El papel del gastroenterólogo en el tratamiento mediante infusión intestinal continua de levodopa-carbidopa de la enfermedad de Parkinson

La Enfermedad de Parkinson es un trastorno crónico, progresivo que con el paso de los años desarrolla complicaciones motoras en forma de fluctuaciones, discinesias e inestabilidad postural. Junto a los trastornos motores se presentan síntomas no motores como los trastornos cognitivos, la depresión o las alteraciones del sueño. Todo ello implica un deterioro de la calidad de vida y una alteración de las relaciones sociales. El tratamiento habitual de las fluctuaciones consiste en el fraccionamiento de la dosis de levodopa a lo largo de día. A medida que la enfermedad progresa se acorta la duración de la respuesta a levodopa y la ventana terapéutica se estrecha, lo que resulta en unas fluctuaciones imprevisibles con la aparición brusca y aleatoria de periodos en off, así como la presentación de las discinesias incapacitantes que ejercen un impacto negativo sobre la actividades de la vida diaria y sobre la calidad de vida..

Clinical management of patients with advanced Parkinson's disease treated with continuous intestinal infusion of levodopa/carbidopa

Patients with Parkinson's disease often have a good initial response to dopaminergic therapy but later usually develop motor fluctuations and dyskinesia. In these patients, continuous infusion of levodopa-carbidopa intestinal gel (LCIG) allows for maintaining adequate dopamine levels and for improving motor and nonmotor symptoms, as well as quality of life and autonomy. Adequate candidate selection and follow-up are crucial for treatment success. Management should be multidisciplinary, and patient and caregiver education is a priority. This expert consensus document has been developed by a team of neurologists, gastroenterologists and nurses who have a vast experience in LCIG therapy, with an intention to provide knowledge and tools to facilitate patient management throughout all phases of LCIG treatment process

Atypical diagnosis by endoscopic capsule: Whipple's disease

Whipple's disease is a chronic systemic infection produced by the actinomycete Tropheryma whipplei. Endoscopic tests are key in the diagnosis as they allow biopsy and histopathological examination for definitive diagnosis of this entity. We present a case of Whipple's disease where capsule endoscopy, uncommon for the diagnosis of this condition, was essential for it and its performance before and after antibiotic treatment allows to describe the macroscopic evolution of the findings in the small bowel. This case illustrates the usefulness of capsule endoscopy to allow complete examination of the small bowel disease in which up to 30% of patients may present with normal endoscopy

The specific seroreactivity to ∆Np73 isoforms shows higher diagnostic ability in colorectal cancer patients than the canonical p73 protein

© The Author(s) 2019.The p53-family is tightly regulated at transcriptional level. Due to alternative splicing, up to 40 different theoretical proteoforms have been described for p73 and at least 20 and 10 for p53 and p63, respectively. However, only the canonical proteins have been evaluated as autoantibody targets in cancer patients for diagnosis. In this study, we have cloned and expressed in vitro the most upregulated proteoforms of p73, ΔNp73α and ΔNp73β, for the analysis of their seroreactivity by a developed luminescence based immunoassay test using 145 individual plasma from colorectal cancer, premalignant individuals and healthy controls. ∆Np73α seroreactivity showed the highest diagnostic ability to discriminate between groups. The combination of ∆Np73α, ∆Np73β and p73 proteoforms seroreactivity were able to improve their individual diagnostic ability. Competitive inhibition experiments further demonstrated the presence of unique specific epitopes in ΔNp73 isoforms not present in p73, with several colorectal patients showing unique and specific seroreactivity to the ΔNp73 proteoforms. Overall, we have increased the complexity of the humoral immune response to the p53-family in cancer patients, showing that the proteoforms derived from the alternative splicing of p73 possess a higher diagnostic ability than the canonical protein, which might be extensive for p53 and p63 proteins.This work was supported by the Ramon y Cajal programme of the MINECO and the financial support of the PI17CIII/00045 grant from the AES-ISCIII program to R.B., cofounded by FEDER funds. G.D. acknowledges the financial support of PI15/00246 grant of the FIS and Cátedra UAM-Roche en Medicina de Innovación. M.G-A. was supported by a contract of the Programa Operativo de Empleo Juvenil y la Iniciativa de Empleo Juvenil (YEI) with the participation of the Consejería de Educación, Juventud y Deporte de la Comunidad de Madrid y del Fondo Social Europeo. We thank the excellent technical support of Maricruz Sánchez. A.M-C. is a recipient of a FPU fellowship from the Ministerio de Educación, Cultura y Deporte

Identification of tumor-associated antigens with diagnostic ability of colorectal cancer by in-depth immunomic and seroproteomic analysis

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer related death worldwide. Its diagnosis at early stages would significantly improve the survival of CRC patients. The humoral immune response has been demonstrated useful for cancer diagnosis, predating clinical symptoms up to 3 years. Here, we employed an in-depth seroproteomic approach to identify proteins that elicit a humoral immune response in CRC patients. The seroproteomic approach relied on the immunoprecipitation with patient-derived autoantibodies of proteins from CRC cell lines with different metastatic properties followed by LC-MS/MS. After bioinformatics, we focused on 31 targets of CRC autoantibodies. After WB and IHC validation, ERP44 and TALDO1 showed potential to discriminate disease-free and metastatic CRC patients, and time to recurrence of CRC patients in stage II. Using plasma samples of 30 healthy individuals, 28 premalignant individuals, and 32 CRC patients, nine out of 13 selected targets for seroreactive analysis showed significant diagnostic ability to discriminate either CRC patients or premalignant subjects from controls. Our results suggest that the here defined panel of CRC autoantibodies and their target proteins should be included in CRC blood-based biomarker panels to get a clinically useful blood-based diagnostic signature for CRC detection. Significance: Colorectal cancer is one of the deadliest cancer types mainly due to its late diagnosis. Its early diagnosis, therefore, is of great importance since it would significantly improve the survival of CRC patients. In our work, the in-depth seroproteomic analysis of colorectal cancer using isolated IgGs from colorectal cancer patients and controls and protein extract of colorectal cancer cells provide the identification of valuable biomarkers with diagnostic and prognostic ability of the disease

Importance of endoscopist quality metrics for findings at surveillance colonoscopy: The detection‐surveillance paradox

Background: Guidelines recommend surveillance colonoscopies based exclusively on findings at baseline colonoscopy. This recommendation leads to the paradox that the higher the baseline colonoscopy quality, the more surveillance colonoscopies will be indicated according to current guidelines. Objective: The aim of this study was to evaluate the effect on follow-up findings of different quality metrics of the endoscopist performing the baseline colonoscopy. Methods: This retrospective cohort study included individuals with advanced adenomas at baseline colonoscopy. Adenoma detection rate (ADR) and adenomas per colonoscopy rate (APCR) were determined for 44 endoscopists. Surveillance colonoscopies were checked after systematic tracking. Results: A total of 574 individuals were diagnosed with advanced adenomas, of whom 270 received a surveillance colonoscopy. Patients whose baseline colonoscopy endoscopist had an ADR lower than the median of 33.8% had significantly higher rates of advanced neoplasia at follow-up (13.1% vs 4.0%; p = 0.001). On univariate analysis, high-risk advanced adenomas at baseline (HR 0.43; 95% CI 0.19-0.97) and ADR (HR 0.94; 95% CI 0.89-0.99) showed a significant relationship with advanced neoplasia at surveillance. In a multivariate Cox model, the ADR of the endoscopist who performed the baseline colonoscopy was the only independent predictor of risk for developing advanced neoplasia at follow-up (HR 0.94; 95% CI 0.89-0.99). Conclusions: Our results suggest that the risk of identifying advanced adenomas at follow-up is closely related to the quality metrics of the endoscopist who performs the baseline colonoscopy