A wide skull osteolytic metastasis in advanced breast cancer

We present a case report of a large and deep osteolytic metastasis radiological documented involving the skull in a woman affected by advanced breast cancer during endocrine therapy

Evaluation of gingival biotype and recession following non-surgical periodontal treatment using 3-dimensional scan methods

The study evaluated the position of gingival margins in anterior teeth using clinical and 3-dimensional (3D) optical scanning method among patients subjected to nonsurgical periodontal treatment (NSPT). A single arm, longitudinal study was undertaken at the Archway Dental Center, University of Manchester, UK. History and clinical examination were done. Gingival recession, attachment loss (AL), and periodontal probing depth (PD) were recorded at baseline and 12-weeks follow-up. NSPT was done using hand and ultrasonic instruments. Impressions were made, the resultant gypsum models were scanned to generate 3D images. The change in the gingival level and thickness of facial gingiva were assessed. Out of eight patients recruited, three were lost to follow up. The 3D scan showed a poor correlation with the clinical assessment of gingival recession in anterior teeth following NSPT (r=-0.0089). Recession did not improve after NSPT (p≤ 0.20)

A metanalysis on cabozantinib and bone metastases: True story or commercial gimmick?

Is it true that cabozantinib should be the preferred option treating patients with bone metastases? Are there any reliable comparisons between this drug and other standard options in this subgroup? To address the issue, we performed a systematic review and metanalysis of randomized trials with cabozantinib, to assess its effectiveness, in terms of overall survival, according to the presence of bone metastases. We included (a) randomized controlled trials; (b) any solid tumors and therapeutic line; and (c) overall survival data available according to the site of disease. Cabozantinib improved overall survival both for the group with bone metastases, with risk of death decreased by 53% (hazard ratio, 0.47; 95% confidence interval, 0.26–0.87; P=0.02) and for the group without bone metastases, decreasing the risk of death by 44% (hazard ratio, 0.56; 95% confidence interval, 0.40–0.79; P=0.001) over the standard of care. The difference was not significantly different between the two groups. Despite cabozantinib can be undoubtedly listed as a good therapeutic option for cancer patients with bone metastases, it seems that its preclinical profile against bone remodeling does not translate into an actual clinical relevance, preventing from considering the presence of bone metastases as principal criterion for the choice of this drug

Bernstein modes in a weakly relativistic electron-positron plasma

The kinetic theory of weakly relativistic electron-positron plasmas, producing dispersion relations for the electrostatic Bernstein modes was addressed. The treatment presented preserves the full momentum dependence of the cyclotron frequency, albeit with a relaxation on the true relativistic form of the distribution function. The implications of this new treatment were confined largely to astrophysical plasmas, where relativistic electronpositron plasmas occur naturally

Soft Tissue Substitutes at Immediate Postextractive Implants to Reduce Tissue Shrinkage – 3-year Results From a Randomized Controlled Trial

PURPOSE. The aim of this parallel randomized controlled trial (RCT) was to evaluate whether placement of a soft tissue graft substitute (STGS) could decrease peri-implant tissue shrinkage at immediate post-extractive implants. MATERIALS AND METHODS. Twenty patients with one missing tooth between two adja-cent healthy teeth in aesthetic areas and at least 4 mm of bone apically to the tooth apex were randomly allocated after tooth extraction to receive or not a subepithelial buccal STGS. Implants were inserted with a torque of at least 30 Ncm and sites were grafted with a cancellous particulate allograft. Ten patients received a buccal STGS and 10 patients did not (control group). All patients were restored with non-occluding immediate provisional screw-retained crowns, replaced after 6 months by definitive metal-ceramic crowns, and were followed to 3-year after grafting/loading. RESULTS. Three-year after loading, no drop-out, crown or implant failure or complication occurred. No statistically significant difference or trends in aesthetics (difference = 0.2, 95% CI:-0.81 to 1.21; P = 0.97), peri-implant marginal bone loss (difference = 0.14 mm; 95% CI:-0.27 to 0.57; P = 0.58) and keratinized mucosa heights (difference = 0.8 mm; 95% CI:-1.79 to 3.39; P = 0.57) between the two groups were observed. CONCLUSIONS. Acknowledging that the sample size was small, no clinical benefits could be observed using a soft tissue graft substitute at immediate post-extractive implants up to 3-year after grafting. CONFLICT OF INTEREST STATEMENT. The manufacturer (BEGO Implant Systems, Bremen, Germany) of the implants used in this investigation, partially supported this trial, however data belonged to the authors and by no means the sponsor interfered with the conduct of the trial or the publication of its results

Conventional Drills Versus Piezoelectric Surgery Preparation for Placement of Four Immediately Loaded Zygomatic Oncology Implants in Edentulous Maxillae: 3 Year Results of a Within Person Randomised Controlled Trial

PURPOSE. A within-person randomised controlled trial to compare the outcome of site preparation for two zygomatic oncology implants per zygoma using conventional preparation with rotary drills or piezoelectric surgery with dedicated inserts. MATERIALS AND METHODS. Twenty edentulous patients with severely atrophic maxillae and insufficient bone volumes for placing dental implants with less than 4 mm of bone height subantrally had their hemi-maxillae randomised according to a within-patient study design into implant site preparation with either conventional rotational drills or piezoelectric surgery. Two zygomatic oncology implants (unthreaded coronal portion) were placed in each hemi-maxilla. Implants that achieved an insertion torque of greater than 40 Ncm were immediately loaded with provisional screw-retained metal-reinforced acrylic prostheses. Outcome measures were: prosthesis and implant failures, any com-plications, time to place the implants, presence of post-operative haematoma, and patient preference, as assessed by blinded assessors when possible. All patients were followed up for 3 years after loading. RESULTS. In two patients, drills had to be used in the piezoelectric surgery arm in order to prepare implant sites properly. One implant from the conventional drill group did not achieve an insertion torque of greater than 40 Ncm since the zygoma fractured. Three patients dropped out. Two distal oncology implants failed in the same patient (one per group), who was not prosthetically rehabilitated. Six patients experienced at least one complication at drilled sites and five at piezoelectric surgery sites (three patients had bilateral complications), the difference not being statistically significant (odds ratio = 1.5; P [McNemar’s test] = 1.0; 95% CI of odds ratio: 0.25 to 8.98). Implant placement with con-vention drills took on average 14.35±1.76 minutes vs. 23.50±2.26 minutes with piezoelectric surgery, the implant placement time being significantly shorter with conventional drilling (difference = 9.15±1.69 minutes; 95%CI: 8.36 to 9.94 minutes; P = 0.000). Post-operative haematomas were larger at drilled sites in 11 patients and similar at both sides in nine patients (chi-square = 20.4; df = 3; P = 0.0001), and 16 patients found both techniques equally acceptable while four preferred piezoelectric surgery (chi-square = 34.4; df = 3; P<0.0001). CONCLUSIONS. Although these results may be system-dependent, and therefore cannot be generalised to other zygomatic systems with confidence, both drilling techniques achieved similar clinical outcomes. However, conventional drilling required 9 minutes less and could be used in all instances, though it was more aggressive

Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program

Background: The Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval. Methods: Pts with previously treated advanced or mRCC were eligible to receive nivolumab 3 mg/kg every 2 weeks. Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for drug-related adverse events (drAEs) using CTCAE v.4.0. Immune-related (ir) AEs were defined as AEs displaying a certain, likely or possible correlation with immunotherapy (cutaneous, endocrine, hepatic, gastro-intestinal and pulmonary). The association between overall survival (OS) and irAEs was assessed, and associations between variables were evaluated with a logistic regression model. Results: A total of 389 pts were enrolled between July 2015 and April 2016. Overall, the objective response rate was 23.1%. At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7-6.2) and the 12-month overall survival rate was 63%. Any grade and grade 3-4 drAEs were reported in 124 (32%) and 27 (7%) of pts, respectively, and there were no treatment-related deaths. Any grade irAEs occurred in 76 (20%) of patients, 8% cutaneous, 4% endocrine, 2% hepatic, 5% gastro-intestinal and 1% pulmonary. Of the 22 drAEs inducing treatment discontinuation, 10 (45%) were irAEs. Pts with drAEs had a significantly longer survival than those without drAEs (median OS 22.5 versus 16.4 months, p = 0.01). Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8 months, p = 0.002), confirmed at the landmark analysis at 6 weeks. The occurrence of irAEs displayed a strong association with OS in univariable (HR 0.48, p = 0.003) and multivariable (HR 0.57, p = 0.02) analysis. Conclusions: The appearance of irAEs strongly correlates with survival benefit in a real-life population of mRCC pts treated with nivolumab

The impact of direct acting antivirals on hepatitis C virus disease burden and associated costs in four european countries

Background and Aims We assessed the clinical and economic impact of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) in England, Italy, Romania and Spain.Methods An HCV progression Markov model was developed considering DAA eligibility and population data during the years 2015-2019. The period of time to recover the investment in DAAs was calculated as the cost saved by avoiding estimated clinical events for 1000 standardized treated patients. A delayed treatment scenario because of coronavirus disease (COVID-19) was also developed.Results The estimated number of avoided hepatocellular carcinoma, decompensated cirrhosis and liver transplantations over a 20-year time horizon was: 1,057 in England; 1,221 in Italy; 1,211 in Romania; and 1,103 in Spain for patients treated during 2015-2016 and 640 in England; 626 in Italy; 739 in Romania; and 643 in Spain for patients treated during 2017-2019. The cost-savings ranged from euro 45 to euro 275 million. The investment needed to expand access to DAAs in 2015-2019 is estimated to be recovered in 6.5 years in England; 5.4 years in Italy; 6.7 years in Romania; and 4.5 years in Spain. A delay in treatment because of COVID-19 will increase liver mortality in all countries.Conclusion Direct-acting antivirals have significant clinical benefits and can bring substantial cost-savings over the next 20 years, reaching a Break-even point in a short period of time. When pursuing an exit strategy from strict lockdown measures for COVID-19, providing DAAs should remain high on the list of priorities in order to maintain HCV elimination efforts

A meta-analysis of comparative transcriptomic data reveals a set of key genes involved in the tolerance to abiotic stresses in rice

Several environmental factors, such as drought, salinity, and extreme temperatures, negatively affect plant growth and development, which leads to yield losses. The tolerance or sensitivity to abiotic stressors are the expression of a complex machinery involving molecular, biochemical, and physiological mechanisms. Here, a meta-analysis on previously published RNA-Seq data was performed to identify the genes conferring tolerance to chilling, osmotic, and salt stresses, by comparing the transcriptomic changes between tolerant and susceptible rice genotypes. Several genes encoding transcription factors (TFs) were identified, suggesting that abiotic stress tolerance involves upstream regulatory pathways. A gene co-expression network defined the metabolic and signalling pathways with a prominent role in the differentiation between tolerance and susceptibility: (i) the regulation of endogenous abscisic acid (ABA) levels, through the modulation of genes that are related to its biosynthesis/catabolism, (ii) the signalling pathways mediated by ABA and jasmonic acid, (iii) the activity of the \u201cDrought and Salt Tolerance\u201d TF, involved in the negative regulation of stomatal closure, and (iv) the regulation of flavonoid biosynthesis by specific MYB TFs. The identified genes represent putative key players for conferring tolerance to a broad range of abiotic stresses in rice; a fine-tuning of their expression seems to be crucial for rice plants to cope with environmental cues