TREAT AF (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation): A Randomized Clinical Trial.

OBJECTIVES: This study was a sham-controlled, double-blind, randomized clinical trial to examine the effect of chronic low level tragus stimulation (LLTS) in patients with paroxysmal AF. BACKGROUND: Low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve at the tragus (LLTS) acutely suppresses atrial fibrillation (AF) in humans, but the chronic effect remains unknown. METHODS: LLTS (20 Hz, 1 mA below the discomfort threshold) was delivered using an ear clip attached to the tragus (active arm) (n = 26) or the ear lobe (sham control arm) (n = 27) for 1 h daily over 6 months. AF burden over 2-week periods was assessed by noninvasive continuous electrocardiogram monitoring at baseline, 3 months, and 6 months. Five-minute electrocardiography and serum were obtained at each visit to measure heart rate variability and inflammatory cytokines, respectively. RESULTS: Baseline characteristics were balanced between the 2 groups. Adherence to the stimulation protocol (≤4 sessions lost per month) was 75% in the active arm and 83% in the control arm (p > 0.05). At 6 months, the median AF burden was 85% lower in the active arm compared with the control arm (ratio of medians: 0.15; 95% confidence interval: 0.03 to 0.65; p = 0.011). Tumor necrosis factor-alpha was significantly decreased by 23% in the active group relative to the control group (ratio of medians: 0.77; 95% confidence interval: 0.63 to 0.94; p = 0.0093). Frequency domain indices of heart rate variability were significantly altered with active versus control stimulation (p < 0.01). No device-related side effects were observed. CONCLUSIONS: Chronic, intermittent LLTS resulted in lower AF burden than did sham control stimulation, supporting its use to treat paroxysmal AF in selected patients. (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation [TREAT-AF]; NCT02548754).

Effects of immunization with natural and recombinant lysine decarboxylase on canine gingivitis development.

Periodontal disease, gingival inflammation (gingivitis) and periodontal attachment loss (periodontitis), causes tooth loss and susceptibility to chronic inflammation. Professionally scaling and cleaning the teeth regularly controls the disease, but is expensive in companion animals. Eikenella corrodens is common in canine oral cavities where it is a source of lysine decarboxylase (LDC). In human dental biofilms (plaques), LDC converts lysine to cadaverine and impairs the gingival epithelial barrier to bacteria. LDC vaccination may therefore retard gingivitis development. Year-old beagle dogs provided blood samples, and had weight and clinical measurements (biofilm and gingivitis) recorded. After scaling and cleaning, two dogs were immunized subcutaneously with 0.2mg native LDC from E. corrodens and 2 sets of four dogs with 0.2mg recombinant LDC purified from Escherichia coli. A third set of 4 dogs was immunized intranasally. Rehydragel(®), Emulsigen(®), Polygen™ or Carbigen™ were used as adjuvant. Four additional pairs of dogs were sham-immunized with each adjuvant alone (controls). Immunizations were repeated twice, 3 weeks apart, and clinical measurements were obtained after another 2 weeks, when the teeth were scaled and cleaned again. Tooth brushing was then stopped and the diet was changed from hard to soft chow. Clinical measurements were repeated after 1, 2, 3, 4, 6 and 8 weeks. Compared with sham-immunized dogs, gingivitis was reduced over all 8 weeks of soft diet after subcutaneous immunization with native LDC, or after intranasal immunization with recombinant LDC in Carbigen™, but for only 6 of the 8 weeks after subcutaneous immunization with recombinant LDC in Emulsigen(®) (repeated measures ANOVA). Subcutaneous vaccination induced a strong serum IgG antibody response that decreased during the soft diet period, whereas intranasal immunization induced a weak serum IgA antibody response that did not decrease. Immunization with recombinant LDC may provide protection from gingivitis if procedures are optimized.

The effect of subantimicrobial-dose-doxycycline periodontal therapy on serum biomarkers of systemic inflammation: a randomized, double-masked, placebo-controlled clinical trial.

BACKGROUND: Periodontitis has been reported to be associated with coronary artery disease (CAD). Research is needed to determine if therapies that improve periodontal health also reduce systemic measures of inflammation associated with both diseases. METHODS: The study registrar randomly assigned 128 eligible postmenopausal women with chronic periodontitis to a twice-daily regimen of subantimicrobial-dose-doxycycline (SDD) or placebo tablets for two years as an adjunct to periodontal maintenance therapy. Through a supplement to the main trial, in which they investigated alveolar bone and clinical attachment level changes, the authors assayed inflammatory mediators and lipid profiles in baseline, one-year and two-year serum samples. The authors analyzed the data by using generalized estimating equations. RESULTS: In the intent-to-treat analysis across two years, SDD treatment reduced median high-sensitivity C-reactive protein (hs-CRP) by 18 percent (primary outcome; P = .02) and reduced serum matrix metalloproteinase (MMP)-9 (92 kilodalton gelatinase; difference in mean scanning units, -28.44; P < .001), with no significant effect on serum lipids. However, in women more than five years postmenopausal, SDD elevated the level of high-density lipoprotein (HDL) cholesterol (difference in means [milligrams per deciliter], 5.99; P = .01). CONCLUSION: A two-year SDD regimen in postmenopausal women significantly reduced the serum inflammatory biomarkers hs-CRP and MMP-9 and, among women more than five years postmenopausal, increased the HDL cholesterol level. CLINICAL IMPLICATIONS: SDD significantly reduced the systemic inflammatory biomarkers hs-CRP and MMP-9. More research is needed to determine whether SDD has a role in managing the care of patients at risk of developing CAD.

Finding the optimal dose of vitamin D following Roux-en-Y gastric bypass: a prospective, randomized pilot clinical trial.

BACKGROUND: Vitamin D deficiency is common following bariatric surgery and is due to a combination of baseline deficiency and postoperative malabsorption. There are few prospective studies evaluating the appropriate dose of vitamin D to prevent and treat vitamin D deficiency following bariatric surgery. METHODS: We evaluated three doses of vitamin D3 (800, 2,000, and 5,000 IU/day) in a prospective, randomized pilot trial of 45 patients undergoing Roux-en-Y gastric bypass. Serum 25 hydroxy Vitamin D (25OHD), intact PTH (iPTH), calcium, and urine calcium/creatinine ratios were measured at 6, 12, and 24 months postoperatively. Due to a high dropout rate at 24 months, we focus on the 12-month data. RESULTS: At 12 months, the 800-, 2,000-, and 5,000-IU groups had a mean +/- SD increase in 25OHD of 27.5 +/- 40.0, 60.2 +/- 37.4, and 66.1 +/- 42.2 nmol/L, respectively (p = 0.09) with a maximum increase in each group of 87.4, 114.8, and 129.8 nmol/L. Forty-four percent, 78%, and 70% achieved 25OHD levels >or=75 nmol/L (p = 0.38). Results for the 6- and 24-month time points were similar to the 12-month results. Mean weight loss at 24 months of the study was not different among groups (p = 0.52). Serum calcium did not change significantly, and there were no cases of hypercalcemia or sustained hypercalciuria. CONCLUSIONS: Higher doses of vitamin D supplementation trend towards higher levels of 25OHD. Vitamin D replacement as high as 5,000 IU /day is safe and necessary in many patients to treat vitamin D deficiency following Roux-en-Y gastric bypass yet is still suboptimal in others.

Low-level laser effect on mandibular distraction osteogenesis.

PURPOSE: The purpose of this study was to determine whether low-level laser (LLL) application during distraction osteogenesis could accelerate bone regeneration and decrease the length of the consolidation phase and thereby reduce potential patient morbidity. MATERIALS AND METHODS: Nine adult female New Zealand white rabbits underwent bilateral mandibular corticotomies and placement of unidirectional distraction devices (KLS-Martin LP, Jacksonville, FL). Each rabbit served as its own internal control. After a latency of 1 day, distraction progressed bilaterally at 1 mm per day for 10 days. Immediately after each device activation, the experimental side, chosen randomly, was treated with real LLL (Laser Medical Systems, Hedehusene, Denmark) of 6.0 J x 6 transmucosal sites in the area of the distraction gap. Radiographs were taken presurgically, immediately postsurgically, and weekly until sacrifice, and the bone was analyzed using a semiquantitative 4-point scale (Bone Healing Score [BHS]). Three animals each were sacrificed at 2, 4, and 6 weeks postdistraction, and each hemimandible was prepared for histologic examination in a blinded fashion. RESULTS: Ten millimeters of distraction was achieved in each rabbit bilaterally. Radiographically, the BHS was higher for the LLL-treated group at all time periods. Histologically, the area of new bone trabeculation and ossification was more advanced for the LLL-treated group, with less intervening fibrovascular intermediate zone in the bony regenerate, at all time periods. The formation of a complete inferior border occurred sooner in the treatment group than in the controls. CONCLUSIONS: LLL accelerates the process of bone regeneration during the consolidation phase after distraction osteogenesis. The adjunctive use of LLL may allow a shortened period of consolidation and therefore permit earlier device removal, with the avoidance of morbidity associated with prolonged device retention.