Metabolomics profiling predicts outcome of tocilizumab in rheumatoid arthritis: an exploratory study.

INTRODUCTION: To study metabolic signatures can be used to identify predictive biomarkers for a patient's therapeutic response. OBJECTIVES: We hypothesized that the characterization of a patients' metabolic profile, utilizing one-dimensional nuclear magnetic resonance (1H-NMR), may predict a response to tocilizumab in patients with rheumatoid arthritis (RA). METHODS: 40 active RA patients meeting the 2010 ACR/EULAR classification criteria initiating treatment with tocilizumab were recruited. Clinical outcomes were determined at baseline, and after six and twelve months of treatment. EULAR response criteria at 6 and 12 months to categorize patients as responders and non-responders. Blood was collected at baseline and after six months of tocilizumab therapy. 1H-NMR was used to acquire a spectra of plasma samples. Chenomx NMR suite 8.5 was used for metabolite identification and quantification. SPSS v.27 and MetaboAnalyst 4.0 were used for statistical and pathway analysis. RESULTS: Isobutyrate, 3-hydroxybutyrate, lysine, phenylalanine, sn-glycero-3-phosphocholine, tryptophan and tyrosine were significantly elevated in responders at the baseline. OPLS-DA at baseline partially discriminated between RA responders and non-responders. A multivariate diagnostic model showed that concentrations of 3-hydroxybutyrate and phenylalanine improved the ability to specifically predict responders classifying 77.1% of the patients correctly. At 6 months, levels of methylamine, sn-glycero-3-phosphocholine and tryptophan tended to still be low in non-responders. CONCLUSION: The relationship between plasma metabolic profiles and the clinical response to tocilizumab suggests that 1H-NMR may be a promising tool for RA therapy optimization. More studies are needed to determine if metabolic profiling can predict the response to biological therapies in RA patients.

Communication between the obese patient and bariatric surgeon.

Communication between the bariatric surgeon and the obese patient is very important as it influences the expectations of patients with regard to surgery, aim of the surgery and the understanding of the mechanisms of failure of surgery. Furthermore, the incidence of certain psychopathology in these patients makes it necessary for the surgeon to have the ability to communicate to the patient the need for motivation and the maintenance of healthy life habits. Although the topic is subjective, in this article we review several useful recommendations to optimize communication before and after surgery. Finally, we emphasize the need to create workshops to train the bariatric surgeon in these issues that we consider so important.

[Evaluation of the aesthetic results perceived by patients after 3-port laparoscopic appendectomy]. / Valoración del resultado estético percibido por los pacientes apendicectomizados vía laparoscópica mediante tres incisiones.

INTRODUCTION: The aesthetic result has lately been used in General Surgery as an argument for the development of new approaches. On numerous occasions attempts have been made to evaluate the perception that the patients themselves have after their operation by whatever approach, with the aim of finding where we differ and if there is a real option for improvement. The objective of this study was to analyse, using a simple questionnaire, the assessment of the aesthetic results as perceived by patients after appendectomy, and to attempt to determine what are the variables involved in an aspect so subjective as this. PATIENTS AND METHOD: The variables collected were: age, sex, time since operation, infection of surgical wound, and presence of a drainage, as well as the responses on the aesthetic result of 70 patients who had a 3-port laparoscopic appendectomy. RESULTS: Infection of the surgical wound, as well as the age of the patients and the time since the operation determined statistically significant differences in their opinions as regards the number, size and overall aesthetic result of the laparoscopic appendectomy. The median overall satisfaction of the aesthetic result was 9 on a scale from 0 to 10. CONCLUSIONS: The assessment of the aesthetic result by patients after a 3-port laparoscopic appendectomy is good and is difficult to improve. It is recommended to prevent infection of the three ports after the intervention to obtain better results.

Actin-mediated delivery of astral microtubules instructs Kar9p asymmetric loading to the bud-ward spindle pole.

In Saccharomyces cerevisiae, Kar9p, one player in spindle alignment, guides the bud-ward spindle pole by linking astral microtubule plus ends to Myo2p-based transport along actin cables generated by the formins Bni1p and Bnr1p and the polarity determinant Bud6p. Initially, Kar9p labels both poles but progressively singles out the bud-ward pole. Here, we show that this polarization requires cell polarity determinants, actin cables, and microtubules. Indeed, in a bud6 Delta bni1 Delta mutant or upon direct depolymerization of actin cables Kar9p symmetry increased. Furthermore, symmetry was selectively induced by myo2 alleles, preventing Kar9p binding to the Myo2p cargo domain. Kar9p polarity was rebuilt after transient disruption of microtubules, dependent on cell polarity and actin cables. Symmetry breaking also occurred after transient depolymerization of actin cables, with Kar9p increasing at the spindle pole engaging in repeated cycles of Kar9p-mediated transport. Kar9p returning to the spindle pole on shrinking astral microtubules may contribute toward this bias. Thus, Myo2p transport along actin cables may support a feedback loop by which delivery of astral microtubule plus ends sustains Kar9p polarized recruitment to the bud-ward spindle pole. Our findings also explain the link between Kar9p polarity and the choice setting aside the old spindle pole for daughter-bound fate.

[Surgical treatment of high-grade dysplasia in Barrett's esophagus]. / Tratamiento quirúrgico de la displasia de alto grado en el esófago de Barrett.

INTRODUCTION: Barrett's esophagus undergoes malignant transformation in 0.5-1% of patients per year following the sequence of low-grade dysplasia, high-grade dysplasia and adenocarcinoma. The aim of the present study was to present our experience in the surgical treatment of Barrett's esophagus with high-grade dysplasia. PATIENTS AND METHOD: Of a group of 128 patients with a diagnosis of Barrett's esophagus, 8 (6.2%) developed high-grade dysplasia during a median follow-up of 7 years (2-25). A further 5 patients with high-grade dysplaing out side the study were referred for evaluation and surgical treatment. Eight patients were under medical treatment with omeprazole (40 mg daily) while the remaining 5 patients had undergone open Nissen fundoplication, with a diagnosis of high-grade dysplasia at a median of 5 years (1-16) after treatment initiation. After confirmation of the diagnosis by a second pathologist and tumoral staging, transthoracic esophagectomy with anastomosis at the apex of the thorax was performed in all patients. RESULTS: Postoperative mortality was nil. Morbidity was 36% (5 patients). Definitive histological analysis of the surgical specimen revealed high-grade dysplasia in 7 patients (54%) and adenocarcinoma in 6 (46%). All patients remain alive after a median follow-up of 4.7 years (1-14). CONCLUSIONS: In patients with Barrett's esophagus with high-grade dysplasia, the best therapeutic option is surgical resection, which can be performed with nil mortality in experienced centers. In almost half of surgical patients, the surgical specimen shows adenocarcinoma. Five-year survival is higher than 90%.