An overview of dental implant biomaterials

Regardless of stomatognathic system atrophy, illness, or injury, modern dentistry endeavours to restore the patient to normal shape, function, comfort, aesthetics, speech, and health. Predictable success is now a reality for the rehabilitation of many difficult conditions as a result of ongoing research in treatment planning, implant designs, materials, and methodologies. The medical fields have long placed a strong emphasis on the biocompatibility properties of synthetic materials (biomaterials) used to replace biological tissues. In addition, implant biomaterials must be suitable in terms of mechanical strength, biocompatibility, and structural biostability in order to function at their best. In this article, the various implant biomaterials with their properties and applicability to implant dentistry are discussed

08. IMSA Oral Histories

https://digitalcommons.imsa.edu/class_of_1995/1006/thumbnail.jp

Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer

Background Selective cyclooxygenase inhibitors may retard the progression of cancer, but they have enhanced thrombotic potential. We report on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer. Methods All serious adverse events that were cardiovascular thrombotic events were reviewed in 2434 patients with stage II or III colorectal cancer participating in a randomized, placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated prematurely owing to worldwide withdrawal of rofecoxib. To examine possible persistent risks, we examined cardiovascular thrombotic events reported up to 24 months after the trial was closed. Results The median duration of active treatment was 7.4 months. The 1167 patients receiving rofecoxib and the 1160 patients receiving placebo were well matched, with a median follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months (27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events, 16 occurred in the rofecoxib group during or within 14 days after the treatment period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards model; 95% confidence interval [CI], 1.03 to 6.86; P = 0.04). Analysis of the Antiplatelet Trialists’ Collaboration end point (the combined incidence of death from cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction; and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative risk of 1.60 (95% CI, 0.57 to 4.51; P = 0.37). Fourteen more cardiovascular thrombotic events, six in the rofecoxib group, were reported within the 2 years after trial closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94; P = 0.24). Four patients in the rofecoxib group and two in the placebo group died from thrombotic causes during or within 14 days after the treatment period, and during the follow-up period, one patient in the rofecoxib group and five patients in the placebo group died from cardiovascular causes. Conclusions Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months’ duration. (Current Controlled Trials number, ISRCTN98278138.

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

David Kinney, Amy (Timm) Kinney, Ravi Duvvuri, and Christian Nøkkentved

Three members of the class of 1995 look back on their IMSA experiences twenty years after they graduated. David Kinney says he applied to IMSA because he wanted to get out of the house. Amy (Timm) Kinney had grown up in the Chicago area before her family moved to southern Illinois, where she didn\u27t feel she fit in and she wasn\u27t challenged enough academically. Ravi Duvvuri grew up in central Illinois and likewise didn\u27t feel challenged enough at home. Duvvuri heard about IMSA from a math teacher. Amy Kinney had participated in a summer camp. A grade school science teacher recommended that David Kinney apply to IMSA. On arrival, David Kinney recalls finding the building layout very confusing. Amy Kinney recalls the diversity of the student population, and also feeling like she fit in among other smart, motivated students. Duvvuri remembers meeting the other people in his dorm and everyone trying to negotiate their newfound independence, as well as their new classmates. Amy Kinney recalls how important roommates and wingmates were for new friendships, because when they came to IMSA they did not have easy ways to keep in touch with friends at home, only letters or phone calls. She reflects on how different it is for students now. Because more students stayed at school on the weekends then, they had more opportunities to learn to live independently and live together. Duvvuri reflects on the formative experience of living at IMSA and the friendships it fostered. In terms of classes, they all remember the novelty of problem-based learning and ways it was present throughout the curriculum, from science and math classes to history. Duvvuri talks about Dr. Hollister\u27s history class where he wanted the students to think. At first they treated it as free time, until he got his first ever C on a report card with a note that he needed to try harder . After that he approached his own learning differently. He also remembers liking his physics and English classes, as well as a scientific writing class he had junior year. Amy Kinney liked being able to choose electives her senior year, particularly Modern Irish Writing and Ecology, particularly in the latter case where they got to go out in the field. She also stayed active playing in band and orchestra. David Kinney\u27s favorite classes were all in the humanities, though he also fondly remembers math teachers who took the time to get to know him and help him. Duvvuri participated in the mentorship (now SIR) program his senior year, working at Argonne National Laboratory, and talks about the work he did there and participating in Presentation Day. Neither David nor Amy Kinney participated in the mentorship program, though David Kinney recalls a formative moment when he visited a lab at Northwestern. A researcher there described a eureka moment when he knew what he wanted to study, and on the bus ride back Kinney realized he felt the same way about computer programming. Though none of the interviewees participated in international student trips while at IMSA, the languages they learned were useful, particularly the immersive way they were taught. Amy Kinney studied Spanish at IMSA and in college and ended up teaching bilingual grade school classes. David Kinney took Latin, while Duvvuri took French. In terms of what they took away from their IMSA experience, Amy and David Kinney met and started dating their sophomore year, and while they went their separate ways in college, they ended up getting married ten years later. Duration: 33:33https://digitalcommons.imsa.edu/oral_histories/1013/thumbnail.jp

Nonsteroidal Anti-inflammatory Drugs for Chemoprevention in Patients With Familial Adenomatous Polyposis: A Systematic Review and Meta-Analysis

Background and Aims: Published literature shows mixed reports of the benefits of nonsteroidal anti-inflammatory drugs (NSAIDs) on reducing colorectal polyps in patients with familial adenomatous polyposis (FAP). We conducted a systematic review and performed a meta-analysis to assess the impact of NSAIDs on colorectal polyp burden in patients with FAP. Methods: We searched PubMed, EMBASE, and Cochrane for randomized controlled trials (RCTs) comparing the effect of NSAIDs vs placebo on the percent change in polyp number and polyp size in patients with FAP. Mean differences between the 2 study arms were pooled using RevMan. The risk of bias (RoB) was assessed using the Cochrane Risk of Bias tool for RCTs, and certainty in the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Results: The search strategy identified 1021 studies, out of which we included 8 RCTs with a total of 279 patients. Treatment for 6.4 ± 2.2 months with NSAIDs reduced polyp numbers by −17.4% (95% confidence interval −26.41%, −8.29%) (low certainty [I2 89%] due to imprecision and issues with RoB) and polyp size by −15.9% (95% confidence interval −24.98%, −6.73%) (very low certainty (I2 84%) due to imprecision, inconsistency, and issues with RoB). The most common gastrointestinal adverse events reported were stomatitis, diarrhea, and abdominal pain. Side effects leading to drug discontinuation were gastroenteritis and drug allergy. Conclusion: Short-term use of NSAIDs reduced polyp number and polyp size but with low to very low certainty of evidence. Further large multicenter studies are needed to further explore NSAIDs as a chemopreventive measure in patients with FAP