[Interpretation of the Implant Dentistry Core Outcome Set and Measurement international consensus report].

Selection and measurement of clinical outcome are key components of clinical research in implant dentistry. Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine took the lead and collaborated with multiple internationally renowned colleges of stomatology to develop an international consensus on the core outcome set and measurement in implant dentistry, which took two years and was published in May, 2023 in Journal of Clinical Periodontology and Clinical Oral Implants Research simultaneously. The consensus, aiming at identifying the full spectrum of benefits and harms of interventions, provides a comprehensive, agreed, and standardized set of outcomes that should be measured and reported as a minimum in clinical trials relating with implant dentistry, bone augmentation, and soft tissue augmentation. The present review describes the methodology and key elements of the consensus to help Chinese clinical researchers fully understand and appropriately apply the core outcome set and improve the overall quality of Chinese clinical research in implant dentistry.

Performance of neuroretinal rim thickness measurement by Cirrus high-definition optical coherence tomography in myopic eyes.

Neuroretinal rim (NRR) measurement can aid the diagnosis of glaucoma. A few studies reported that Cirrus optical coherence tomography (OCT) had NRR segmentation errors. The current study investigated segmentation success of NRR in myopic eyes using the Cirrus built-in software and to determine the number of acquisitions required to identify NRR thinning. Right eye of 87 healthy adult myopes had an optic disc scanned using Cirrus HD-OCT for five successive acquisitions. A masked examiner evaluated 36 radial line images of each scan to screen for segmentation errors using the built-in software at the Bruch's membrane opening (BMO) and/or internal limiting membrane (ILM). Participants with three accurate NRR acquisitions had their average NRR thickness determined. This result was compared with average of the two acquisitions and the first acquisition. Among 435 OCT scans of the optic disc (87 eyes × 5 acquisitions), 129 (29.7%) scans had segmentation errors that occurred mainly at the ILM. The inferior-temporal and superior meridians had slightly more segmentation errors than other meridians, independent of axial length, amount of myopia, or presence of peripapillary atrophy. Sixty-five eyes (74.7%) had at least three accurate NRR measurements. The three acquisitions had high reliability in NRR thickness in the four quadrants (intraclass correlation coefficient > 0.990, coefficient of variation < 3.9%). NRR difference between the first acquisition and the average of three acquisitions was small (mean difference 2 ± 13 µm, 95% limits of agreement within ± 30 µm) among the four quadrants. Segmentation errors in NRR measurements appeared regardless of axial length, amount of myopia, or presence of peripapillary atrophy. Cirrus segmentation lines should be manually inspected when measuring NRR thickness.

Host Genetic Associations with Salivary Microbiome in Oral Cancer.

Despite the growing recognition of a host genetic effect on shaping gut microbiota composition, the genetic determinants of oral microbiota remain largely unexplored, especially in the context of oral diseases. Here, we performed a microbiome genome-wide association study in 2 independent cohorts of patients with oral squamous cell carcinoma (OSCC, n = 144 and 67) and an additional group of noncancer individuals (n = 104). Besides oral bacterial dysbiosis and signatures observed in OSCC, associations of 3 loci with the abundance of genus-level taxa and 4 loci with ß diversity measures were detected (q < 0.05) at the discovery stage. The most significant hit (rs10906082 with the genus Lachnoanaerobaculum, P = 3.55 × 10-9 at discovery stage) was replicated in a second OSCC cohort. Moreover, the other 2 taxonomical associations, rs10973953 with the genus Kingella (P = 1.38 × 10-9) and rs4721629 with the genus Parvimonas (P = 3.53 × 10-8), were suggestive in the meta-analysis combining 2 OSCC cohorts. Further pathway analysis revealed that these loci were enriched for genes in regulation of oncogenic and angiogenic responses, implicating a genetic anchor to the oral microbiome in estimation of casual relationships with OSCC. Our findings delineate the role of host genotypes in influencing the structure of oral microbial communities.

The influence of the shock-absorbing restorative materials on the stress distributions of short dental implant rehabilitations.

OBJECTIVE: Polymer materials with shock-absorbing ability may offer better stress distribution with short dental implants (SDI). The present study aimed to evaluate the effect of abutment and crown materials on the stress distributions in short implant-prosthesis-complex (6 mm) and standard implant-prosthesis-complex (10 mm) using 3D finite element analysis (FEA). MATERIALS AND METHODS: Two FEA models were designed to simulated single implant restoration of mandibular first molar, one each for short implant (6 mm) (Group S) and standard implant (10 mm) (Group C). In each group, two abutment materials were used, Polyetheretherketone (PEEK) and Zirconia (Zr), with two types of crowns, PEEK and Polymer-infiltrated ceramic-network (PICN). A vertical force of 200 N was applied to each central fossa. Stress distribution was evaluated via the von Mises stress analysis. RESULTS: Using the PEEK abutment, the stress was better dispersed with PEEK crowns, as compared to PICN crowns. The stress was concentrated on the platforms of Ti-bases and the head and middle part of abutment screws. In zirconia abutment, the stress was greatly concentrated on the axial angle regions when placed with the PEEK crowns, while the stress was dispersed when placed with PICN crowns. The stress was concentrated on the connector regions of Ti-bases and the middle part of abutment screws. For implants, the stress was concentrated on the neck of the two implants, regardless of crown materials and abutment materials. The PEEK materials were found to be suitable for the hybrid-retained prostheses of SDI. CONCLUSIONS: Our study indicates that the PEEK material is more suitable for the hybrid restorations of SDI. If the Zr abutment is used, the PICN crown would be better. Further, in-vivo clinical trials comparing these materials are needed to strengthen evidence.

[Prevention and management of hardware and biological complications in implant dentistry].

Due to the highly predictable long-term clinical outcomes, modern implant dentistry has become one of the most preferred treatment modalities for restoring missing teeth. However, the complications of implant therapy compromise the long-term implant success and remain a great challenge to clinicians. Hardware complications include the mechanical complications which are related to the manufacturer-fabricated components of the prosthesis, such as abutment/screw loosening, fracture and implant fracture; and the technical complication which are related to laboratory-fabricated components of the prosthesis, such as veneer chipping. The biological complications mainly include peri-implant mucositis and peri-implantitis. It is crucial to figure out how to effectively avoid and manage the complications of implant therapy. This article reported the definitions, incidences, risk factors, prevention and treatment of both mechanical and biological complications of implant therapy.

Clostridium innocuum is a vancomycin-resistant pathogen that may cause antibiotic-associated diarrhoea.

OBJECTIVES: Clostridium innocuum can cause extraintestinal infection in patients with underlying diseases. The role of C. innocuum in antibiotic-associated diarrhoea (AAD) remains unknown. METHODS: Clinical information of 103 patients from whom C. innocuum was isolated was reviewed. We carried out cellular and animal experiments to examine the pathogenic potential of C. innocuum in AAD. RESULTS: Eighty-eight per cent (91/103) of the 103 patients received antibiotics within 2 weeks of diarrhoea onset. Patients were further classified into two groups, severe colitis and diarrhoea, according to clinical severity level. The mortality rate was 13.6% (14/103) among the patients from whom C. innocuum was isolated. The lowest concentrations at which 90% of the isolates were inhibited for metronidazole and vancomycin were 0.5 and 16 mg/L, respectively. All isolates tested were susceptible to metronidazole but resistant to vancomycin. Nineteen randomly selected isolates (ten from severe colitis group, nine from diarrhoea group) were subjected to further in vitro cellular examinations. The level of cytotoxicity to Vero cells was significantly higher in isolates from the severe colitis group at both 24 and 48 hours after inoculation (24 and 48 hours, p 0.042 and 0.033, respectively). We observed apoptotic changes that subsequently led to cell death in C. innocuum-infected Vero cells. Tissue damages, necrotic changes and oedema were observed in the mouse ileal loop infected by C. innocuum. CONCLUSIONS: Vancomycin-resistant C. innocuum may play a potential role as a causative agent of AAD. The clinical manifestations of AAD caused by C. innocuum were diarrhoea or severe colitis, including pseudomembranous colitis.

[The combined interpretation schemes including VCA-IgA, EA-IgA and Rta-IgG in the diagnosis of nasopharyngeal carcinoma].

Objective:To compare the performances of VCA-IgA, EA-IgA and Rta-IgG in the diagnosis of nasopharyngeal carcinoma, and find the most appropriate combined interpretation scheme. Method:The current study included a total of 346 subjects. Ninety-six subjects were nasopharyngeal carcinoma cases which were pathologically verified by the biopsy under electronic laryngoscope. The remaining 250 subjects, who received EBV tests at the same period, were normal healthy individuals without nasopharyngeal carcinoma. VCA-IgA, EA-IgA and Rta-IgG were detected in all cases. The clinial data were analyzed retrospectively. Result:Best cutoff points of VCA-IgA, EA-IgA and Rta-IgG in the diagnosis of nasopharyngeal carcinoma were 1.37 s/co, 0.706 s/co and 0.817 s/co; the sensitivities were 88.5%,49.0% and 65.6%; the specificities were 88.8%,96.0% and 95.2%, respectively. The diagnostic accuracy of VCA-IgA was significantly higher than that of EA-IgA and Rta-IgG (P<0.05). Three combined interpretation schemes were developed based on the VCA-IgA: ①VCA-IgA+EA-IgA; ②VCA-IgA+Rta-IgG; ③VCA-IgA+EA-IgA+Rta-IgG. Compared to the VCA-IgA, all the combined interpretation schemes had increased sensitivities and decreased specificities. The scheme 3 had the highest sensitivity. And the scheme 2 had the highest Youden index, and a comparable diagnosis accuracy to that of VCA-IgA (P>0.05). Conclusion:VCA-IgA, EA-IgA and Rta-IgG were all helpful indicators in the diagnosis of nasopharyngeal carcinoma. VCA-IgA was more accurate than the EA-IgA and Rta-IgG. Combined interpretation schemes were helpful in improving the sensitivity. Because the clinical symptoms of nasopharyngeal carcinoma are often insidious and the missed diagnosis by serological examination may lead to serious consequences. It is of clinical value to adopt the combined interpretation schemes to improve the diagnostic sensitivity of nasopharyngeal carcinoma.

Antrodia cinnamomea reduces obesity and modulates the gut microbiota in high-fat diet-fed mice.

BACKGROUND: Obesity is associated with gut microbiota dysbiosis, disrupted intestinal barrier and chronic inflammation. Given the high and increasing prevalence of obesity worldwide, anti-obesity treatments that are safe, effective and widely available would be beneficial. We examined whether the medicinal mushroom Antrodia cinnamomea may reduce obesity in mice fed with a high-fat diet (HFD). METHODS: Male C57BL/6J mice were fed a HFD for 8 weeks to induce obesity and chronic inflammation. The mice were treated with a water extract of A. cinnamomea (WEAC), and body weight, fat accumulation, inflammation markers, insulin sensitivity and the gut microbiota were monitored. RESULTS: After 8 weeks, the mean body weight of HFD-fed mice was 39.8±1.2 g compared with 35.8±1.3 g for the HFD+1% WEAC group, corresponding to a reduction of 4 g or 10% of body weight (P<0.0001). WEAC supplementation reduced fat accumulation and serum triglycerides in a statistically significant manner in HFD-fed mice. WEAC also reversed the effects of HFD on inflammation markers (interleukin-1ß, interleukin-6, tumor necrosis factor-α), insulin resistance and adipokine production (leptin and adiponectin). Notably, WEAC increased the expression of intestinal tight junctions (zonula occludens-1 and occludin) and antimicrobial proteins (Reg3g and lysozyme C) in the small intestine, leading to reduced blood endotoxemia. Finally, WEAC modulated the composition of the gut microbiota, reducing the Firmicutes/Bacteroidetes ratio and increasing the level of Akkermansia muciniphila and other bacterial species associated with anti-inflammatory properties. CONCLUSIONS: Supplementation with A. cinnamomea produces anti-obesogenic, anti-inflammatory and antidiabetic effects in HFD-fed mice by maintaining intestinal integrity and modulating the gut microbiota.

Zopiclone use associated with increased risk of acute pancreatitis: a case-control study in Taiwan.

BACKGROUND: The purpose of this study was to assess the relationship between zopiclone use and the risk of acute pancreatitis in Taiwan. METHODS: This was a population-based case-control study. The data source was from the database of the Taiwan National Health Insurance Program since 2000-2011. We identified 5169 subjects aged 20-84 years with a first-time attack of acute pancreatitis as the patients and 20,676 sex-matched and age-matched subjects without acute pancreatitis as the controls. Active use of zopiclone was defined as subjects who received at least one prescription for zopiclone within 30 days before the date of diagnosing acute pancreatitis. The lack of zopiclone prescription was defined as 'never use'. We calculated the odds ratio (OR) and 95% confidence interval (CI) to assess the risk of acute pancreatitis associated with zopiclone use by the multivariable logistic regression model. RESULTS: After adjustment for potential confounding variables, the adjusted OR of acute pancreatitis was 2.36 for subjects with active use of zopiclone (95% CI 1.70-3.28), as compared with those with never use of zopiclone. In further analysis, as a reference of subjects with never use of zopiclone and without alcohol-related disease and biliary stone, the adjusted OR increased to 14.44 in those with active use of zopiclone and with alcohol-related disease or biliary stone (95% CI 7.47-27.89). CONCLUSIONS: Subjects actively using zopiclone are associated with increased risk of acute pancreatitis. Clinicians should take acute pancreatitis risk into account when prescribing zopiclone, particularly comorbid with alcohol-related disease or biliary stone.

Knockdown of c-MET induced apoptosis in ABCB1-overexpressed multidrug-resistance cancer cell lines.

Inappropriate c-MET signaling in cancer can enhance tumor cell proliferation, survival, motility, and invasion. Inhibition of c-MET signaling induces apoptosis in a variety of cancers. It has also been recognized as a novel anticancer therapy approach. Furthermore, reports have also indicated that constitutive expression of P-glycoprotein (ABCB1) is involved in the HGF/c-MET-related pathway of multidrug resistance ABCB1-positive human hepatocellular carcinoma cell lines. We previously reported that elevated expression levels of PKCδ and AP-1 downstream genes, and HGF receptor (c-MET) and ABCB1, in the drug-resistant MES-SA/Dx5 cells. Moreover, leukemia cell lines overexpressing ABCB1 have also been shown to be more resistant to the tyrosine kinase inhibitor imatinib mesylate. These findings suggest that chemoresistant cancer cells may also develop a similar mechanism against chemotherapy agents. To circumvent clinical complications arising from drug resistance during cancer therapy, the present study was designed to investigate apoptosis induction in ABCB1-overexpressed cancer cells using c-MET-targeted RNA interference technology in vitro and in vivo. The results showed that cell viability decreased and apoptosis rate increased in c-MET shRNA-transfected HGF/c-MET pathway-positive MES-SA/Dx5 and MCF-7/ADR2 cell lines in a dose-dependent manner. In vivo reduction of tumor volume in mice harboring c-MET shRNA-knockdown MES-SA/Dx5 cells was clearly demonstrated. Our study demonstrated that downregulation of c-MET by shRNA-induced apoptosis in a multidrug resistance cell line.

Screening whole spine magnetic resonance imaging in multiple myeloma.

BACKGROUND: Magnetic resonance imaging (MRI) is the most sensitive method for detecting focal spinal disease (FSD) in multiple myeloma (MM). It is unclear whether whole spine MRI (WS-MRI) should be employed as a screening test at diagnosis of MM. AIM: To determine the utility of screening WS-MRI at diagnosis of MM. METHODS: A retrospective analysis of data from January 2008 to January 2013 at the Townsville Hospital was performed. At this centre, WS-MRI is used routinely in all newly diagnosed MM. The findings of WS-MRI in patients with and without an agreed guideline indication for WS-MRI were compared. Clinical predictors of FSD were determined. RESULTS: Seventy-one patients were included in the analysis. Forty-four (62%) had an agreed indication for MRI; 33 (75%) of these had FSD. Within this group, 17 required urgent intervention and 13 had spinal plasmacytomas. Within a second group without a guideline indication, 4 of 27 (15%) were found to have FSD on MRI - none required urgent intervention and or had plasmacytomas. Three of eight smouldering myeloma patients were reclassified as symptomatic myeloma by documenting lytic lesions not identified on plain film. The strongest predictors of FSD were back pain (P < 0.001) and vertebral compression fracture (P = 0.003). CONCLUSION: WS-MRI in patients without a guideline indication did not detect any lesions that threatened the spinal cord. WS-MRI is essential in those with guideline indications. WS-MRI is of benefit to patients with smouldering myeloma where documentation of lesions not seen on plain film will result in treatment rather than observation.

Left circumflex coronary-to-pulmonary artery fistula as the exclusive collateral to the occluded left anterior descending artery.

A 64 year-old male presented with a five month history of effort angina. Non-invasive studies demonstrated preserved left ventricular function and a modest stress-induced myocardial perfusion defect at the anterior wall. Coronary angiography revealed occlusion of the proximal left anterior descending coronary artery with its distal segment well supplied by collaterals branching from a left circumflex-to-main pulmonary artery fistula. The occluded left anterior descending coronary artery was recanalised by percutaneous interventions, the collaterals vanished immediately, and the patient lived free of symptoms for the following five months.

An EMT spectrum defines an anoikis-resistant and spheroidogenic intermediate mesenchymal state that is sensitive to e-cadherin restoration by a src-kinase inhibitor, saracatinib (AZD0530).

The phenotypic transformation of well-differentiated epithelial carcinoma into a mesenchymal-like state provides cancer cells with the ability to disseminate locally and to metastasise. Different degrees of epithelial-mesenchymal transition (EMT) have been found to occur in carcinomas from breast, colon and ovarian carcinoma (OC), among others. Numerous studies have focused on bona fide epithelial and mesenchymal states but rarely on intermediate states. In this study, we describe a model system for appraising the spectrum of EMT using 43 well-characterised OC cell lines. Phenotypic EMT characterisation reveals four subgroups: Epithelial, Intermediate E, Intermediate M and Mesenchymal, which represent different epithelial-mesenchymal compositions along the EMT spectrum. In cell-based EMT-related functional studies, OC cells harbouring an Intermediate M phenotype are characterised by high N-cadherin and ZEB1 expression and low E-cadherin and ERBB3/HER3 expression and are more anoikis-resistant and spheroidogenic. A specific Src-kinase inhibitor, Saracatinib (AZD0530), restores E-cadherin expression in Intermediate M cells in in vitro and in vivo models and abrogates spheroidogenesis. We show how a 33-gene EMT Signature can sub-classify an OC cohort into four EMT States correlating with progression-free survival (PFS). We conclude that the characterisation of intermediate EMT states provides a new approach to better define EMT. The concept of the EMT Spectrum allows the utilisation of EMT genes as predictive markers and the design and application of therapeutic targets for reversing EMT in a selective subgroup of patients.

c-Kit mediates chemoresistance and tumor-initiating capacity of ovarian cancer cells through activation of Wnt/ß-catenin-ATP-binding cassette G2 signaling.

Cisplatin and paclitaxel are standard chemotherapy for metastatic ovarian cancer, but with limited efficacy. Cancer stem/progenitor cells (or tumor-initiating cells, TICs) are hypothesized to be chemoresistant, and the existence of TICs in ovarian cancer has been previously demonstrated. However, the key signals and molecular events regulating the formation and expansion of ovarian tumor-initiating cells (OTICs) remain elusive. Here, we show that c-Kit is not just a marker of OTICs, but also a critical mediator of the phenotype that can be a viable target for the treatment of ovarian cancer. In contrast to non-OICs, c-Kit was overexpressed in OTICs. Moreover, the use of small interfering RNA to inhibit c-Kit expression markedly attenuated the number and size of OTIC subpopulations, inhibited the expression of stem cell markers and decreased the tumorigenic capabilities of OTICs. Imatinib (Gleevec), a clinical drug that blocks c-Kit kinase activity, also demonstrated its inhibition potency on OTICs. In addition, cisplatin/paclitaxel, which killed non-OTICs, with c-Kit knockdown or imatinib revealed that this was critically required for intervening ovarian cancer progression and recurrence in vitro and in xenograft tumors in vivo. Similar results were obtained with OTICs derived from ovarian carcinoma patients. Studies into the mechanisms suggest an important role for the activation of Wnt/ß-catenin and ATP-binding cassette G2 downstream of c-Kit. The tumor-promoting microenvironment, such as hypoxia, could promote OTICs via upregulation of c-Kit expression. These results unravel an integral role for c-Kit in ovarian neoplastic processes and shed light on its mechanisms of action.

CpG island shore methylation regulates caveolin-1 expression in breast cancer.

Caveolin-1 (Cav1) is an integral membrane, scaffolding protein found in plasma membrane invaginations (caveolae). Cav1 regulates multiple cancer-associated processes. In breast cancer, a tumor suppressive role for Cav1 has been suggested; however, Cav1 is frequently overexpressed in aggressive breast cancer subtypes, suggesting an oncogenic function in advanced-stage disease. To further delineate Cav1 function in breast cancer progression, we evaluated its expression levels among a panel of cell lines representing a spectrum of breast cancer phenotypes. In basal-like (the most aggressive BC subtype) breast cancer cells, Cav1 was consistently upregulated, and positively correlated with increased cell proliferation, anchorage-independent growth, and migration and invasion. To identify mechanisms of Cav1 gene regulation, we compared DNA methylation levels within promoter 'CpG islands' (CGIs) with 'CGI shores', recently described regions that flank CGIs with less CG-density. Integration of genome-wide DNA methylation profiles ('methylomes') with Cav1 expression in 30 breast cancer cell lines showed that differential methylation of CGI shores, but not CGIs, significantly regulated Cav1 expression. In breast cancer cell lines having low Cav1 expression (despite promoter CGI hypomethylation), we found that treatment with a DNA methyltransferase inhibitor induced Cav1 expression via CGI shore demethylation. In addition, further methylome assessments revealed that breast cancer aggressiveness associated with Cav1 CGI shore methylation levels, with shore hypermethylation in minimally aggressive, luminal breast cancer cells and shore hypomethylation in highly aggressive, basal-like cells. Cav1 CGI shore methylation was also observed in human breast tumors, and overall survival rates of breast cancer patients lacking estrogen receptor α (ERα) negatively correlated with Cav1 expression. Based on this first study of Cav1 (a potential oncogene) CGI shore methylation, we suggest this phenomenon may represent a new prognostic marker for ERα-negative, basal-like breast cancer.