Effect of topical vancomycin powder on surgical site infection prevention in major orthopaedic surgery: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.

BACKGROUND: Evidence has been mixed regarding the effect of topical vancomycin (VCM) powder in reducing surgical site infection (SSI). AIM: To clarify the effect of topical VCM powder for the prevention of SSI in major orthopaedic surgeries. METHODS: The MEDLINE, Embase, CENTRAL, ICTRP, and ClinicalTrials.gov databases were searched from their inception to September 25th, 2023. Randomized controlled trials comparing topical VCM powder and controls for the prevention of SSI in major orthopaedic surgeries were included. Two reviewers independently screened the title and abstract and extracted relevant data, followed by the assessment of the risk of bias and the certainty of the evidence. Main outcome measures were overall SSI, reoperation, and adverse events. Summary results were obtained using random-effects meta-analysis. Trial sequential analysis (TSA) was performed. FINDINGS: Eight randomized controlled trials yielded data on 4307 participants. VCM powder showed no difference in reducing overall SSI. The cumulative number of patients did not exceed the required information size of 19,233 in our TSA, and the Z-curves did not cross the trial sequential monitoring or futility boundary, suggesting an inconclusive result of the meta-analysis. No difference was found for reoperation. Among SSIs, VCM powder showed a statistically significant difference in reducing Gram-positive cocci SSI. However, the certainty of this evidence was very low. CONCLUSION: This systematic review and meta-analysis suggests inconclusive results regarding the effect of VCM powder in reducing SSI in major orthopaedic surgeries. Further trials using rigorous methodologies are required to elucidate the effect of this intervention.

Body Weight Loss After Orthognathic Surgery: Comparison Between Postoperative Intermaxillary Fixation with Metal Wire and Elastic Traction, Factors Related to Body Weight Loss.

INTRODUCTION: The aim of this study was to compare body weight loss between postoperative intermaxillary fixation with metal wire and elastic traction and to investigate factors related to body weight loss after orthognathic surgery. MATERIALS AND METHODS: Subjects were 59 patients with dentofacial deformity, comprising 31 patients treated with intermaxillary fixation (IMF) and 28 patients treated with elastic traction without IMF (ELT) just after surgery. Body weight loss was measured at 1 week (T1) and 2 weeks (T2) after surgery. Body weight loss was compared between IMF and ELT, and factors related to body weight loss were statistically analyzed. RESULTS: Body weight loss ratio was significantly increased in IMF (2.6%) rather than in ELT (1.4%) at T1, but only tended to be increased in both groups at T2, showing no statistical difference. Body weight loss ratio was significantly increased at T2 compared to T1 in both groups. Body weight loss was significantly greater at T2 than at T1. CONCLUSION: Both IMF and ELT cause body weight loss after orthognathic surgery, but IMF causes body weight loss earlier than ELT and increased early body weight loss increases continuous body weight loss after orthognathic surgery.

Relations between anterior disc displacement and maxillomandibular morphology in skeletal anterior open bite with changes to the mandibular condyle.

In this study we investigated the relation between anterior disc displacement (ADD) and maxillomandibular morphology in skeletal anterior open bite with changes to the mandibular condyle. Thirty female patients (60 joints) with both conditions were evaluated. Magnetic resonance imaging of the temporomandibular joint (TMJ) was used to diagnose both ADD and changes to the mandibular condyle (erosion, osteophyte, and deformity). The relations among ADD, changes to the mandibular condyle, and maxillomandibular morphology were examined statistically. Changes to the mandibular condyle had a higher score than sym anterior open bite, the deviated side in asymmetric anterior open bite, and the non-deviated side. The score for disc displacement on the non-deviated side was lower than both the sym side and the deviated side. Unilateral changes to the mandibular condyle and unilateral disc displacement were not apparent in sym anterior open bite, but a unilateral non-displaced disc was seen only on the asymmetric side. Mandibular condylar changes were significantly more common on the deviated, than on the non-deviated, side. The SNB angle was significantly smaller, and the ANB, GZN, and SN-mandibular plane angles were significantly larger in sym anterior open bite. Overjet, ANB angle, GZN angle, and SN-MP angle were significantly larger, and the SNB angle was significantly smaller, in the presence of ADD without reduction and mandibular condylar deformity. We conclude that the prevalence of ADD without reduction and changes to the mandibular condyle were related to mandibular asymmetry and mandibular morphology in anterior open bite. This retrospective study suggests that ADD without reduction and mandibular condylar bone changes may be related to the progression of skeletal class II open bite and mandibular asymmetry in cases of skeletal open bite.

Interaction between phenytoin and enteral nutrients and its influence on gastrointestinal absorption.

The gastrointestinal absorption of phenytoin (PHT), an antiepileptic drug, is often affected by its interaction with co-administered enteral nutrients through a nasogastric (NG) tube, resulting in decreased plasma PHT concentration. In this study, we measured the recovery rate (%) of PHT (Aleviatin® powder) passed through an NG tube when co-administered with distilled water or enteral nutrients (F2α®, Racol® NF, Ensure Liquid® and Renalen® LP). We also measured plasma PHT levels in rats, after oral co-administration of PHT with enteral nutrients. We demonstrate that PHT recovery rate was close to 100 % in all cases after passage through the NG tube. In the rat study, the AUC0→∞ of PHT concentration after oral administration significantly decreased when it was co-administered with F2α® and Racol® NF compared to distilled water. However, the AUC0→∞ of PHT was unchanged when co-administered with F2α® 2 h after initial PHT administration. We therefore conclude that the co-administration of PHT with F2α® and Racol® NF caused a reduction in the absorption of PHT from the gastrointestinal tract to the blood, without adsorption to the NG tube. The administration of enteral nutrients 2 h after PHT is one clear way to prevent a decrease in plasma PHT concentration.

Incidence of anterior disc displacement without reduction of the temporomandibular joint in patients with dentofacial deformity.

The aim of this study was to investigate the incidence of anterior disc displacement without reduction (ADDwoR) of the temporomandibular joint (TMJ) in patients with dentofacial deformity. Eighty-eight female patients (176 joints) with skeletal class III malocclusion and 33 female patients (66 joints) with skeletal class II malocclusion, with or without anterior open bite and asymmetry, were evaluated. Magnetic resonance imaging (MRI) of the TMJ was used to diagnose ADDwoR. A statistical analysis was performed to examine the relationship between ADDwoR and skeletal structure. ADDwoR was present in 37 of the 66 joints (56.1%) in class II compared to 34 of the 176 joints (19.3%) in class III (P<0.05). In class III, ADDwoR was significantly more common in joints with mandibular asymmetry (24/74; 32.4%) than in joints with open bite (9/62; 14.5%) and joints with open bite and without mandibular asymmetry (1/38; 2.6%). In class II, ADDwoR was significantly less common in joints with mandibular asymmetry and without open bite (1/8; 12.5%). ADDwoR was only observed on the deviated side in both class III and class II with mandibular asymmetry. The prevalence of ADDwoR differed according to the dentofacial morphology.

γ-H2AX formation in the urinary bladder of rats treated with two norharman derivatives obtained from o-toluidine and aniline.

Aminomethylphenylnorharman (AMPNH) and aminophenylnorharman (APNH) are mutagenic norharman derivatives obtained from o-toluidine and aniline, respectively. APNH is carcinogenic to the urinary bladder of rats and present in urine samples of healthy volunteers, indicating that norharman derivatives may be associated with cancer development in the urinary bladder of humans. To evaluate the possible role of AMPNH and APNH in bladder carcinogenesis, we examined the formation of γ-H2AX, a DNA damage response marker, in the urinary bladder of rats. Seven-week-old male F344 rats were treated with 400 ppm AMPNH or 40 ppm APNH in the diet for 4 weeks. Animals were killed at the end of administration or after 2 weeks of recovery, and immunohistochemistry for γ-H2AX and Ki67, a cell proliferation marker, was performed. At week 4, γ-H2AX formation in bladder epithelial cells was significantly increased by APNH treatment as compared with that in controls. AMPNH also induced upregulation of γ-H2AX formation, although there was no statistical significance. After the recovery period, γ-H2AX-positive cells were reduced but remained significantly higher in AMPNH and APNH groups than in the control group. Ki67-positive cells were significantly increased by AMPNH and APNH at week 4 and reduced to the same level as the control after 2 weeks of recovery. Expression of KRT14, a bladder stem cell marker, was also increased in the basal layer by the two norharman derivatives. Thus, AMPNH and APNH showed in vivo genotoxicity in the bladder epithelium of rats, and APNH may be a potent causative agent of bladder carcinogenesis.

Morphology of the inferior border of the mandible: correct relation between the lowest position of the outer and inner contours of the cortex for a successful split.

For a sagittal split ramus osteotomy to be secure, the relation between the outer and inner contours of the cortex at the inferior border of the mandible is critical. The lowest point of the outer contour is not always immediately below that of the inner contour, and the former is placed more lingually than the latter in about a third of all cases. This tendency is much more noticeable in skeletal class I and II malocclusions than class III. It is therefore important to examine the lowest point of the inferior border in every case, and to carry the inferior part of the buccal cut on to the lingual side if necessary.

Dutasteride-mediated morphological changes in the genitourinary tract associated with altered expression patterns of the androgen and estrogen receptors in male rats.

We evaluated the effects of dutasteride on the genitourinary tract using fifteen 8-week-old male Sprague-Dawley rats. Animals were divided into three groups comprising five animals each and treated as follows. Group A was a control group, members of Group B received oral administration of dutasteride 0.1 mg/kg/day from the age of 8 to 16 weeks, and members of Group C were castrated at the age of 8 weeks. All rats were killed at the age of 16 weeks for the sample collection of blood, bladder, prostate, seminal vesicles, and penis. Then, we evaluated the pathological examination for evaluating the tissue fibrosis and hormonal receptor expression. The results showed that the mean size of the prostate and seminal vesicles was smaller in Group B and Group C than in Group A. Serum and tissue concentrations of both testosterone and dihydrotestosterone were remarkably reduced in serum and all tissues in Group C compared with Group A. On the other hand, in Group B, only dihydrotestosterone was reduced in serum and penis. Histopathological examination revealed that Group C showed statistically significant histological changes, such as an increase in fibrotic tissue in the bladder, prostate, and penis. Similarly, Group B showed fibrotic changes in the prostate and penis compared with the Group A. Immunofluorescent staining revealed that the androgen receptor was more strongly expressed than the estrogen receptor beta in Group A. On the other hand, in Group C, weak expression of the androgen receptor and strong expression of the estrogen receptor beta was noted. In Group B, these changes were noted in the prostate and penis. These findings suggest that dutasteride cause morphological changes not only in prostate but also in penis. These changes are associated with altered expression patterns of androgen receptor and estrogen receptor.

Risk prediction of major complications in individuals with diabetes: the Atherosclerosis Risk in Communities Study.

AIMS: To develop a prediction equation for 10-year risk of a combined endpoint (incident coronary heart disease, stroke, heart failure, chronic kidney disease, lower extremity hospitalizations) in people with diabetes, using demographic and clinical information, and a panel of traditional and non-traditional biomarkers. METHODS: We included in the study 654 participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, with diagnosed diabetes (visit 2; 1990-1992). Models included self-reported variables (Model 1), clinical measurements (Model 2), and glycated haemoglobin (Model 3). Model 4 tested the addition of 12 blood-based biomarkers. We compared models using prediction and discrimination statistics. RESULTS: Successive stages of model development improved risk prediction. The C-statistics (95% confidence intervals) of models 1, 2, and 3 were 0.667 (0.64, 0.70), 0.683 (0.65, 0.71), and 0.694 (0.66, 0.72), respectively (p < 0.05 for differences). The addition of three traditional and non-traditional biomarkers [ß-2 microglobulin, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C-based eGFR] to Model 3 significantly improved discrimination (C-statistic = 0.716; p = 0.003) and accuracy of 10-year risk prediction for major complications in people with diabetes (midpoint percentiles of lowest and highest deciles of predicted risk changed from 18-68% to 12-87%). CONCLUSIONS: These biomarkers, particularly those of kidney filtration, may help distinguish between people at low versus high risk of long-term major complications.

Wireless Multichannel Neural Recording With a 128-Mbps UWB Transmitter for an Implantable Brain-Machine Interfaces.

Simultaneous recordings of neural activity at large scale, in the long term and under bio-safety conditions, can provide essential data. These data can be used to advance the technology for brain-machine interfaces in clinical applications, and to understand brain function. For this purpose, we present a new multichannel neural recording system that can record up to 4096-channel (ch) electrocorticogram data by multiple connections of customized application-specific integrated circuits (ASICs). The ASIC includes 64-ch low-noise amplifiers, analog time-division multiplexers, and 12-bit successive approximation register ADCs. Recorded data sampled at a rate of 1 kS/s are multiplexed with time division via an integrated multiplex board, and in total 51.2 Mbps of raw data for 4096 ch are generated. This system has an ultra-wideband (UWB) wireless unit for transmitting the recorded neural signals. The ASICs, multiplex boards, and UWB transmitter unit are designed with the aim of implanting them. From preliminary experiments with a human body-equivalent liquid phantom, we confirmed 4096-ch UWB wireless data transmission at 128 Mbps for distances below 20 mm .

Seminal level of clusterin in infertile men as a significant biomarker reflecting spermatogenesis.

The objective of this study was to assess the impact of seminal clusterin level on spermatogenesis in infertile men. This study included 89 men who visited our clinic due to infertility, consisting of 28, 33, and 28 diagnosed with normospermia, oligozoospermia and nonobstructive azoospermia (NOA) respectively. The seminal clusterin concentrations measured by enzyme-linked immunosorbent assay were 47.9, 28.2 and 18.4 ng ml-1 in men with normospermia, oligozoospermia and NOA, respectively, with significant differences among these three groups (P < 0.01). Microdissection testicular sperm extraction (MD-TESE) was performed in the 28 men with NOA, and spermatozoon was successfully retrieved from 9. There was a significant correlation between seminal clusterin level and testicular clusterin protein expression evaluated by immunohistochemical staining in these men with NOA (P = 0.026). Of several parameters available before MD-TESE, the univariate analysis identified serum follicle-stimulating hormone (FSH) level <10 IU ml-1 and seminal clusterin level ≥18 ng ml-1 as significant predictors of sperm retrieval, and of these, only serum FSH level <10 IU ml-1 was shown to be independently associated with sperm retrieval in the multivariate analysis. Accordingly, it might be worthy to further evaluate the significance of seminal clusterin level as a biomarker for the assessment of spermatogenic status in infertile men.

Prospective assessment of health-related quality of life in men with late-onset hypogonadism who received testosterone replacement therapy.

The objective of this study was to characterise the status of health-related quality of life (HRQOL) in Japanese men with late-onset hypogonadism (LOH) treated with testosterone replacement therapy (TRT). HRQOL in 69 consecutive Japanese men with LOH undergoing TRT for at least 6 months was prospectively evaluated before and 6 months after the initiation of TRT using the Medical Outcomes Study 8-Item Short-Form Health Survey (SF-8). All eight-scale scores except for bodily pain (BP) in the 69 patients at 6 months after the introduction of TRT significantly improved compared with those before TRT; however, all scale scores except for BP in the 69 patients were significantly inferior to those in age-matched Japanese controls irrespective of the timing of SF-8. Multivariate analyses of several parameters revealed that both age and Aging Male Symptom (AMS) score had an independent impact on mental health (MH), despite the lack of an independent association between any score and the remaining factors examined. TRT appeared to significantly improve the status of HRQOL in men with LOH; however, even after the introduction of TRT, HRQOL associated with MH remained significantly impaired in elderly men and/or those with a high AMS score.

Adenovirus-mediated FIR demonstrated TP53-independent cell-killing effect and enhanced antitumor activity of carbon-ion beams.

Combination therapy of carbon-ion beam with the far upstream element-binding protein (FBP)-interacting repressor, FIR, which interferes with DNA damage repair proteins, was proposed as an approach for esophageal cancer treatment with low side effects regardless of TP53 status. In vivo therapeutic antitumor efficacy of replication-defective adenovirus (E1 and E3 deleted adenovirus serotype 5) encoding human FIR cDNA (Ad-FIR) was demonstrated in the tumor xenograft model of human esophageal squamous cancer cells, TE-2. Bleomycin (BLM) is an anticancer agent that introduces DNA breaks. The authors reported that Ad-FIR involved in the BLM-induced DNA damage repair response and thus applicable for other DNA damaging agents. To examine the effect of Ad-FIR on DNA damage repair, BLM, X-ray and carbon-ion irradiation were used as DNA damaging agents. The biological effects of high linear energy transfer (LET) radiotherapy used with carbon-ion irradiation are more expansive than low-LET conventional radiotherapy, such as X-rays or γ rays. High LET radiotherapy is suitable for the local control of tumors because of its high relative biological effectiveness. Ad-FIR enhanced BLM-induced DNA damage indicated by γH2AX in vitro. BLM treatment increased endogenous nuclear FIR expression in TE-2 cells, and P27Kip1 expression was suppressed by TP53 siRNA and BLM treatment. Further, Ad-FIRΔexon2, a dominant-negative form of FIR that lacks exon2 transcriptional repression domain, decreased Ku86 expression. The combination of Ad-FIR and BLM in TP53 siRNA increased DNA damage. Additionally, Ad-FIR showed synergistic cell toxicity with X-ray in vitro and significantly increased the antitumor efficacy of carbon-ion irradiation in the xenograft mouse model of TE-2 cells (P=0.03, Mann-Whitney's U-test) and was synergistic with the sensitization enhancement ratio (SER) value of 1.15. Therefore, Ad-FIR increased the cell-killing activity of the carbon-ion beam that avoids late-phase severe adverse effects independently of the TP53 status in vitro. Our findings indicated the feasibility of the combination of Ad-FIR with DNA damaging agents for future esophageal cancer treatment.

Diesel exhaust particles exacerbate allergic rhinitis in mice by disrupting the nasal epithelial barrier.

BACKGROUND: Diesel exhaust particles (DEP), traffic-related air pollutants, are considered environmental factors that affect allergic diseases adversely. However, the exact effect of DEP on allergic rhinitis (AR) is unclear. OBJECTIVE: We thought to investigate the effect of DEP on seasonal AR using a mouse model. METHODS: Ragweed-pollen-sensitized mice were nasally challenged with ragweed pollen in the presence or absence of DEP. The frequency of sneezing was evaluated immediately after each nasal challenge. The expression of a tight junction (TJ) protein, zonula occludens-1 (ZO-1), was examined by immunohistochemistry in AR mice. RPMI 2650 cells were used for in vitro examination of paracellular permeability. RESULTS: Mice challenged with ragweed pollen plus DEP showed increased frequency of sneezing compared with mice challenged with pollen alone. Interestingly, intranasal DEP pretreatment before ragweed pollen challenge increased ragweed-pollen-induced sneezing to levels comparable with the co-administration group. In vitro examination revealed that DEP reduced ZO-1 expression in RPMI 2650 cells. In addition, intranasal administration of DEP, but not ragweed pollen, disrupted nasal mucosal TJs in vivo. The effect of a single DEP treatment on ragweed-induced sneezing and ZO-1 expression persisted for at least 4 days and was inversely correlated. Finally, an antioxidant substance, N-acetyl-L-cysteine, inhibited DEP-mediated TJ disruption and exacerbation of sneezing in AR. CONCLUSIONS AND CLINICAL RELEVANCE: DEP disrupts TJs by a reactive oxygen species-mediated pathway, leading to the increased permeability of nasal epithelial cells. This may result in the promotion of allergen delivery into subepithelial tissues contributing to the exacerbation of immediate allergic responses.

Clusterin produced by Sertoli cells inhibits heat stress-induced apoptosis in the rat testis.

The objectives of this study were to determine whether the inhibition of clusterin expression in rat Sertoli cells enhances heat stress-induced apoptosis. The scrotums of rats were immersed in a water bath of 43 °C for 15 min. Testicular weight and germ cell number markedly decreased after the heat treatment in a time-dependent manner. In contrast, clusterin mRNA and protein expression levels were significantly up-regulated and peaked on day 21. The apoptotic index was markedly increased 1 day after the heat treatment. We then purified Sertoli cells from the rat testes, and an expression vector containing siRNA targeting the clusterin gene was transiently transfected into Sertoli cells. Following exposure to heat stress at 41 °C for 12 h, clusterin mRNA was markedly up-regulated after transfection with the control vector; however, the transfection of siRNA targeting the clusterin resulted in >70% reduction in the expression of clusterin mRNA. Furthermore, the apoptotic index in these Sertoli cells was significantly higher after the treatment with siRNA targeting the clusterin than control, and the most prominent difference was observed within 24 h after the heat treatment. These results suggest that an increase in the secretion of clusterin by Sertoli cells protects the testes from heat stress-induced injury.