Biomarker screening for pulmonary hypertension in VLBW infants at risk for bronchopulmonary dysplasia.

BACKGROUND: Very low birth weight (VLBW) infants demonstrate altered alveolar and pulmonary vascular development and carry an increased risk of developing bronchopulmonary dysplasia (BPD) and pulmonary hypertension (PH). Risk stratification for BPD-associated PH (BPD-PH) in at-risk infants may help tailor management, improve outcomes, and optimize resource utilization. METHODS: VLBW infants were screened for PH with blood gas measurements, serum NT-proBNP and bicarbonate (HCO3) levels, and echocardiograms if they remained on respiratory support at 34 weeks corrected gestational age. We then tested 11 models using different cutoffs for NT-proBNP and HCO3 to predict infants at low risk of BPD-PH. RESULTS: We identified PH in 34 of 192 (17.6%) VLBW infants. The median NT-proBNP in VLBWs with PH was 2769 pg/mL versus 917 pg/mL in those without PH (p < 0.0001). A model with NT-proBNP < 950 pg/mL and HCO3 < 32 mmol/L had a sensitivity of 100%, specificity of 34.2%, and negative predictive value of 100%. Using this model, 54 of 192 (28%) of the patients in this study would have been categorized as low risk for PH and could have avoided a screening echocardiogram. CONCLUSION: NT-proBNP and HCO3 together may serve as sensitive and cost-effective screening tools for BPD-PH in VLBW infants. IMPACT: NT-proBNP and HCO3 concentrations obtained together may help identify very low birth weight infants at risk for bronchopulmonary dysplasia who should undergo screening for pulmonary hypertension with echocardiography. This large dataset demonstrates that NT-proBNP and HCO3 levels together are more sensitive than NT-proBNP alone in identifying VLBW infants to undergo echocardiography. The combination of NT-proBNP and HCO3 levels may identify VLBW infants at low risk for pulmonary hypertension and thus those who may be able to avoid screening echocardiography.

Angiographic and Histopathological Characteristics of a Novel Polyacrylate Liquid Embolic Agent Compared to EVOH in a Large Animal Model.

PURPOSE: To study the in vivo safety and efficacy of a novel radiopaque non-adhesive polyacrylate peripheral liquid embolic system (PA, AMBER SEL-P) relative to ethylene vinyl alcohol copolymer (EVOH, OnyxTM) in a healthy swine endovascular model. MATERIALS AND METHODS: Twenty-five swine underwent rete mirabile and bilateral kidney embolization with PA or EVOH and were followed up for 24 hours (n=5) and 30 days (n=10), and 3 (n=10) months. Angiographic features (penetrability, radiopacity, catheter entrapment, fragmentation, occlusion, and vasospasm) were evaluated. Necropsy and histology were used to evaluate the non-target embolization, safety, target-embolization effectiveness by recanalization and to analyze the vascular response. RESULTS: No adverse events occurred during the embolization process or study period. The angiographic performance confirmed a significant positive effect of PA compared to EVOH in terms of penetrability (p=0.007), catheter entrapment (p=0.007), fragmentation (p=0.007), vascular occlusion (p=0.038), vasospasm (p=0.038), and follow-up vascular occlusion (p=0.038). Pre-necropsy angiography found no vascular recanalization in the organs treated with PA, while it was detected at 3 months in two samples treated with EVOH. Histologically, PA was classified as non-irritant compared with EVOH under the study conditions according to ISO 10993-6:2016 as modified. No systemic effects during necropsy were detected in the animals treated with these agents. CONCLUSION: This in vivo study concludes that the angiographic behavior of PA has advantages compared to EVOH. The embolization and biocompatibility of PA are similar to those of EVOH. PA is safe and effective for transarterial embolization in an acute, subacute, and chronic endovascular embolization model.

Preclinical evaluation of a new synthetic carbonate apatite bone substitute on periodontal regeneration in intrabony defects.

OBJECTIVE: To evaluate the potential of a novel synthetic carbonate apatite bone substitute (CO3 Ap-BS) on periodontal regeneration. BACKGROUND: The use of various synthetic bone substitutes as a monotherapy for periodontal regeneration mainly results in a reparative healing pattern. Since xenografts or allografts are not always accepted by patients for various reasons, a synthetic alternative would be desirable. METHODS: Acute-type 3-wall intrabony defects were surgically created in 4 female beagle dogs. Defects were randomly allocated and filled with CO3 Ap-BS (test) and deproteinized bovine bone mineral (DBBM) or left empty (control). After 8 weeks, the retrieved specimens were scanned by micro-CT, and the percentages of new bone, bone substitute, and soft tissues were evaluated. Thereafter, the tissues were histologically and histometrically analyzed. RESULTS: Healing was uneventful in all animals, and defects were present without any signs of adverse events. Formation of periodontal ligament and cementum occurred to varying extent in all groups without statistically significant differences between the groups. Residues of both bone substitutes were still present and showed integration into new bone. Histometry and micro-CT revealed that the total mineralized area or volume was higher with the use of CO3 Ap-BS compared to control (66.06 ± 9.34%, 36.11 ± 6.40%; p = .014, or 69.74 ± 2.95%, 42.68 ± 8.68%; p = .014). The percentage of bone substitute surface covered by new bone was higher for CO3 Ap-BS (47.22 ± 3.96%) than for DBBM (16.69 ± 5.66, p = .114). CONCLUSIONS: CO3 Ap-BS and DBBM demonstrated similar effects on periodontal regeneration. However, away from the root surface, more new bone, total mineralized area/volume, and higher osteoconductivity were observed for the CO3 Ap-BS group compared to the DBBM group. These findings point to the potential of CO3 Ap-BS for periodontal and bone regeneration.

Gastric preconditioning via percutaneous angioembolization before esophagectomy in patients at high risk for esophageal leak.

Anastomotic leaks and stenoses remain critical complications in esophagectomy and are related to conduit perfusion. Surgical gastric preconditioning has been described but requires additional surgery and creates scar tissue, potentially hindering future operation. We sought to evaluate the feasibility and safety of percutaneous gastric preconditioning by angioembolization to improve perfusion of gastric conduits before esophagectomy in a high-risk patient cohort. Patients pending an esophagectomy for cancer and deemed to be high risk for anastomotic complications underwent preconditioning by image-guided angioembolization. Preconditioning was performed on an outpatient basis by means of superselective embolization of the left gastric and short gastric arteries. Intraoperative conduit perfusion evaluation with indocyanine green and postoperative surgical outcomes was reviewed. Seventeen patients underwent gastric preconditioning, with no complications observed. Thirteen of the 17 patients ultimately underwent esophagectomy; the remaining four patients were not candidates for an operation. Patients proceeded to surgery a median of 23 days (interquartile range, 21-27 days) after preconditioning. The intraoperative indocyanine green perfusion of all conduits was appropriate, with no tip demarcation and with a median time to dye uptake of 20s (interquartile range, 15-20s). There were no anastomotic stenoses or leaks noted within the series. Gastric conduit preconditioning by percutaneous angioembolization of the left gastric and short gastric arteries can be performed safely and without operative delay in high-risk patients. Further evaluation of preconditioning for conduit optimization is warranted to limit the critical complications of anastomotic leak and stenosis in esophagectomy.

Influence of familial forms of inflammatory bowel disease on the use of immunosuppressants, biological agents, and surgery in the era of biological therapies. Results from the ENEIDA project.

BACKGROUND AND AIMS: Familial inflammatory bowel disease (IBD) history is a controversial prognostic factor in IBD. We aimed to evaluate the impact of a familial history of IBD on the use of medical and surgical treatments in the biological era. METHODS: Patients included in the prospectively maintained ENEIDA database and diagnosed with IBD after 2005 were included. Familial forms were defined as those cases with at least one first-degree relative diagnosed with IBD. Disease phenotype, the use of biological agents, or surgical treatments were the main outcomes. RESULTS: A total of 5263 patients [2627 Crohn's disease (CD); 2636 ulcerative colitis (UC)] were included, with a median follow-up of 31 months. Of these, 507 (10%) corresponded to familial forms. No clinical differences were observed between familial and sporadic IBD forms except a lower age at IBD diagnosis and a higher rate of males in familial forms of UC. In CD, the proportions of patients treated with thiopurines (54.4% vs 46.7%; P = .015) and survival time free of thiopurines (P = .009) were lower in familial forms. No differences were found regarding the use of biological agents. Concerning surgery, a higher rate of intestinal resections was observed in sporadic CD (14.8% vs 9.9%, P = .027). No differences were observed in UC. CONCLUSIONS: In the era of biological therapies, familial and sporadic forms of IBD show similar phenotypes and are managed medically in a similar way; whether these is due to lack of phenotypical differences or an effect of biological therapies is uncertain. What is already known on this topic: IBD's etiopathogenesis points to an interaction between environmental and genetic factors, being familial history a controversial prognostic factor. Biological agents use and need for surgery regarding familial or sporadic forms of IBDs present conflicting results. What this study adds: Familial and sporadic forms of IBD have similar phenotypes and are managed medically and surgically in a similar way. How this study might affect research, practice or policy: Familial aggregation should not be considered a factor associated with more aggressive disease.

Risk allocation schemes between public and private sectors in green energy projects.

In this research, we analyse how project risk allocation strategies impact the volume of private investment in renewable energy projects with the participation of both the public and private sectors. To this purpose, we analyse a sample formed by 2215 projects performed in 73 developing countries in the period 1997-2019 involving the following technologies: solar, hydro, wind, waste, biogas, biomass, and geothermal. Our findings reveal that those projects performed through governance schemes in which the private partner takes more project responsibilities attract more private money. Additional drivers for attracting private investment at the project level and institutional level are found. Furthermore, we reveal that the transference of project risks to the private partner emerges as a very relevant project feature that interacts with some of the project and institutional factors, revealing both complementary and substitution effects. The significance of this research extends beyond academia, since there are factors influencing private investment that can be controlled by various stakeholders in projects (such as policymakers, private investors, and project managers). Understanding their impact, significance, and interaction effects-factors that sometimes moderate or accentuate private investment-is crucial. The identified patterns illuminate optimal risk allocation practices, offering practical insights to enhance the effectiveness and sustainability of projects.

Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Patient-reported persistent symptoms after radiotherapy and association with quality of life for prostate cancer survivors.

PURPOSE: To evaluate the persistence of symptoms after radiotherapy (RT) for localised prostate cancer (PCa) and the association with quality of life (QOL). MATERIALS AND METHODS: Prospective patient-reported outcome (PRO) from a multi-institutional study on PCa treated with radical RT (2010-2014) was analysed. Data was collected at baseline (BL) and follow-ups (FUPs) up to 5 years. Patients with BL and ≥3 late FUPs (≥6 months) were analysed. PRO was scored by means of the IPSS and ICIQ-SF (urinary), LENT-SOMA (gastrointestinal [GI]), and EORTC-C30 (pain, insomnia, fatigue, and QOL) questionnaires. Symptoms were defined 'persistent' if the median score over FUPs was ≥3 (urinary) or ≥2 (GI, pain, insomnia, and fatigue), and worse than BL. Different thresholds were chosen to have enough events for each symptom. QOL was linearly transformed on a continuous scale (0-100). Linear-mixed models were used to identify significant differences between groups with and without persistent symptoms including age, smoking status, previous abdominal surgery, and diabetes as confounders. Mean QOL differences between groups were evaluated longitudinally over FUPs. RESULTS: The analysis included 293 patients. Persistent urinary symptoms ranged from 2% (straining) to 12% (weak stream, and nocturia). Gastrointestinal symptoms ranged from 7% (rectal pain, and incontinence) to 30% (urgency). Proportions of pain, insomnia, and fatigue were 6, 13, and 18%. Significant QOL differences of small-to-medium clinical relevance were found for urinary incontinence, frequency, urgency, and nocturia. Among GI symptoms, rectal pain and incontinence showed small-to-medium differences. Fatigue was associated with the largest differences. CONCLUSIONS: The analysis showed that symptoms after RT for PCa occur with different persistence and their association with QOL varies in magnitude. A number of persistent urinary and GI symptoms showed differences in a comparable range. Urinary incontinence and frequency, rectal pain, and faecal incontinence more often had significant associations. Fatigue was also prevalent and associated with largely deteriorated QOL.

Spontaneous regeneration of keratinized tissue at implants and teeth.

AIM: To investigate the spontaneous regeneration of the implanto-mucosal and dento-gingival unit after complete removal of keratinized tissue (KT). MATERIALS AND METHODS: One hemi-mandible per dog (n = 4) was allocated to receive three dental implants (test sites, premolar region), whereas three premolars on the contralateral side were controls. After osseointegration, the entire KT (buccal + lingual) was surgically excised on all test and control sites, leaving the bone exposed. Clinical measurements were performed before excision (T0 ) and after 12 weeks (T1 ). Following healing, the animals were euthanized, and the specimens were histologically processed. Descriptive statistical analyses were performed. RESULTS: Clinical measurements revealed that at T1 , on all teeth, a band of KT was spontaneously regenerated (mean width: 2.60 ± 0.66 mm), whereas on implants, KT was detected only occasionally at mesial or distal but not at buccal sites (mean total: 0.35 ± 0.53 mm; p < .0001). Histologically, spontaneous regeneration of the dento-gingival unit was evident, displaying masticatory mucosa. At the implant sites, on the other hand, the implanto-mucosal unit was characterized by a non-keratinized epithelium and elastic fibres, indicating the characteristics encountered in alveolar mucosa. CONCLUSION: After excision of KT at implant sites, the spontaneous regeneration of the soft tissue is characterized by a non-keratinized epithelium typical for alveolar mucosa, while at tooth sites the spontaneous regeneration was characterized by soft tissue resembling gingiva.

Immediate placement of one-piece zirconia implants with or without xenograft into the buccal gap. Soft tissues as secondary outcomes of an experimental in vivo study.

OBJECTIVE: To histologically evaluate soft tissue healing following immediately placed one-piece zirconia implant and grafting a xenograft into the buccal gap. MATERIALS AND METHODS: The third and fourth premolars (PM3 and PM4) in both quadrants of the mandible of nine dogs were used for this experiment. Those teeth were removed flapless and implants were placed into the distal sockets in a lingual position. In one side of the jaw, the gap between the implant and the socket walls was grafted (test) while no grafting was performed in the contralateral side (control), randomly selected. After 6 months of healing, biopsies were obtained and prepared for histological analysis. Soft tissue measures like supracrestal soft tissue height (STH), length of barrier epithelium (BE), and connective tissue (CTC) were measured at buccal and lingual surfaces. RESULTS: The marginal mucosa was in a coronal position on the test side compared with the control side. At the buccal surface, the BE was longer in the test side than in the control side, while the CTC was longer in the control side than in the test side. For the STH (BE + CTC), the difference between the groups was not statistically significant. CONCLUSION: The placement of a xenograft into the gap between a 1-piece zirconia implant and the buccal wall in dogs modified the process of soft tissue healing, providing less soft tissue recession. The gap size seems to have a modifying effect on the application of this protocol.

Clinical and histologic evaluation of heterotopic mucosa transpositioning at teeth and dental implants.

AIM: To investigate the healing after heterotopic mucosa transpositioning at dental implants and teeth. MATERIALS AND METHODS: One hemimandible per dog (n = 4) was allocated to receive 3 implants (test), whereby 3 premolars on the contralateral side served as controls. After osseointegration, a Z-plasty was performed on the buccal aspect of the test and control sites to heterotopically move the zone of keratinized tissue (KT) into a region with non-keratinized tissue (nKT) and vice versa. Clinical measurements were performed before (T0) and at 12 weeks following heterotopic transposition (T1). Thereafter, specimens were processed for histological analysis. RESULTS: Clinical measurements revealed that at T1, a band of KT was reestablished at teeth (mean: 2.944 ± 1.866 mm), whereas at implants, the transpositioned nKT resulted in a mucosa without any signs of keratinization (mean: 0 mm; p < .0001). At implant sites, the probing attachment level loss was more pronounced compared to tooth sites (-1.667 ± 1.195 mm and -1.028 ± 0.878 mm, respectively; p = .0076). Histologically, the transpositioned nKT, was accompanied by the formation of KT at the tooth but not at implant sites. The supracrestal soft tissues were statistically significantly higher at tooth compared to implant sites (2.978 ± 0.483 mm and 2.497 ± 0.455 mm, p = .0083). The transpositioned KT remained mostly unaltered in its morphological characteristics. CONCLUSIONS: The findings of this study indicate that: (a) transpositioned KT may retain its morphological characteristics; and (b) transpositioned nKM was accompanied by the formation of KT at the tooth but not at implant sites.

Sequential osseointegration of a novel implant system based on 3D printing in comparison with conventional titanium implants.

OBJECTIVES: To evaluate the sequential osseointegration of a novel titanium implant system based on a 3D printing technology in comparison with conventional titanium implants. MATERIAL AND METHODS: Two novel titanium implants based on 3D printing were tested in the mandible of eight Beagle dogs. As a control, two different commercially available titanium implants were used. The implants were staged to accommodate healing periods of 2 and 6 weeks. The primary outcome variable was bone-to-implant contact (BIC) in non-decalcified tissue sections and micro-CT analysis. RESULTS: Histomorphometrically, the proportions of tissues adjacent to the implant surfaces were similar for all implants, whereas the BIC percentage of new mineralized bone was greater for the control implants after both 2 and 6 weeks (p < .05). Micro-CT analysis revealed increasing osseous volume and BIC from 2 to 6 weeks. In contrast to the histomorphometry, the BIC evaluation with the micro-CT data revealed a significantly higher BIC for the two test implants compared with controls (p < .001). The analysis of the total implant surface area disclosed a value that was approximately double as high for the test compared to the control implants. CONCLUSIONS: The novel titanium implant system based on 3D printing yielded values for osseointegration that were adequate and satisfactory. The higher percentage of new mineralized bone in the control implants is explained by the fact of a completely different three-dimensional surface area.

Fostering research in pediatric interventional radiology: needs assessment and suggestions for support.

BACKGROUND: Due to the rarity of pediatric diseases, collaborative research is the key to maximizing the impact of research studies. A research needs assessment survey was created to support initiatives to foster pediatric interventional radiology research. OBJECTIVE: To assess the status of pediatric interventional radiology research, identify perceived barriers, obtain community input on areas of research/education/support, and create metrics for evaluating changes/responses to programmatic initiatives. MATERIALS AND METHODS: A survey link was sent to approximately 275 members of the Society for Pediatric Interventional Radiology (SPIR) between May and October 2020. Data was collected using a web-based interface. Data collected included practice setting, clinical role, research experience, research barriers, and suggestions for future initiatives. RESULTS: Fifty-nine surveys were analyzed with a staff physician survey response rate of 28% (56/198). A wide range of practice sizes from 15 countries were represented. Respondents were predominantly staff physicians (95%; 56/59) with an average of 11 years (range: 1-25 years) of clinical experience working at academic or freestanding children's hospitals. A total of 100% (59/59) had research experience, and 70% (41/58) had published research with a mean of 30 peer-reviewed publications (range: 1-200). For job security, 56% (33/59) of respondents were expected or required to publish, but only 19% (11/58) had research support staff, and 42% (25/59) had protected research time, but of those, 36% (9/25) got the time "sometimes or never." Lack of support staff, established collaborative processes, and education were identified as top barriers to performing research. CONCLUSIONS: The needs assessment survey demonstrated active research output despite several identified barriers. There is a widespread interest within the pediatric interventional radiology community for collaborative research.

A Systematic Review and a Meta-analysis of Randomized Controlled Trials' Control Groups in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC).

PURPOSE OF REVIEW: Determining the risk for progression or survival after standard androgen deprivation treatment (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) is essential for stratifying patients according to expected outcomes in future studies of treatment combination. This systematic review and meta-analysis aims to estimate the progression-free survival (PFS) and overall survival (OS) probabilities in the control group of randomized controlled trials (RCTs) of different regimens of standard androgen deprivation treatment (ADT) in mHSPC and to identify possible predictors of outcomes. RECENT FINDINGS: Studies reporting time-dependent outcomes (progression or death) after standard ADT treatment of mHSPC were searched in MEDLINE, CANCERLIT, the Cochrane Controlled Trials Register, and the Cochrane Library from inception through June 2021. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using a distribution-free summary survival curve. Primary outcomes were actuarial probabilities of disease progression and survival. Fifteen studies met the inclusion criteria. The pooled estimate of the actuarial PFS rate was 35.2% at two years. The pooled actuarial OS rate was 62.5% at three years. Heterogeneity among studies was highly significant for all outcomes. By univariate meta-regression analyses, high-volume disease and the presence of visceral metastases were associated with shorter survival. Our findings show that PFS and OS are highly variable in patients with mHSPC treated with ADT, providing a helpful benchmark for indirect comparisons of the benefits of the combination of chemotherapy and second-generation hormonotherapy.

Regeneration of keratinized tissue around teeth and implants following coronal repositioning of alveolar mucosa with and without a connective tissue graft: An experimental study in dogs: Fifty years after Karring's landmark study: Fifty years after Karring's 71 landmark study.

AIM: To compare clinical and histological keratinized tissue formation around teeth and implants following coronal repositioning of alveolar mucosa with or without a connective tissue graft (CTG). MATERIALS AND METHODS: In nine beagle dogs, the third and fourth premolars (P3 and P4) were extracted from one side of the maxilla. Three months after the tooth extraction, a full-thickness buccal flap was raised and two implants were placed in those healed areas. On the contra-lateral side, a buccal flap was also raised at the P3 and P4 areas. Before suturing, the dogs were randomly assigned to three study groups (control, non-keratinized tissue [NKT], and non-keratinized tissue CTG [NKT-CTG]). In the control group, the buccal flaps were re-positioned around the teeth (P3 and P4) on one side, and implants on the other side, presenting an adequate band of keratinized tissue (KT). For the NKT and NKT-CTG groups, this buccal KT was then excised. In the NKT group, the buccal flap without KT (alveolar mucosa) was re-positioned around the teeth and implants. In the NKT-CTG group, a CTG taken from the excised KT was sutured to the buccal alveolar mucosa and then both were re-positioned around the teeth and implants. The clinical height of the KT was measured at baseline and at 1, 2, and 3 months of healing. The animals were sacrificed at 3 months, at which point the KT height was measured histologically. RESULTS: The control group presented normal healing with a band of KT surrounding the teeth and implants. In the NKT and NKT-CTG groups, a new KT band approximately 2 mm in height (measured clinically and histologically) spontaneously formed around all teeth, regardless of whether a CTG had been placed. In the NKT implant group, no new KT was observed (clinically or histologically). Around the implants in the NKT-CTG group, a small amount of KT was formed in just two of the six implants. CONCLUSIONS: After surgical excision of KT, spontaneous KT is formed around teeth but not around implants, regardless of the placement of a CTG.

Development of a new preclinical model to study early implant loss: a validation study in the beagle dog.

OBJECTIVES: To develop a new preclinical model to study early implant loss, where local infection conditions would impair the implant osseointegration. MATERIALS AND METHODS: Forty-eight smooth, 2.9-mm diameter experimental implants were placed in the mandible of 8 beagle dogs (3 in each side). In half of the animals (test group, n = 24 implants), the implants received ligatures around the implant-abutment connection. In the other half, no ligatures were placed (control group, n = 24 implants). Four weeks later, implants were extracted in a flapless approach and standard 3.3-mm diameter SLActive implants were placed into the same osteotomy site without any further drilling. Eight weeks after the second implantation, animals were sacrificed and analyzed in terms of implant survival. RESULTS: After 8 weeks of healing, 4 implants were lost in the control group and 14 in the test group. This corresponded to a 17.4% of early implant loss in the control group and 58.3% in the test. Most of the early failures occurred within the first 5 weeks of healing. CONCLUSIONS: Implants placed in a pre-contaminated site present higher early loss than those placed in a non-contaminated site. This study represents a valid and robust preclinical model to study mechanisms and reduction of early implant loss as new technologies become available. CLINICAL RELEVANCE: Scientific rationale for the study: There is lack of animal models to study early implant loss. Thus, a proposal of a new model is presented. With the validation of this model, new technologies can be implemented to prevent early implant loss.

Adherence improvement in patients with ulcerative colitis: a multidisciplinary consensus document.

OBJECTIVES: a) to analyze the evidence available about poor adherence/non-adherence, including prevalences, associated factors, and interventions in ulcerative colitis (UC) patients; b) to provide a framework to improve poor adherence/non-adherence. METHODS: a qualitative approach was used. A literature review was performed using Medline. Primary searches were performed with Mesh and free texts to identify articles that analyzed prevalence, causes, associated factors, and interventions designed to improve poor adherence/non-adherence in UC patients. Study quality was evaluated using the Oxford scale. The results were presented and discussed in a nominal group meeting comprising a multidisciplinary committee of six gastroenterologists, one psychologist, one nurse, and one patient. Several overarching principles and recommendations were generated. A consensus procedure was implemented via a Delphi process, during which each committee member produced a score ranging from 0 = totally disagree to 10 = totally agree. Agreement was considered when at least 70 % of participants had voted ≥ 7. RESULTS: the literature review included 75 articles. Non-adherence rates ranged from 7 % to 72 %. We found a great variability in the methods employed to assess adherence, associated factors, and interventions designed to improve adherence. Overall, eight overarching principles and six recommendations were generated, all of them achieving the pre-established agreement level, including, among others, the identification, classification, and management of non-adherence. CONCLUSIONS: Poor adherence/non-adherence are common in UC patients, this being a relevant clinical concern. Health professionals should address this issue and actively involve their patients in implementing effective, individualized interventions to improve adherence.

In vivo tumor growth inhibition by Solanum tuberosum aspartic protease 3 (StAP3) treatment.

Solanum tuberosum aspartic Proteases (StAPs) show selective plasma membrane permeabilization, inducing cytotoxicity of cancer cells versus normal cells in vitro. Herein, we aimed to evaluate both StAP3 systemic toxicity and antitumoral activity against human melanoma in vivo. The toxicity of a single high dose of StAP3 (10 µg/g body weight, intraperitoneally) was assessed in a Balb/c mice model. Subcutaneous A375 human melanoma xenografts in athymic nude (nu/nu) mice were induced. Once tumors developed (mean larger dimension = 3.8 ± 0.09 mm), mice were StAP3-treated (6 µg/g body weight, subcutaneously under the tumor at a single dose). For both models, controls were treated with physiologic saline solution. StAP3-treated mice showed a significant inhibition of tumor growth (p < 0.05) compared with controls. No signs of toxicity were detected in StAP3-treated mice in both models. These results suggest the potential of these plant proteases as anticancer agents.

Oncological and obstetrical outcomes after neo-adjuvant chemotherapy followed by fertility-sparing surgery in patients with cervical cancer ≥2 cm.

OBJECTIVE: There is significant debate between up-front radical trachelectomy versus neo-adjuvant chemotherapy before fertility-sparing surgery in patients with tumors ≥2 cm. The aim of this study was to report on the oncological and obstetrical outcome of neo-adjuvant chemotherapy followed by fertility-sparing surgery, in patients diagnosed with cervical cancer ≥2 cm. METHODS: This was a retrospective review of patients diagnosed with cervical cancer measuring ≥2 cm to ≤6 cm, who were scheduled to undergo neo-adjuvant chemotherapy before fertility-sparing surgery, at six institutions from four Latin American countries between February 2009 and February 2019. Data collected included: age, International Federation of Gynecology and Obstetrics (FIGO) 2009 stage, histology, tumor size, pre-treatment imaging work-up, chemotherapy agents and number of cycles, toxicity, clinical and imaging response rate, type of fertility-sparing surgery, pathology results, timing of lymphadenectomy, follow-up time, and obstetrical and oncological outcomes. RESULTS: A total of 25 patients were included, with a median age of 27 years (range 20-37): 17 patients had stage IB1, 7 had stage IB2 cervical cancer, and 1 patient had stage IIA1 (FIGO 2009); 23 patients had squamous cell carcinoma and 2 patients had adenocarcinoma. The median number of chemotherapy cycles was 3 (range 3-6) and no toxicity grade 3-4 was reported. Lymphadenectomy was performed before chemotherapy in 6 (24%) patients. After neo-adjuvant chemotherapy 20 patients were scheduled for radical trachelectomy (11 abdominal and 9 laparoscopic) and 5 patients for conization. After surgery, no residual disease was found in 11 patients (44%). Fertility was preserved in 23 patients (92%) and 10 patients became pregnant (43.5%). After a median follow-up time of 47 months (13-133), 3 patients had recurrent disease (3/23=13%), 2 were alive without disease, and 1 patient had disease at last contact. CONCLUSION: Neo-adjuvant chemotherapy followed by fertility-sparing surgery is feasible in well selected patients with cervical tumors ≥2 cm. Future studies should focus on the timing of lymphadenectomy and type of cervical surgery.

Immediate one-piece zirconia implants with/without xenograft in the buccal gap: A 6-month pre-clinical study.

OBJECTIVE: To histologically evaluate healing following grafting a xenogenous bone substitute in the buccal gap around the immediately placed one-piece zirconia implant. MATERIALS AND METHODS: The third and fourth premolars (PM3 and PM4) in both quadrants of the mandible of nine Mongrel Hound dogs were used for this experiment. They have been removed, and the recipient sites were prepared. The implants were placed in a lingual position in the socket. In one side of the jaw, the gap between the implant and the socket walls was grafted (test) while no grafting was performed in the contralateral side (control), randomly selected. After 6 months of healing, biopsies were obtained and prepared for histological analysis. Vertical and horizontal measures were recorded in buccal and lingual surface. RESULTS: The hard tissue was in a coronal position on the test side compared with the control side. The bone thickness around ZLA (zirconia large-grit sandblasted and acid-etched surface) level was larger on the test side. On the test side, the first bone-implant contact and bone crest, at the buccal aspect, were more coronal to ZLA in PM4 while in PM3 the same happened with the bone crest. The width of the buccal bone wall was larger in PM4 than in PM3 at the ZLA level and 1 mm apical to ZLA. CONCLUSION: The placement of a xenograft in the gap between 1-piece zirconia implant and the buccal wall in dogs modified the process of hard tissue healing, providing additional amount of hard tissue.