Fluid and tissue biomarkers in Parkinson's disease: Immunodetection or seed amplification? Central or peripheral?

Over the last two decades there have been meaningful developments on biomarkers of neurodegenerative diseases, extensively (but not solely) focusing on their proteinopathic nature. Accordingly, in Alzheimer's disease determination of levels of total and phosphorylated tau (τ and p-τ, usually p-τ181) along with amyloid-beta1-42 (Aß1-42) by immunodetection in cerebrospinal fluid (CSF) and currently even in peripheral blood, have been widely accepted and introduced to routine diagnosis. In the case of Parkinson's disease, α-synuclein as a potential biomarker (both for diagnosis and progression tracking) has proved more elusive under the immunodetection approach. In recent years, the emergence of the so-called seed amplification assays is proving to be a game-changer, with mounting evidence under different technical approaches and using a variety of biofluids or tissues, yielding promising diagnostic accuracies. Currently the least invasive but at once more reliable source of biosamples and techniques are being sought. Here we overview these advances.

Linfoma testicular primario tipo B de célula grande: aspectos clínicos, histopatológicos, diagnóstico terapéutico y pronósticos / Large cell type B primary testicular lymphoma: clinical, histopathological, therapeutic diagnosis and prognostic aspects

RESUMEN Fundamento: el linfoma testicular constituye entre el 1 y el 9 % de los tumores testiculares, es el tumor testicular maligno más frecuente en los varones mayores de 50 años. El pronóstico es reservado debido a una gran tendencia a la propagación sistémica temprana. La presentación clínica más habitual, dolor testicular a la palpación y espontáneo, con aumento del volumen y de la consistencia testicular. Su tratamiento se sustenta en tres pilares fundamentales: orquiectomía, quimioterapia y radioterapia. Objetivo: describir un enfermo con linfoma testicular tipo B de célula grande. Presentación del caso: paciente masculino de 55 años de edad, hipertenso, fumador 10 cigarrillos al día, bebedor ocasional. Acude a consulta por aumento de volumen testicular izquierdo. En la analítica se observa elevación del lactato deshidrogenasa. Ecografía: teste izquierdo con ecogenicidad muy heterogénea, parénquima desestructurado, sin lesiones nodulares. Engrosamiento difuso del epidídimo. Vascularización incrementada. Se realiza orquiectomía radical inguinal, al ser el diagnóstico anatomopatológico linfoma difuso de células grandes tipo B, en la actualidad ha sido tratado con quimioterapia, por presentar además afectación ósea. Pero ha evolucionado favorablemente. Conclusiones: el linfoma testicular es una enfermedad poco frecuente, a pesar de ser considerado el tumor testicular más común en mayores de 60 años. En su mayoría se trata de linfomas no Hodgkin difusos de grado intermedio alto de malignidad e inmunofenotipo B. El pronóstico siempre es reservado debido a su gran tendencia a la propagación sistémica. El tratamiento está basado en la cirugía (orquiectomía radical inguinal), quimioterapia y radioterapia.

ABSTRACT Background: testicular lymphoma constitutes between 1 and 9 % of testicular tumors; it is the most frequent malignant testicular tumor in men over 50 years of age. The prognosis is reserved due to a great tendency to early systemic spread. The most common clinical presentation is testicular pain on palpation and spontaneous, with increased volume and testicular consistency. Its treatment is based on three fundamental pillars: orchiectomy, chemotherapy and radiotherapy. Objective: to describe a patient with large cell type B testicular lymphoma. Case report: 55-year-old male patient, hypertensive, smoker 10 cigarettes a day, occasional drinker. He goes to consultation due to left testicular volume increase. In the laboratory tests, the lactate dehydrogenase is elevated. Ultrasound Scand: Left testicle with very heterogeneous echogenicity, unstructured parenchyma, no nodular lesions. Diffuse thickening of the epididymis. Increased vascularization. Inguinal radical orchiectomy is performed, the anatomic-pathological diagnosis being diffuse large B cell type lymphoma, it has now been treated with chemotherapy, because he alsopresented bone involvement. But he has evolved favorably. Conclusions: testicular lymphoma is a very rare entity, despite being considered the most common testicular tumor in people over 60 years of age. The majority are diffuse non-Hodgkin lymphomas of high intermediate degree of malignancy and immune-phenotype B. The prognosis is always reserved due to its great tendency to systemic spread. The treatment is based on surgery (radical inguinal orchiectomy), chemotherapy and radiotherapy.

Synthesis and Characterization of Covalently Crosslinked pH-Responsive Hyaluronic Acid Nanogels: Effect of Synthesis Parameters.

Stable hyaluronic acid nanogels were obtained following the water-in-oil microemulsion method by covalent crosslinking with three biocompatible crosslinking agents: Divinyl sulfone, 1,4-butanediol diglycidyl ether (BDDE), and poly(ethylene glycol) bis(amine). All nanoparticles showed a pH-sensitive swelling behavior, according to the pKa value of hyaluronic acid, as a consequence of the ionization of the carboxylic moieties, as it was corroborated by zeta potential measurements. QELS studies were carried out to study the influence of the chemical structure of the crosslinking agents on the particle size of the obtained nanogels. In addition, the effect of the molecular weight of the biopolymer and the degree of crosslinking on the nanogels dimensions was also evaluated for BDDE crosslinked nanoparticles, which showed the highest pH-responsive response.

[Enterolithotomy and early cholecystectomy, an application of damage control surgery for patients with gallstone ileus]. / Enterolitotomía más colecistectomía precoz, una aplicación de cirugía de control de daños para pacientes con íleo biliar.

BACKGROUND: Recurrent gallstone ileus is an uncommon mechanical intestinal obstruction secondary to occlusion of the intestine by an intraluminal biliary calculus. CLINICAL CASE: Female, 75 years old, ischaemic heart disease (stent), arrived in our department complaining of abdominal pain and vomiting. Computed tomography showed gallstone ileus. The patient underwent an enterotomy with gallstone removal. Three months later, the patient came back with the same clinical symptoms and signs. A new computed tomography highlighted a gallstone ileus again. Enterolithotomy and gallstone removal, cholecystectomy and closure of cholecystoduodenal fistula were performed. The patient had a prolonged hospital stay due to the development of congestive heart failure. Case 2. Male, 71 years old, ischaemic heart disease and aortocoronary bypass, seen in our department complaining of vomiting. Computed tomography showed aerobilia and gallstone ileus. The patient underwent an urgent enterolithotomy. Seven months later, the patient came back with the same clinical symptoms and signs. Computed tomography showed a new gallstone ileus. An enterotomy and gallstone removal, cholecystectomy and closure of cholecystoduodenal fistula were performed. The patient died due to multi-organ failure in post-surgery period. CONCLUSION: In the elderly patients with concomitant medical illnesses with the risk of a second laparotomy, it is justifiable to reconsider the definitive repair in the treatment of gallstone ileus. The enterolithotomy in acute phase followed by early cholecystectomy (4-8 weeks) may be a safe method for eliminating, not only the possibility of recurrent gallstone ileus, and probably the need for a second laparotomy, but also the exceptional possibility of developing a gallbladder carcinoma.

Frequency of abnormal esophageal acid exposure in patients eligible for bariatric surgery.

BACKGROUND: Obesity and gastroesophageal reflux disease (GERD) are both high-prevalence diseases in developed nations. Obesity has been identified as an important risk factor in the development of GERD. The objective of this study was to determine the frequency of abnormal esophageal acid exposure in patients candidate for bariatric surgery and its relationship with any clinical and endoscopic findings before surgery. METHODS: Data collected from a group of 88 patients awaiting bariatric surgery included a series of demographic variables and symptoms typical of GERD. The tests patients underwent included manometry, pH monitoring, and upper gastrointestinal endoscopy. Univariate and multivariate analyses were conducted on the variables related to the onset of reflux. RESULTS: Esophageal pH monitoring tests were positive in 65% of the patients. Manometries showed lower esophageal sphincter hypotonia in 46%, while 20% returned abnormal upper endoscopy results. Out of the 45% of patients who were asymptomatic or returned normal endoscopies, half returned positive esophageal pH tests. In turn, among the 55% of patients who had symptoms or an abnormal upper endoscopy, three quarters had pH tests that diagnosed reflux. pH tests were also positive in 80% of symptomatic patients and 100% of patients with esophagitis (P<.042). No statistically significant relationship was found between body mass index, sex, age, manometry, or hiatus hernia and the positive pH monitoring. CONCLUSION: Frequency of abnormal esophageal acid exposure among obese patients is high. There is a relationship between the presence of symptoms and reflux. But the absence of symptoms does not rule out the presence of abnormal esophageal function tests.

El íleo biliar como causa de abdomen agudo. Importancia del diagnóstico precoz para el tratamiento quirúrgico / Gallstone ileus as a cause of acute abdomen. Importance of early diagnosis for surgical treatment

El íleo biliar es una causa poco frecuente de obstrucción intestinal mecánica, causada por el paso del cálculo a través de la luz intestinal, de difícil diagnóstico preoperatorio en el Servicio de Urgencias. Presentamos un estudio retrospectivo de 5 casos de íleo biliar tratados entre 2000 y 2010. Se analizaron las características clínicas, las pruebas diagnósticas y el tratamiento quirúrgico realizado. Se incluyó a 5 pacientes, 2 empezaron con una obstrucción intestinal típica, otros 2 presentaron un íleo biliar recurrente previamente intervenido y el último presentó una peritonitis secundaria a la perforación de un divertículo ileal. En todos los casos, la TAC permitió el diagnóstico preoperatorio. En nuestra experiencia, el íleo biliar puede aparecer con clínica diferente a la obstrucción intestinal. En lo casos de sospecha, una TAC puede ser útil para disminuir el retraso diagnóstico relacionado con mayor número de complicaciones (AU)

Gallstone ileus is an uncommon type of mechanical intestinal obstruction caused by an intraluminal gallstone, and preoperative diagnosis is difficult in the Emergency department. This study is a retrospective analysis of the clinical presentation of 5 patients with gallstone ileus treated between 2000-2010. Clinical features, diagnostic testing, and surgical treatment were analyzed. Five patients were included: 2 cases showed bowel obstruction; 2 patients presented a recurrent gallstone ileus with prior surgical intervention; and one patient presented acute peritonitis due to perforation of an ileal diverticula. In all cases CT confirmed the preoperative diagnosis. In our experience, gallstone ileus may present with clinical features other than intestinal obstruction. In suspicious cases CT may be useful to decrease diagnostic delay, which is associated with more complications (AU)

[Gallstone ileus as a cause of acute abdomen. Importance of early diagnosis for surgical treatment]. / El íleo biliar como causa de abdomen agudo. Importancia del diagnóstico precoz para el tratamiento quirúrgico.

Gallstone ileus is an uncommon type of mechanical intestinal obstruction caused by an intraluminal gallstone, and preoperative diagnosis is difficult in the Emergency department. This study is a retrospective analysis of the clinical presentation of 5 patients with gallstone ileus treated between 2000-2010. Clinical features, diagnostic testing, and surgical treatment were analyzed. Five patients were included: 2 cases showed bowel obstruction; 2 patients presented a recurrent gallstone ileus with prior surgical intervention; and one patient presented acute peritonitis due to perforation of an ileal diverticula. In all cases CT confirmed the preoperative diagnosis. In our experience, gallstone ileus may present with clinical features other than intestinal obstruction. In suspicious cases CT may be useful to decrease diagnostic delay, which is associated with more complications.