Examination and prognostic implications of the unique microenvironment of breast cancer brain metastases

Purpose: Brain metastases (BM) are a complication of advanced breast cancer (BC). Histology of melanoma BM offers prognostic value; however, understanding the microenvironment of breast cancer brain metastases (BCBM) is less characterized. This study reports on four histological biomarkers, gliosis, immune infiltrate, hemorrhage, necrosis, and their prognostic significance in BCBM. Methods: A biobank of 203 human tissues from patients who underwent craniotomy for BCBM was created across four academic institutions. Degree of gliosis, immune infiltrate, hemorrhage, and necrosis were identified and scored via representative H&E stain (0–3+). Overall survival (OS) was estimated using the Kaplan–Meier method. Cox proportional hazards regression evaluated prognostic value of the biomarkers in the context of standard clinical characteristics. Results: BCBM subtype (available for n = 158) was 36% Her2+, 26% hormone receptor (HR)+/Her2− 38% HR−/Her2− (triple negative, TN). Gliosis was observed in 82% (116/141) of BCBM, with immune infiltrate 44% (90/201), hemorrhage 82% (166/141), and necrosis 87% (176/201). Necrosis was significantly higher in TNBC (p < 0.01). Presence of gliosis, immune infiltrate, and hemorrhage correlated with improved OS (p = 0.03, p = 0.03, p = 0.1), while necrosis correlated with inferior OS (p = 0.01). Improved OS was associated with gliosis in TN (p = 0.02), and immune infiltrate (p = 0.001) and hemorrhage (p = 0.07) in HER2+. In a multivariable model for OS, incorporating these biomarkers with traditional clinical variables improved the model fit (p < 0.001). Conclusion: Gliosis confers superior prognosis in TNBC BM; immune infiltrate and hemorrhage correlate with superior prognosis in HER2+ BCBM. Understanding the metastatic microenvironment of BCBM refines prognostic considerations and may unveil novel therapeutic strategies

Survival and Complication Rates of Fixed Restorations Supported by Locking-Taper Implants: A Prospective Study with 1 to 10 Years of Follow-Up

The aim of this 10-year follow-up study was to evaluate the implant survival and complication rates of fixed restorations supported by locking-taper implants.Over a 10-year period (January 2002 to December 2011) all patients referred to a single private practice for treatment with fixed restorations (single crowns, SCs; fixed partial prostheses, FPPs; fixed full arches, FFAs) supported by dental implants were considered for inclusion in the study. At each annual follow-up session, clinical, radiographic, and prosthetic parameters were assessed. The surviving implant-supported restorations were defined as "complication free" in the absence of any biological or prosthetic (mechanical or technical) complication. The cumulative implant survival and the "complication-free" survival of fixed implant-supported restorations were identified using the Kaplan-Meier method. The Log-rank test was used to identify correlations between the study variables.In total, 1494 locking-taper implants (727 maxilla, 767 mandible) were placed in 642 patients (356 males, 286 females). Nineteen implants (12 maxilla, 7 mandible) failed. Implant failures were attributed to lack of osseointegration (14 implants), peri-implantitis (4 implants), and mechanical overloading (1 implant). An overall 10-year cumulative implant survival rate of 98.7\% (98.3\% maxilla, 99.1\% mandible) was found. The implant survival rates did not significantly differ with respect to implant location, position, bone type, implant length and diameter, and type of restorations. Among the surviving implant-supported restorations (478 SC, 242 FPP, 19 FFA), a few biological (11/739: 1.4\%) and prosthetic (27/739: 3.6\%) complications were reported. The incidence of mechanical complications was low (3/739: 0.4\%), with three loosened abutments in three SCs (3/478: 0.6\%), and no abutment fractures; technical complications were more frequent (24/739: 3.2\%), with an incidence of decementation of 2.0\% (SC 2.0\%, FPP 1.6\%, FFA 5.2\%) and ceramic/veneer chipping/fracture of 1.2\% (SC 0.0\%, FPP 2.8\%, FFA 10.5\%). A 10-year cumulative "complication-free" survival of restorations of 88.6\% (SC 91.7\%, FPP 83.1\%, FFA 73.8\%) was reported. The complication rates differ significantly with respect to the type of restoration (p < 0.05).Fixed restorations on locking-taper implants seem to be a successful procedure for the rehabilitation of partially and completely edentulous arches

Clinical outcome of narrow-diameter (3.3-mm) locking-taper implants: a prospective study with 1 to 10 years of follow-up

To evaluate the outcome of narrow-diameter (3.3-mm) locking-taper implants used in the rehabilitation of partially and fully edentulous patients over a 10-year period. Between January 2002 and December 2011, all patients referred to a private dental clinic for treatment with narrow-diameter implants were enrolled in this study. At each annual follow-up session, clinical and radiographic parameters were assessed; the outcome measurements were implant failure, peri-implant marginal bone loss (distance between the implant shoulder and the first visible bone-to-implant contact [DIB]), and biologic and technical complications. The cumulative survival rate (CSR) was assessed using the Kaplan-Meier survival estimator; Tarone-Ware and chi-square analyses were used to evaluate correlations between the study variables. The statistical analysis was performed at the patient- and implant-level. A total of 324 narrow-diameter implants were placed in 279 patients (159 men, 120 women; age: 25 to 73 years). Four implants failed, for an overall CSR of 98.5% (patient-based) and 98.7% (implant-based) at the 10-year follow-up. The survival rate did not differ significantly with respect to patients' sex, age, smoking or parafunctional habits, bone type, prosthetic restoration, or implant location, position, or length. Among the surviving implants, a mean DIB of 0.31 \ub1 0.23 mm, 0.45 \ub1 0.27 mm, and 0.69 \ub1 0.28 mm was observed at the 1-, 5-, and 10-year follow-up examinations, respectively. A few biologic (1.2%) and technical complications (7.5%) were reported. Within the limitations of this study, it can be concluded that narrow-diameter locking-taper implants represent a good treatment option for the prosthetic rehabilitation of partially and totally edentulous patients

Esthetic evaluation of single-tooth Morse taper connection implants placed in fresh extraction sockets or healed sites.

Abstract Aim: The aim of this study was to compare the esthetic outcome of single implants placed in fresh extraction sockets with that of fully healed sites of the anterior maxilla. Materials and methods: This retrospective study was based on data from patients treated with single-tooth Morse taper connection implants placed in fresh extraction sockets and in fully healed sites of the anterior maxilla. Only single implant treatments were considered with both neighboring teeth present. Additional prerequisites for immediate implant treatment were intact socket walls and a thick gingival biotype. The esthetic outcome was objectively rated using the pink esthetic/white esthetic score (PES/WES). The Mann-Whitney test was used to compare the PES and WES scores between the two groups. Results: Twenty-two patients received an immediate implant and 18 patients had conventional implant surgery. The mean follow-up was 31.09 months (SD 5.57; range 24-46) and 34.44 months (SD 7.10; range 24-48) for immediate and conventionally inserted implants, respectively. No implants were lost. All implants fulfilled the success criteria. The mean PES/WES was 14.50 (SD 2.52; range 9-19) and 15.61 (SD 3.20; range 8-20) for immediately and conventionally placed implants, respectively. Immediate implants had a mean PES of 7.45 (SD 1.62; range 4-10) and a mean WES of 7.04 (SD 1.29; range 5-10). Conventional implants had a mean PES of 7.83 (SD 1.58; range 4-10) and a mean WES of 7.77 (SD 1.66; range 4-10). The difference between the two groups was not significant.Conclusions: Immediate and conventional single implant treatment yielded comparable esthetic outcomes

School Improvement: Reality and Illusion

School improvement is much sought and often claimed. However, it is questionable whether overall achievement in countries such as the USA or England has improved by any significant amount over thirty years. Several school improvement programmes have been claimed as successful, but evaluations, even where they exist, are generally poor: based on the perceptions of participants, lacking any counterfactual or reporting selectively. Accounts of improvement in individual schools are numerous, but are inevitably selective; the attribution of causality is problematic and knowledge of the conditions under which such phenomena are likely to be replicated is limited. School effectiveness research also has yet to identify specific strategies with clear causal effects. In short, many claims of school improvement are illusory. Nevertheless, there are some improvement strategies that are well-defined, feasible and robustly shown to be effective. In future, we need greater clarity and agreement about what constitutes success. Evaluation must be taken more seriously, and its results treated more critically