Ipilimumab and nivolumab for recurrent neuroendocrine cervical carcinoma.

Neuroendocrine carcinoma of the cervix is a rare subtype of cervical cancer with a poor prognosis. Primary treatment of this disease involves a combination of surgery, chemotherapy, and radiation. The majority of patients will experience disease recurrence, for which there exist no treatment guidelines. Because of histologic similarities, small cell lung cancer has often informed management of extrapulmonary neuroendocrine carcinomas. Immunotherapy regimens, including a combination of ipilimumab and nivolumab, have been shown to have activity in small cell lung cancer. In this report, we present the cases of 3 patients with recurrent neuroendocrine carcinoma of the cervix who experienced durable response to a combination of ipilimumab and nivolumab.

Surgery and Platinum/Etoposide-Based Chemotherapy for the Treatment of Epithelioid Trophoblastic Tumor.

OBJECTIVE: Epithelioid trophoblastic tumor (ETT) is a rare variant of gestational trophoblastic neoplasia that develops from chorionic-type intermediate trophoblast, simulates carcinoma, presents years after a pregnancy event, is associated with low or normal human chorionic gonadotropin levels, and is relatively resistant to chemotherapy. Our aim was to identify the role of surgery in combination with platinum/etoposide-based chemotherapy in the management of both localized and metastatic ETT. METHODS: A retrospective review was performed of women with ETT treated at a gestational trophoblastic disease center from 2010 to 2016. RESULTS: Five patients were identified who had complete records. Mean age was 38.0 years. Three women presented with abnormal uterine bleeding, 2 women presented with respiratory complaints, and 1 woman was asymptomatic. Two women had no identifiable antecedent pregnancy, 2 women had spontaneous abortions, and 1 woman had a normal term delivery before diagnosis. Four (80%) of 5 women had metastatic pulmonary disease. All 5 women underwent hysterectomy, and 3 women had resection of metastatic pulmonary disease. The 4 women with metastatic disease were also treated with chemotherapy. All 5 women are currently without evidence of disease. CONCLUSIONS: Surgery, including hysterectomy and resection of metastatic disease, is an important component in the treatment of women with ETT. Adjuvant chemotherapy with a platinum/etoposide-containing regimen should be used in women with metastatic disease. All 5 women with ETT in this series were cured using this approach, including the 4 who had metastatic disease.

Diabetes and oral disease: implications for health professionals.

"Diabetes and Oral Disease: Implications for Health Professionals" was a one-day conference convened by the Columbia University College of Dental Medicine, the Columbia University College of Physicians and Surgeons, and the New York Academy of Sciences on May 4, 2011 in New York City. The program included an examination of the bidirectional relationship between oral disease and diabetes and the interprofessional working relationships for the care of people who have diabetes. The overall goal of the conference was to promote discussion among the healthcare professions who treat people with diabetes, encourage improved communication and collaboration among them, and, ultimately, improve patient management of the oral and overall effects of diabetes. Attracting over 150 members of the medical and dental professions from eight different countries, the conference included speakers from academia and government and was divided into four sessions. This report summarizes the scientific presentations of the event.

Oral microbial biofilm stimulation of epithelial cell responses.

Oral bacterial biofilms trigger chronic inflammatory responses in the host that can result in the tissue destructive events of periodontitis. However, the characteristics of the capacity of specific host cell types to respond to these biofilms remain ill-defined. This report describes the use of a novel model of bacterial biofilms to stimulate oral epithelial cells and profile select cytokines and chemokines that contribute to the local inflammatory environment in the periodontium. Monoinfection biofilms were developed with Streptococcus sanguinis, Streptococcus oralis, Streptococcus gordonii, Actinomyces naeslundii, Fusobacterium nucleatum, and Porphyromonas gingivalis on rigid gas-permeable contact lenses. Biofilms, as well as planktonic cultures of these same bacterial species, were incubated under anaerobic conditions with a human oral epithelial cell line, OKF4, for up to 24h. Gro-1α, IL1α, IL-6, IL-8, TGFα, Fractalkine, MIP-1α, and IP-10 were shown to be produced in response to a range of the planktonic or biofilm forms of these species. P. gingivalis biofilms significantly inhibited the production of all of these cytokines and chemokines, except MIP-1α. Generally, the biofilms of all species inhibited Gro-1α, TGFα, and Fractalkine production, while F. nucleatum biofilms stimulated significant increases in IL-1α, IL-6, IL-8, and IP-10. A. naeslundii biofilms induced elevated levels of IL-6, IL-8 and IP-10. The oral streptococcal species in biofilms or planktonic forms were poor stimulants for any of these mediators from the epithelial cells. The results of these studies demonstrate that oral bacteria in biofilms elicit a substantially different profile of responses compared to planktonic bacteria of the same species. Moreover, certain oral species are highly stimulatory when in biofilms and interact with host cell receptors to trigger pathways of responses that appear quite divergent from individual bacteria.

U.S. dental school applicants and enrollees, 2009 entering class.

Over the past two decades, interest in dentistry in the United States has shown a steady period of growth. There were 12,210 individuals who applied to the 2009 entering class of U.S. dental schools. The number of first-time enrollees was 4,871, the highest figure since 1990. Men continue to comprise the majority of applicants and enrollees; however, the percentages of women continue to increase. While the 2009 underrepresented minority applicants comprised 12 percent of both the applicant and first-time enrollee pools, the percentage of underrepresented minority enrollees of underrepresented minority applicants decreased from 2008. Seventy-one percent of enrollees earned a baccalaureate degree in biological science or chemistry/physical science. Regardless of major fields of study, the percent rates of enrollment generally exceeded 32 percent.

Novel model for multispecies biofilms that uses rigid gas-permeable lenses.

Oral biofilms comprise complex multispecies consortia aided by specific inter- and intraspecies interactions occurring among commensals and pathogenic bacterial species. Oral biofilms are primary initiating factors of periodontal disease, although complex multifactorial biological influences, including host cell responses, contribute to the individual outcome of the disease. To provide a system to study initial stages of interaction between oral biofilms and the host cells that contribute to the disease process, we developed a novel in vitro model system to grow biofilms on rigid gas-permeable contact lenses (RGPLs), which enable oxygen to permeate through the lens material. Bacterial species belonging to early- and late-colonizing groups were successfully established as single- or three-species biofilms, with each group comprising Streptococcus gordonii, Streptococcus oralis, and Streptococcus sanguinis; S. gordonii, Actinomyces naeslundii, and Fusobacterium nucleatum; or S. gordonii, F. nucleatum, and Porphyromonas gingivalis. Quantification of biofilm numbers by quantitative PCR (qPCR) revealed substantial differences in the magnitude of bacterial numbers in single-species and multispecies biofilms. We evaluated cell-permeable conventional nucleic acid stains acridine orange, hexidium iodide, and Hoechst 33258 and novel SYTO red, blue, and green fluorochromes for their effect on bacterial viability and fluorescence yield to allow visualization of the aggregates of individual bacterial species by confocal laser scanning microscopy (CLSM). Substantial differences in the quantity and distribution of the species in the multispecies biofilms were identified. The specific features of these biofilms may help us better understand the role of various bacteria in local challenge of oral tissues.

Guidinq change one school at a time.

Liaison teams have been developed in order to ensure that national initiatives identified in the American Dental Education Association's Commission on Change and Innovation (ADEA CCI) are implemented at the level of individual schools. Teams of four faculty members each have been identified at 43 United States and Canadian schools. These teams receive training at ADEA annual meeting and at summer institutes. Representative projects from three schools are described.

What the ADEA CCI series of articles means to me: reflections of a mid-career dental faculty member.

In this reflection article, Dr. Karen Novak, a mid-career faculty member at a U.S. dental school, identifies important messages and insights she gained from a series of twenty-one articles about the future of dental education published in the Journal of Dental Education from October 2005 to February 2009. This article addresses four questions: 1) What influence have these articles had on an academic dentist's perspectives about her role and priorities as a dental school faculty member and her own career plans and future directions? 2) What are the key messages in these articles for other dental educators who are at similar places in their careers? 3) What additional topics concerning the future of academic dentistry should be covered in future articles? and 4) What issues and priorities should receive the most attention from academic dentistry in the next decade? The American Dental Education Association's Commission on Change and Innovation in Dental Education (ADEA CCI) was established to provide a mechanism for stakeholders in academic dentistry to meet and consider future directions in the education of the nation's dental workforce. Along with ADEA, these stakeholders included dental schools, the American Dental Association (ADA) Board of Trustees, the Commission on Dental Accreditation (CODA), the ADA Council on Dental Education and Licensure (CDEL), the Joint Commission on National Dental Examinations (JCNDE), the dental licensure community, the ADA Foundation, and advanced dental education programs. The ADEA CCI was created to build consensus within the dental community for innovative changes in the education of general dentists. One outcome of this process was a series of articles intended to raise awareness and stimulate dialogue about issues and forces shaping the future of dental education. Collectively, this series of articles is known as the Perspectives and Reflections in Dental Education (PRIDE) series to acknowledge the commitment of the academic dental community to reflect on current practices and future directions and also to represent the pride of dental school faculty members in their educational responsibilities and accomplishments.

Effects of caloric restriction on inflammatory periodontal disease.

OBJECTIVE: Dietary caloric restriction (CR) has been found to reduce systemic markers of inflammation and may attenuate the effects of chronic inflammatory conditions. The purpose of this study was to examine the effects of long-term CR on naturally occurring chronic inflammatory periodontal disease in a nonhuman primate model. METHODS: The effects of long-term CR on extent and severity of naturally occurring chronic periodontal disease, local inflammatory and immune responses, and periodontal microbiology, were evaluated in a cohort of 81 (35 female and 46 male; 13-40 y of age) rhesus monkeys (Macaca mulatta) with no previous exposure to routine oral hygiene. CR monkeys had been subjected to 30% CR for 13-17 y relative to control-fed (CON) animals starting at 3-5 y of age. RESULTS: Same sex CR and CON monkeys exhibited similar levels of plaque, calculus, and bleeding on probing. Among CON animals, males showed significantly greater periodontal breakdown, as reflected by higher mean clinical attachment level and periodontal probing depth scores, than females. CR males exhibited significantly less periodontal pocketing, lower IgG antibody response, and lower IL-8 and ss-glucuronidase levels compared to CON males, whereas CR females showed a lower IgG antibody response but comparable clinical parameters and inflammatory marker levels relative to CON females. Long-term CR had no demonstrable effect on the periodontal microbiota. CONCLUSION: Males demonstrated greater risk for naturally occurring periodontal disease than females. Long-term CR may differentially reduce the production of local inflammatory mediators and risk for inflammatory periodontal disease among males but not females.

Periodontal bacterial profiles in pregnant women: response to treatment and associations with birth outcomes in the obstetrics and periodontal therapy (OPT) study.

BACKGROUND: A recent clinical trial (Obstetrics and Periodontal Therapy [OPT] Study) demonstrated that periodontal therapy during pregnancy improved periodontal outcomes but failed to impact preterm birth. The present study evaluated seven target bacteria, Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, Treponema denticola, Tannerella forsythia (previously T. forsythensis), Prevotella intermedia, Campylobacter rectus, and Fusobacterium nucleatum, in subgingival dental plaque of pregnant women in the OPT Study and their association with birth outcomes. METHODS: Pregnant women were randomly assigned to receive periodontal treatment before 21 weeks' gestation or after delivery. Subgingival plaque was sampled at baseline (13 to 16 weeks; 6 days of gestation) and at 29 to 32 weeks. We analyzed subgingival plaque samples from women who experienced fetal loss, delivered a live preterm infant (preterm women), or delivered a full-term infant (full-term women). Samples were analyzed using quantitative polymerase chain reaction. Associations between preterm birth and bacterial counts and percentages were tested using multiple linear regression. RESULTS: No significant differences were observed at baseline between preterm and full-term women for any measured bacterial species or group of species, after accounting for multiple comparisons. Changes in bacterial counts and proportions during pregnancy also were not associated with birth outcomes. In full-term and preterm women, periodontal therapy significantly reduced (P <0.01) counts of all target species except for A. actinomycetemcomitans. CONCLUSIONS: In pregnant women with periodontitis, non-surgical periodontal therapy significantly reduced levels of periodontal pathogens. Baseline levels of selected periodontal pathogens or changes in these bacteria resulting from therapy were not associated with preterm birth.

The effects of a calorie-reduced diet on periodontal inflammation and disease in a non-human primate model.

BACKGROUND: Low-calorie diets are commonplace for reducing body weight. However, no information is available on the effects of a reduced-calorie diet on periodontal inflammation and disease. The purpose of this study was to evaluate the clinical effects of a long-term calorie-restriction (CR) diet on periodontitis in an animal model of periodontitis. METHODS: Periodontitis was induced in 55 young, healthy, adult rhesus monkeys (Macaca mulatta) by tying 2.0 silk ligatures at the gingival margins of maxillary premolar/molar teeth. Animals on a CR diet (30% CR; N = 23) were compared to ad libitum diet controls (N = 32). Clinical measures, including the plaque index (PI), probing depth (PD), clinical attachment level (CAL), modified gingival index (GI), and bleeding on probing (BOP) were recorded at baseline and 1, 2, and 3 months after ligature placement. RESULTS: Significant effects of CR were observed on the development of inflammation and the progression of periodontal destruction in this model. Compared to controls, CR resulted in a significant reduction in ligature-induced GI (P <0.0001), BOP (P <0.0015), PD (P <0.0016), and CAL (P <0.0038). Periodontal destruction, as measured by CAL, progressed significantly more slowly in the CR animals than in the controls (P <0.001). CONCLUSIONS: These clinical findings are consistent with available evidence that CR has anti-inflammatory effects. Moreover, these experimental findings are the first observations, to the best of our knowledge, that CR dampens the inflammatory response and reduces active periodontal breakdown associated with an acute microbial challenge.

Should we treat periodontal disease during gestation to improve pregnancy outcomes?

Until recently many physicians in the United States including obstetrician gynecologists have been relatively unconcerned with oral health. During most physical examinations, the oral cavity is given only a rudimentary examination. With the recognition of the oral-systemic health care link, physicians have been keenly interested in the findings from their dental colleagues in periodontal medicine which have convincingly linked periodontal disease with such diverse systemic health complications as aging, Alzheimer disease, cardiovascular disease, diabetes, and also pregnancy complications including low birth weight, preterm delivery, preeclampsia, and early pregnancy loss. Intervention trials designed to improve oral health during pregnancy have proven to be safe; however, the outcomes have been inconsistent. Further studies will be required to determine the nature of the association and the optimal timing and efficacy of intervention.

Efficacy of the de novo-derived antimicrobial peptide WLBU2 against oral bacteria.

The efficacy of a novel synthetic antimicrobial peptide (WLBU2) was evaluated against three oral microorganisms (grown planktonically): Streptococcus gordonii, Fusobacterium nucleatum, and Porphyromonas gingivalis. WLBU2 killed all three species, with F. nucleatum being the most susceptible. WLBU2 also reduced the bacterial burden of S. gordonii and F. nucleatum biofilms.

Periodontitis and gestational diabetes mellitus: exploring the link in NHANES III.

OBJECTIVES: The authors hypothesized that women with a history of gestational diabetes mellitus (GDM) during pregnancy would exhibit more severe periodontal disease than controls without a history of diabetes during pregnancy. METHODS: Data from NHANES Ill provided information for 4,244 women ages 20-59. One hundred and thirteen had a history of GDM (GDM+), while 4,131 had no history of diabetes before or during their pregnancies (GDM-). Women were further classified by the presence or absence of diabetes mellitus (DM+ or DM-) at the time of their NHANES Ill examination. Periodontal disease (PD) was defined as one or more teeth with one or more sites with probing depth > or = 4mm, loss of attachment > or = 2mm, and bleeding on probing. RESULTS: The PD prevalence among women who were GDM+DM- was 9.0% and 4.8% for those who were GDM-DM-. PD prevalence for women who were GDM+DM+ was 30.5% and 11.6% for GDM-DM+ subjects, respectively. A logistic regression model, controlling for age, calculus, smoking, and income estimated women who were GDM+DM+ were more likely to have periodontal disease than women who were GDM-DM- and women who were GDM-DM+. The GDM+DM- group also tended to be more likely to have PD than the GDM-DM- and GDM-DM+ groups. However, the odds ratios were not statistically significant. CONCLUSIONS: These results support the hypothesis that women with gestational diabetes mellitus (GDM) during pregnancy may be at greater risk for developing more severe periodontal disease than pregnant women without GDM.

Factors associated with comprehensive dental care following an initial emergency dental visit.

PURPOSE: The purpose of this study was to characterize the patient population utilization of a dental home as grouped by: (1) age; (2) sex; and (3) payment method. METHODS: A retrospective chart review of 1,020 patients, who initially presented for an emergency visit, was performed. From the original data pool, 2 groups were delineated: (1) those patients who returned for comprehensive dental care; and (2) those who did not return for comprehensive dental care. RESULTS: Patients with private dental insurance or Medicaid dental benefits were statistically more likely to return for comprehensive oral health care than those with no form of dental insurance. Younger patients (< or =3 years of age) were least likely to return for comprehensive dental care. CONCLUSIONS: Socioeconomic factors play a crucial role in care-seeking behaviors. These obstacles are often a barrier to preventive and comprehensive oral health care.

Agency nurse assessment for competency.

The goal of this study is to make the agency nurse's performance standards equivalent to that of hospital nurse levels of performance based in hospital staff observation to provide continuity of safe, quality patient care. To attain this goal, the following should be done: (1) develop orientation process that includes module for general orientation; (2) agencies pay for nurse orientation to include 8-hour session and a 4-hour skills assessment; (3) develop flip cards for agency nurses as a resource tool; (4) annual general assessment for hospital employees to be completed by agency nurses; and (5) develop process to document and distribute information to charge nurses about agency nurse competency. Leaders should ensure that the process for identifying and managing are defined and implemented. The intent of this standard is to hold leaders within the healthcare organizations accountable.

Students' perceived importance of diversity exposure and training in dental education.

Intercultural competence is an important component of the doctor-patient relationship in the multicultural climate evolving in the United States. We hypothesized that 1) exposure to racial and ethnic diversity in the student body, faculty, staff, and patient population in dental school and 2) a dental school curriculum that includes presentations on issues concerning racial and ethnic diversity will contribute to students' feeling more competent and confident to enter the multicultural work environment that is rapidly developing in the United States. A Likert-type scale questionnaire was administered to 627 fourth-year dental students enrolled in seven dental schools representing geographically diverse regions of the United States. Of these, 376 questionnaires were returned for a response rate of 60 percent. Results indicated that both the perception of diversity in the school environment and the presentation of diversity-specific content in the curriculum had moderately positive and significant correlations with the students' perception of their competency or ability to serve and work with diverse populations. The respective Pearson correlation coefficients for diversity in the school environment and diversity curriculum were .497 (p<.001) and .459 (p<.001). These results support the hypotheses that diversity exposure and training in the dental school environment are important for dental students entering a multicultural workplace.

A model for assessing the ethical environment in academic dentistry.

Weber's "Institutional Ethics Audit" model was designed as a tool for assessment of an organization's effort to institutionalize ethics into its operations. In this model, the overall ethical environment of an organization is evaluated through an assessment of its 1) ethical cultures, 2) ethics policy, 3) enforcement mechanisms, and 4) ethical training. Assessment of these components allows the organization to be placed along a continuum that spans aethical firms, compliance firms, emerging firms, and integrity firms. This paper presents the conceptual framework for this model. We propose that application of this model to academic institutions, including dental schools, could provide appropriate information to improve the ethical climate of the institution.