Examination of micro-superficial lesions of up to 5 mm in size in the pharyngolaryngeal region.

OBJECTIVE: For low-grade intraepithelial neoplasia cases, pharyngolaryngeal lesions equal to or less than 5 mm in size do not generally progress to invasive carcinoma. However, micro-superficial lesions equal to or less than 5 mm that showed rapid growth have been recently encountered. This study aimed to identify the characteristics of preferential progression of lesions equal to or less than 5 mm in size. METHOD: Gross findings, endoscopic findings and pathological results of 55 lesions measuring equal to or less than 5 mm in diameter were retrospectively reviewed to identify factors that distinguish squamous cell carcinoma or high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia or non-atypia lesions. RESULTS: The overall sensitivity, specificity, accuracy, and positive and negative predictive value of background colouration and intrapapillary capillary loop pattern in differentiation of squamous cell carcinoma or high-grade intraepithelial neoplasia from low-grade intraepithelial neoplasia or non-atypia lesions were all 100 per cent. CONCLUSION: Diagnosis based on background colouration and the intrapapillary capillary loop pattern on narrow-band imaging facilitates the pathological examination of lesions measuring equal to or less than 5 mm.

Development of a core outcome domain set for clinical research on capillary malformations (the COSCAM project).

BACKGROUND: Due to a large variety in treatment outcomes reported in therapeutic trials and lacking patient-relevant outcomes, it is hard to adequately compare and improve current therapies for patients with capillary malformations (CMs). The Core Outcome Set for Capillary Malformations (COSCAM) project aims to develop a core outcome set (COS) for use in future CM trials, in which we will first develop a core outcome (sub)domain set (CDS). Here, we describe the methods for the development of a CDS and present the results of the first development stage. METHODS: The COSCAM project is carried out according to the recommendations of the Cochrane Skin Core OUtcomes Set INitiative (CS-COUSIN) and the Core Outcome Measures in Effectiveness Trials (COMET) initiative. During the first stage, we identified all potentially relevant outcome subdomains based on a systematic review, two focus group sessions and input from patient representatives of Dutch patient organizations and the COSCAM-founding group. In stage two, we will present the subdomains in a three-round e-Delphi study and online consensus meeting, in which CM patients, parents/caregivers and CM experts worldwide rate the importance of the proposed subdomains, hereby finalizing the core outcome (sub)domains of the CDS. RESULTS: A total of 67 potential outcome subdomains were included; sixteen were previously used in the literature, 20 were proposed by Dutch patients and their parents/caregivers (n = 13) in focus group sessions and 38 were suggested by the experts of the COSCAM-founding group. Seven were excluded because of overlap. CONCLUSION: The final CDS may serve as a minimum standard in future CM trials, thereby facilitating adequate comparison of treatment outcomes. After this CDS development, we will select appropriate outcome measurement instruments to measure the core outcome subdomains.

Rebound-associated vertebral fractures after discontinuation of denosumab for the treatment of maxillitis.

We reported a 69-year-old female who discontinued denosumab due to dental treatment and subsequently suffered rebound-associated vertebral fractures 10 months after the last injection. This case raised an alarm regarding the discontinuation of denosumab for dental treatment. Denosumab, a human monoclonal antibody administered by subcutaneous injection, to the best of our knowledge, is the only fully investigated inhibitor of receptor activator of nuclear factor kappa B ligand. Discontinuation of denosumab leads to bone turnover rebound and rapid bone mineral density loss. Several studies have reported rebound-associated vertebral fractures after discontinuation of denosumab. We report on a new case of rebound-associated vertebral fractures after discontinuation of denosumab. A 69-year-old female, who withdrew from denosumab treatment after 3 years due to maxillitis, presented to our hospital with severe low back pain without any history of trauma. Ten months had passed since the last injection. Magnetic resonance imaging showed five acute vertebral fractures, which appeared to be rebound-associated vertebral fractures caused by discontinuation of denosumab due to dental treatment. This case clearly demonstrates the risk of discontinuation of denosumab for dental treatment.

Importance of absorbable surgical sutures for the prevention of stitch abscess after surgery in patients with oral squamous cell carcinoma.

BACKGROUND: To elucidate the significance of absorbable surgical sutures in the occurrence of stitch abscess after surgery in patients with oral squamous cell carcinoma (SCC). MATERIAL AND METHODS: The subjects were 251 patients who underwent excision and/or reconstruction and/or neck dissection for oral SCC using absorbable surgical sutures. Detection rates and characteristics of patients with stitch abscess were retrospectively evaluated by comparing between our present and previous data. RESULTS: There was only one stitch abscess among the 251 patients. A significant difference in the incidence of stitch abscess was found between the present data and our previous data. Of course, no significant correlations were found between the occurrence of stitch abscess using absorbable surgical sutures and the various factors seen in our previous analysis. CONCLUSIONS: A complete switch of surgical sutures from silk to absorbable surgical sutures is needed for surgery in patients with oral SCC.

Assessing the progression of chronic periodontitis using subgingival pathogen levels: a 24-month prospective multicenter cohort study.

BACKGROUND: The diagnosis of the progression of periodontitis presently depends on the use of clinical symptoms (such as attachment loss) and radiographic imaging. The aim of the multicenter study described here was to evaluate the diagnostic use of the bacterial content of subgingival plaque recovered from the deepest pockets in assessing disease progression in chronic periodontitis patients. METHODS: This study consisted of a 24-month investigation of a total of 163 patients with chronic periodontitis who received trimonthly follow-up care. Subgingival plaque from the deepest pockets was recovered and assessed for bacterial content of Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans using the modified Invader PLUS assay. The corresponding serum IgG titers were measured using ELISA. Changes in clinical parameters were evaluated over the course of 24 months. The sensitivity, specificity, and prediction values were calculated and used to determine cutoff points for prediction of the progression of chronic periodontitis. RESULTS: Of the 124 individuals who completed the 24-month monitoring phase, 62 exhibited progression of periodontitis, whereas 62 demonstrated stable disease. The P. gingivalis counts of subgingival plaque from the deepest pockets was significantly associated with the progression of periodontitis (p < 0.001, positive predictive value = 0.708). CONCLUSIONS: The P. gingivalis counts of subgingival plaque from the deepest pockets may be associated with the progression of periodontitis.

Transient receptor potential ankyrin 1 agonists improve intestinal transit in a murine model of postoperative ileus.

BACKGROUND: Stimulation of transient receptor potential ankyrin 1 (TRPA1), which abundantly expressed in enterochromaffin cells (ECC), has been reported to exert apparently contradictory results in in vitro contractility and in vivo gastrointestinal (GI) transit evaluations. The pharmaceutical-grade Japanese traditional medicine daikenchuto (TU-100) has been reported to be beneficial for postoperative ileus (POI) and accelerate GI transit in animals and humans. TU-100 was recently shown to increase intestinal blood flow via stimulation of TRPA1 in the epithelial cells of the small intestine (SI). METHODS: The effects of various TRPA1 agonists on motility were examined in a manipulation-induced murine POI model, in vitro culture of SI segments and an ECC model cell line, RIN-14B. KEY RESULTS: Orally administered TRPA1 agonists, aryl isothiocyanate (AITC) and cinnamaldehyde (CA), TU-100 ingredients, [6]-shogaol (6S) and γ-sanshool (GS), improved SI transit in a POI model. The effects of AITC, 6S and GS but not CA were abrogated in TRPA1-deficient mice. SI segments show periodic peristaltic motor activity whose periodicity disappeared in TRPA1-deficient mice. TU-100 augmented the motility. AITC, CA and 6S increased 5-HT release from isolated SI segments and the effects of all these compounds except for CA were lost in TRPA1-deficient mice. 6S and GS induced a release of 5-HT from RIN-14B cells in a dose- and TRPA1-dependent manner. CONCLUSIONS & INFERENCES: Intraluminal TRPA1 stimulation is a potential therapeutic strategy for GI motility disorders. Further investigation is required to determine whether 5-HT and/or ECC are involved in the effect of TRPA1 on motility.

A retrospective analysis of nonresponse to daily teriparatide treatment.

UNLABELLED: Some patients with osteoporosis do not respond to teriparatide treatment. Prior bisphosphonate use, lower bone turnover marker (BTMs) concentrations, and lower early increases in BTMs were significantly associated with a blunted lumbar spine (LS) bone mineral density (BMD) response to daily treatment with teriparatide, although the impact was limited. INTRODUCTION: Some osteoporosis patients do not respond to teriparatide treatment. To better understand the factors underlying treatment nonresponses, we compared nonresponders' and responders' characteristics. METHODS: We retrospectively analyzed 354 male and female patients with osteoporosis who were administered teriparatide (20 µg/day) for 24 months. The patients were categorized as responders (≥3 % lumber spine (LS) bone mineral density (BMD) increase) or nonresponders (<3 % LS BMD increase), and the groups were compared. RESULTS: The univariate analyses determined that prior bisphosphonate use, a lower baseline procollagen type I N-terminal propeptide (PINP) concentration and a lower urinary N-telopeptide of type I collagen (uNTX) concentration at baseline were significantly associated with teriparatide nonresponses, but these factors were not significant following multivariate analysis. Diminished early increases in the bone turnover markers (BTMs) were also related to nonresponses after teriparatide treatment began. In the nonresponders, the mean (standard deviation (SD)) absolute LS and femoral neck (FN) BMD changes were -0.002 g/cm(2) (0.032) and -0.010 g/cm(2) (0.045), respectively. In the responders, the mean (SD) absolute LS and FN BMD changes were 0.118 g/cm(2) (0.056) and 0.021 g/cm(2) (0.046), respectively. The serum PINP and uNTX levels increased rapidly in both groups, but the responders showed higher early absolute serum PINP and uNTX increases. CONCLUSIONS: The factors associated with nonresponses were prior bisphosphonate use, lower baseline BTM levels, and lower early increases in the BTMs after starting teriparatide treatment, but the impact of these factors on achieving a ≥3 % LS BMD increase at 24 months was limited.

Effects of heat-killed Lactobacillus kunkeei YB38 on human intestinal environment and bowel movement: a pilot study.

It is well known that lactic acid bacteria supplementation is beneficial for intestinal conditions such as microbiota; however, the effects of killed-lactic acid bacteria on intestinal conditions are largely unclear. This study aimed to evaluate the effect of heat-killed Lactobacillus kunkeei YB38 (YB38) at a dose of approximately 10 mg/day on human intestinal environment and bowel movement. This single-blind study enrolled 29 female subjects with a low defecation frequency who consumed heat-killed YB38 at four increasing dosage levels: 0 (placebo), 2, 10, and 50 mg. Each dose was consumed daily for two weeks, with a two-week baseline period preceding the dosing-period and a two-week washout period ending the study. Observed levels of Bacteroides fragilis group significantly decreased with intake of heat-killed YB38 at ≥10 mg/day compared with levels during placebo intake (P<0.01). Faecal pH significantly decreased with 10 and 50 mg/day intake (P<0.01 and 0.05, respectively). Acetic acid levels tended to increase in faeces at the 50 mg/day dose (P<0.1). Bowel movement tended to increase in all heat-killed YB38 intake periods (P<0.1). In conclusion, heat-killed YB38 altered human intestinal microbiota at doses of ≥10 mg/day and tended to increase bowel movement at ≥2 mg/day. This is the first study to show the intestinal microbiota-altering effect of L. kunkeei and to report the bowel movement-improving effect of heat-killed lactic acid bacteria.

The kinetics of VEGF and MCP-1 in the second vitrectomy cases with proliferative diabetic retinopathy.

PurposeTo determine whether the concentrations of vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein (MCP)-1 in the vitreous changed after vitrectomy in patients with proliferative diabetic retinopathy (PDR).ParticipantsTwenty-one eyes of 21 patients who needed a second surgery for PDR were included. The reasons for the second surgery were tractional retinal detachment (TRD), neovascular glaucoma, persistent vitreous hemorrhage, macular pucker, and secondary intraocular lens (IOL) implant.MethodsWe measured the VEGF and MCP-1 levels using sandwich enzyme-linked immunosorbent assays in vitreous samples collected from patients with PDR before pars plana vitrectomy (without IOL implantation), and from the same patients during the second surgery.ResultsThere was not significant change in mean VEGF concentrations when comparing first (0.81±0.88 ng/ml) and second surgeries (1.09±1.51 ng/ml). The MCP-1 level was significantly elevated at the time of second surgery (2.20±2.21 ng/ml) compared with the first vitrectomy (0.72±0.57 ng/ml). The MCP-1 levels of the second surgery cases with TRD (3.18±2.27 ng/ml) increased significantly compared with those with other complications (1.72±2.10 ng/ml).ConclusionsAt the second vitrectomy, VEGF did not change significantly in the vitreous of the patients examined. The MCP-1 concentration was markedly elevated at the second vitrectomy, implying an association between the prolonged inflammation after vitrectomy and complications, especially TRD.

Salivary pathogen and serum antibody to assess the progression of chronic periodontitis: a 24-mo prospective multicenter cohort study.

BACKGROUND AND OBJECTIVE: A diagnosis of periodontitis progression is presently limited to clinical parameters such as attachment loss and radiographic imaging. The aim of this multicenter study was to monitor disease progression in patients with chronic periodontitis during a 24-mo follow-up program and to evaluate the amount of bacteria in saliva and corresponding IgG titers in serum for determining the diagnostic usefulness of each in indicating disease progression and stability. MATERIAL AND METHODS: A total of 163 patients with chronic periodontitis who received trimonthly follow-up care were observed for 24 mo. The clinical parameters and salivary content of Porphyromonas gingivalis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were assessed using the modified Invader PLUS assay, and the corresponding serum IgG titers were measured using ELISA. The changes through 24 mo were analyzed using cut-off values calculated for each factor. One-way ANOVA or Fisher's exact test was used to perform between-group comparison for the data collected. Diagnostic values were calculated using Fisher's exact test. RESULTS: Of the 124 individuals who completed the 24-mo monitoring phase, 62 exhibited periodontitis progression, whereas 62 demonstrated stable disease. Seven patients withdrew because of acute periodontal abscess. The ratio of P. gingivalis to total bacteria and the combination of P. gingivalis counts and IgG titers against P. gingivalis were significantly related to the progression of periodontitis. The combination of P. gingivalis ratio and P. gingivalis IgG titers was significantly associated with the progression of periodontitis (p = 0.001, sensitivity = 0.339, specificity = 0.790). CONCLUSIONS: It is suggested that the combination of P. gingivalis ratio in saliva and serum IgG titers against P. gingivalis may be associated with the progression of periodontitis.

Usefulness of daily teriparatide treatment in elderly patients over 80 years of age.

UNLABELLED: The percent and absolute lumbar spine and femoral neck bone mineral densities and procollagen type I N-terminal propeptide (PINP) and urinary N-telopeptide level increases noted after teriparatide 20 µg/day treatment for 24 months were similar in the older (age ≥ 80 years) and younger (age < 80 years) subgroups. INTRODUCTION: Many individuals are living into their eighth and ninth decades, but little is known about the efficacy of osteoporosis medication for this population. We retrospectively compared usefulness of daily teriparatide therapy in osteoporosis patients ≥80 and <80 years to detect possible age-related differences. METHODS: We analyzed 628 osteoporosis patients treated with teriparatide 20 µg/day for 24 months. The primary efficacy measures were changes in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) over 24 months. Changes in serum procollagen type I N-terminal propeptide levels and urinary N-telopeptide (uNTX) excretion were also measured. Patients were divided into age subgroups (older, ≥80 years; younger, <80 years) for BMD and bone turnover marker comparison. RESULTS: In the older subgroup, the percent LS BMD significantly increased by 14.6 ± 10.4 % (mean ± SD) and FN BMD significantly increased by 4.5 ± 10.7 % at 24 months. In the younger subgroup, the percent LS BMD significantly increased by 12.2 ± 8.5 % and FN BMD significantly increased by 2.9 ± 8.3 % at 24 months. In the older subgroup, the mean absolute LS BMD change was 0.111 ± 0.071 g/cm(2) and FN BMD change was 0.019 ± 0.043 g/cm(2). In the younger subgroup, the mean absolute LS BMD change was 0.098 ± 0.065 g/cm(2) and FN BMD change was 0.016 ± 0.045 g/cm(2). The percent and absolute BMD increases in LS and FN and changes in PINP and uNTX were similar between the subgroups. CONCLUSIONS: The usefulness of daily teriparatide treatment is not age dependent.

Nitric oxide stress and activation of AMP-activated protein kinase impair ß-cell sarcoendoplasmic reticulum calcium ATPase 2b activity and protein stability.

The sarcoendoplasmic reticulum Ca(2+) ATPase 2b (SERCA2b) pump maintains a steep Ca(2+) concentration gradient between the cytosol and ER lumen in the pancreatic ß-cell, and the integrity of this gradient has a central role in regulated insulin production and secretion, maintenance of ER function and ß-cell survival. We have previously demonstrated loss of ß-cell SERCA2b expression under diabetic conditions. To define the mechanisms underlying this, INS-1 cells and rat islets were treated with the proinflammatory cytokine interleukin-1ß (IL-1ß) combined with or without cycloheximide or actinomycin D. IL-1ß treatment led to increased inducible nitric oxide synthase (iNOS) gene and protein expression, which occurred concurrently with the activation of AMP-activated protein kinase (AMPK). IL-1ß led to decreased SERCA2b mRNA and protein expression, whereas time-course experiments revealed a reduction in protein half-life with no change in mRNA stability. Moreover, SERCA2b protein but not mRNA levels were rescued by treatment with the NOS inhibitor l-NMMA (NG-monomethyl L-arginine), whereas the NO donor SNAP (S-nitroso-N-acetyl-D,L-penicillamine) and the AMPK activator AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) recapitulated the effects of IL-1ß on SERCA2b protein stability. Similarly, IL-1ß-induced reductions in SERCA2b expression were rescued by pharmacological inhibition of AMPK with compound C or by transduction of a dominant-negative form of AMPK, whereas ß-cell death was prevented in parallel. Finally, to determine a functional relationship between NO and AMPK signaling and SERCA2b activity, fura-2/AM (fura-2-acetoxymethylester) Ca(2+) imaging experiments were performed in INS-1 cells. Consistent with observed changes in SERCA2b expression, IL-1ß, SNAP and AICAR increased cytosolic Ca(2+) and decreased ER Ca(2+) levels, suggesting congruent modulation of SERCA activity under these conditions. In aggregate, these results show that SERCA2b protein stability is decreased under inflammatory conditions through NO- and AMPK-dependent pathways and provide novel insight into pathways leading to altered ß-cell calcium homeostasis and reduced ß-cell survival in diabetes.

Analysis of daily teriparatide treatment for osteoporosis in men.

UNLABELLED: The percent and absolute lumbar spine and femoral neck bone mineral densities and absolute procollagen type I N-terminal propeptide (PINP) increases following a 20-µg/day teriparatide treatment for 12 months were similar in men and women regardless of sex differences. INTRODUCTION: Several placebo-controlled studies have measured the effects of daily teriparatide in men and postmenopausal women with osteoporosis but none have directly compared the effects between these groups. We retrospectively compared the effects of daily teriparatide therapy in men and postmenopausal women with osteoporosis and investigated biochemical markers of bone turnover to detect possible sex differences. METHODS: Patients (563; 75 men and 488 women) with osteoporosis were retrospectively investigated. All patients were administered with teriparatide at 20 µg/day for 12 months. The primary efficacy measure was changed in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD) after 12 months of treatment. The change in serum levels of procollagen type I N-terminal propeptide (PINP) and urinary N-telopeptide (uNTX) excretion after 4, 8 and 12 months of treatment were also measured. RESULTS: In men, the percent LS BMD significantly increased by 11.3 ± 9.9 % (mean ± standard deviation (SD)) and the FN BMD increased by 0.4 ± 6.4 % without a significant difference at 12 months. In postmenopausal women, the percent LS BMD significantly increased by 9.6 ± 8.1 % and the FN BMD significantly increased by 2.4 ± 7.8 % at 12 months. The percent and absolute BMD increases in LS and FN between men and women were similar. The absolute increases in PINP were similar in both groups at 4, 8 and 12 months. However, the absolute increases in uNTX were significantly lower in men than in women at 8 and 12 months. CONCLUSION: Daily teriparatide treatment was as effective in men as in postmenopausal women regardless of sex differences.

Cost-effective development of highly polymorphic microsatellite in Japanese quail facilitated by next-generation sequencing.

Next-generation sequencing technologies permit rapid and cost-effective identification of numerous putative microsatellite loci. Here, from the genome sequences of Japanese quail, we developed microsatellite markers containing dinucleotide repeats and employed these for characterisation of genetic diversity and population structure. A total of 385 individuals from 12 experimental and one wild-derived Japanese quail lines were genotyped with newly developed autosomal markers. The maximum number of alleles, expected heterozygosity and polymorphic information content (PIC) per locus were 10, 0.80 and 0.77 respectively. Approximately half of the markers were highly informative (PIC ≥ 0.50). The mean number of alleles per locus and observed heterozygosity within a line were in the range of 1.3-4.1 and 0.11-0.53 respectively. Compared with the wild-derived line, genetic diversity levels were low in the experimental lines. Genetic differentiation (FST ) between all pairs of the lines ranged from 0.13 to 0.83. Genetic clustering analyses based on multilocus genotypes of individuals showed that most individuals formed clearly defined clusters corresponding to the origins of the lines. These results suggest that Japanese quail experimental lines are highly structured. Microsatellite markers developed in this study may be effective for future genetic studies of Japanese quail.

An algorithm using the early changes in PINP to predict the future BMD response for patients treated with daily teriparatide.

UNLABELLED: About two thirds of patients with a procollagen type I N-terminal propeptide (PINP) increase of >80 µg/l at 1 month after starting teriparatide therapy showed a ≥10 % increase in lumbar spine (LS) bone mineral density (BMD) from baseline at 12 months. We recommend this algorithm as an aid in the clinical management of patients treated with daily teriparatide. INTRODUCTION: An algorithm using PINP is provided in osteoporotic patients with teriparatide treatment. The correlations between the early changes in PINP and the subsequent BMD changes after daily teriparatide therapy were studied to develop an algorithm to monitor patients. METHODS: We evaluated whether early changes in PINP correlated with the changes in BMD at 12 months and developed an algorithm using the early changes in PINP to predict the upcoming BMD increases. RESULTS: The highest correlation coefficient for the relationship between PINP and LS BMD response was determined for the absolute change in PINP at 1 month and the percent change in LS BMD at 12 months (r = 0.36, p <0.01). Using a receiver operator curve analysis, we determined that an 80 µg/l increase in PINP was the most convenient predictor of a 10% increase in LS BMD from baseline (area under curve = 0.72). Using a cut-off value of 80 µg/l, the positive predictive value for predicting a 10% increase in LS BMD from baseline to 12 months was 65%. CONCLUSION: Greater short-term changes in PINP with teriparatide therapy are associated with greater 12-month increases in LS BMD. About two thirds of patients with a PINP increase of >80 µg/l at 1 month after starting treatment showed a ≥10 % increase in LS BMD from baseline at 12 months. We recommend this algorithm as an aid in the clinical management of patients treated with teriparatide.