Efficacy of Magnesium Trihydrate of Ursodeoxycholic Acid and Chenodeoxycholic Acid for Gallstone Dissolution: A Prospective Multicenter Trial

Background/Aims

Cholecystectomy is necessary for the treatment of symptomatic or complicated gallbladder (GB) stones, but oral litholysis with bile acids is an attractive alternative therapeutic option for asymptomatic or mildly symptomatic patients. This study was conducted to evaluate the efficacy of magnesium trihydrate of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on gallstone dissolution and to investigate improvements in gallstone-related symptoms.

Methods

A prospective, multicenter, phase 4 clinical study to determine the efficacy of orally administered magnesium trihydrate of UDCA and CDCA was performed from January 2011 to June 2013. The inclusion criteria were GB stone diameter ≤15 mm, GB ejection fraction ≥50%, radiolucency on plain X-ray, and asymptomatic/mildly symptomatic patients. The patients were prescribed one capsule of magnesium trihydrate of UDCA and CDCA at breakfast and two capsules at bedtime for 6 months. The dissolution rate, response rate, and change in symptom score were evaluated.

Results

A total of 237 subjects were enrolled, and 195 subjects completed the treatment. The dissolution rate was 45.1% and the response rate was 47.2% (92/195) after 6 months of administration of magnesium trihydrate of UDCA and CDCA. Only the stone diameter was significantly associated with the response rate. Both the symptom score and the number of patients with symptoms significantly decreased regardless of stone dissolution. Adverse events necessitating discontinuation of the drug, surgery, or endoscopic management occurred in 2.5% (6/237) of patients.

Conclusions

Magnesium trihydrate of UDCA and CDCA is a well-tolerated bile acid that showed similar efficacy for gallstone dissolution and improvement of gallstone-related symptoms as that shown in previous studies.     

The efficacy and safety of prone positioning in adults patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials

Background

Prone positioning for acute respiratory distress syndrome (ARDS) has no impact on mortality despite significant improvements in oxygenation. However, a recent trial demonstrated reduced mortality rates in the prone position for severe ARDS. We evaluated effects of prone position duration and protective lung strategies on mortality rates in ARDS.

Methods

We extensively searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to identify randomized controlled trials (RCTs) reporting on prone positioning during acute respiratory failure in adults for inclusion in our meta-analysis.

Results

Eight trials met our inclusion criteria, Totals of 1,099 and 1,042 patients were randomized to the prone and supine ventilation positions. The mortality rates associated with the prone and supine positions were 41% and 47% [risk ratio (RR), 0.90; 95% confidence interval (CI), 0.82-0.98, P=0.02], but the heterogeneity was moderate (P=0.01, I²=61%). In a subgroup analysis, the mortality rates for lung protective ventilation (RR 0.73, 95% CI, 0.62-0.86, P=0.0002) and duration of prone positioning >12 h (RR 0.75, 95% CI, 0.65-0.87, P<0.0001) were reduced in the prone position. Prone positioning was not associated with an increased incidence of cardiac events (RR 1.01, 95% CI, 0.87-1.17) or ventilator associated pneumonia (RR 0.88, 95% CI, 0.71-1.09), but it was associated with an increased incidence of pressure sores (RR 1.23, 95% CI, 1.07-1.41) and endotracheal dislocation (RR 1.33, 95% CI, 1.02-1.74).

Conclusions

Prone positioning tends to reduce the mortality rates in ARDS patients, especially when used in conjunction with a lung protective strategy and longer prone position durations. Prone positioning for ARDS patients should be prioritized over other invasive procedures because related life-threatening complications are rare. However, further additional randomized controlled design to study are required for confirm benefit of prone position in ARDS.     

An Enhanced Method of Transcutaneously Stimulating the Tibial Nerve for the Treatment of Overactive Bladder

Transcutaneous electrical nerve stimulation (TENS) can be used to electrically stimulate the tibial nerve for the purpose of treating overactive bladder. Although clinical benefits can be achieved, the overall therapeutic efficacy of TENS is limited. Inconsistent activation of the intended neural target and co-activation of cutaneous sensory fibers are considered key limiting factors. In this study, we propose a novel approach that combines TENS with an implanted, electrically-conductive nerve cuff to reduce the stimulation amplitude needed to activate the tibial nerve. This enhanced version of TENS (called eTENS) was designed using a computational model of the rat tibial nerve and subsequently tested in anesthetized rats. Our computational model showed that eTENS can reduce the nerve activation threshold by a factor of up to 2.6. Similar effects were also achieved by in vivo experiments (1.4 ± 0.1-fold decrease, n = 5). Among various design parameters, spatial alignment between the surface electrode and the nerve cuff was identified as an important factor. Our results show that eTENS can improve the selective activation of the rat tibial nerve, but further work is needed to evaluate its use in clinical therapies.     

Age-dependent alterations in serum cytokines,peripheral blood mononuclear cell cytokine production,natural killer cell activity,and prostaglandin F<Subscript>2α</Subscript>

This study aimed to determine age-dependent alterations in serum cytokines, peripheral blood mononuclear cell (PBMC) cytokine production, natural killer (NK) cell activity, and urinary 8-epi-prostaglandin F_2α (PGF_2α). Nine hundred eighty-seven healthy and nonobese subjects were divided into five age groups: 20–34 (group 1), 35–44 (group 2), 45–54 (group 3), 55–64 (group 4), and 65–80 (group 5) years of age. After adjusting for BMI, sex, and smoking and drinking status, serum interferon (IFN)-γ levels decreased in groups 3, 4, and 5 compared with those in groups 1 and 2. Production of IFN-γ by unstimulated PBMCs was lower in the older groups (groups 4 and 5) than in the younger groups (groups 1 and 3). Serum interleukin (IL)-12 was lower in group 5 than in groups 1 and 2. In contrast, both serum and PBMC IL-6 were higher in group 5 than in groups 1, 2, and 3. Urinary 8-epi-PGF_2α increased in group 3 compared with that in group 1 and further increased in group 5. Multiple linear regression analysis revealed that serum IFN-γ levels were negatively affected by age, and NK cell activity at a ratio of E:T = 5:1 was positively affected by PBMC IFN-γ. This study shows the age-related reductions in serum and PBMC IFN-γ and serum IL-12 and age-related increases in serum and PBMC IL-6 and oxidative stress in healthy nonobese subjects. Additionally, circulating IL-6 levels may be a better marker of the chronic low-grade inflammatory activity associated with aging than systemic levels of high-sensitivity C-reactive protein, TNF-α, and IL-1β.     

Neutrophil extracellular traps (NETs) in autoimmune diseases: A comprehensive review

Neutrophil extracellular traps (NETs) are fibrous networks which protrude from the membranes of activated neutrophils. NETs are found in a variety of conditions such as infection, malignancy, atherosclerosis, and autoimmune diseases including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV), psoriasis, and gout. Studies suggest that an imbalance between “NETosis,” which is a process by which NETs are formed, and NET degradation may be associated with autoimmune diseases. Neutrophils, interleukin-8, ANCA and other inflammatory molecules are considered to play a key role in NET formation. Prolonged exposure to NETs-related cascades is associated with autoimmunity and increases the chance of systemic organ damage. In this review, we discuss the roles of various inflammatory molecules in relation to NETs. We also describe the role of NETs in the pathogenesis of autoimmune diseases and discuss the possibility of using targeted therapies directed to NETs and associated molecules to treat autoimmune diseases.