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.

The HSACat Project: A Prospective Multicenter Observational Study of Spontaneous Subarachnoid Hemorrhage in Catalonia, Spain.

BACKGROUND: Incidence, clinical course, and fatality of spontaneous subarachnoid hemorrhage (SAH) are evolving, with prevalence of risk factors diminishing, implementation of early detection programs and strategies for priority aneurysm exclusion, technical refinement with less invasive procedures, and improvements in neurocritical care. Modern epidemiological and prognostic data are lacking, especially in southern European and Mediterranean populations. METHODS: A prospective multicenter observational study on SAH was held in Catalonia, Northeast Spain, from 2020 to 2022 (HSACat project). All public tertiary hospitals participated in a common registry. Primary end points were functional outcomes (modified Rankin Scale) and mortality at 12 months. Secondary aims included epidemiological data, passage of patients between referral and tertiary hospitals, diagnostic and treatment delays, and in-hospital complications. RESULTS: Of 550 SAH cases reported in Catalonia (2020-2022), a complete registry for analysis was available for 474. Death rate was 20.6% during hospital admission and 26.9% at 1 year. Good functional outcome (modified Rankin Scale score 0-2) was observed in 63.4%, 70.1%, and 76.0% at 3, 6, and 12 months. Age at presentation was younger in men, patients who smoked, and patients with hypertension (P < 0.05). The female-to-male ratio was 3:2 except in the nonaneurysmal group. Time from onset to tertiary hospital admission was longer in rural than in metropolitan areas (7.0 hours vs. 4.7 hours, P < 0.01). Aneurysm occlusion in the first 72 hours was achieved in 83.3%; mainly endovascularly (77.5%) followed by microsurgically (19.3%). CONCLUSIONS: Even when most patients received timely aneurysm treatment, case fatality rates were considerably high. Data provided by the HSACat project may have public health effects and be used to guide prevention programs and screening strategies.

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.

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.

A methodological approach for enhancing visualization of country data representation in the presence of significant spatial disparity.

In this article, we present a methodological approach to address spatial disparity in global data representation, introducing an algorithm called Flexible Mapping to Understand Spatial Analysis (FLEMUSA). We utilize world maps to depict various data points across countries, revealing substantial variation among them. However, conventional choropleth maps often fail to effectively represent regions with sparse data, obscuring valuable insights. To mitigate this issue, we propose interactive graphical methods in both two and three dimensions, implemented through open-source Python code accessible via Google Colab. Our approach includes several contributions such as excluding countries without data from the representation, scaling magnitudes within country borders, focusing on regional analysis, and using logarithmic scales for bubble maps proportional to country sizes. Additionally, we offer interactive 2D and 3D representations, rotatable 3D representations, and zoomable options, facilitating enhanced visualization of regional similarities amidst data heterogeneity. Through this algorithm, we aim to improve the clarity and interpretability of spatial data analysis, integrating solutions for extreme data overdispersion, all programmed with open-source code.-Utilization of world maps for visual representation of data across countries mitigating the overdispersion step by step.-Implementation of graphical methods, including interactive 2D and 3D maps, to address spatial disparity.-Provision of open-source code for customizable graphical representations, facilitating implementation in online journals as interactive code snippets.

Unusual adult-onset cardiac rhabdomyomas in tuberous sclerosis complex: a case report.

Background: Tuberous sclerosis complex is a genetic neurocutaneous autosomal dominant syndrome, characterized by the development of multiple benign tumors (hamartomas) affecting various systems. Heart-benign tumors that result from the complex are called cardiac rhabdomyomas. Unlike hamartomas that occur in other organs, cardiac rhabdomyomas are most prevalent in infants and very young children with tuberous sclerosis complex. We present a case of a young adult with tuberous sclerosis who had an unusually late diagnosis of cardiac rhabdomyomas. Case report: A 22-year-old male patient of Afro-descendant, diagnosed with tuberous sclerosis complex in childhood, presented with refractory epilepsy and was treated only with lacosamide. The patient came to medical consultation due to a recent history of episodic, persistent chest pain in the sternal region, associated with physical effort. Echocardiography revealed a non-dilated left ventricle, with several rounded masses of high echogenicity without pedicles at the apical level, the largest measuring 14 × 11 mm, consistent with cardiac rhabdomyomas. Conclusion: Cardiac rhabdomyomas rarely develop in adulthood for individuals with tuberous sclerosis. These late-onset cases can exhibit various symptoms, from simple to complex presentations. Regular clinical checkups are essential for adults with tuberous sclerosis complex.

Transcatheter pseudo-vascular isolation for localization and concentration of a large molecule theranostic probe into a transgenic OncoPIG kidney tumor.

INTRODUCTION: Great strides have been made identifying molecular and genetic changes expressed by various tumor types. These molecular and genetic changes are used as pharmacologic targets for precision treatment using large molecule (LM) proteins with high specificity. Theranostics exploits these LM biomolecules via radiochemistry, creating sensitive diagnostic and therapeutic agents. Intravenous (i.v.) LM drugs have an extended biopharmaceutical half-life thus resulting in an insufficient therapeutic index, permitting only palliative brachytherapy due to unacceptably high rates of systemic nontarget radiation doses to normal tissue. We employ tumor arteriole embolization isolating a tumor from the systemic circulation, and local intra-arterial (i.a.) infusion to improve uptake of a LM drug within a porcine renal tumor (RT). METHODS: In an oncopig RT we assess the in vivo biodistribution of 99mTc-labeled macroaggregated albumin (MAA) a surrogate for a LM theranostics agent in the RT, kidney, liver, spleen, muscle, blood, and urine. Control animals underwent i.v. infusion and experimental group undergoing arteriography with pseudovascular isolation (PVI) followed by direct i.a. injection. RESULTS: Injected dose per gram (%ID/g) of the LM at 1 min was 86.75 ± 3.76 and remained elevated up to 120 min (89.35 ± 5.77) with i.a. PVI, this increase was statistically significant (SS) compared to i.v. (13.38 ± 1.56 and 12.02 ± 1.05; p = 0.0003 p = 0.0006 at 1 and 120 min respectively). The circulating distribution of LM in the blood was less with i.a. vs i.v. infusion (2.28 ± 0.31 vs 25.17 ± 1.84 for i.v. p = 0.033 at 1 min). Other organs displayed a trend towards less exposure to radiation for i.a. with PVI compared to i.v. which was not SS. CONCLUSION: PVI followed by i.a. infusion of a LM drug has the potential to significantly increase the first pass uptake within a tumor. This minimally invasive technique can be translated into clinical practice, potentially rendering monoclonal antibody based radioimmunotherapy a viable treatment for renal tumors.

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.

Long Electrical Stability on Dual Acceptor p-Type ZnO:Ag,N Thin Films.

p-type Ag-N dual acceptor doped ZnO thin films with long electrical stability were deposited by DC magnetron reactive co-sputtering technique. After deposition, the films were annealed at 400 °C for one hour in a nitrogen-controlled atmosphere. The deposited films were amorphous. However, after annealing, they crystallize in the typical hexagonal wurtzite structure of ZnO. The Ag-N dual acceptors were incorporated substitutionally in the structure of zinc oxide, and achieving that; the three samples presented the p-type conductivity in the ZnO. Initial electrical properties showed a low resistivity of from 1 to 10-3 Ω·cm, Hall mobility of tens cm2/V·s, and a hole concentration from 1017 to 1019 cm-3. The electrical stability analysis reveals that the p-type conductivity of the ZnO:Ag,N films is very stable and does not revert to n-type, even after 36 months of aging. These results reveal the feasibility of using these films for applications in short-wavelength or transparent optoelectronic devices.

Interventional oncology in children: Where are we now?

Paediatric Interventional Oncology (IO) lags behind adult IO due to a scarcity of specific outcome data. The suboptimal way to evolve this field is relying heavily on adult experiences. The distinct tumour types prevalent in children, such as extracranial germ cell tumours, sarcomas, and neuroblastoma, differ strongly from those found in adults, presenting a completely different biological behaviour. Compounding this challenge, paediatric interventional radiology often employs adapted or off-label techniques, potentially compromising optimal outcomes. This review outlines the present indications for interventional radiology in paediatric cancer, from biopsy to supportive care, including complication management. It emphasises the role of locoregional approaches, and explores the status of common paediatric oncological diseases, highlighting areas where IO has made progress identifying potential opportunities for future advancements in this evolving field.

Treatment options in first-line metastatic renal carcinoma: A meta-analysis of 2556 patients treated with immune checkpoint inhibitors-based combinations in randomised controlled trials.

BACKGROUND & AIMS: The average five-year survival of metastatic renal cell carcinoma (mRCC) is 71%. However, there is significant variability in patient prognosis. Immune checkpoint inhibitors (ICIs) have been introduced into the treatment landscape of mRCC. This meta-analysis aimed to estimate progression-free and overall survival probabilities and identify possible outcome predictors of mRCC patients treated with ICI combination as first-line treatment. METHODS: Studies comparing the combination of ICI combinations versus standard of therapy for first-line treatment of advanced renal-cell carcinoma were searched in MEDLINE, CANCERLIT, the Cochrane Controlled Trials Register, and the Cochrane Library from inception through September 2023. Data on patient populations and outcomes were extracted from each study by three independent observers and combined using the DerSimonian and Laird methods. RESULTS: Six studies met the inclusion criteria. Globally, 5121 patients were included in this meta-analysis: 2556 patients treated with immune checkpoint inhibitors and 2565 with sunitinib as control. The ICI combination was associated with improved PFS (hazard ratio (HR) 0.68; 95 % confidence interval (CI), 0.56-0.81, p < 0.0001). Furthermore, ICI combination was also associated with OS improvement (HR 0.85; 95 % CI, 0.78-0.92, p = 0.001). There is no statistical increase in adverse events. CONCLUSIONS: Our findings show that PFS and OS are statistically increased in mRCC with ICI combination treatment by 32% and 15%, respectively.

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.

Pelvic bone marrow dose-volume predictors of late lymphopenia following pelvic lymph node radiation therapy for prostate cancer.

BACKGROUND AND PURPOSE: Given the substantial lack of knowledge, we aimed to assess clinical/dosimetry predictors of late hematological toxicity on patients undergoing pelvic-nodes irradiation (PNI) for prostate cancer (PCa) within a prospective multi-institute study. MATERIALS AND METHODS: Clinical/dosimetry/blood test data were prospectively collected including lymphocytes count (ALC) at baseline, mid/end-PNI, 3/6 months and every 6 months up to 5-year after PNI. DVHs of the Body, ileum (BMILEUM), lumbosacral spine (BMLS), lower pelvis (BMPELVIS), and whole pelvis (BMTOT) were extracted. Current analysis focused on 2-year CTCAEv4.03 Grade ≥ 2 (G2+) lymphopenia (ALC < 800/µL). DVH parameters that better discriminate patients with/without toxicity were first identified. After data pre-processing to limit overfitting, a multi-variable logistic regression model combining DVH and clinical information was identified and internally validated by bootstrap. RESULTS: Complete data of 499 patients were available: 46 patients (9.2 %) experienced late G2+ lymphopenia. DVH parameters of BMLS/BMPELVIS/BMTOT and Body were associated to increased G2+ lymphopenia. The variables retained in the resulting model were ALC at baseline [HR = 0.997, 95 %CI 0.996-0.998, p < 0.0001], smoke (yes/no) [HR = 2.9, 95 %CI 1.25-6.76, p = 0.013] and BMLS-V ≥ 24 Gy (cc) [HR = 1.006, 95 %CI 1.002-1.011, p = 0.003]. When acute G3+ lymphopenia (yes/no) was considered, it was retained in the model [HR = 4.517, 95 %CI 1.954-10.441, p = 0.0004]. Performances of the models were relatively high (AUC = 0.87/0.88) and confirmed by validation. CONCLUSIONS: Two-year lymphopenia after PNI for PCa is largely modulated by baseline ALC, with an independent role of acute G3+ lymphopenia. BMLS-V24 was the best dosimetry predictor: constraints for BMTOT (V10Gy < 1520 cc, V20Gy < 1250 cc, V30Gy < 850 cc), and BMLS (V24y < 307 cc) were suggested to potentially reduce the risk.

In vivo assessment of marine vs bovine origin collagen-based composite scaffolds promoting bone regeneration in a New Zealand rabbit model.

The ability of human tissues to self-repair is limited, which motivates the scientific community to explore new and better therapeutic approaches to tissue regeneration. The present manuscript provides a comparative study between a marine-based composite biomaterial, and another composed of well-established counterparts for bone tissue regeneration. Blue shark skin collagen was combined with bioapatite obtained from blue shark's teeth (mColl:BAp), while bovine collagen was combined with synthetic hydroxyapatite (bColl:Ap) to produce 3D composite scaffolds by freeze-drying. Collagens showed similar profiles, while apatite particles differed in their composition, being the marine bioapatite a fluoride-enriched ceramic. The marine-sourced biomaterials presented higher porosities, improved mechanical properties, and slower degradation rates when compared to synthetic apatite-reinforced bovine collagen. The in vivo performance regarding bone tissue regeneration was evaluated in defects created in femoral condyles in New Zealand rabbits twelve weeks post-surgery. Micro-CT results showed that mColl:BAp implanted condyles had a slower degradation and an higher tissue formation (17.9 ± 6.9 %) when compared with bColl:Ap implanted ones (12.9 ± 7.6 %). The histomorphometry analysis provided supporting evidence, confirming the observed trend by quantifying 13.1 ± 7.9 % of new tissue formation for mColl:BAp composites and 10.4 ± 3.2 % for bColl:Ap composites, suggesting the potential use of marine biomaterials for bone regeneration.

Enhancing the correlation between in vitro and in vivo experiments in dental implant osseointegration: investigating the role of Ca ions.

This study delves into the osteogenic potential of a calcium-ion modified titanium implant surface, unicCa, employing state-of-the-art proteomics techniques both in vitro (utilizing osteoblasts and macrophage cell cultures) and in vivo (in a rabbit condyle model). When human osteoblasts (Hobs) were cultured on unicCa surfaces, they displayed a marked improvement in cell adhesion and differentiation compared to their unmodified counterparts. The proteomic analysis also revealed enrichment in functions associated with cell migration, adhesion, extracellular matrix organization, and proliferation. The analysis also underscored the involvement of key signalling pathways such as PI3K-Akt and mTOR. In the presence of macrophages, unicCa initially exhibited improvement in immune-related functions and calcium channel activities at the outset (1 day), gradually tapering off over time (3 days). Following a 5-day implantation in rabbits, unicCa demonstrated distinctive protein expression profiles compared to unmodified surfaces. The proteomic analysis highlighted shifts in adhesion, immune response, and bone healing-related proteins. unicCa appeared to influence the coagulation cascade and immune regulatory proteins within the implant site. In summary, this study provides a comprehensive proteomic analysis of the unicCa surface, drawing correlations between in vitro and in vivo results. It emphasizes the considerable potential of unicCa surfaces in enhancing osteogenic behavior and immunomodulation. These findings significantly contribute to our understanding of the intricate molecular mechanisms governing the interplay between biomaterials and bone cells, thereby facilitating the development of improved implant surfaces for applications in bone tissue engineering.

Pesticides in soil, groundwater and food in Latin America as part of one health.

We here report of a conference about "Pesticides in Soil, Groundwater and Food in Latin America as part of One Health" that took place at the "IV Seminario Internacional de Sanidad Agropecuaria (SISA)" in Varadero, Cuba, 8-12 May 2023. Researchers of Latin America (Argentina, Brazil, Chile, Costa Rica, Colombia, Cuba, Mexico) and Switzerland (workshop initiator) held presentations about occurrence and effects of pesticides on the environment, human health, the replacement of highly hazardous pesticides (HHP) by agroecological alternatives and the agri-food value chain. In a subsequent round table discussion, the presenters identified deficits, needs, interests and opportunities. According to them, the lack of awareness of pesticide use affects the health and safety of workers applying the chemicals. Despite Latin America representing the main agricultural area in the world with a very intense pesticide use, monitoring data of pesticides in soil, surface and groundwaters, food, as well as in humans are missing. Risks of pesticides to humans should be assessed so that authorities can withdraw or limit within "short time" the access to corresponding formulations on the market. Also, communication is not state of the art and should be improved as, e.g. the teaching of workers and farmers, how to correctly use and apply pesticides or the briefing of decision makers. Pollinators suffer from multiple stressors not the least due to pesticides, and alternatives are badly needed. On the technical side, the different analytical methods to determine residues of active ingredients and transformation products in matrices of concern should be harmonized among laboratories.Seven future actions and goals were identified to overcome the above deficits. Next steps after the publishing of this conference report are to harmonize and complete the information status of the presenters by exchanging the results/data already present. Therefore, a platform of interaction to address issues described above and to enhance collaboration shall be created. Samples of different matrices shall be exchanged to harmonize the chemical analysis and establish interlaboratory comparisons. Such activities might be facilitated by joining international associations or organizations, where researchers can offer their expertise, or by forming a new pesticide network for Central and South America that could present tailored projects to national and international organizations and funding agencies.

Worsening of 2-year patient-reported intestinal functionality after radiotherapy for prostate cancer including pelvic node irradiation.

BACKGROUND AND PURPOSE: To quantify patient-reported 2-year intestinal toxicity (IT) from pelvic nodal irradiation (PNI) for prostate cancer. The association between baseline/acute symptoms and 2-year worsening was investigated. MATERIALS AND METHODS: Patient-reported IT was prospectively assessed through the Inflammatory Bowel Disease Questionnaire (IBDQ), filled in at baseline, radiotherapy mid-point and end, at 3 and 6 months and every 6 months until 5 years. Two-year deterioration of IBDQ scores relative to the Bowel Domain was investigated for 400 patients with no severe baseline symptoms and with questionnaires available at baseline, 2 years, RT mid-point and/or end and at least three follow-ups between 3 and 18 months. The significance of the 2-year differences from baseline was tested. The association between baseline values and ΔAcute (the worst decline between baseline and RT mid-point/end) was investigated. RESULTS: In the IBDQ lower scores indicate worse symptoms. A significant (p < 0.0001) 2-year mean worsening, mostly in the range of -0.2/-0.4 points on a 1-7 scale, emerged excepting one question (IBDQ29, "nausea/feeling sick"). This decline was independent of treatment intent while baseline values were associated with 2-year absolute scores. The ΔAcute largely modulated 2-year worsening: patients with ΔAcute greater than the first quartile (Q1) and ΔAcute less or equal than Q1 showed no/minimal and highly significant (p < 0.0001) deterioration, respectively. Rectal incontinence, urgency, frequency and abdominal pain showed the largest mean changes (-0.5/-1): risk of severe worsening (deemed to be of clinical significance if ≤ 2) was 3-5 fold higher in the ΔAcute ≤ Q1 vs ΔAcute > Q1 group (p < 0.0001). CONCLUSION: A modest but significant deterioration of two-year patient-reported intestinal symptoms from PNI compared to baseline was found. Patients experiencing more severe acute symptoms are at higher risk of symptom persistence at 2 years, with a much larger prevalence of clinically significant symptoms.

Controversies in the management of anti-TNF therapy in patients with Crohn's disease: a Delphi consensus.

BACKGROUND: Despite research, there are still controversial areas in the management of Crohn's disease (CD). OBJECTIVE: To establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD. METHODS: Clinical controversies in the management of CD using anti-TNF therapies were identified. A comprehensive literature review was performed, and a national survey was launched to examine current clinical practices when using anti-TNF therapies. Their results were discussed by expert gastroenterologists within a nominal group meeting, and a set of statements was proposed and tested in a Delphi process. RESULTS: Qualitative study. The survey and Delphi process were sent to 244 CD-treating physicians (response rate: 58%). A total of 14 statements were generated. All but two achieved agreement. These statements cover: (1) use of first-line non-anti-TNF biological therapy; (2) role of HLA-DQA1*05 in daily practice; (3) attitudes in primary non-response and loss of response to anti-TNF therapy due to immunogenicity; (4) use of ustekinumab or vedolizumab if a change in action mechanism is warranted; (5) anti-TNF drug level monitoring; (6) combined therapy with an immunomodulator. CONCLUSION: This document sought to pull together the best evidence, experts' opinions, and treating physicians' attitudes when using anti-TNF therapies in patients with CD.

Does faster weight trajectory lead to improved neurodevelopmental outcomes in ELBW infants with bronchopulmonary dysplasia?

OBJECTIVE: Examine the relationship between weight trajectory and 2-year neurodevelopmental outcomes for extremely low birthweight (ELBW) infants with BPD. STUDY DESIGN: Secondary analysis of infants born from 2010 to 2019. The predictor was BPD severity and the outcome was neurodevelopmental impairment, defined as any Bayley Scales of Infant Development (BSID) III score <70 at 24 months' corrected age. Repeated measures logistic regression was performed. RESULTS: In total, 5042 infants were included. Faster weight trajectory was significantly associated with a decreased probability of having at least one BSID III score <70 for infants with grade 1-2 BPD (p < 0.0001) and an increased probability of at least one BSID III score <70 for infants with grade 3 BPD (p < 0.009). There was no significant association between weight trajectory and BSID III score <70 for infants with grade 0 BPD. CONCLUSION: The association between postnatal weight trajectory and neurodevelopmental outcome in this study differs by BPD severity.

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.