Effectiveness of Palosuran in Bleomycin-Induced Experimental Scleroderma

Systemic sclerosis (SSc) is a disease characterized by skin and internal organ involvement. There is progressive accumulation of extracellular matrix components in the skin and involved organs. Tissue fibrosis is the prominent reason for mortality, and still, there is no satisfactory treatment. The aim of this study was to evaluate the effects of urotensin-II (U-II) antagonist palosuran in an animal model of scleroderma. We also planned to measure U-II, endothelin-1 (ET-1), and transforming growth factor-β1 (TGF-β1) levels, as well as the association of these levels with dermal thickness. Twenty-four male mice were included in this study and they were divided into three groups—group 1: control group, group 2: fibrosis group, and group 3: fibrosis + palosuran treatment group. Fibrosis + palosuran treatment in group 3 reduced ET-1, U-II, and TGF-β1 levels. In total, the diminished values were statistically significant in the ET-1 and TGF-β1 levels (p?<?0.05). Dermal thickness was higher in the fibrosis group, when compared with the other groups. There was no significant relationship between dermal thickness and ET-1, U-II, or TGF-β1 levels (p?>?0.05). It is believed that U-II is an important mediator in SSc, and its antagonism with palosuran could be a new treatment choice in SSc.     

Urotensin Inhibition with Palosuran Could Be a Promising Alternative in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a progressive and a life-threatening disease with its high morbidity and mortality ratios. On searching for new shining targets in pathogenesis, we noticed, in our previous studies, urotensin-II (UII) in systemic sclerosis with potent angiogenic and pro-fibrotic features. Owing to the mimicking properties of UII with endothelin-1 (ET1), we attempted to investigate the effect of palosuran in a PAH rat model. Thirty rats were randomly divided into three groups, with each group comprising 10 rats: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran group) received subcutaneous MCT and palosuran. Serum UII, ET1, transforming growth factor-β1 (TGF-β1) levels, pulmonary arteriolar pathology of different diameter vessels, and cardiac indices were evaluated. The ET1, TGF-β1, and UII levels were significantly diminished in the treatment group, similar to the controls (p?<?0.001). Right ventricular hypertrophy index and mean pulmonary arterial pressure scores were also significantly reduced in the treatment group (p?=?0.001). Finally, in the 50–125-μm diameter arterioles, in contrast to Groups 3 and 1, there was a statistically significant thickness (p?<?0.01) in the arteriolar walls of rats in Group 2. The treatment effect on arteries of more than 125-μm diameters was found to be valuable but not significant. Owing to its healing effect on hemodynamic, histological, and biochemical parameters of MCT-induced PAH, palosuran as an antagonist of UII might be an optional treatment alternative for PAH.     

Magnetic resonance image-guided stereotactic body radiation therapy for liver rhabdoid tumor in infancy: A case report

Extracranial malignant rhabdoid tumors are rare and aggressive tumors that typically occur in the pediatric age group and have a poor prognosis. Herein, we report a case of a one year and five months old male infant who was referred with the diagnosis of malignant rhabdoid tumor of the liver. Magnetic resonance guided stereotactic body radiotherapy was administered with concomitant chemotherapy. Treatment was well tolerated with no severe acute side effects. A 40.8% volumetric reduction of the tumor was observed at the last fraction of MR guided radiotherapy.     

What Is the Relationship Between Depressive Symptoms and Pain During Functional Tasks in Persons Undergoing TKA? A 6-year Perioperative Cohort Study

Background

Preoperative depressive symptoms have been shown in some but not all studies to be associated with poor self-reported pain and function outcomes. In addition, depressive symptoms after surgery have been shown to improve relative to preoperative levels.

Questions/purposes

We hypothesized that (1) preoperative depressive symptoms would predict postoperative pain; (2) depressive symptoms would decrease after surgery; and (3) preoperative depressive symptoms would increase as the scheduled surgery date approached.

Methods

Data from the Osteoarthritis Initiative, a National Institutes of Health-funded prospective multiyear cohort study, were used in this retrospective analysis. Persons from four communities were eligible if they had radiographic knee osteoarthritis or were at risk for developing knee osteoarthritis based on occupational, medical history, or body weight risk factors. A total of 4796 persons participated and rates of followup were 80% or greater over the course of the study. Participants completed a validated depressive symptom scale and the Knee Injury and Osteoarthritis Outcome Scale pain scale each year for 3 years before and 3 years after TKA. Latent growth curve modeling was used to model intercepts and slopes of pre- and postoperative depression and pain. Preoperative trajectories and intercepts were then used to predict postoperative pain and depressive symptoms adjusting for confounding variables.

Results

After adjustment for potential confounding, we found no evidence that preoperative depressive symptoms predicted postoperative pain with function (estimate, 0.1; 95% confidence interval, −0.31 to 0.50; p = 0.64) or that depressive symptoms were reduced after surgery (z = 0.06, p = 0.80). We also found no evidence to indicate that preoperative depressive symptoms increased as the date of surgery approached (linear slope = 0.28, SE = 0.19, p = 0.15).

Conclusions

Preoperative and postoperative depressive symptoms in patients before and after TKA did not appreciably change over a 6-year perioperative period. Patient depressive symptoms were not reduced after surgery and did not appear to be related to less pain postoperatively. Our findings of no association between preoperative depressive symptom severity and postoperative pain and no reduction in postoperative depressive symptoms run counter to other available evidence, potentially attributable, in part, to a data collection process that occurred outside of orthopaedic surgeons’ offices. Future research is needed to more fully explore the potential role of social desirability, the concept that patients respond in a way that they think the researcher or clinician wants them to respond in lieu of responding in a way that truly reflects the patient’s status. Social desirability may influence a TKA patient’s pain and function outcome assessment.

Level of Evidence

Level I, prognostic study.