The TRIPLEX study: use of patient-derived tumor organoids as an innovative tool for precision medicine in triple-negative breast cancer.

BACKGROUND: Triple negative breast cancers (TNBC) account for approximately 15% of all breast cancers and are associated with a shorter median survival mainly due to locally advanced tumor and high risk of metastasis. The current neoadjuvant treatment for TNBC consists of a regimen of immune checkpoint blocker and chemotherapy (chemo-ICB). Despite the frequent use of this combination for TNBC treatment, moderate results are observed and its clinical benefit in TNBC remains difficult to predict. Patient-derived tumor organoids (PDTO) are 3D in vitro cellular structures obtained from patient's tumor samples. More and more evidence suggest that these models could predict the response of the tumor from which they are derived. PDTO may thus be used as a tool to predict chemo-ICB efficacy in TNBC patients. METHOD: The TRIPLEX study is a single-center observational study conducted to investigate the feasibility of generating PDTO from TNBC and to evaluate their ability to predict clinical response. PDTO will be obtained after the dissociation of biopsies and embedding into extra cellular matrix. PDTO will be cultured in a medium supplemented with growth factors and signal pathway inhibitors. Molecular and histological analyses will be performed on established PDTO lines to validate their phenotypic proximity with the original tumor. Response of PDTO to chemo-ICB will be assessed using co-cultures with autologous immune cells collected from patient blood samples. PDTO response will finally be compared with the response of the patient to evaluate the predictive potential of the model. DISCUSSION: This study will allow to assess the feasibility of using PDTO as predictive tools for the evaluation of the response of TNBC patients to treatments. In the event that PDTO could faithfully predict patient response in clinically relevant time frames, a prospective clinical trial could be designed to use PDTO to guide clinical decision. This study will also permit the establishment of a living biobank of TNBC PDTO usable for future innovative strategies evaluation. TRIAL REGISTRATION: The clinical trial (version 1.2) has been validated by local research ethic committee on December 30th 2021 and registered at ClinicalTrials.gov with the identifier NCT05404321 on June 3rd 2022, version 1.2.

Reporting and Abstracting Variability in Technical Standards for Breast Cancer Operations.

BACKGROUND: The American College of Surgeons Commission on Cancer has incorporated documentation of critical elements outlined in Operative Standards for Cancer Surgery into revised standards for cancer center accreditation. This study assessed the current documentation of critical elements in partial mastectomy (PM) and sentinel lymph node biopsy (SLNB) operative reports. MATERIALS AND METHODS: Operative reports for PM + SLNB at a single academic institution from 2013 to 2018 were reviewed for compliance and surveyor interobserver reliability with the Oncologic Elements of Operative Record defined in Operative Standards and compared with a nonredundant American Society of Breast Surgeons Mastery of Breast Surgery (MBS) quality measure for specimen orientation. RESULTS: Ten reviewers each evaluated 66 PM + SLNB operative reports for 13 Oncologic Elements and one MBS measure. No operative records reported all critical elements for PM + SLNB or PM alone. Residents completed 36.4% of operative reports: Element documentation was similar for PM but varied significantly for SLNB between resident and attending authorship. Combined reporting performance and interrater reliability varied across all elements and was highest for the use of SLNB tracer (97.1% and κ = 0.95, respectively) and lowest for intraoperative assessment of SLNB (30.6%, κ = 0.43). MBS specimen orientation had both high proportion reported (87.0%) and interrater reliability (κ = 0.84). CONCLUSIONS: Adherence to reporting critical elements for PM and SLNB varied. Whether differential compliance was tied to discrepancies in documentation or reviewer abstraction, clarification of synoptic choices may improve reporting consistency. Evolving techniques or technologies will require continuous appraisal of mandated reporting for breast surgery.

Ethnic and racial disparities of pancreatic adenocarcinoma in Florida.

BACKGROUND: Racial disparities are known to negatively impact survival in patients with pancreatic adenocarcinoma. However, data regarding the Hispanic ethnicity are scarce in the pancreatic cancer literature. Therefore, the aim of this study is to analyze whether race and ethnicity are independent predictors of survival in patients with pancreatic adenocarcinoma in Florida. METHODS: A retrospective study was performed utilizing all patients diagnosed with pancreatic adenocarcinoma between 1983 and 2013 in the Florida Cancer Data System (FCDS). Statistical analysis was performed using Cox proportional hazard regression models, and Kaplan-Meier survival analysis. RESULTS: Of 36,756 patients identified with pancreatic adenocarcinoma in the FCDS, 9.1% were Hispanic and 91% were non-Hispanic. Ethnicity was associated with improved survival among Hispanics compared to non-Hispanics (HR 0.86, 95% CI 0.82-0.90, both p = 0.001). Furthermore, 90% of patients were White, and 9% were Black. Compared to Whites, Blacks had a significantly decreased survival (HR 1.07, 95% CI 1.03-1.13, p = 0.003). CONCLUSION: In Florida patients with pancreatic adenocarcinoma, Hispanic ethnicity is associated with improved survival compared to Non-Hispanics. Additionally, Blacks present at an earlier age and later stage of diagnosis with worse survival compared to Whites and Others.

Reconstitution of recombination-associated DNA synthesis with human proteins.

The repair of DNA breaks by homologous recombination is a high-fidelity process, necessary for the maintenance of genome integrity. Thus, DNA synthesis associated with recombinational repair must be largely error-free. In this report, we show that human DNA polymerase delta (δ) is capable of robust DNA synthesis at RAD51-mediated recombination intermediates dependent on the processivity clamp PCNA. Translesion synthesis polymerase eta (η) also extends these substrates, albeit far less processively. The single-stranded DNA binding protein RPA facilitates recombination-mediated DNA synthesis by increasing the efficiency of primer utilization, preventing polymerase stalling at specific sequence contexts, and overcoming polymerase stalling caused by topological constraint allowing the transition to a migrating D-loop. Our results support a model whereby the high-fidelity replicative DNA polymerase δ performs recombination-associated DNA synthesis, with translesion synthesis polymerases providing a supportive role as in normal replication.

Distance of Biopsy-Confirmed High-Risk Breast Lesion from Concurrently Identified Breast Malignancy Associated with Risk of Carcinoma at the High-Risk Lesion Site.

High-risk breast lesions including incidental intraductal papilloma without atypia (IPA), lobular hyperplasia (LCIS or ALH), flat epithelial atypia (FEA) and complex sclerosing lesion (CSL) are not routinely excised due to low upgrade rates to carcinoma. We aim to identify features of these lesions predictive of upgrade when identified concurrently with invasive disease. Methods: A single-center retrospective cohort study was performed for patients who underwent multi-site lumpectomies with invasive disease at one site and a high-risk lesion at another site between 2006 and 2021. A multinomial logistic regression was performed. Results: Sixty-five patients met the inclusion criteria. Four patients (6.2%) had an upgrade to in situ disease (DCIS) and one (1.5%) to invasive carcinoma. Three upgraded high-risk lesions were ipsilateral to the concurrent carcinoma and two were contralateral. In the multivariate model, a high-risk lesion within 5 cm of an ipsilateral malignancy was associated with increased risk of upgrade. The 3.8% upgrade rate for high-risk lesions located greater than 5 cm from ipsilateral malignancy or in the contralateral breast suggests that omission of excisional biopsy may be considered. Excisional biopsy of lesions within 5 cm of ipsilateral malignancy is recommended given the 25% upgrade risk in our series.

Mentorship of Junior Surgical Faculty Across Academic Programs in Surgery.

Importance: Because mentorship is critical for professional development and career advancement, it is essential to examine the status of mentorship and identify challenges that junior surgical faculty (assistant and associate professors) face obtaining effective mentorship. Objective: To evaluate the mentorship experience for junior surgical faculty and highlight areas for improvement. Design, Setting, and Participants: This qualitative study was an explanatory sequential mixed-methods study including an anonymous survey on mentorship followed by semistructured interviews to expand on survey findings. Junior surgical faculty from 18 US academic surgery programs were included in the anonymous survey and interviews. Survey responses between "formal" (assigned by the department) vs "informal" (sought out by the faculty) mentors and male vs female junior faculty were compared using χ2 tests. Interview responses were analyzed for themes until thematic saturation was achieved. Survey responses were collected from November 2022 to August 2023, and interviews conducted from July to December 2023. Exposure: Mentorship from formal and/or informal mentors. Main Outcomes and Measures: Survey gauged the availability and satisfaction with formal and informal mentorship; interviews assessed broad themes regarding mentorship. Results: Of 825 survey recipients, 333 (40.4%) responded; 155 (51.7%) were male and 134 (44.6%) female. Nearly all respondents (319 [95.8%]) agreed or strongly agreed that mentorship is important to their surgical career, especially for professional networking (309 respondents [92.8%]), career advancement (301 [90.4%]), and research (294 [88.3%]). However, only 58 respondents (18.3%) had a formal mentor. More female than male faculty had informal mentors (123 [91.8%] vs 123 [79.4%]; P = .003). Overall satisfaction was higher with informal mentorship than formal mentorship (221 [85.0%] vs 40 [69.0%]; P = .01). Most male and female faculty reported no preferences in gender or race and ethnicity for their mentors. When asked if they had good mentor options if they wanted to change mentors, 141 (47.8%) responded no. From the interviews (n = 20), 6 themes were identified, including absence of mentorship infrastructure, preferred mentor characteristics, and optimizing mentorship. Conclusions and Relevance: Academic junior surgical faculty agree mentorship is vital to their careers. However, this study found that few had formal mentors and almost half need more satisfactory options if they want to change mentors. Academic surgical programs should adopt a framework for facilitating mentorship and optimize mentor-mentee relationships through alignment of mentor-mentee goals and needs.

Omitting axillary staging in selected patients: Rationale of Choosing Wisely in breast cancer treatment.

Axillary surgery for breast cancer has continually evolved, with sentinel lymph node biopsy for clinically node-negative women with invasive breast cancer having long replaced axillary lymph node dissection. The information obtained from axillary staging has been important in providing prognostic information and guiding adjuvant treatment recommendations. However, recent studies suggest that sentinel lymph node biopsy should be omitted in select low-risk patients whose axillary surgery provides minimal prognostic value. This was highlighted by the Society of Surgical Oncology Choosing Wisely Guidelines, advocating against routine axillary staging in older women with early-stage hormone receptor-positive breast cancer. Since the guideline release, ongoing research has continued to identify the subset of low-risk patients who would benefit from the omission of axillary staging and improve adherence to Choosing Wisely to prevent overtreatment in older people.

Masculinizing hormone therapy effect on breast tissue: Changes in estrogen and androgen receptors in transgender female-to-male mastectomies.

PURPOSE: Almost two percent of individuals in the United States identify as gender non-conforming. In the female-to-male (FTM) transgender population, masculinizing hormone therapy with testosterone is commonly prescribed in gender transition. To date, the effects of exogenous androgens on breast tissue and its roles in altering breast cancer risk are poorly understood. This study examines the histopathologic findings in gender affirming mastectomy (GAM) in transgender FTM patients and the effects of exogenous androgens on estrogen receptors (ER) and androgen receptors (AR). METHODS: A retrospective review of pathology specimens obtained between 2017 and 2020 was performed comparing androgen exposed breast tissue with breast tissue without androgen exposure. Breast specimens were obtained from patients who underwent FTM GAM with recorded exogenous androgen exposure. Control breast specimens were obtained from reduction mammoplasty (RM) procedures in cisgender women which were aged matched to the GAM cohort, as well as postmenopausal women with benign/prophylactic mastectomy procedures; all controls were without androgen exposure. The histopathologic findings were assessed. Immunohistochemistry for AR and ER was performed and the score interpreted by digital image analysis. RESULTS: Androgen-exposed breast tissue revealed dense fibrotic stroma, lobular atrophy, thickened lobular basement membranes, and gynecomastoid changes. Longer duration of androgen exposure resulted in a more pronounced effect. The incidence of atypia or cancer was lower in GAM than RM cohort. ER and AR expression was highest in transgender male breast tissue with intermediate duration of exogenous androgen exposure. CONCLUSION: Increased androgen exposure is associated with lobular atrophy and gynecomastoid changes in breast parenchyma. Overall, ER and AR are expressed strongly in lobular epithelium in patients with prolonged androgen exposure. Exogenous testosterone does not appear to increase risk for breast cancer. Additional studies are needed to investigate the mechanism responsible for these changes at a cellular level and its role in cancer development.

Evaluation of current practice: management of chemotherapy-related toxicities.

Adverse effects induced by cytotoxic chemotherapy (CT) have been mostly evaluated in clinical trials. The aim of this study was to assess in a nonselected patients group the incidence of CT-related toxicities and to identify risk factors in daily practice. Patients treated with CT (except cisplatin-based or carboplatin-based CT), for a solid tumour, were included in a prospective multicentre observational study. Clinical parameters, renal function and albumin level were assessed at baseline. Multivariate logistic regression was used to identify risk factors of CT-related toxicities. A total of 502 patients were recruited in different types of oncology departments. During CT, 62% of patients experienced grade 2-4 toxicities. Haematological toxicities affected 34% of patients and 20% of patients developed an infection requiring antibiotics. For 55% of patients, toxicities induced dose reduction (59% of cases), CT delay (25%) or discontinuation (16%) according to the management habits in the investigating centre. Performance status≥1, breast cancer, lymphopenia, hypoalbuminaemia and clearance creatinine<60 ml/min were risk factors for haematological toxicity. Performance status≥1, hypoalbuminaemia, proteinuria and clearance creatinine<90 ml/min were risk factors for change of CT schedule. A majority of patients receiving CT experienced significant toxicity leading to change of standard CT protocol. Albumin, creatinine clearance and lymphocyte should be routinely monitored at baseline to manage CT and to prevent their toxicities.

Association of antimicrobial and clinical efficacy: periodontitis therapy with minocycline microspheres.

OBJECTIVE: The objective of this study was to investigate the association between the antimicrobial and clinical efficacy of minocycline hydrochloride microspheres when used adjunctively with scaling and root planing. METHODS: 127 subjects with moderate-to-advanced chronic periodontitis were randomly assigned to receive either minocycline microspheres plus scaling and root planing (n = 62) or scaling and root planing alone (n = 65). Deoxyribose nucleic acid analysis and clinical data were obtained at baseline and 30 days after treatment. End points included changes in the mean sum of red complex bacteria, pocket depth, number of deep pockets, bleeding on probing, and clinical attachment level from baseline to day 30. Regression analysis determined the association between microbiological and clinical efficacy. RESULTS: Minocycline microspheres plus scaling and root planing reduced pocket depth, the number of deep pockets and bleeding on probing, and increased clinical attachment level significantly more than scaling and root planing alone (p < 0.05). Comparing minocycline microspheres plus scaling and root planing with scaling and root planing alone, the number needed to treat for a 2 mm pocket depth reduction difference was 6.5. Pocket depth reduction correlated significantly with a decrease in the numbers and proportions of red complex bacteria. Minocycline microspheres significantly improved all clinical parameters compared to scaling and root planing alone. CONCLUSIONS: The addition of minocycline microspheres to scaling and root planing led to a greater reduction in the proportions and numbers of red complex bacteria. The reduction in pocket depth was significantly correlated with the reduction of the proportions and numbers of red complex bacteria. Additionally, there were statistically greater improvements in all clinical parameters examined.

Periodontal disease status in gullah african americans with type 2 diabetes living in South Carolina.

BACKGROUND: African Americans have a disproportionate burden of diabetes. Gullah African Americans are the most genetically homogeneous population of African descent in the United States, with an estimated European admixture of only 3.5%. This study assessed the previously unknown prevalence of periodontal disease among a sample of Gullah African Americans with diabetes and investigated the association between diabetes control and the presence of periodontal disease. METHODS: Two hundred thirty-five Gullah African Americans with type 2 diabetes were included. Diabetes control was assessed by percentage of glycosylated hemoglobin (HbA1c) and divided into three categories: well controlled, <7%; moderately controlled, 7% to 8.5%; and poorly controlled, >8.5%. Participants were categorized as healthy (no clinical attachment loss [AL] or bleeding on probing) or as having early periodontitis (clinical AL > or =1 mm in at least two teeth), moderate periodontitis (three sites with clinical AL > or =4 mm and at least two sites with probing depth [PD] > or =3 mm), or severe periodontitis (clinical AL > or =6 mm in at least two teeth and PD > or =5 mm in at least one site). Observed prevalences of periodontitis were compared to rates reported for the National Health and Nutrition Examination Survey (NHANES) studies. RESULTS: All subjects had evidence of periodontal disease: 70.6% had moderate periodontitis and 28.5% had severe disease. Diabetes control was not associated with periodontal disease. The periodontal disease proportions were significantly higher than the reported national prevalence of 10.6% among African Americans without diabetes. CONCLUSION: Our sample of Gullah African Americans with type 2 diabetes exhibited a higher prevalence of periodontal disease compared to African Americans, with and without diabetes, as reported in NHANES III and NHANES 1999-2000.

Results from the Periodontitis and Vascular Events (PAVE) Study: a pilot multicentered, randomized, controlled trial to study effects of periodontal therapy in a secondary prevention model of cardiovascular disease.

BACKGROUND: In the Periodontitis and Vascular Events (PAVE) pilot study, periodontal therapy was provided as an intervention in a secondary cardiac event prevention model through five coordinated cardiac-dental centers. METHODS: Subjects were randomized to either community care or protocol provided scaling and root planing to evaluate effects on periodontal status and systemic levels of high-sensitivity C-reactive protein (hs-CRP). RESULTS: After 6 months, there was a significant reduction in mean probing depth and extent of 4- or 5-mm pockets. However, there were no significant differences in attachment levels, bleeding upon probing, or extent of subgingival calculus comparing subjects assigned to protocol therapy (n = 151) to those assigned to community care (n = 152). Using intent-to-treat analyses, there was no significant effect on serum hs-CRP levels at 6 months. However, 48% of the subjects randomized to community care received preventive or periodontal treatments. Secondary analyses demonstrated that consideration of any preventive or periodontal care (i.e., any treatment) compared to no treatment showed a significant reduction in the percentage of people with elevated hs-CRP (values >3 mg/l) at 6 months. However, obesity nullified the periodontal treatment effects on hs-CRP reduction. The adjusted odds ratio for hs-CRP levels >3 mg/l at 6 months for any treatment versus no treatment among non-obese individuals was 0.26 (95% confidence interval: 0.09 to 0.72), adjusting for smoking, marital status, and gender. CONCLUSION: This pilot study demonstrated the critical role of considering obesity as well as rigorous preventive and periodontal care in trials designed to reduce cardiovascular risk.

Costs and Complications: Delayed Gastric Emptying after Pancreaticoduodenectomy.

Postoperative delayed gastric emptying (DGE) is a very common complication after a pancreaticoduodenectomy (PD). This along with other complications can lead to increased health-care costs. This study investigates the costs and length of stay (LOS) associated with these. A retrospective study of 131 patients undergoing PD between 2000 and 2016 at Loma Linda University Health was performed. Chi-squared test was used to determine statistically significant differences between patients with and without DGE (according to the definition of the International Study Group of Pancreatic Surgery). Multiple logistic and linear regression analyses were performed to obtain adjusted odds ratios for variables of interest in association with DGE and relationship to LOS. Of 150 patients undergoing PD, 131 patients with tumors were analyzed. The overall incidence of DGE was 56 per cent. No pre- or postoperative factors were associated with increased risk of DGE. The median LOS for patients with DGE was 15 days versus 9 days for patients without DGE. Patients with DGE added $21,198 to the overall cost of hospitalization. Fourteen patients (10.7%) were readmitted, of whom 11 were because of DGE. Further studies assessing the utility of intraoperative G-tube placement in decreasing hospital costs and readmissions are needed.

The Periodontitis and Vascular Events (PAVE) pilot study: recruitment, retention, and community care controls.

BACKGROUND: Population-based clinical and laboratory studies have reported findings providing support for a possible relationship between periodontal disease and cardiovascular disease. The Periodontitis and Vascular Events (PAVE) pilot study was conducted to investigate the feasibility of a randomized secondary prevention trial to test whether treatment of periodontal disease reduces the risk for cardiovascular disease. METHODS: Five clinical centers recruited participants who had documented coronary heart disease and met study criteria for periodontal disease. Eligible participants were randomized to receive periodontal therapy provided by the study or community dental care. Follow-up telephone calls and clinic visits were planned to alternate at 3-month intervals after randomization, with all participants followed until at least the 6-month clinic visit. Participants were followed for adverse events and periodontal and cardiovascular outcomes. RESULTS: A total of 303 participants were randomized. Recruitment that involved active participation of a cardiologist with responsibility for the patients worked best among the strategies used. Of those who had not withdrawn, 93% completed the 6-month contact. During follow-up, 11% of the 152 subjects in the community dental care group reported receiving periodontal therapy outside of the study. CONCLUSIONS: If appropriate recruitment strategies are used, this pilot study demonstrated that it is feasible to conduct a secondary prevention trial of periodontal therapy in patients who have had coronary heart disease. If a community dental care group is used, sample size estimation needs to take into account that a non-trivial proportion of participants in this group may receive periodontal therapy outside of the study.

The Periodontitis and Vascular Events (PAVE) pilot study: adverse events.

BACKGROUND: During the last 15 years, a substantial number of population-based, clinical, laboratory, and animal studies have been published that reported findings on the relationship between periodontal disease and cardiovascular disease. The Periodontitis and Vascular Events (PAVE) pilot study was conducted to investigate the feasibility of a randomized secondary prevention trial to test whether treatment of periodontal disease reduces the risk for cardiovascular disease. This article describes the occurrence of adverse events during the pilot study. METHODS: The PAVE pilot study was a multicenter, randomized trial comparing periodontal therapy to community dental care. Baseline and follow-up clinic visits included a periodontal examination; blood, subgingival plaque, and crevicular fluid specimen collection; and medical and dental histories. Telephone follow-up contacts were scheduled to occur 3 months after randomization and every 6 months thereafter to assess adverse events or endpoints. RESULTS: Cardiovascular adverse events occurred with similar frequency (23 versus 24 [P = 0.85] in the community control and the treatment groups, respectively). There were 15 serious adverse events (SAEs) with a non-significantly higher percentage occurring in the community care group (6.6% versus 3.3%; P = 0.19). A time-to-event analysis of patterns of SAEs indicated that subjects in the periodontal therapy group tended to be less likely to experience an SAE over the entire 25 months of the study. CONCLUSION: For those individuals who remained in the study, it appears that provision of periodontal scaling and root planing treatment to individuals with heart disease resulted in a similar pattern of adverse events as seen in the community care group, which also received some treatment.

Validity of self-reported measures for surveillance of periodontal disease in two western New York population-based studies.

BACKGROUND: Public health and other population-based studies often depend on participants' self-reported disease status to assess prevalence, incidence, and disease trends. We sought to assess the feasibility of self-reported periodontal disease measures using dental history questions combined with demographic and medical history to predict periodontal disease. METHODS: We evaluated results from two separate population-based studies carried out at the University at Buffalo, Buffalo, New York, i.e., the "Periodontal Infection and Risk for Myocardial Infarction Study," a study of 1,578 adults assessing the association between periodontal disease and myocardial infarction and the "Periodontal Disease Research Center" (the Erie County Study), an epidemiologic risk assessment study of 1,438 adults. In each study, an extensive list of oral health questions was asked, and a comprehensive medical history, blood analysis using chemistry and hematology tests, and demographic data were collected. RESULTS: Using a predefined measure of severity of periodontal disease, we compared patients with severe disease to all others (i.e., those with moderate and no or mild disease). We examined areas under the curve (AUC) of the receiver operating curve to determine the best models, adding one, two, or three dental variables in all possible combinations. The AUC maximized at 0.76, and the combined sensitivity and specificity maximized at 142 and were comparable in both studies. CONCLUSIONS: Self-reported measures of periodontal disease are moderately predictive of clinical attachment loss. The demographic variables of age, race, smoking, gender, and diabetes mellitus accounted for much of the predictive power for self-reported periodontal disease; however, increases in sensitivity and specificity in the C statistics occurred when questions, including "Gum surgery in the past?," "Sore gums in the past?," "Scaling in the past?," "Bleeding gums now?," "Periodontal surgery in the past 2 years?," and "Chewing satisfaction?," were added to the model.

Mechanical therapy with adjunctive minocycline microspheres reduces red-complex bacteria in smokers.

BACKGROUND: Smoking increases the risk for periodontal disease and reduces the healing response. We examined the antimicrobial and clinical effects of scaling and root planing (SRP) with and without minocycline HCl 1 mg microspheres (MM) relative to smoking status in subjects with periodontitis. METHODS: A total of 127 subjects (46 never smokers, 44 former smokers, and 37 current smokers) with moderate to advanced periodontitis were randomized to receive MM + SRP (N = 62) or SRP alone (N = 65). Subgingival plaque samples collected at baseline and day 30 were examined for the presence of 40 periodontal bacteria by DNA probe analysis. RESULTS: MM + SRP reduced red-complex bacteria (RCB) numbers and proportions to a greater extent than SRP alone, irrespective of smoking status. RCB numbers were not reduced by SRP in current smokers. The difference in the reduction in numbers of RCB by SRP relative to MM + SRP in current smokers was statistically significant (P <0.05). Numbers and proportions of orange complex bacteria (OCB) were reduced in all groups treated with MM + SRP. Proportions of OCB increased in current smokers treated with SRP alone. In current smokers, MM + SRP significantly reduced probing depth (PD), increased clinical attachment level (CAL), and reduced bleeding on probing (BOP) to a greater extent than SRP alone (P <0.05). CONCLUSIONS: SRP alone was ineffective at reducing numbers or proportions of RCB or OCB in current smokers, whereas MM + SRP significantly reduced both. MM + SRP also improved PD, BOP, and CAL to a greater extent than SRP alone independent of smoking status.

Minocycline HCl microspheres reduce red-complex bacteria in periodontal disease therapy.

BACKGROUND: The objective of this trial was to measure the antimicrobial effects of a minocycline HCl microsphere (MM) local drug-delivery system when used as an adjunct to scaling and root planing (SRP). DNA probe analysis for 40 bacteria was used to evaluate the oral bacteria of 127 subjects with moderate to advanced chronic periodontitis. METHODS: Subjects were randomly assigned to either SRP alone (N = 65) or MM + SRP (N = 62). The primary endpoints of this study were changes in numbers and proportions of the red-complex bacteria (RCB) and the sum of Porphyromonas gingivalis, Tannerella forsythia (formally T. forsythensis), and Treponema denticola relative to 40 oral bacteria at each test site from baseline to day 30. Numbers of RCB from the five test sites were averaged to provide a value for each subject. RESULTS: MM + SRP reduced the proportion of RCB by 6.49% and the numbers by 9.4 x 10(5). The reduction in RCB proportions and numbers by SRP alone (5.03% and 5.1 x 10(5), respectively) was significantly less. In addition, MM + SRP reduced probing depth by 1.38 mm (compared to 1.01 mm by SRP alone), bleeding on probing was reduced by 25.2% (compared to 13.8% by SRP alone), and a clinical attachment level gain of 1.16 mm (compared to 0.80 mm by SRP alone) was achieved. CONCLUSION: These observations support the hypothesis that RCBs are responsible for periodontal disease and that local antimicrobial therapy using MM + SRP effectively reduces numbers of RCBs and their proportions to a greater extent than SRP alone.

Supragingival plaque may modify the effects of subgingival bacteria on attachment loss.

BACKGROUND: Bacterial interactions in response to local and systemic factors may explain important features of the pathogenesis of periodontal disease. This study evaluates the role of supragingival plaque level on the relationship between subgingival microorganisms and the risk of attachment loss. METHODS: The study population consisted of 386 white women aged 45 years and older who had at least seven teeth. Subgingival plaque samples were taken from the mesio-buccal surface of six maxillary and six mandibular teeth using paper point technique. The samples were pooled, and immunofluorescence microscopy was performed to identify the following target microorganisms: Actinobacillus actinomycetemcomitans (Aa), Tannerella forsythensis (Tf), Campylobacter rectus (Cr), Prevotella intermedia (Pi), Capnocytophaga species (Cs), Porphyromonas gingivalis (Pg), Eubacterium saburreum (Es), and Fusobacterium nucleatum (Fn). The presence or absence of supragingival plaque and clinical attachment loss (CAL) were assessed at the same 12 sites where subgingival plaque samples were taken. The association of each microorganism with CAL was tested using multiple logistic regressions controlling for age, smoking status, and diabetes. Odds ratios (OR) and their 95% confidence intervals (CI) were calculated. RESULTS: At low supragingival plaque levels, only the presence of Pg was significantly associated with CAL (OR: 6.41, 95% CI: 1.30 to 31.70); all remaining microorganisms were also associated with increased but non-significant risk of CAL. At high supragingival plaque levels, the presence of Tf (OR: 2.40, 95% CI: 1.42 to 4.04) and Pg (OR: 3.71, 95% CI: 1.63 to 8.42) was significantly associated with increased risk of attachment loss. By contrast, the presence of Cs (OR: 0.55, 95% CI: 0.30 to 1.01) and Es (OR: 0.35, 95% CI: 0.15 to 0.82) was associated with decreased risk of attachment loss. Fn, Pi, and Cr were not significantly associated with CAL at either low or high supragingival plaque levels. CONCLUSIONS: This study suggests that the association of certain subgingival microorganisms with CAL changes in relation to supragingival plaque levels in older adult women. It also suggests that the overall effect of dental plaque is a function of the balance between pathogenic and other microorganisms that colonize this environment. Therefore, all microorganisms in the biofilm, including those with no apparent association with overt disease and those with negative associations, may play roles in the pathogenesis of periodontal diseases.

Study design for calibration of clinical examiners measuring periodontal parameters.

BACKGROUND: We present an approach to examiner calibration study design where the number of calibration subjects is based on a specified margin of error (half-width of the 95% confidence interval [CI]) of the percentage of agreement (exact and within 1 mm) for both intra- and interexaminer reliability assessments. METHODS: An experienced standard examiner (S) trained three dental hygienists (A, B, and C) in correct procedures for obtaining a variety of periodontal measures. Duplicate measurements of probing depth (PD [mm]) and the free gingival margin to the cemento-enamel junction (CEJ-GM [mm]) were obtained in a pilot study to design a formal examiner calibration study, where sample sizes were adjusted for the effects of within-subject clustering of binary indices of agreement. RESULTS: Within-subject clustering of agreement indices resulted in an approximate four-fold increase in the variance of the estimates of percentage of agreement with the standard. PD and CEJ-GM percentage of exact agreement measurements (95% CI) for each examiner-standard pair, respectively, were as follows: AS=55% (48%, 61%) and 70% (62%, 78%); BS=52% (45%, 59%) and 73% (63%, 82%); and CS=55% (50%, 61%) and 72% (65%, 79%). The corresponding 95% CIs unadjusted for the effects of clustering underestimated the margin of error associated with the estimates of exact agreement by as much as 57% for PD and 68% for CEJ-GM. CONCLUSION: Failure to account for dependence among site-level agreement indices results in a false sense of precision in the resulting reliability estimates and can lead to faulty inference.