Decoding clinical and molecular pathways of liver dysfunction in Psoriatic Arthritis: Impact of cumulative methotrexate doses.

BACKGROUND: The occurrence of liver abnormalities in Psoriatic Arthritis (PsA) has gained significant recognition. Identifying key factors at the clinical and molecular level can help to detect high-risk patients for non-alcoholic fatty liver disease in PsA. OBJECTIVES: to investigate the influence of PsA and cumulative doses of methotrexate on liver function through comprehensive in vivo and in vitro investigations. METHODS: A cross-sectional study involving 387 subjects was conducted, 200 patients with PsA, 87 NAFLD-non-PsA patients, and 100 healthy donors (HDs), age and sex-matched. Additionally, a retrospective longitudinal study was carried out, including 83 PsA patients since initiation with methotrexate. Detailed clinical, and laboratory parameters along with liver disease risk were analyzed. In vitro, experiments with hepatocyte cell line (HEPG2) were conducted. RESULTS: PsA patients present increased liver disease risk associated with the presence of cardiometabolic comorbidities, inflammatory markers, onychopathy, and psoriasis. The treatment with PsA serum on hepatocytes encompassed inflammatory, fibrotic, cell stress, and apoptotic processes. At the molecular level, methotrexate impacts liver biology, although the cumulative doses did not affect those alterations, causing any potential damage to liver function at the clinical level. Finally, anti-PDE-4 or anti-JAK decreased the inflammatory profile induced by PsA serum on hepatocytes. CONCLUSION: 1)This study identifies the complex link between liver disease risk, comorbidities, and disease-specific features in PsA patients. 2)Methotrexate dose in PsA patients had no significant effect on liver parameters, confirmed by hepatocyte in vitro studies. 3)Anti-PDE-4 and anti-JAK therapies show promise in reducing PsA serum-induced hepatocyte activation, potentially aiding liver complication management.

The colon revisited or the key to wellness, health and disease.

The hypothesis being advanced in this paper is that there is a new medical paradigm emerging from the biomedical research carried out in this century, mainly due to the explosion of the so called "omics" and associated techniques. The main idea is that there is a common pathway from wellbeing and health to chronic disease ("chronopathy") and even to death, which comprises following steps: 1) unhealthy diet, sedentary life style and permanent exposition to xenobiotics and all kinds of noxious stimuli;→2) intestinal dysbiosis;→3) alteration of the intestinal mucus layer (especially that of the colon);→4) disruption of the endothelial tight junctions;→5) metabolic endotoxemia+bacterial translocation;→6) inflammation;→7) exacerbation of the enteric nervous system (ENS) and consequent maladaptation and malfunctioning of the colon;→8) epigenetic manifestations;→9) "chronopathy" and premature death. Therefore, in order to maintain a good health or to improve or even reverse chronic diseases in a person, the main outcome to look for is a homeostatic balance of the intestinal microbiota (eubiosis), most of which is located in the colon. Lynn Margulis was one of the main scientists to highlight the importance of the role played by bacteria not only in the origin of all biological species now present on earth, but also on their role in global homeostasis. Bacteria do not rely on other living beings for their existence, while the latter depend completely on the former. Humans are no exemption, and new evidence emerges each day about the pivotal role of intestinal microbiota in human health, disease and, in general, in its wellbeing. The following facts about intestinal microbiota are nowadays generally accepted: there are about 10 times more bacteria in the gut than human cells in every human being; the microbioma is about 100-150 times bigger that the human genome, and there is a clear link between intestinal microbiota and many of the most common chronic diseases, from obesity and diabetes to depression and Parkinson disease and different kinds of cancer. The main implication of this theory is that we should become a sort of microbiota farmers, that is, we ought to be more conscious of our intestinal microbiota, take care of it and monitor it permanently. Thus, as part of our good life habits (healthy eating, physical exercise), we should probably undergo periodic seasons of fasting and colon cleansing, as it was common in older times.

Pelvic MRI findings in relapsed prostate cancer after radical prostatectomy.

PURPOSE/OBJECTIVE: Little is known about the clinical impact of using multiparametric MRI to plan early salvage radiotherapy after radical prostatectomy. We aimed to evaluate the incidence and location of recurrence based on pelvic multiparametric MRI findings and to identify clinical variables predictive of positive imaging results. MATERIALS AND METHODS: We defined radiological criteria of local and lymph node malignancy and reviewed records and MRI studies of 70 patients with PSA recurrence after radical prostatectomy. We performed univariate and multivariate analysis to identify any association between clinical, pathological and treatment-related variables and imaging results. RESULTS: Multiparametric MRI was positive in 33/70 patients. We found local and lymph node recurrence in 27 patients and 7 patients, respectively, with a median PSA value of 0.38 ng/ml. We found no statistically significant differences between patients with positive and negative multiparametric MRI for any variable. Shorter PSADT was associated with positive lymph nodes (median PSADT: 5.12 vs 12.70 months; p: 0.017). CONCLUSIONS: Nearly half the patients had visible disease in multiparametric MRI despite low PSA. Positive lymph nodes incidence should be considered when planning salvage radiotherapy, particularly in patients with a short PSADT.

Evaluation of the precision obtained with a fixed surgical template in the placement of implants for rehabilitation of the completely edentulous maxilla: a clinical report.

The fabrication of a complete maxillary implant-supported prosthesis in a patient with slight resorption of the alveolar ridge and a high lip line presents a professional challenge. The implants must be placed with high precision to achieve good esthetics, phonetics, and function. A fixed surgical template using microimplants has been developed for this purpose. The objective of this investigation was to compare a fixed surgical template (FST) to a conventional movable surgical template (MST) for the precise placement of implants in the slightly resorbed edentulous maxilla. Three patients (28 implants), edentulous in the maxilla, with slight ridge resorption, in whom the implants were placed with an FST, were compared with 5 controls having the same characteristics and implants placed with an MST (35 implants). After completion of the prosthesis, occlusal photographs (1:1) were taken, and these images were scanned and transferred to a drawing program in which the contours of the teeth, the ideal emergence position of the occlusal hole of the abutment screw, and its real position were drawn. A blind evaluation was made using the following variables: frequency of location of the abutment screw hole outside of the tooth contour, and the relative measurements of the area of coincidence between the circle that represents the ideal position and real position. A significantly smaller frequency of implants outside the tooth contour was seen with the FST (7%) than with the MST (46%) (P < .0008). Also, a significantly higher relative area of coincidence was observed between ideal position and real position in the FST (0.61) than in the MST (0.38) (P < .003). This study revealed that considerably higher precision was associated with the use of an FST.

[Cerebrospinal fluid drainage to protect the spinal cord during surgical repair of thoracoabdominal aortic aneurysm]. / Drenaje de líquido cefalorraquídeo como protección de la médula espinal durante la reparación quirúrgica de un aneurisma aórtico toracoabdominal.

Spinal cord injury is a serious complication of aortic cross-clamping during thoracoabdominal aortic surgery. We report the case of a 59-year-old man whose mycotic pseudoaneurysm in the thoracoabdominal aorta was repaired surgically. Cerebrospinal fluid pressure was monitored and the fluid was drained to protect the spinal cord while the aorta was clamped. A 19-G epidural catheter was inserted into the subarachnoid space using a paramedian approach form L2-L3. The aorta was clamped at the thoracic level in the descending distal portion and at the abdominal level above the kidney, for a period of 61 minutes. A total of 65 ml of cerebrospinal fluid was drained. The early postoperative period was uneventful and tubes were removed 40 hours after surgery. The results of neurological examination were normal. One week later the patient developed a respiratory infection, which was followed by multi-organ failure and died 22 days after the operation. We discuss the case and review the various alternatives available for protecting the spinal cord during surgery on the thoracoabdominal aorta.

[Effect of isoflurane on gas exchange and systemic and pulmonary hemodynamics in man during single lung ventilation]. / Efecto del isoflurano sobre el intercambio gaseoso y la hemodinámica sistémica y pulmonar en el hombre durante la ventilación a un solo pulmón.

OBJECTIVE: We studied the effect of 1.5% isoflurane end expiratory fraction on arterial oxygenation and on systemic and pulmonary hemodynamics during nonsurgical single lung ventilation. MATERIAL AND METHODS: The study includes 6 patients undergoing surgical thoracotomy. In all cases a double lumen endotracheal tube was inserted and pulmonary ventilation was performed with a FiO2 = 1. Patients were placed on lateral decubitus position. The following variables were measured: mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), central venous pressure (CVP), capillary pulmonary pressure (CPP), cardiac output (CO), and Qs/Qt. Measurements were taken at three different situations. The first was done under bilateral pulmonary ventilation and intravenous anesthesia with thiopental, fentanyl, and diazepam. The nondependent lung was collapsed by means of a selective ventilation of the dependent lung, and the second series of measurements was done 20 min after intravenous anesthesia. The third block of data was obtained after 15 min of respiratory ventilation with 1.5% isoflurane. RESULTS: Single lung ventilation induced a significant decrease of Pa O2 (379 +/- 96 mmHg vs 208 +/- 93 mmHg) and a significant increase in Qs/Qt (20 +/- 8% vs 30 +/- 10%). However, during isoflurane ventilation there were no significant changes in PaO2 (208 +/- 93 mmHg vs 204 +/- 94 mmHg) nor in Qs/Qt (30 +/- 10 vs 28 +/- 8). Isoflurane elicited a significant decrease of the CO, whereas MPAP, RVS, and PvO2 did not show significant variations. CONCLUSIONS: We conclude that 1.5% isoflurane end expiratory concentrations did not significantly affect pulmonary oxygenation during single lung ventilation.