The aim of this prospective study was to document radiographically tissue remodeling patterns around ITI implants placed according to an osteotome technique. In 19 consecutive patients from a private practice, 25 implants of the ITI Dental Implant System were placed subjacent to the sinus floor. Implant beds were pre-prepared with pilot drills and/or using the Summers Osteotome Kit. Bio Oss particles were mixed with autologous bone and inserted into the apex area. Implants were placed self-tapping. The sinus floors were thereby pushed up with attempts not to sever the Schneiderian membrane. Healing occurred submerged or semi-submerged and was uneventful in 24/25 implants. At 1 year, all implants had been restored with crowns or short fixed partial dentures. One implant was lost in the first 3 weeks, but was replaced 6 months later in a second attempt. Intraoral radiographs were obtained presurgically and postsurgically at 3 and 12 months. The mean preoperative distance between the sinus floor and the crest was 7.0 mm (range 2.3-10.3 mm). The mean distances between the implant apex and the initial sinus floor were: 3.66 +/- 1.74 mm mesially and 4.44 +/- 1.62 mm distally. The mean height of the new bone reaching apically and mesially to the implants was 1.52 +/- 2.48 mm at surgery, but was reduced significantly to 1.24 +/- 1.30 mm at 3 months and 0.29 +/- 1.91 mm after 12 months (Hotelling's test P< or =0.01). Similar values were obtained at the disto-apical aspects. In an attempt to assess periapical bone/graft remodeling, a novel index was applied: 0=no bone/graft visible, 1=cloudy appearance of new bone/graft, 2=clearly visible new bone/graft disappearing structures of original sinus floor, 3=new bone/graft with new cortical plate and the former boundary of the sinus floor disappearing. This index increased statistically significantly from baseline to 12 months (Hotelling's test P< or =0.02). In conclusion, this study shows that in areas with reduced bone height subjacent to the sinus, an osteotome technique may provide a minimally invasive way to obtain implant abutments predictably. The grafted area apical to the implants undergoes shrinkage and remodeling. The original boundary of the sinus is eventually consolidated and replaced by a new cortical plate. In addition to the linear measurements, the novel index may assist in assessing periapical remodeling at implants placed with an osteotome technique.

The aim of this study was to investigate the effects of quetiapine, an atypical antipsychotic, on polysomnographic sleep structure and subjective sleep quality. This double-blind, placebo-controlled, randomized cross-over study investigated the polysomnographic sleep structure and subjective sleep quality of 14 healthy male subjects given placebo, quetiapine 25 mg or quetiapine 100 mg. Volunteers were studied 3 times for 3 consecutive nights (N0, adaptation; N1, standard sleep conditions; N2, acoustic stress) 4 days apart. Treatment was administered orally 1 h before bedtime on nights 1 and 2. Quetiapine 25 mg and 100 mg significantly improved sleep induction and continuity under standard and acoustic stress conditions. Increases in total sleep time, sleep efficiency, percentage sleep stage 2 and subjective sleep quality were seen. A significant increase in periodic leg movements during sleep was observed with quetiapine 100 mg. The sleep-improving properties of quetiapine may be important in counteracting different aspects of psychopathology in schizophrenia and other disorders. These sleep-inducing and sleep-modifying properties are probably related to quetiapine's receptor-binding profile, including its antihistaminergic, antidopaminergic and antiadrenergic properties. Other mechanisms might be relevant as well and further investigation is required.

Purpose Neoadjuvant chemotherapy followed by radical cystectomy (RC) is a standard of care for the management of muscle-invasive bladder cancer (MIBC). Dose-dense cisplatin-based regimens have yielded favorable outcomes compared with standard-dose chemotherapy, yet the optimal neoadjuvant regimen remains undefined. We assessed the efficacy and tolerability of six cycles of neoadjuvant dose-dense gemcitabine and cisplatin (ddGC) in patients with MIBC. Patients and Methods In this prospective, multicenter phase II study, patients received ddGC (gemcitabine 2,500 mg/m on day 1 and cisplatin 35 mg/m on days 1 and 2) every 2 weeks for 6 cycles followed by RC. The primary end point was pathologic downstaging to non-muscle-invasive disease (< pT2N0). Patients who did not undergo RC were deemed nonresponders. Pretreatment tumors underwent next-generation sequencing to identify predictors of chemosensitivity. Results Forty-nine patients were enrolled from three institutions. The primary end point was met, with 57% of 46 evaluable patients downstaged to < pT2N0. Pathologic response correlated with improved recurrence-free survival and overall survival. Nineteen patients (39%) required toxicity-related dose modifications. Sixty-seven percent of patients completed all six planned cycles. No patient failed to undergo RC as a result of chemotherapy-associated toxicities. The most frequent treatment-related toxicity was anemia (12%; grade 3). The presence of a presumed deleterious DNA damage response (DDR) gene alteration was associated with chemosensitivity (positive predictive value for < pT2N0 [89%]). No patient with a deleterious DDR gene alteration has experienced recurrence at a median follow-up of 2 years. Conclusion Six cycles of ddGC is an active, well-tolerated neoadjuvant regimen for the treatment of patients with MIBC. The presence of a putative deleterious DDR gene alteration in pretreatment tumor tissue strongly predicted for chemosensitivity, durable response, and superior long-term survival.

Purpose To evaluate the associations between clinical outcomes and radiomics-derived inter-site spatial heterogeneity metrics across multiple metastatic lesions on CT in high-grade serous ovarian cancer (HGSOC). Methods IRB-approved retrospective study of 38 HGSOC patients. All sites of suspected HGSOC involvement on preoperative CT were manually segmented. Gray-level correlation matrix-based textures were computed from each tumor site, and grouped into five clusters using a Gaussian Mixture Model. Pairwise inter-site similarities were computed, generating an inter-site similarity matrix (ISM). Inter-site texture heterogeneity metrics were computed from the ISM and compared to clinical outcomes. Results Of the 12 inter-site texture heterogeneity metrics evaluated, those capturing the differences in texture similarities across sites were associated with shorter overall survival (inter-site similarity entropy, similarity level cluster shade, and inter-site similarity level cluster prominence; p≤0.05) and incomplete surgical resection (similarity level cluster shade, inter-site similarity level cluster prominence and inter-site cluster variance; p≤0.05). Neither the total number of disease sites per patient nor the overall tumor volume per patient was associated with overall survival. Amplification of 19q12 involving cyclin E1 gene (CCNE1) predominantly occurred in patients with more heterogeneous inter-site textures. Conclusion Quantitative metrics non-invasively capturing spatial inter-site heterogeneity may predict outcomes in patients with HGSOC.

Therefore, this double-blind, placebo-controlled, randomized cross-over study investigated the influence of the atypical antipsychotics quetiapine and olanzapine in comparison with haloperidol and placebo on plasma adrenocorticotropic hormone (ACTH), cortisol, and prolactin levels. Eleven healthy male volunteers were studied during four sessions one week apart, orally receiving placebo, quetiapine (50 mg), olanzapine (5 mg), or haloperidol (3 mg). Blood samples were taken at hourly intervals from 0900 until 1700 hours. For ACTH, cortisol, and prolactin a significant effect of treatment condition (p < or = 0.005; p < or = 0.035; p < or = 0.0001, respectively) for area under the curve (AUC) was found. In comparison to placebo, quetiapine and olanzapine significantly reduced ACTH (p < or = 0.002; p < or = 0.05, respectively) and cortisol (p < or = 0.005; p < or = 0.03, respectively). No effect of haloperidol on AUC of ACTH or cortisol levels was observed. In comparison with placebo, haloperidol (p < or = 0.0001) and olanzapine (p < or = 0.0001) elevated AUC of prolactin plasma levels, whereas no significant effect was observed for quetiapine as a main effect of treatment condition. The atypical antipsychotics' strong influence on HPA-function with pronounced ACTH and cortisol lowering is possibly related to the atypicals' blockade of serotonergic receptors, but blockade of adrenergic or histaminergic receptors may play a role as well. The observed HPA-axis down-regulation may be clinically important for the atypicals' effects on depressive symptomatology and cognitive functioning.

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