Discrimination of Etiologically Different Cholestasis by Modeling Proteomics Datasets.

Cholestasis is characterized by disrupted bile flow from the liver to the small intestine. Although etiologically different cholestasis displays similar symptoms, diverse factors can contribute to the progression of the disease and determine the appropriate therapeutic option. Therefore, stratifying cholestatic patients is essential for the development of tailor-made treatment strategies. Here, we have analyzed the liver proteome from cholestatic patients of different etiology. In total, 7161 proteins were identified and quantified, of which 263 were differentially expressed between control and cholestasis groups. These differential proteins point to deregulated cellular processes that explain part of the molecular framework of cholestasis progression. However, the clustering of different cholestasis types was limited. Therefore, a machine learning pipeline was designed to identify a panel of 20 differential proteins that segregate different cholestasis groups with high accuracy and sensitivity. In summary, proteomics combined with machine learning algorithms provides valuable insights into the molecular mechanisms of cholestasis progression and a panel of proteins to discriminate across different types of cholestasis. This strategy may prove useful in developing precision medicine approaches for patient care.

Molecular basis of progressive familial intrahepatic cholestasis 3. A proteomics study.

Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a severe rare liver disease that affects between 1/50,000 and 1/100,000 children. In physiological conditions, bile is produced by the liver and stored in the gallbladder, and then it flows to the small intestine to play its role in fat digestion. To prevent tissue damage, bile acids (BAs) are kept in phospholipid micelles. Mutations in phosphatidyl choline transporter ABCB4 (MDR3) lead to intrahepatic accumulation of free BAs that result in liver damage. PFIC3 onset usually occurs at early ages, progresses rapidly, and the prognosis is poor. Currently, besides the palliative use of ursodeoxycholate, the only available treatment for this disease is liver transplantation, which is really challenging for short-aged patients. To gain insight into the pathogenesis of PFIC3 we have performed an integrated proteomics and phosphoproteomics study in human liver samples to then validate the emerging functional hypotheses in a PFIC3 murine model. We identified 6246 protein groups, 324 proteins among them showing differential expression between control and PFIC3. The phosphoproteomic analysis allowed the identification of 5090 phosphopeptides, from which 215 corresponding to 157 protein groups, were differentially phosphorylated in PFIC3, including MDR3. Regulation of essential cellular processes and structures, such as inflammation, metabolic reprogramming, cytoskeleton and extracellular matrix remodeling, and cell proliferation, were identified as the main drivers of the disease. Our results provide a strong molecular background that significantly contributes to a better understanding of PFIC3 and provides new concepts that might prove useful in the clinical management of patients.

Luxación esternoclavicular posterior / Posterior sternoclavicular dislocation / Luxação posterior esternoclavicular

La luxación esternoclavicular posterior es una patología extremadamente infrecuente, que se presenta, sobre todo, en varones jóvenes como consecuencia de un traumatismo de alta energía. Hasta en un 25% de los casos pueden aparecer complicaciones potencialmente letales por compresión de estructuras mediastínicas, que requieren de la reducción urgente de la luxación. El diagnóstico radiográfico puede ser difícil, siendo de gran utilidad la tomografía computerizada para determinar el tipo y grado de desplazamiento, así como la relación anatómica con las estructuras mediastínicas. Se presenta el caso de una paciente de 14 años de edad que presentó una luxación esternoclavicular posterior traumática aguda tras una caída practicando karate

Posterior sternoclavicular joint dislocation is an extremely rare condition, usually seen in males after high energy concussion. Potentially lethal complications may appear in 25% of cases, due to compression of mediastinic structures. Radiological diagnose may be difficult, why computed tomography is usually used to determine type and grade of displacement and relation with mediastinic structures. We present a case of a 14 year-old woman who presented a posterior sternoclavicular dislocation due to a fall while playing karate

A luxação posterior esternoclavicular é a condição extremamente rara, que ocorre principalmente em homens jovens, como resultado de trauma de alta impacto. Em até 25% dos casos, podem acontecer complicações potencialmente fatais por compressão de estruturas do mediastino, que exigem a redução urgente da luxação. O diagnóstico radiográfico pode ser difícil, sendo a tomografia computadorizada considerada útil para determinar o tipo e grau de deslocamento e a relação anatômica com as estruturas do mediastino. Aqui se apresenta o caso de um jovem de 14 anos que apresentou uma luxação esternoclavicular posterior traumática aguda após uma queda durante a prática de karatê