Multi-omic lineage tracing predicts the transcriptional, epigenetic and genetic determinants of cancer evolution.

Cancer is a highly heterogeneous disease, where phenotypically distinct subpopulations coexist and can be primed to different fates. Both genetic and epigenetic factors may drive cancer evolution, however little is known about whether and how such a process is pre-encoded in cancer clones. Using single-cell multi-omic lineage tracing and phenotypic assays, we investigate the predictive features of either tumour initiation or drug tolerance within the same cancer population. Clones primed to tumour initiation in vivo display two distinct transcriptional states at baseline. Remarkably, these states share a distinctive DNA accessibility profile, highlighting an epigenetic basis for tumour initiation. The drug tolerant niche is also largely pre-encoded, but only partially overlaps the tumour-initiating one and evolves following two genetically and transcriptionally distinct trajectories. Our study highlights coexisting genetic, epigenetic and transcriptional determinants of cancer evolution, unravelling the molecular complexity of pre-encoded tumour phenotypes.

Induction avelumab followed by chemoimmunotherapy and maintenance versus chemotherapy alone as first-line therapy in cis-ineligible metastatic urothelial carcinoma (INDUCOMAIN): a randomized phase II study.

BACKGROUND: Platinum-based chemotherapy (ChT) has been the standard first-line treatment for metastatic urothelial carcinoma (mUC). The purpose of this study was to evaluate the use of induction avelumab followed by avelumab in combination with carboplatin-gemcitabine (carbo/gem) followed by avelumab maintenance. We tested the hypothesis that induction immunotherapy (IO) could enhance the response to ChT and prevent its detrimental effect on immune cells. MATERIALS AND METHODS: INDUCOMAIN is a multicenter, randomized, investigator-initiated, open-label phase II study evaluating the safety and efficacy of induction avelumab before carboplatin-gemcitabine-avelumab, followed by avelumab maintenance (arm A), compared to carbo/gem (arm B). Eligibility criteria included patients with mUC, no prior systemic therapy, and ineligibility for cisplatin by Galsky criteria. Patients were stratified by the presence/absence of visceral metastasis and Eastern Cooperative Oncology Group performance status 0-1 versus 2. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Eighty-five patients were included and randomized to arm A (n = 42) and arm B (n = 43), respectively. ORR was similar between treatment arms: 59.5% in arm A and 53.5% in arm B (P = 0.57). Fourteen patients (33%) in arm A early progressed/died before or at first response assessment, compared to three patients (7%) in arm B. Median OS was 11.1 months in arm A and 13.2 months in arm B [hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.57-1.46, P = 0.69]. Median PFS was 6.9 months in arm A versus 7.4 months in arm B (HR 0.99, 95% CI 0.61-1.60, P = 0.95). Treatment-related adverse events of grade 3-4 occurred in 70.7% of patients in arm A and in 72.1% in arm B. No predictive role of programmed death-ligand 1 expression was found. CONCLUSIONS: The hypothesis that induction avelumab could enhance the efficacy of subsequent ChT was not proven. Administering IO alone as induction before ChT is not an adequate strategy.

One-pot chemo- and photo-enzymatic linear cascade processes.

The combination of chemo- and photocatalyses with biocatalysis, which couples the flexible reactivity of the photo- and chemocatalysts with the highly selective and environmentally friendly nature of enzymes in one-pot linear cascades, represents a powerful tool in organic synthesis. However, the combination of photo-, chemo- and biocatalysts in one-pot is challenging because the optimal operating conditions of the involved catalyst types may be rather different, and the different stabilities of catalysts and their mutual deactivation are additional problems often encountered in one-pot cascade processes. This review explores a large number of transformations and approaches adopted for combining enzymes and chemo- and photocatalytic processes in a successful way to achieve valuable chemicals and valorisation of biomass. Moreover, the strategies for solving incompatibility issues in chemo-enzymatic reactions are analysed, introducing recent examples of the application of non-conventional solvents, enzyme-metal hybrid catalysts, and spatial compartmentalization strategies to implement chemo-enzymatic cascade processes.

Genomic characterisation of hormone receptor-positive breast cancer arising in very young women.

BACKGROUND: Very young premenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained. PATIENTS AND METHODS: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the Suppression of Ovarian Function Trial (SOFT) to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1276 patients (deep targeted sequencing, n = 1258; whole-exome sequencing in a young-age, case-control subsample, n = 82). We defined copy number (CN) subgroups and assessed for features suggestive of homologous recombination deficiency (HRD). Genomic alteration frequencies were compared between young premenopausal women (<40 years) and older premenopausal women (≥40 years), and assessed for associations with distant recurrence-free interval (DRFI) and overall survival (OS). RESULTS: Younger women (<40 years, n = 359) compared with older women (≥40 years, n = 917) had significantly higher frequencies of mutations in GATA3 (19% versus 16%) and CN amplifications (CNAs) (47% versus 26%), but significantly lower frequencies of mutations in PIK3CA (32% versus 47%), CDH1 (3% versus 9%), and MAP3K1 (7% versus 12%). Additionally, they had significantly higher frequencies of features suggestive of HRD (27% versus 21%) and a higher proportion of PIK3CA mutations with concurrent CNAs (23% versus 11%). Genomic features suggestive of HRD, PIK3CA mutations with CNAs, and CNAs were associated with significantly worse DRFI and OS compared with those without these features. These poor prognostic features were enriched in younger patients: present in 72% of patients aged <35 years, 54% aged 35-39 years, and 40% aged ≥40 years. Poor prognostic features [n = 584 (46%)] versus none [n = 692 (54%)] had an 8-year DRFI of 84% versus 94% and OS of 88% versus 96%. Younger women (<40 years) had the poorest outcomes: 8-year DRFI 74% versus 85% and OS 80% versus 93%, respectively. CONCLUSION: These results provide insights into genomic alterations that are enriched in young women with HR+HER2- EBC, provide rationale for genomic subgrouping, and highlight priority molecular targets for future clinical trials.

Efficacy and safety of pembrolizumab in metastatic urothelial carcinoma: results from KEYNOTE-045 and KEYNOTE-052 after up to 5 years of follow-up.

BACKGROUND: Immune checkpoint inhibitors are a standard therapy in metastatic urothelial carcinoma (UC). Long-term follow-up is necessary to confirm durability of response and identify further safety concerns. PATIENTS AND METHODS: In KEYNOTE-045, patients with metastatic UC that progressed on platinum-containing chemotherapy were randomly assigned 1:1 to receive pembrolizumab or investigator's choice of paclitaxel, docetaxel, or vinflunine. Primary endpoints were progression-free survival per RECIST version 1.1 by blinded independent central review (BICR) and overall survival. In KEYNOTE-052, cisplatin-ineligible patients with metastatic UC received first-line pembrolizumab. The primary endpoint was objective response rate per RECIST version 1.1 by BICR. RESULTS: A total of 542 patients (pembrolizumab, n = 270; chemotherapy, n = 272) were randomly assigned in KEYNOTE-045. The median follow-up was 62.9 months (range 58.6-70.9 months; data cut-off 1 October 2020). At 48 months, overall survival rates were 16.7% for pembrolizumab and 10.1% for chemotherapy; progression-free survival rates were 9.5% and 2.7%, respectively. The median duration of response (DOR) was 29.7 months (range 1.6+ to 60.5+ months) for pembrolizumab and 4.4 months (range 1.4+ to 63.1+ months) for chemotherapy; 36-month DOR rates were 44.4% and 28.3%, respectively. A total of 370 patients were enrolled in KEYNOTE-052. The median follow-up was 56.3 months (range 51.2-65.3 months; data cut-off 26 September 2020). The confirmed objective response rate was 28.9% (95% confidence interval 24.3-33.8), and the median DOR was 33.4 months (range 1.4+ to 60.7+ months); the 36-month DOR rate was 44.8%. Most treatment-related adverse events for pembrolizumab in either study were grade 1 or 2 and manageable, which is consistent with prior reports. CONCLUSION: With ∼5 years of follow-up, pembrolizumab monotherapy continued to demonstrate durable efficacy with no new safety signals in patients with platinum-resistant metastatic UC and as first-line therapy in cisplatin-ineligible patients. CLINICAL TRIAL REGISTRY AND ID: With ClinicalTrials.gov NCT02256436 (KEYNOTE-045); https://clinicaltrials.gov/ct2/show/NCT02256436 and NCT02335424 (KEYNOTE-052); https://clinicaltrials.gov/ct2/show/NCT02335424.

Prognostic factors for complications after loop ileostomy reversal.

BACKGROUND: Defunctioning ileostomy creation and closure are both associated with morbidity. There is little data available about complications after ileostomy closure. The aim of this study was to evaluate morbidity related to loop ileostomy closure (LIC) and to determine if patients with postoperative complications in primary surgery suffer from more postoperative complications during stoma closure. METHODS: This was a retrospective study on prospectively registered consecutive patients undergoing elective LIC in a single centre in Spain between April 2010 and December 2017. Baseline characteristics, postoperative complications after primary surgery and after stoma closure were recorded. Primary surgery included any colorectal resection, elective or urgent associated with a diverting loop ileostomy either as a protective stoma or rescue procedure. A logistic regression model was used to assess the effects of baseline variables and postoperative complications after primary surgery on the existence of postoperative complications related to LIC. RESULTS: Four hundred and twenty-eight patients (288 men, median age 64.5 years [IQR 55.1-72.3 years]) were included in the study, and 37.4%, developed complications after LIC. The most common was paralytic ileus. Only chronic kidney disease (OR 2.31; 95% CI 1.03-5.33, p = 0.043), existence of postoperative complications after primary surgery (OR 2.25; 95% CI 1.41-3.66, p = < 0.001) and ileostomy closure later than 10 months after primary surgery (OR 1.52; 95% CI 1.00-2.33, p = 0.049) were statistically significant in the multivariate analysis. CONCLUSIONS: Patients with chronic kidney disease, those who had any complication after primary surgery and those who had LIC > 10 months after primary surgery have a significantly higher risk of developing postoperative complications.

Height difference between the vestibular and palatal walls and palatal width: a cone beam computed tomography approach.

BACKGROUND: The objective of this study was to measure two parameters involved in tri-dimensional implant planning: the position of the buccal and palatal bone wall and the palatal thickness. METHODS: Cone beam computed tomography (CBCT) images (Planmeca ProMax 3D) of 403 teeth (208 upper teeth and 195 lower teeth) were obtained from 49 patients referred to the Dental School of Seville from January to December 2014. The height difference between the palatal and buccal walls was measured on the most coronal point of both walls. The thickness of the palatal wall was measured 2 mm from the most coronal point of the palatal wall. RESULTS: The mean values in the maxilla were 1.7 ± 0.9 mm for central and lateral incisors, 2.2 ± 1.7 mm for canines, 1.6 ± 0.9 mm for premolars and 1.9 ± 1.5 mm for molars. In the lower jaw, the mean values were 1.3 ± 0.8 mm for incisors, 1.7 ± 1.2 mm for canines, 2.3 ± 1.3 mm for premolars, and 2.6 ± 1.7 mm for molars. In the upper jaw, more than 55% of maxillary teeth (excluding second premolars and molars) presented mean height differences greater than 1 mm. In the mandible, more than 60% of incisors showed a buccal bone thickness of 1 mm from the apical to lingual aspect. All teeth except the second premolar presented a buccal wall located more than 1 mm more apically than the lingual bone wall. CONCLUSIONS: The buccal bone wall is located more apically (greater than 1 mm) than the palatal or lingual table in most of the cases assessed. The thickness of the palatal or lingual table is also less than 2 mm in the maxilla and mandible, except in the upper canines and premolars and the lower molars.

SEOM clinical guidelines for the treatment of advanced prostate cancer (2020).

The treatment of advanced prostate cancer has evolved due to recent advances in molecular research and new drug development. Dynamic aberrations in the androgen receptor, DNA repair genes, PTEN-PI3K, and other pathways drive the behavior of advanced prostate cancer allowing a better selection of therapies in each patient. Tumor testing for BRCA1 and BRCA2 is recommended for patients with metastatic prostate cancer, also considering a broad panel to guide decisions and genetic counseling. In symptomatic metastatic patients, castration should be stared to palliate symptoms and prolong survival. In high-risk or high-volume metastatic hormone-naïve patients, castration should be combined with docetaxel, abiraterone, enzalutamide or apalutamide. Radiotherapy to the primary tumor combined with systemic therapy is recommended in low-volume mHNPC patients. In patients with non-metastatic castration-resistant tumors, risk stratification can define the frequency of imaging. Adding enzalutamide, darolutamide or apalutamide to these patients prolongs metastasis-free and overall survival, but potential adverse events need to be taken into consideration. The choice of docetaxel, abiraterone or enzalutamide for treating metastatic castration-resistant patients depends on previous therapies, with cabazitaxel being also recommended after docetaxel. Olaparib is recommended in BRCA1/BRCA2 mutated castration-resistant patients after progression on at least one new hormonal therapy. Aggressive variants of prostate cancer respond to platinum-based chemotherapy. To optimize treatment efficiency, oncologists should incorporate all of these advances into an overall therapeutic strategy.

Latest progress in molecular biology and treatment in genitourinary tumours.

The management of genitourinary cancer, including bladder, prostate, renal and testicular cancer, has evolved dramatically in recent years due to a better understanding of tumour genetic mutations, alterations in molecular pathways, and to the development of new kinds of drugs such as targeted therapies and immunotherapies. In the field of immunotherapy, new drugs focused on stimulating, enhancing and modulating the immune system to detect and destroy cancer, have been recently discovered. Research in oncology moves quickly and new data of great relevance for clinical practice are communicated every year. For this reason, a group of experts, focused exclusively on the treatment of genitourinary tumours and who get together every year in the BestGU conference to assess the latest progress in this field have summarized the most important advances in a single review, along with a critical assessment of whether these results should alter daily clinical practice.

Relevant Design Aspects to Improve the Stability of Titanium Dental Implants.

Post-extractional implants and immediate loading protocols are becoming much more frequent in everyday clinical practice. Given the existing literature about tapered implants, the objective of this paper was to understand whether implant shape had a direct influence on the results of the insertion torque (IT) and implant stability quotient (ISQ). Seven tapered implant prototypes were developed and distributed into three groups and compared with a control cylindrical implant-VEGA by Klockner Implant System. The implants were inserted into bovine bone type III according to Lekholm and Zarb Classification. The sample size was n = 30 for the three groups. Final IT was measured with a torquemeter, and the ISQ was measured with Penguin Resonance Frequency Analysis (RFA). Modifications done to the Prototype I did not reveal higher values of the ISQ and IT when compared to VEGA. In the second group, when comparing the five prototypes (II-VI) with VEGA, it was seen that the values of the ISQ and IT were not always higher, but there were two values of the ISQ that were statistically significantly higher with the 4.0 mm diameter Prototypes II (76.3 ± 6.1) and IV (78 ± 3.7). Prototype VII was the one with higher and significant values of the ISQ and IT. In both diameters and in both variables, all differences were statistically significant enough to achieve the higher values of primary stability values (IT and ISQ). Given the limitations of this study, it can be concluded that when there is an increase of the diameter of the implant and body taper, there is an increase of the ISQ and IT, showing that the diameter of the implant is an important criteria to obtain higher values of primary stability.

Fatigue of Narrow Dental Implants: Influence of the Hardening Method.

The use of narrow titanium dental implants (NDI) for small ridges, reduced interdental space, or missing lateral incisors can be a viable option when compared to the conventional wider dental implants. Furthermore, in many cases, standard diameter implant placement may not be possible without grafting procedures, which increases the healing time, cost, and morbidity. The aim of this study was to analyze the mechanical viability of the current narrow implants and how narrow implants can be improved. Different commercially available implants (n = 150) were tested to determine maximum strength, strain to fracture, microhardness, residual stress, and fatigue obtaining the stress-number of cycles to fracture (SN) curve. Fractography was studied by scanning electron microscopy. The results showed that when the titanium was hardened by the addition of 15% of Zr or 12% cold worked, the fatigue limit was higher than the commercially pure grade 4 Ti without hardening treatment. Grade 4 titanium without hardening treatment in narrow dental implants can present fractures by fatigue. These narrow implants are subjected to high mechanical stresses and the mechanical properties of titanium do not meet the minimal requirements, which lead to frequent fractures. New hardening treatments allow for the mechanical limitations of conventional narrow implants to be overcome in dynamic conditions. These hardening treatments allow for the design of narrow dental implants with enhanced fatigue life and long-term behavior.

Repeatability of the resonance frequency analysis values in implants with a new technology.

BACKGROUND: Assess the reliability (by means of reproducibility and repeatability) of the PenguinRFA system, analyse the ISQ values of different implant types and correlate the ISQ with the insertion torque during the placement of the implant. MATERIAL AND METHODS: 120 rough surface implants were placed in bovine bone (type II and III). The implants were divided into groups, according to its design. Once the implants were in place, the exact insertion torque was registered. Then, primary stability was measured by means of the resonance frequency analysis with the PenguinRFA and the Osstell ISQ devices. In each implant two transducers of each device were used. Three measurements were obtained with each transducer. RESULTS: The mean ISQ (implant stability quotient) of the whole sample is 67,70 ± 5,51. The Intraclass Correlation Coefficient (ICC) is 0,933 and 0,944 for transducers 1 and 2 respectively. The reproducibility is 0,906. The mean insertion torque is 24,54 ± 8,96N. The correlation between the ISQ and the insertion torque is 0,507 p<0,000 (MultiPeg 1) and 0,468 p<0,000 (MultiPeg 2) for bone type II and 0,533 p<0,801 (MultiPeg 1) and 0,193 p<0,140 (MultiPeg 2) for bone type III. CONCLUSIONS: The results of the present trial suggest that the PenguinRFA presents excellent reproducibility and repeatability, so it could be very useful in the monitoring of the stability of implants over time. Additionally, according to the results, the correlation between the IT and the RFA is low and there are no statistically significant differences in between implant types.

Crestal module design optimization of dental implants: finite element analysis and in vivo studies.

The aim of this study was to evaluate the biomechanical behavior of Bone Level dental implants with four different neck designs in contact with cortical bone. Numerical simulations were performed using a Finite Element Method (FEM) based-model. In order to verify the FEM model, the in silico results were compared with the results obtained from histological analysis performed in an in vivo study with New Zealand rabbits. FEM was performed using a computerized 3D model of Bone Level dental implants inserted in the lower jaw bone with an applied axial load of 100 N. The analysis was performed using four different implant neck designs: even surfaced, screwed, three-ring design and four-ring design. Interface are of bone growth was evaluated by analyzing the Bone-Implant-Contact (BIC) parameter obtained from in vivo histological process and analyzed by Scanning Electron Microscopy (SEM). Bone Level implants were inserted in the rabbit tibia, placing two implants per tibia. The BIC was evaluated after three and six weeks of implantation. FEM studies showed that the three-ring design presented lower values of stress distribution compared to the other studied designs. The lower levels of mechanical stress were then correlated with the in vivo studies, showing that the three-ring design presented the highest BIC value after 3 and 6 weeks of implantation. In silico and in vivo results both concluded that the implants with three-ring neck design presented the best biomechanical and histological behavior in terms of new bone formation, enhanced mechanical stability and optimum osseointegration.

Randomized phase III KEYNOTE-045 trial of pembrolizumab versus paclitaxel, docetaxel, or vinflunine in recurrent advanced urothelial cancer: results of >2 years of follow-up.

BACKGROUND: Novel second-line treatments are needed for patients with advanced urothelial cancer (UC). Interim analysis of the phase III KEYNOTE-045 study showed a superior overall survival (OS) benefit of pembrolizumab, a programmed death 1 inhibitor, versus chemotherapy in patients with advanced UC that progressed on platinum-based chemotherapy. Here we report the long-term safety and efficacy outcomes of KEYNOTE-045. PATIENTS AND METHODS: Adult patients with histologically/cytologically confirmed UC whose disease progressed after first-line, platinum-containing chemotherapy were enrolled. Patients were randomly assigned 1 : 1 to receive pembrolizumab [200 mg every 3 weeks (Q3W)] or investigator's choice of paclitaxel (175 mg/m2 Q3W), docetaxel (75 mg/m2 Q3W), or vinflunine (320 mg/m2 Q3W). Primary end points were OS and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) by blinded independent central radiology review (BICR). A key secondary end point was objective response rate per RECIST v1.1 by BICR. RESULTS: A total of 542 patients were enrolled (pembrolizumab, n = 270; chemotherapy, n = 272). Median follow-up as of 26 October 2017 was 27.7 months. Median 1- and 2-year OS rates were higher with pembrolizumab (44.2% and 26.9%, respectively) than chemotherapy (29.8% and 14.3%, respectively). PFS rates did not differ between treatment arms; however, 1- and 2-year PFS rates were higher with pembrolizumab. The objective response rate was also higher with pembrolizumab (21.1% versus 11.0%). Median duration of response to pembrolizumab was not reached (range 1.6+ to 30.0+ months) versus chemotherapy (4.4 months; range 1.4+ to 29.9+ months). Pembrolizumab had lower rates of any grade (62.0% versus 90.6%) and grade ≥3 (16.5% versus 50.2%) treatment-related adverse events than chemotherapy. CONCLUSIONS: Long-term results (>2 years' follow-up) were consistent with those of previously reported analyses, demonstrating continued clinical benefit of pembrolizumab over chemotherapy for efficacy and safety for treatment of locally advanced/metastatic, platinum-refractory UC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02256436.

Thickness of the buccal bone wall and root angulation in the maxilla and mandible: an approach to cone beam computed tomography.

BACKGROUND: The objective of this paper is to anatomically describe the bone morphology in the maxillary and mandibular tooth areas, which might help in planning post-extraction implants. METHODS: CBCT images (Planmeca ProMax 3D) of 403 teeth (208 upper teeth and 195 lower teeth) were obtained from 49 patients referred to the Dental School of Seville from January to December 2014. The thickness of the facial wall was measured at the crest, point A, 4 mm below, point B, and at the apex, point C. The second parameter was the angle formed between the dental axis and the axis of the basal bone. RESULTS: A total of 403 teeth were measured. In the maxilla, 89.4% of incisors, 93.94% of canines, 78% of premolars and 70.5% of molars had a buccal bone wall thickness less than the ideal 2 mm. In the mandible, 73.5% of incisors, 49% of canines, 64% of premolars and 53% of molars had < 1 mm buccal bone thickness as measured at point B. The mean angulation in the maxilla was 11.67 ± 6.37° for incisors, 16.88 ± 7.93° for canines, 13.93 ± 8.6° for premolars, and 9.89 ± 4.8° for molars. In the mandible, the mean values were 10.63 ± 8.76° for incisors, 10.98 ± 7.36° for canines, 10.54 ± 5.82° for premolars and 16.19 ± 11.22° for molars. CONCLUSIONS: The high incidence of a buccal wall thickness of less than 2 mm in over 80% of the assessed sites indicates the need for additional regeneration procedures, and several locations may also require custom abutments to solve the angulation problems for screw-retained crowns.

Unravelling the effect of macro and microscopic design of dental implants on osseointegration: a randomised clinical study in minipigs.

Several dental implants are commercially available and new prototype design are constantly being fabricated. Nevertheless, it is still unclear what parameters of the design affect most the osseointegration of dental implants. The purpose of this study is to assess the effects of the microscopic and macroscopic design of dental implants in the osseointegration by comparing three macroscopic designs (Straumann tissue level (STD), essential cone (ECD) and prototype design (PD)) and six surface treatments. A total of 96 implants were placed in 12 minipigs. The implant stability quotient (ISQ), was assessed at the time of implantation, as well as at 2, 4 and 8 weeks. Histomorphometric and statistical analyses were conducted at the different sacrifice times, being 2, 4 and 8 weeks, to analyse the bone to implant contact (BIC), the bone area density (BAT) and the density of bone outside the thread region (ROI). The macroscopic design results showed higher ISQ values for the ECD, whereas the histomorphometric analysis showed higher ossoeintegration values for the STD. Regarding the microscopic design, both Sandblasted plus acid etching (hydrochloric/sulphuric acid) in a nitrogen atmosphere (SLActive) and Shot-blasted or bombarded with alumina particles and posterior alkaline immersion and thermal treatment (ContacTi) showed superior results in terms of osseointegration and reduced the osseointegration times from 8 weeks to 4 weeks compared to the other analysed surfaces. In conclusion, each of the macroscopic and microscopic designs need to be taken into account when designing novel dental implants to enhance the osseointegration process.

Correction to: SEOM clinical guidelines for the treatment of metastatic prostate cancer (2017).

The original article shows two mistakes, which are listed here.