Cetuximab continuation after first progression in metastatic colorectal cancer (CAPRI-GOIM): A randomized phase II trial of FOLFOX plus cetuximab versus FOLFOX

Background: Cetuximab plus chemotherapy is a first-line treatment option in metastatic KRAS and NRAS wild-type colorectal cancer (CRC) patients. No data are currently available on continuing anti-epidermal growth factor receptor (EGFR) therapy beyond progression. Patients and methods: We did this open-label, 1:1 randomized phase II trial at 25 hospitals in Italy to evaluate the efficacy of cetuximab plus 5-fluorouracil, folinic acid and oxaliplatin (FOLFOX) as second-line treatment of KRAS exon 2 wild-type metastatic CRC patients treated in first line with 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) plus cetuximab. Patients received FOLFOX plus cetuximab (arm A) or FOLFOX (arm B). Primary end point was progressionfree survival (PFS). Tumour tissues were assessed by next-generation sequencing (NGS). This report is the final analysis. Results: Between 1 February 2010 and 28 September 2014, 153 patients were randomized (74 in arm A and 79 in arm B). Median PFS was 6.4 [95% confidence interval (CI) 4.7-8.0] versus 4.5 months (95% CI 3.3-5.7); [hazard ratio (HR), 0.81; 95% CI 0.58-1.12; P = 0.19], respectively. NGS was performed in 117/153 (76.5%) cases; 66/117 patients (34 in arm A and 32 in arm B) had KRAS, NRAS, BRAF and PIK3CA wild-type tumours. For these patients, PFS was longer in the FOLFOX plus cetuximab arm [median 6.9 (95% CI 5.5-8.2) versus 5.3 months (95% CI 3.7-6.9); HR, 0.56 (95% CI 0.33-0.94); P = 0.025]. There was a trend in better overall survival: median 23.7 [(95% CI 19.4-28.0) versus 19.8 months (95% CI 14.9-24.7); HR, 0.57 (95% CI 0.32-1.02); P = 0.056]. Conclusions: Continuing cetuximab treatment in combination with chemotherapy is of potential therapeutic efficacy in molecularly selected patients and should be validated in randomized phase III trials

Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium::Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions

Periodontal health is defined by absence of clinically detectable inflammation. There is a biological level of immune surveillance that is consistent with clinical gingival health and homeostasis. Clinical gingival health may be found in a periodontium that is intact, i.e. without clinical attachment loss or bone loss, and on a reduced periodontium in either a non-periodontitis patient (e.g. in patients with some form of gingival recession or following crown lengthening surgery) or in a patient with a history of periodontitis who is currently periodontally stable. Clinical gingival health can be restored following treatment of gingivitis and periodontitis. However, the treated and stable periodontitis patient with current gingival health remains at increased risk of recurrent periodontitis, and accordingly, must be closely monitored. Two broad categories of gingival diseases include non-dental plaque biofilm-induced gingival diseases and dental plaque-induced gingivitis. Non-dental plaque biofilm-induced gingival diseases include a variety of conditions that are not caused by plaque and usually do not resolve following plaque removal. Such lesions may be manifestations of a systemic condition or may be localized to the oral cavity. Dental plaque-induced gingivitis has a variety of clinical signs and symptoms, and both local predisposing factors and systemic modifying factors can affect its extent, severity, and progression. Dental plaque-induced gingivitis may arise on an intact periodontium or on a reduced periodontium in either a non-periodontitis patient or in a currently stable "periodontitis patient" i.e. successfully treated, in whom clinical inflammation has been eliminated (or substantially reduced). A periodontitis patient with gingival inflammation remains a periodontitis patient (Figure 1), and comprehensive risk assessment and management are imperative to ensure early prevention and/or treatment of recurrent/progressive periodontitis. Precision dental medicine defines a patient-centered approach to care, and therefore, creates differences in the way in which a "case" of gingival health or gingivitis is defined for clinical practice as opposed to epidemiologically in population prevalence surveys. Thus, case definitions of gingival health and gingivitis are presented for both purposes. While gingival health and gingivitis have many clinical features, case definitions are primarily predicated on presence or absence of bleeding on probing. Here we classify gingival health and gingival diseases/conditions, along with a summary table of diagnostic features for defining health and gingivitis in various clinical situations

The positive effect of tenting screws for primary horizontal guided bone regeneration: A retrospective study based on cone‐beam computed tomography data

Objectives: To radiographically evaluate the effect of the adjunctive use of tenting screws (TS) for primary horizontal guided bone regeneration (GBR). Materials & methods: Twenty-eight patients in need of staged bone augmentation were consecutively treated in a private practice. A xenogenic particulate bone substitute material (DBBM) and a resorbable collagen membrane were used in all patients. Subjects were divided into two groups: control (conventional GBR; n = 22) and test (tenting screws in conjunction with GBR - TS; n = 22). CBCT images were obtained before augmentation and after 6-8 months. CBCTs were superimposed, and linear horizontal measurements were performed. Alveolar ridge width (RW) and ridge width change (RWchange) were assessed at 1, 3, 5, and 7 mm below the bone crest. Results: Forty-four sites in 28 patients were evaluated. No differences between the groups were detected for RW at baseline (TS: 5.87 ± 2.41; control: 5.36 ± 1.65). Regarding RWchange, TS promoted an additional effect at 1 and 3 mm below the crest compared to control (p < .05; RWchange-1 TS: 3.72 ± 2.46; control: 1.25 ± 3.05; RWchange-3 TS: 3.98 ± 2.53; control: 2.50 ± 2.02). The final RW was greater in group TS compared to the control group at the 1, 3, and 5 mm level (p < .05). Conclusions: The use of tenting screws exerted a positive effect on staged GBR with a greater final RW at the 3 mm level. In addition, GBR in conjunction with TS was able to provide consistent bone augmentation at lingual/palatal sites. Keywords: alveolar ridge augmentation; bone regeneration; cone-beam computed tomography; dental implants

Deproteinized bovine bone mineral is non-inferior to deproteinized bovine bone mineral with 10% collagen in maintaining the soft tissue contour post-extraction: A randomised trial

OBJECTIVES To test the non-inferiority of demineralized bovine bone mineral (DBBM) compared to demineralized bovine bone mineral with 10% collagen (DBBM-C) for the maintenance of the soft tissue contour after tooth extraction in the esthetic zone. MATERIAL AND METHODS Sixty-five patients randomly received ridge preservation at a single site in the anterior maxilla with DBBM or DBBM-C. Both, DBBM and DBBM-C were covered with a collagen matrix. Profilometric analyses were performed at baseline (BL), immediately after treatment (PO) and at 4 months (FU; day of implant placement). The main outcome was the horizontal mean change (HC) at the buccal aspect. The measurements also included changes of the estimated soft tissue thickness (eTT) at 1mm, 3mm and 5mm below the buccal gingival margin. Descriptive analysis was performed and differences between groups were analyzed using independent samples t-test. The non-inferiority test was performed for HC. RESULTS At 4 months, the horizontal mean change (HC) was -1.43mm (±0.53mm) (DBBM-C) and -1.32mm (±0.53mm) (DBBM). Change of the estimated soft tissue thickness (eTT) between baseline (BL) and four months of follow-up (FU) at 1mm, 3mm and 5mm amounted to -4.58mm (±2.02mm), -2.40mm (±0.97mm) and -1.37mm (±0.78mm) for DBBM-C and to -4.12mm (±1.80mm), -2.09mm (±0.91mm) and -1.23mm (±0.72mm) for DBBM. The differences between the groups were not statistically significantly for any of the outcome measures (p > .05). CONCLUSIONS DBBM is non-inferior to DBBM-C for the maintenance of the soft tissue contour 4 months after tooth extraction

Quantitative detection of periodontopathic bacteria in atherosclerotic plaques from coronary arteries

Oral pathogens, including periodontopathic bacteria, are thought to be aetiological factors in the development of cardiovascular disease. In this study, the presence of Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum-periodonticum-simiae group, Porphyromonas gingivalis, Prevotella intermedia, Prevotella nigrescens and Tannerella forsythia in atheromatous plaques from coronary arteries was determined by real-time PCR. Forty-four patients displaying cardiovascular disease were submitted to periodontal examination and endarterectomy of coronary arteries. Approximately 60-100 mg atherosclerotic tissue was removed surgically and DNA was obtained. Quantitative detection of periodontopathic bacteria was performed using universal and species-specific TaqMan probe/primer sets. Total bacterial and periodontopathic bacterial DNA were found in 94.9 and 92.3 %, respectively, of the atheromatous plaques from periodontitis patients, and in 80.0 and 20.0%, respectively, of atherosclerotic tissues from periodontally healthy subjects. All periodontal bacteria except for the F. nucleatum-periodonticum-simiae group were detected, and their DNA represented 47.3 % of the total bacterial DNA obtained from periodontitis; patients. Porphyromonas gingivalis, A. actinomycetemcomitans and Prevotella intermedia were detected most often. The presence of two or more periodontal species could be observed in 64.1 % of the samples. In addition, even in samples in which a single periodontal species was detected, additional unidentified microbial DNA could be observed. The significant number of periodontopathic bacterial DNA species in atherosclerotic tissue samples from patients with periodontitis suggests that the presence of these micro-organisms in coronary lesions is not coincidental and that they may in fact contribute to the development of vascular diseases.Fundacao do Amparo Pesquisa do Estado de Sin Paulo (FAPESP)[04/03199-3]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundacao do Amparo Pesquisa do Estado de Sin Paulo (FAPESP)[07/51016-3]Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Gingival Overgrowth Among Patients Medicated With Cyclosporin A and Tacrolimus Undergoing Renal Transplantation: A Prospective Study

Background: the aim of this study is to make a longitudinal evaluation of the incidence and severity of gingival overgrowth (GO) induced by immunosuppressive agents, such as tacrolimus (Tcr) and cyclosporin A (CsA), in the absence of calcium channel blockers in patients undergoing renal transplantation (RT).Methods: This longitudinal study is conducted in 49 patients with RT who were divided into a CsA group (n = 25) and Tcr group (n = 24). the individuals were assessed at four time intervals: before transplant and 30, 90, and 180 days after RTs. Demographic data and periodontal clinical parameters (plaque index, cemento-enamel junction to the gingival margin, probing depth, clinical attachment level, bleeding on probing [BOP], and GO) were collected at all time intervals.Results: the mean GO index was significantly lower in the Tcr group compared to the CsA group after 30 (P = 0.03), 90 (P = 0.004), and 180 (P = 0.01) days of immunosuppressive therapy. One hundred eighty days after RTs, a clinically significant GO was observed in 20.0% of individuals in the CsA group and 8.3% of individuals in the Tcr group. However, this difference was not statistically significant (P = 0.41). There was a reduction in periodontal clinical parameters regarding the time of immunosuppressive therapy for PI and BOP (P<0.001) in both groups.Conclusion: Although there was no statistical difference in the incidences of clinically significant GO after 180 days of immunosuppressive therapy, it was observed that GO occurred later in the Tcr group, and the severity of GO in this group was lower than in patients who used CsA. J Periodontol 2011;82:251-258.Foundations that Support Research in the State of São Paulo, São Paulo, S.P., BrazilUniv São Paulo, Sch Dent, Dept Stomatol, Div Periodont, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Paulista Med Sch, Div Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Paulista Med Sch, Div Nephrol, São Paulo, BrazilFoundations that Support Research in the State of São Paulo, São Paulo, S.P., Brazil: 04/13167-1Web of Scienc