virtual Communities of Practices (vCoP) offer patients the possibility to interact and share tools and knowledge necessary for their empowerment. This paper describes the co-design process of a vCoP for the empowerment of people with ischemic heart disease (IHD). METHODS: We used a modified experience-based design approach to co-design the vCoP in collaboration with people with IHD and health professionals consisting of two phases: exploratory and development phase. Data collection techniques included listening labs, workshops, and online participation. RESULTS: Twenty-five people with IHD and ten health professionals participated. Experiences and needs for empowerment in IHD were identified in the exploratory phase allowing for the development of a Patient Journey Map. In the development phase, people with IHD prioritized needs to be addressed by the vCoP content framework in addition to content proposals. DISCUSSION: The Patient Journey Map helped to easily visualize the empowerment needs of people with IHD and it might be transferable for the development of other people-centred interventions. The co-design process also allowed the development of training materials adapted to the priorities of people with IHD. CONCLUSION: A people-centred co-design process of a vCoP may facilitate the empowerment of people with IHD.

Effectiveness and cost-effectiveness of a virtual community of practice to improve the empowerment of patients with ischaemic heart disease: study protocol of a randomised controlled trial.

INTRODUCTION: Virtual Communities of Practice (VCoP) or knowledge-sharing virtual communities offer ubiquitous access to information and exchange possibilities for people in similar situations, which might be especially valuable for the self-management of patients with chronic diseases. In view of the scarce evidence on the clinical and economic impact of these interventions on chronic conditions, we aim to evaluate the effectiveness and cost-effectiveness of a VCoP in the improvement of the activation and other patient empowerment measures in patients with ischaemic heart disease (IHD). METHODS AND ANALYSIS: A pragmatic randomised controlled trial will be performed in Catalonia, Madrid and Canary Islands, Spain. Two hundred and fifty patients with a recent diagnosis of IHD attending the participating centres will be selected and randomised to the intervention or control group. The intervention group will be offered participation for 12 months in a VCoP based on a gamified web 2.0 platform where there is interaction with other patients and a multidisciplinary professional team. Intervention and control groups will receive usual care. The primary outcome will be measured with the Patient Activation Measure questionnaire at baseline, 6, 12 and 18 months. Secondary outcomes will include: clinical variables; knowledge (Questionnaire of Cardiovascular Risk Factors), attitudes (Self-efficacy Managing Chronic Disease Scale), adherence to the Mediterranean diet (Mediterranean Diet Questionnaire), level of physical activity (International Physical Activity Questionnaire), depression (Patient Health Questionnaire), anxiety (Hospital Anxiety Scale-A), medication adherence (Adherence to Refill Medication Scale), quality of life (EQ-5D-5L) and health resources use. Data will be collected from self-reported questionnaires and electronic medical records. ETHICS AND DISSEMINATION: The trial was approved by Clinical Research Ethics Committee of Gregorio Marañón University Hospital in Madrid, Nuestra Señora de Candelaria University Hospital in Santa Cruz de Tenerife and IDIAP Jordi Gol in Barcelona. The results will be disseminated through workshops, policy briefs, peer-reviewed publications, local/international conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03959631). Pre-results.

Multicomponent Interventions for the Prevention of Delirium in Hospitalized Older People: A Meta-Analysis.

OBJECTIVES: To comprehensively assess the effects of multicomponent interventions for prevention of delirium in hospitalized older people. DESIGN: Systematic review with meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses methods. PARTICIPANTS: All randomized controlled trials were included. Included studies were conducted in hospitalized older people (aged ≥65 years). MEASUREMENTS: The electronic databases MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were consulted (search date: 2015 to March 2019). Predefined criteria were used to determine inclusion of studies and to assess their methodologic quality. RESULTS: From 1,250 records identified, 10 randomized controlled trials were included (n = 2,850: 1355 medical patients, 1,243 surgical, and 160 intensive care unit). The multicomponent interventions, compared with usual care, reduced the incidence of delirium (risk ratio (RR) = 0.62; 95% confidence interval (CI) = 0.54-0.72; I2 = 0%; k = 10; n = 2,758), duration of delirium (RR = -1.18; 95% CI = -1.95 to -0.40; I2 = 45%; k = 6; n = 276), severity of delirium (standard mean difference = -0.98; 95% CI = -1.46 to -0.49; I2 = 0%; k = 3; n = 82), and pressure ulcers (RR = 0.48; 95% CI = 0.26-0.88; I2 = 0%; k = 2; n = 457). CONCLUSIONS: This meta-analysis suggests that multicomponent interventions to prevent delirium are effective in decreasing its incidence, duration, and severity; as well as the incidence of pressure ulcers in hospitalized older people. Therefore, multicomponent interventions hold great promise to impact in the most important and prevalent conditions affecting fragile older people during hospitalization.

Subcutaneous implantable cardioverter-defibrillator in primary and secondary prevention of sudden cardiac death: A meta-analysis.

BACKGROUND: Subcutaneous implantable cardioverter-defibrillator (S-ICD) is gaining in popularity for primary and secondary prevention of sudden cardiac death. The objective was to evaluate the safety and clinical effectiveness of the S-ICD for prevention of sudden cardiac death compared to transvenous cardioverter-defibrillator (TV-ICD). METHODS: A systematic review with meta-analyses was performed. The electronic databases MEDLINE, EMBASE, SCI, and Cochrane Central Register of Controlled Trials were consulted in March 2018 with no restrictions on publication date. Predefined criteria were used to determine inclusion of studies and to assess their methodologic quality. RESULTS: Ten longitudinal-observational studies with comparison group presenting moderate methodologic flaws were included (N = 7820). The combination of results indicates that health-related quality of life is not significantly different between S-ICD and TV-ICD groups (Physical health: MD = 2.90; 95% CI = -3.88, 9.68/Mental health: MD = 0.13; 95% CI = -2.11, 2.37). Mortality occurred in 4.4% of S-ICD patients and 5.9% of TV-ICD patients died (OR = 0.79; 95% CI = 0.50, 1.24). The incidence of infections (OR = 1.79; 95% CI = 0.93, 3.43) and inappropriate shocks (OR = 1.28, 95% CI = 0.91, 1.78) is not significantly different between both groups. The S-ICD reduces complications related to electrodes/leads (OR = 0.13, 95% CI = 0.05, 0.29) and has lower electrodes/leads movement compared with TV-ICD (OR = 0.26; 95% CI 0.10, 0.67). In contrast, pneumothorax is more likely in TV-ICD than S-ICD (OR = 0.17; 95% CI = 0.03, 0.97). CONCLUSIONS: S-ICD reduces electrodes/leads movement, electrodes/leads related complications, and pneumothorax. Our study did not demonstrate a statistically significant difference in mortality, health-related quality of life, and infection rate between S-ICD and TV-ICD.

Human Albumin Impairs Amyloid ß-peptide Fibrillation Through its C-terminus: From docking Modeling to Protection Against Neurotoxicity in Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative process characterized by the accumulation of extracellular deposits of amyloid ß-peptide (Aß), which induces neuronal death. Monomeric Aß is not toxic but tends to aggregate into ß-sheets that are neurotoxic. Therefore to prevent or delay AD onset and progression one of the main therapeutic approaches would be to impair Aß assembly into oligomers and fibrils and to promote disaggregation of the preformed aggregate. Albumin is the most abundant protein in the cerebrospinal fluid and it was reported to bind Aß impeding its aggregation. In a previous work we identified a 35-residue sequence of clusterin, a well-known protein that binds Aß, that is highly similar to the C-terminus (CTerm) of albumin. In this work, the docking experiments show that the average binding free energy of the CTerm-Aß1-42 simulations was significantly lower than that of the clusterin-Aß1-42 binding, highlighting the possibility that the CTerm retains albumin's binding properties. To validate this observation, we performed in vitro structural analysis of soluble and aggregated 1 µM Aß1-42 incubated with 5 µM CTerm, equimolar to the albumin concentration in the CSF. Reversed-phase chromatography and electron microscopy analysis demonstrated a reduction of Aß1-42 aggregates when the CTerm was present. Furthermore, we treated a human neuroblastoma cell line with soluble and aggregated Aß1-42 incubated with CTerm obtaining a significant protection against Aß-induced neurotoxicity. These in silico and in vitro data suggest that the albumin CTerm is able to impair Aß aggregation and to promote disassemble of Aß aggregates protecting neurons.

Stratification of amyotrophic lateral sclerosis patients: a crowdsourcing approach.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease where substantial heterogeneity in clinical presentation urgently requires a better stratification of patients for the development of drug trials and clinical care. In this study we explored stratification through a crowdsourcing approach, the DREAM Prize4Life ALS Stratification Challenge. Using data from >10,000 patients from ALS clinical trials and 1479 patients from community-based patient registers, more than 30 teams developed new approaches for machine learning and clustering, outperforming the best current predictions of disease outcome. We propose a new method to integrate and analyze patient clusters across methods, showing a clear pattern of consistent and clinically relevant sub-groups of patients that also enabled the reliable classification of new patients. Our analyses reveal novel insights in ALS and describe for the first time the potential of a crowdsourcing to uncover hidden patient sub-populations, and to accelerate disease understanding and therapeutic development.

On the mechanisms of protein interactions: predicting their affinity from unbound tertiary structures.

Motivation: The characterization of the protein-protein association mechanisms is crucial to understanding how biological processes occur. It has been previously shown that the early formation of non-specific encounters enhances the realization of the stereospecific (i.e. native) complex by reducing the dimensionality of the search process. The association rate for the formation of such complex plays a crucial role in the cell biology and depends on how the partners diffuse to be close to each other. Predicting the binding free energy of proteins provides new opportunities to modulate and control protein-protein interactions. However, existing methods require the 3D structure of the complex to predict its affinity, severely limiting their application to interactions with known structures. Results: We present a new approach that relies on the unbound protein structures and protein docking to predict protein-protein binding affinities. Through the study of the docking space (i.e. decoys), the method predicts the binding affinity of the query proteins when the actual structure of the complex itself is unknown. We tested our approach on a set of globular and soluble proteins of the newest affinity benchmark, obtaining accuracy values comparable to other state-of-art methods: a 0.4 correlation coefficient between the experimental and predicted values of ΔG and an error < 3 Kcal/mol. Availability and implementation: The binding affinity predictor is implemented and available at http://sbi.upf.edu/BADock and https://github.com/badocksbi/BADock. Contact: j.planas-iglesias@warwick.ac.uk or baldo.oliva@upf.edu. Supplementary information: Supplementary data are available at Bioinformatics online.

Genetic and functional characterization of disease associations explains comorbidity.

Understanding relationships between diseases, such as comorbidities, has important socio-economic implications, ranging from clinical study design to health care planning. Most studies characterize disease comorbidity using shared genetic origins, ignoring pathway-based commonalities between diseases. In this study, we define the disease pathways using an interactome-based extension of known disease-genes and introduce several measures of functional overlap. The analysis reveals 206 significant links among 94 diseases, giving rise to a highly clustered disease association network. We observe that around 95% of the links in the disease network, though not identified by genetic overlap, are discovered by functional overlap. This disease network portraits rheumatoid arthritis, asthma, atherosclerosis, pulmonary diseases and Crohn's disease as hubs and thus pointing to common inflammatory processes underlying disease pathophysiology. We identify several described associations such as the inverse comorbidity relationship between Alzheimer's disease and neoplasms. Furthermore, we investigate the disruptions in protein interactions by mapping mutations onto the domains involved in the interaction, suggesting hypotheses on the causal link between diseases. Finally, we provide several proof-of-principle examples in which we model the effect of the mutation and the change of the association strength, which could explain the observed comorbidity between diseases caused by the same genetic alterations.