Validation, Deployment, and Real-World Implementation of a Modular Toolbox for Alzheimer's Disease Detection and Dementia Risk Reduction: The AD-RIDDLE Project.

The Real-World Implementation, Deployment, and Validation of Early Detection Tools and Lifestyle Enhancement (AD-RIDDLE) project, recently launched with the support of the EU Innovative Health Initiative (IHI) public-private partnership and UK Research and Innovation (UKRI), aims to develop, test, and deploy a modular toolbox platform that can reduce existing barriers to the timely detection, and therapeutic approaches in Alzheimer's disease (AD), thus accelerating AD innovation. By focusing on health system and health worker practices, AD-RIDDLE seeks to improve and smooth AD management at and between each key step of the clinical pathway and across the disease continuum, from at-risk asymptomatic stages to early symptomatic ones. This includes innovation and improvement in AD awareness, risk reduction and prevention, detection, diagnosis, and intervention. The 24 partners in the AD-RIDDLE interdisciplinary consortium will develop and test the AD-RIDDLE toolbox platform and its components individually and in combination in six European countries. Expected results from this cross-sectoral research collaboration include tools for earlier detection and accurate diagnosis; validated, novel digital cognitive and blood-based biomarkers; and improved access to individualized preventative interventions (including multimodal interventions and symptomatic/disease-modifying therapies) across diverse populations, within the framework of precision medicine. Overall, AD-RIDDLE toolbox platform will advance management of AD, improving outcomes for patients and their families, and reducing costs.

Benefits of a 3-week outpatient balneotherapy programme on patient-reported outcomes.

BACKGROUND: Analysis of the health profile of participants aged over 65 has been initiated in balneotherapy. AIMS: To determine the benefits of a 3-week outpatient balneotherapy program on patient-reported outcomes. METHODS: Our sample consisted of 1471 people. The average age of the study population was 72.5 years (± 5.1) and 67% of the participants were females. Symptoms intensity was measured by visual analogue scale, and health-related quality of life (HRQL) with the EQ5D questionnaire before and after the program. Changes of perceived functional status were rated using a 3-point Likert scale. RESULTS: The results indicated a significant increase in the fear of falling and a decrease in fatigue. EQ5D reveals a significant improvement after the program. The perceived change scores remained stable, except for anxiety/depression. CONCLUSIONS: The study indicated significant improvements of HRQL and a decrease of perception of fatigue and anxiety in elderly people participants in a 3-week balneological programme.

Estudio observacional prospectivo unicéntrico sobre el efecto de la prehabilitación trimodal en cirugía colorrectal / A single-center prospective observational study on the effect of trimodal prehabilitation in colorectal surgery

INTRODUCCIÓN: Se ha diseñado un protocolo de prehabilitación trimodal con el objetivo de valorar si contribuye a disminuir la morbilidad postoperatoria, valorar el efecto de la prehabilitación en la estancia hospitalaria global y analizar la evolución de la capacidad funcional antes y después de cirugía. MÉTODOS: Estudio observacional unicéntrico con pacientes con cáncer colorrectal intervenidos quirúrgicamente con intención curativa después de un protocolo de prehabilitación trimodal. Se recoge morbilidad postoperatoria según el Comprehensive Complication Index y estancia hospitalaria, y se compara con una matriz histórica. También se recoge capacidad funcional antes y después de la aplicación del protocolo de prehabilitación. RESULTADOS: En comparación con la población histórica se consigue disminuir el Comprehensive Complication Index global de forma estadísticamente significativa de 13,2 a 11,5. Desglosando por tipo de morbilidad, todas disminuyen en porcentaje sin conseguir significación (infección espacio quirúrgico del 11,7 al 8,4%; infección nosocomial del 15,8 al 10%, y morbilidad médica del 8,6 al 4,2%). La estancia hospitalaria global pasa de 6 a 4 días y el porcentaje de pacientes que se preparan en casa disminuye de forma estadísticamente significativa en ambos casos. CONCLUSIONES: La prehabilitación trimodal puede contribuir a disminuir la morbilidad postoperatoria y la estancia hospitalaria global de los pacientes intervenidos de neoplasia colorrectal

INTRODUCTION: A trimodal prehabilitation protocol was designed with the aim to evaluate whether it contributes to reducing postoperative morbidity, to evaluate the effect of prehabilitation on overall hospital stay, and to analyze the evolution of functional capacity before and after surgery. METHODS: A single-center observational study of patients with colorectal cancer who underwent surgery with curative intent after a trimodal prehabilitation protocol. We collected data for postoperative morbidity according to the Comprehensive Complication Index and hospital stay, which were compared with a historical matrix. Functional capacity data were also collected before and after the application of the prehabilitation protocol. RESULTS: Compared to the historical population, the overall Comprehensive Complication Index was reduced from 13.2 to 11.5, which was statistically significant. Analyzed by morbidity type, all decreased in percentage, although without achieving significance (surgical site infection from 11.7% to 8.4%, nosocomial infection 15.8 to 10% and medical morbidity 8.6% to 4.2%). The overall hospital stay went from 6 to 4 days, and the decrease in the percentage of patients who prepared at home was statistically significant in both cases. CONCLUSIONS: Trimodal prehabilitation can contribute to lowering the postoperative morbidity and overall hospital stay of patients undergoing colorectal cancer surgery

A single-center prospective observational study on the effect of trimodal prehabilitation in colorectal surgery. / Estudio observacional prospectivo unicéntrico sobre el efecto de la prehabilitación trimodal en cirugía colorrectal.

INTRODUCTION: A trimodal prehabilitation protocol was designed with the aim to evaluate whether it contributes to reducing postoperative morbidity, to evaluate the effect of prehabilitation on overall hospital stay, and to analyze the evolution of functional capacity before and after surgery. METHODS: A single-center observational study of patients with colorectal cancer who underwent surgery with curative intent after a trimodal prehabilitation protocol. We collected data for postoperative morbidity according to the Comprehensive Complication Index and hospital stay, which were compared with a historical matrix. Functional capacity data were also collected before and after the application of the prehabilitation protocol. RESULTS: Compared to the historical population, the overall Comprehensive Complication Index was reduced from 13.2 to 11.5, which was statistically significant. Analyzed by morbidity type, all decreased in percentage, although without achieving significance (surgical site infection from 11.7% to 8.4%, nosocomial infection 15.8 to 10% and medical morbidity 8.6% to 4.2%). The overall hospital stay went from 6 to 4 days, and the decrease in the percentage of patients who prepared at home was statistically significant in both cases. CONCLUSIONS: Trimodal prehabilitation can contribute to lowering the postoperative morbidity and overall hospital stay of patients undergoing colorectal cancer surgery.

A scoring system to predict complex transanal endoscopic surgery.

BACKGROUND: Since the introduction of screening for colorectal cancer, the use of transanal endoscopic surgery (TEM) has become increasingly popular. However, the technical difficulty of this surgery varies widely. The few studies of learning curve in TEM have produced very disparate results. The aim of this study is to distinguish between straightforward and complex procedures, in order to refer more difficult cases to centers with greater experience. METHOD: Observational study with prospective data collection and retrospective analysis was carried out between June 2004 and January 2019. All TEMs performed on rectal tumors were included. The complexity of the procedure was defined according to the weighted mean surgical time for each surgeon. A predictive model of complexity was established, with a score higher than 5 indicating a complex lesion. RESULTS: During the study period, 773 TEMs were performed, 708 of which met the study's inclusion criteria. One hundred and three tumors were defined as complex. Predictors of complexity were as follows: male sex (OR: 1.78, 95% CI 1.1-2.9, score: 1), tumor size > 5 cm (OR: 5.1, 95% CI 3.2-8.2, score: 4), TEM for recurrence (OR: 6.3, 95% CI 2.3-16.7, score: 5), and distance from the upper margin of the tumor to the anal verge > 15 cm (OR: 1.6, 95% CI 0.96-2.7, score: 1). CONCLUSIONS: Rather than establishing the learning curve merely in terms of the number of TEM procedures performed, it is important to consider the surgical difficulty of the interventions. To this end, it is essential to differentiate simple TEMs from the complex ones.

Transanal endoscopic microsurgery in very large and ultra large rectal neoplasia.

BACKGROUND: Transanal endoscopic microsurgery (TEM) has become the treatment of choice for benign rectal lesions and early rectal cancer (T1). The size classification of rectal polyps is controversial. Some articles define giant rectal lesions as those larger than 5 cm, which present a significantly increased risk of complications. The aim of this study was to evaluate the feasibility of TEM in these lesions. METHODS: An observational descriptive study with prospective data collection evaluating the feasibility of TEM in large rectal adenomas was performed between June 2004 and September 2018. Patients were assigned to one of the three groups according to size: < 5 cm, very large (5-7.9 cm) and ultra-large (≥ 8 cm). Descriptive and comparative analyses between groups were performed. RESULTS: TEM was indicated in 761 patients. Five hundred and seven patients (66.6%) with adenoma in the preoperative biopsy were included in the study. Three hundred and nine out of 507 (60.9%) tumors < 5 cm, 162/507 (32%) very large tumors (5-7.9 cm) and 36/507 (7.1%) ultra-large tumors (≥ 8 cm) were reviewed. Morbidity increased with tumor size: 17.5% in tumors < 5 cm, 26.5% in those 5-7.9 cm, and 36.1% in those > 8 cm. Peritoneal perforation, fragmentation, free margins and stenosis were also more common in very large and ultra-large tumors (p < 0.001). There were no statistical differences between the groups in the definitive pathology (p = 0.38). CONCLUSIONS: TEM in these large tumors is associated with higher rates of morbidity, peritoneal perforation, free margins and stenosis. Although these tumors do not require total mesorectal excision and are eligible for TEM, the surgery must be carried out by experienced surgeons.

Transanal endoscopic micro-surgery in elderly and very elderly patients: a safe option? Observational study with prospective data collection.

BACKGROUND: Although the incidence of colorectal cancer increases with the patient's age, the elderly continue to be less likely to be scheduled for surgery. Transanal endoscopic micro-surgery (TEM) is a surgical alternative to total mesorectal excision (TME) in early stage rectal cancer and/or in selected patients that could decrease morbidity and mortality rates in this group of patients. Our main objective is to assess the safety and feasibility of TEM in elderly (75-84 years) and very elderly (≥ 85 years) patients. METHODS: Observational study was conducted with prospective data collection of all consecutive patients who underwent TEM between April 2004 and January 2017. Patients were assigned to groups according to age. Descriptive and comparative analyses between groups were performed. RESULTS: We analyzed 693 patients, 429 patients < 75 years (61.9%), 220 patients between the ages of 75 and 84 (31.7%), and 44 patients ≥ 85 years old (6.3%). The tendency in our series is to increase comorbidities with age. Palliative or consensus intent was more frequently performed in elderly (10.5%, 34/220), and very elderly (45.4%, 20/44), compared with the youngest (6.3%, 27/429), (p < 0.001). Global morbidity presented an increasing trend related to age from 20.3% in < 75 years, to 25.9% in elderly and 34.1% in very elderly. Surgical complications were recorded in 18.5% (128/693) of patients with no significant differences between groups. The most common one was rectal bleeding 16.1% (111/693). Significant differences were found in non-surgical complications, recorded in 7.3% (16/220) in the elderly, and 15.9% (7/44) in the group above 84 years (p = 0.013). CONCLUSIONS: TEM presents acceptable morbidity rates mainly due to non-surgical-related adverse effects in elderly and very elderly patients and may be a feasible and safe alternative in this population in both curative and non-curative indications.

Transanal endoscopic surgery is effective and safe after endoscopic polypectomy of potentially malignant rectal polyps with questionable margins.

AIM: To determine the percentage of residual lesion observed in the pathology study of transanal endoscopic surgery (TEM) specimens after endoscopic polypectomy of malignant rectal polyps with questionable margins, and the need for further surgery. Secondary aims: to determine the morbidity and mortality associated with this procedure and to identify the percentage of recurrence after excision by TEM. METHODS: Observational study with prospective data collection of all patients undergoing TEM after endoscopic polypectomy for malignant rectal polyps or non-invasive high-grade neoplasia, from January 2004 to December 2016. An en bloc full-thickness wall excision of the scar was performed. Variables recorded: histology of TEM specimen, 30-day morbidity and mortality according to the Clavien-Dindo classification, need for salvage surgery and recurrence. RESULTS: Fifty out of 690 patients undergoing TEM during the study period (36 adenocarcinomas, five non-invasive high-grade neoplasias and 9 neuroendocrine tumors) were included. Post-surgery histology showed residual lesion in 21 (42%) patients: 7 neuroendocrine tumors, 10 adenomas and 4 adenocarcinomas (two pT1, one pT2 and one pT3). The pT2 and pT3 patients (4%) underwent salvage surgery. No recurrence was observed, and mean follow-up was 29.1Â ± 21.6 months. The 30-day morbidity rate was 14%, but 4/7 with Clavien-Dindo grade I. CONCLUSIONS: After endoscopic polypectomy of malignant rectal polyps with questionable margins, the presence of residual lesion in the pathology study of transanal resection specimens is high. TEM with full-thickness resection of these lesions is an appropriate treatment, allowing disease control and achieving minimal morbidity.

Study protocol for a multicenter prospective controlled and randomized trial of transanal total mesorectal excision versus laparoscopic low anterior resection in rectal cancer.

PURPOSE: Compared with the open approach, laparoscopic total mesorectal excision (TME) achieves faster patient recovery, reduces morbidity rates, and shortens hospital stay. However, in laparoscopic low anterior resection (L-LAR), conversion to open surgery is required in almost 20% of cases. Transanal TME (Ta-TME) combined with laparoscopy, also called hybrid natural orifice transluminal endoscopic surgery (NOTES), is a less invasive procedure that can overcome some of the limitations of laparoscopic rectal surgery. In this study, we aim to determine whether Ta-TME has a lower rate of conversion to open surgery than L-LAR, and thus achieves faster patient recovery without altering the pathological, functional, or oncological results. The main objective is to compare the results for conversion to open surgery between Ta-TME and L-LAR. METHODS: Multicenter, prospective randomized controlled study of patients diagnosed with rectal adenocarcinoma who will be randomly allocated to Ta-TME or L-LAR groups after the application of inclusion and exclusion criteria. The main endpoint is conversion to open surgery and the secondary endpoints are general morbidity and mortality and hospital stay. Demographic, surgical, and pathological variables will also be studied, along with quality of life and survival. A sample size of 53 patients per group is calculated. With an estimated loss of 10%, the final sample required will be 116 patients. CONCLUSIONS: Ta-TME achieves a lower conversion rate to open surgery than L-LAR, thus improving patient recovery and reducing overall morbidity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02550769. Registration no. Ethical and Clinical Research Committee, Parc Taulí University Hospital: ID 2014/064.

Non-inferiority multicenter prospective randomized controlled study of rectal cancer T2-T3s (superficial) N0, M0 undergoing neoadjuvant treatment and local excision (TEM) vs total mesorectal excision (TME).

PURPOSE: The standard treatment of rectal adenocarcinoma is total mesorectal excision (TME), in many cases requires a temporary or permanent stoma. TME is associated with high morbidity and genitourinary alterations. Transanal endoscopic microsurgery (TEM) allows access to tumors up to 20 cm from the anal verge, achieves minimal postoperative morbidity and mortality rates, and does not require an ostomy. The treatment of T2, N0, and M0 cancers remains controversial. Preoperative chemoradiotherapy (CRT) in association with TEM reduces local recurrence and increases survival. The TAU-TEM study aims to demonstrate the non-inferiority of the oncological outcomes and the improvement in morbidity and quality of life achieved with TEM compared with TME. METHODS: Prospective, multicenter, randomized controlled non-inferiority trial includes patients with rectal adenocarcinoma less than 10 cm from the anal verge and up to 4 cm in size, staged as T2 or T3-superficial N0-M0. Patients will be randomized to two areas: CRT plus TEM or radical surgery (TME). Postoperative morbidity and mortality will be recorded and patients will complete the quality of life questionnaires before the start of treatment, after CRT in the CRT/TEM arm, and 6 months after surgery in both arms. The estimated sample size for the study is 173 patients. Patients will attend follow-up controls for local and systemic relapse. CONCLUSIONS: This study aims to demonstrate the preservation of the rectum after preoperative CRT and TEM in rectal cancer stages T2-3s, N0, M0 and to determine the ability of this strategy to avoid the need for radical surgery (TME). TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01308190. Número de registro del Comité de Etica e Investigación Clínica (CEIC) del Hospital universitario Parc Taulí: TAU-TEM-2009-01.

In vivo setup characterization for pulsed electromagnetic field exposure at 3 GHz.

An in vivo setup for pulsed electric field exposure at 3 GHz is proposed and characterized in this work. The exposure system allows far field, whole-body exposure of six animals placed in Plexiglas cages with a circular antenna. Chronic exposures under 18 W incident average power (1-4 kW peak power) and acute exposures under 56 W incident average power (4.7 kW peak power) were considered. Numerical and experimental dosimetry of the setup allowed the accurate calculation of specific absorption rate (SAR) distributions under various exposure conditions. From rat model numerical simulations, the whole-body mean SAR values were 1.3 W kg(-1) under chronic exposures and 4.1 W kg(-1) under acute exposure. The brain-averaged SAR value was 1.8 W kg(-1) and 5.7 W kg(-1) under chronic and acute exposure, respectively. Under acute exposure conditions, a 10 g specific absorption of 1.8 ± 1.1 mJ · kg(-1) value was obtained. With temperature rises below 0.8 °C, as measured or simulated on a gel phantom under typical in vivo exposures, this exposure system provides adequate conditions for in vivo experimental investigations under non-thermal conditions.

Charge separation and charge recombination photophysical studies in a series of perylene-C60 linear and cyclic dyads.

A new donor­acceptor doubly bridged perylenediimide­fullerene dyad (PDI­C60, DB-3), where the perylenediimide (PDI) acts as a donor, has been synthesized and studied by time-resolved absorption spectroscopy. The DB-3 undergoes an electron transfer (ET) in both polar and non-polar media under photo-excitation. Structurally the DB-3 dyad resembles four other recently studied dyads (R. K. Dubey et al., Chem. Eur. J., 2013, 19, 6791­6806). Analysis of the ET reactions in this series of dyads was carried out in frame of both classic and semi-quantum ET theories. The result of the analysis for DB-3 suggests that the electronic coupling for the ET reaction is roughly 0.005 eV, internal reorganization energy is 0.16 eV, and outer sphere or solvent reorganization energy is 0.5 and 0.3 eV in benzonitrile and toluene, respectively.

Application of a modified Neff classification to patients with uncomplicated diverticulitis.

AIM: Severity of acute diverticulitis (AD) has traditionally been assessed using the Hinchey classification; however, this classification is predominantly a surgical one. The Neff classification provides an alternative classification based on CT findings. The aim of this study was to evaluate a modification of the Neff classification to select patients presenting with early-stage AD to receive outpatient management. METHOD: All patients with AD, presenting to a single unit, were prospectively studied. All patients underwent emergency abdominal CT and were assigned a Neff stage, including a modification (mNeff) to Neff Stage I. The Neff stages used were: Stage 0, uncomplicated diverticulitis; Diverticula, thickening of the wall, increased density of the pericolic fat; Stage I, locally complicated (our modification included substages Ia (localized pneumoperitoneum in the form of air bubbles) and Ib (local abscess); Stage II, complicated with pelvic abscess; Stage III, complicated with distant abscess; and Stage IV, complicated with other distant complications. Patients who presented with Stage 0 or Stage Ia were selectively managed as outpatients. Patients with comorbidity or the presence of the systemic inflammatory response syndrome (SIRS) were excluded. RESULTS: Between February 2010 and January 2013, 205 patients (mean age 59 years; age range 25-90 years) presented with AD. One-hundred and forty-nine met the radiological criteria for potential outpatient treatment. After applying the exclusion criteria, 68 were eventually assigned to an outpatient programme. Sixty-four (94%) successfully completed the outpatient treatment protocol; four patients were readmitted. CONCLUSION: Our mNeff classification allowed selected patients with AD to be successfully managed in an outpatient programme.

[Microbiological stability study of minimally processed cantaloupe (Cucumis melo L) by vacuum]. / Estudio de la estabilidad microbiológica del melón (Cucumis melo L) mínimamente procesado por impregnación al vacío.

In order to design a minimal process for cantaloupe, the water activity of the fruit was reduced until 0.976 through vacuum osmotic dehydration and the optimum combination of microbial preservatives (100 ppm sodium sulfite, 600 ppm potassium sorbate, 0.5% L-ascorbic acid and 1% citric acid), that contributed to minimize (p < 0.05), the content of aerobic mesophilic bacteria, molds and yeast, was determined through a 2k multifactorial design. In the second experimental stage, the conditions previously mentioned were tested together with the application of fruit's blanching (98 degrees C/3 min) with saturated steam and product storage in three different modified atmospheres (6% O2-6% CO2, 5% O2-10% CO2 and atmospheric air). In such sense, the application of microbial preservatives together with fruit's blanching and atmospheric air in high barrier packages (30 mu nylon) contributed to extent the shelf life of the cantaloupe minimally processed during 14 days on the basis of aerobic mesophilic bacteria, psychrotrophic bacteria, acid lactic bacteria, enterobacteria, molds, yeast and the sensory attributes color, odour, taste and texture.

[Vulvar lymphedema: unusual manifestation of metastatic Crohn's disease]. / Linfedema vulvar: una manifestación infrecuente de la enfermedad de Crohn metastásica.

Cutaneous-mucosal lesions constitute one of the most frequent extraintestinal manifestations of Crohn's disease and in some cases may be the first symptom of intestinal disease. We describe the case of a 45-year-old female patient who sought medical help for genital tumefaction of 20 years' evolution. For the previous 15 years, she had been experiencing digestive symptomatology attributed to irritable bowel syndrome. Two months before the consultation, and coinciding with aggravation of the condition, the patient had been diagnosed with colonic Crohn's disease. Skin biopsy of the labia minora revealed sarcoid granulomas. The results of microbiological studies (staining for microorganisms and cultures) were negative. A diagnosis of metastatic vulvar Crohn's disease was made and, treatment with metronidazole was started, which improved the genital edema after 2 months. Genital lymphedema is an exceptionally rare manifestation of metastatic Crohn's disease that may appear several years before intestinal symptomatology develops. Treatment with metronidazole seems to be a good therapeutic option.

Un nuevo caso de lesión traqueal tras intubación difícil / A new case of tracheal lesion after difficult intubation

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Esclerodermatomiositis infantil / Infantile sclerodermatomyositis

La esclerodermatomiositis (EDM) es un síndrome de solapamiento, caracterizado por la presencia de manifestaciones clínicas de esclerosis sistémica y de dermatomiositis, cuyo principal marcador serológico es el anticuerpo anti-PM/Scl. Presentamos el caso clínico de una niña de 10 años diagnosticada de EDM (AU)