Patient care and access to clinical trials in gynaecological oncology: global implications of the early phase of the COVID-19 pandemic.

PURPOSE: Our prospective international survey evaluated the impact of the early phase of the COVID-19 pandemic on the management gynaecological malignancies from the multidisciplinary physicians' perspective with particular focus on clinical infrastructures and trial participation. METHODS: Our survey consisted of 53 COVID-related questions. It was sent to healthcare professionals in gynaecological oncology centres across Europe and Pan-Arabian region via the study groups and gynaecological societies from April 2020 to October 2020. All healthcare professionals treating gynaecological cancers were able to participate in our survey. RESULTS: A total of 255 answers were collected from 30 countries. The majority (73%) of participants were gynaecological oncologists from university hospitals (71%) with at least an Intensive Care Unit with cardiopulmonary support available at their institutions. Most institutions continued to perform elective surgeries only for oncological cases (98%). Patients had to wait on average 2 weeks longer for their surgery appointments compared to previous years (range 0-12 weeks). Most cases that were prioritised for surgical intervention across all gynaecological tumours were early-stage disease (74%), primary situation (61%) and good ECOG status (63%). The radicality of surgery did not change in the majority of cases (78%) across all tumour types. During the pandemic, only 38% of clinicians stated they would start a new clinical trial. Almost half of the participants stated the pandemic negatively impacted the financial structure and support for clinical trials. Approximately 20% of clinicians did not feel well-informed regarding clinical algorithm for COVID-19 patients throughout the pandemic. Thirty percent stated that they are currently having trouble in providing adequate medical care due to staff shortage. CONCLUSION: Despite well-established guidelines, pandemic clearly affected clinical research and patientcare. Our survey underlines the necessity for building robust emergency algorithms tailored to gynaecological oncology to minimise negative impact in crises and to preserve access to clinical trials.

Textbook outcome in patients with biliary duct injury during cholecystectomy.

BACKGROUND: Iatrogenic bile duct injury (BDI) during cholecystectomy is associated with a complex and heterogeneous management owing to the burden of morbidity until their definitive treatment. This study aimed to define the textbook outcomes (TOs) after BDI with the purpose to indicate the ideal treatment and to improve it management. METHODS: We collected data from patients with an BDI between 1990 and 2022 from 27 hospitals. TO was defined as a successful conservative treatment of the iatrogenic BDI or only minor complications after BDI or patients in whom the first repair resolves the iatrogenic BDI without complications or with minor complications. RESULTS: We included 808 patients and a total of 394 patients (46.9%) achieved TO. Overall complications in TO and non-TO groups were 11.9% and 86%, respectively (P < .001). Major complications and mortality in the non-TO group were 57.4% and 9.2%, respectively. The use of end-to-end bile duct anastomosis repair was higher in the non-TO group (23.1 vs 7.8, P < .001). Factors associated with achieving a TO were injury in a specialized center (adjusted odds ratio [aOR], 4.01; 95% CI, 2.68-5.99; P < .001), transfer for a first repair (aOR, 5.72; 95% CI, 3.51-9.34; P < .001), conservative management (aOR, 5.00; 95% CI, 1.63-15.36; P = .005), or surgical management (aOR, 2.45; 95% CI, 1.50-4.00; P < .001). CONCLUSION: TO largely depends on where the BDI is managed and the type of injury. It allows hepatobiliary centers to identify domains of improvement of perioperative management of patients with BDI.

The Crucial Role of Breeder and Dog Owners Associations in Safeguarding Genetic Heritage of Endangered Balearic Dog Breeds: Gender Preference and Registry Adscription.

This study delves into the complex relationships between indigenous dog breeds in the Balearic Isles and their human counterparts, specifically breeders and owners. Using Canonical Correlation Analysis, the research examines variables such as breed registries and the number of breeders/owners, uncovering significant correlations within registries. For example, an increase in female auxiliary registrations corresponds to a decline in foundational registrations, indicating shifts in breed documentation dynamics. Similarly, a rise in definitive female registrations coincides with a decrease in foundational female registrations, suggesting increased pedigree awareness across generations. Beyond registries, the study explores the correlation between breeders/owners and various initial records, highlighting that a notable increase in breeders positively influences initial registrations, definitive totals, and overall counts, underscoring their crucial role in early breed stages. Gender preferences in registrations are noted, with a historical bias towards female entries during foundational stages gradually shifting in favor of males in definitive registrations. In conclusion, the research underscores the interconnected roles of breeders, owners, and comprehensive registries in preserving genetic diversity among Balearic dog breeds, emphasizing the need for ongoing efforts to address gaps in genealogical data for a more accurate understanding of breed dynamics.

Calcium hydroxide-loaded nanoparticles dispersed in thermosensitive gel as a novel intracanal medicament.

AIM: Design, produce and assess the viability of a novel nanotechnological antibacterial thermo-sensible intracanal medicament This involves encapsulating calcium hydroxide (Ca(OH)2) within polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) and dispersing them in a thermosensitive gel (Ca(OH)2-NPs-gel). In addition, perform in vitro and ex vivo assessments to evaluate tissue irritation and penetration capacity into dentinal tubules in comparison to free Ca(OH)2. METHODOLOGY: Reproducibility of Ca(OH)2-NPs was confirmed by obtaining the average size of the NPs, their polydispersity index, zeta potential and entrapment efficiency. Moreover, rheological studies of Ca(OH)2-NPs-gel were carried out with a rheometer, studying the oscillatory stress sweep, the mean viscosity value, frequency and temperature sweeps. Tolerance was assessed using the membrane of an embryonated chicken egg. In vitro Ca(OH)2 release was studied by direct dialysis in an aqueous media monitoring the amount of Ca(OH)2 released. Six extracted human teeth were used to study the depth of penetration of fluorescently labelled Ca(OH)2-NPs-gel into the dentinal tubules and significant differences against free Ca(OH)2 were calculated using one-way anova. RESULTS: Ca(OH)2-NPs-gel demonstrated to be highly reproducible with an average size below 200 nm, a homogeneous NPs population, negative surface charge and high entrapment efficiency. The analysis of the thermosensitive gel allowed us to determine its rheological characteristics, showing that at 10°C gels owned a fluid-like behaviour meanwhile at 37°C they owned an elastic-like behaviour. Ca(OH)2-NPs-gel showed a prolonged drug release and the depth of penetration inside the dentinal tubules increased in the most apical areas. In addition, it was found that this drug did not produce irritation when applied to tissues such as eggs' chorialantoidonic membrane. CONCLUSION: Calcium hydroxide-loaded PLGA NPs dispersed in a thermosensitive gel may constitute a suitable alternative as an intracanal antibacterial medicament.

Microcomputed tomographic evaluation of 6 NiTi files on the pericervical dentin and the smallest dentin thickness zones in mesial root canals of mandibular molars: an in vitro study.

OBJECTIVE: The aim of this study was to evaluate six files on the pericervical dentin (PCD) and the smallest dentin thickness zones (SDTZ) in mesial root canals of mandibular molars. MATERIALS AND METHODS: Sixty mandibular molars with two mesial canals and Vertucci configuration were aleatory allocated in 6 experimental groups of 10 molars and 20 root canals. Specimens were scanned before instrumentation using the SkyScan 1275 (Bruker microCT, Kontich, Belgium). Group 1 was treated with WaveOne Gold (WG), group 2 with Reciproc Blue (RB), group 3 with TRUShape (TS), group 4 with XP-endo Shaper (XP), group 5 with iRace (IR), and group 6 with TruNatomy (TN). After instrumentation, the molars were scanned again and the images recorded were reconstructed with the NRecon v.1.7 (Bruker micro-CT) and analyzed with CTAn v.1.20.8 software (Bruker micro-CT) quantifying the changes produced in the surface, volume, structure thickness, SMI, and centroids at the Pericervical Dentin area of the root canals (PCD) located from the root canal orifices at the floor of the pulp chamber to 4 mm in the apical direction, and the changes in the Smallest Dentin Thickness Zones (SDTZ) located (from the furcation to 4 mm and 7 mm in the apical direction. The data obtained were compared using Wilcoxon and ANOVA with a 5% significance level. RESULTS: XP and TN were similar in all the parameters (P >.05) at the PCD, but TN showed significant differences from WG, RB, TS, and IR (P <.05), while XP showed significant differences from WG (P <.05) in volume, surface, and structure thickness. Regarding the changes in the SDTZ, the amount of dentin removed was similar between the groups in both canals at the middle 1/3, at the cervical 1/3 for MB canals, and in ML canals for RB, TS, XP, IR, and TN (P>.05). The action of WG was significantly different from that of XP and TN in the cervical 1/3 of the ML canal (P <.05). CONCLUSIONS: XP and TN rotatory files with small taper and volume maintained better with minor changes at the PCD and SDTZ, while WG reciprocation file produced the largest change. All the files were maintained centered at the PCD, and their performances were safe with a minimal thickness higher 0.5 mm at the SDTZ, and without risk of perforation. TRIAL REGISTRATION: No clinical trials were indicated in this study. CLINICAL RELEVANCE: The choice of endodontic files is a relevant factor in the conservative performance of root canal treatments.

Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6-7 Months of age: A Phase 1/2 Randomized Trial.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. METHODS: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. RESULTS: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. CONCLUSIONS: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.

¿Cómo construir un Cuerpo Académico... y tener éxito? / How to integrate an Academic Group... and be successful?

Introducción: para las universidades públicas, uno de los indicadores fundamentales es consolidar los grupos de investigación en Cuerpos Académicos (CA). Sin embargo, no existe una guía que apoye la transición. El propósito es exponer algunas recomendaciones para conformar un CA con éxito, con base en las experiencias de trabajo del Cuerpo Académico Intervenciones para el Cuidado de la Salud. Desarrollo: los CA están conformados por docentes-investigadores de tiempo completo que comparten y desarrollan una línea de investigación en temas disciplinares o multidisciplinares, enfocados en objetivos académicos comunes. La reflexión que plantea este manuscrito contribuye a identificar las fortalezas y áreas de oportunidad de los grupos de investigación, así mismo se describen algunas estrategias para transitar y consolidar un CA: 1. Selección de los integrantes, 2. Línea de investigación, 3. Proyectos, 4. Servicio a la sociedad, 5. Trabajo colegiado, 6. Redes de investigación, 7. Integración de estudiantes y 8. Liderazgo transformacional. Conclusión: la creación de CA es fundamental en el desarrollo de las instituciones de educación superior en México, para alcanzar este reto es necesario integrar estrategias innovador... (AU)

Abstract Introduction: For public universities, a fundamental indicator is to consolidate research groups in Academic Bodies (AB). However, there is no guide to support the transition. Purpose: to present some recommendations to form AB successfully based on the work experiences of the Academic Body Interventions for Health Care. Development: The academic bodies are made up of full-time professors-researchers who share and develop a line of research on disciplinary or multidisciplinary topics and which entail a set of common academic objectives and goals. The reflection proposed by this manuscript contributes to identifying the strengths and areas of opportunity of the research groups, as well as describing some strategies to consolidate as an academic body: 1. The selection of the members, 2. The line of research, 3. Projects, 4. Service to society, 5. Collegiate work, 6. Research networks, 7. Integration of students and 8. Transformational leadership. Conclusion: Creating Academic Bodies is essential in the development of higher education institutions in Mexico, to meet this challenge it is necessary to integrate innovative strategies to generate and disseminate knowledge and the disposition of the members for collegiate work.

Baseline rotational thromboelastometry (ROTEM) values in a healthy, diverse obstetric population and parameter changes by pregnancy-induced comorbidities.

Background: Point-of-care testing provides a representation of the patient's coagulability status during effective postpartum hemorrhage management. Baseline values of rotational thromboelastometry (ROTEM) have not yet been reported in a heterogeneous obstetric population. This study aimed to establish a baseline for a diverse population representative of the United States. The secondary aim was to evaluate the association of these hematologic parameters with comorbidities, race, and socioeconomic factors. Methods: The study was a retrospective review of collected ROTEM values of women undergoing vaginal or cesarean delivery with a history of or at risk for postpartum hemorrhage. Patients were divided into healthy and comorbid groups. Exclusion criteria for both groups included active or recent bleeding, receipt of blood products or clot-enhancing factors, and liver disease. Mean values of ROTEM by race and comorbidities were included. Median values were reported for intrinsic pathway thromboelastometry (INTEM), extrinsic pathway thromboelastometry (EXTEM), and fibrin polymerization thromboelastometry (FIBTEM) amplitude at 10 minutes (A10) and 20 minutes (A20), coagulation time, clot formation time, and maximum clot firmness. Results: A total of 681 records were reviewed; 485 met inclusion criteria, and 267 met healthy criteria. The mean (standard deviation) demographics for maternal age (years), body mass index (kg/m2), and gestational age (weeks) were 32.2 (5.7), 34 (7.3), and 35.4 (5), respectively. The median INTEM, EXTEM, and FIBTEM A10 were 63, 65, and 23 mm. The mean for INTEM, EXTEM, and FIBTEM A10 was increased for those who were Black or obese, whereas a decreased FIBTEM and EXTEM A10 was noted in those who were Asian or those who had the hemolysis, elevated liver enzymes, low platelet syndrome. Conclusions: Our heterogeneous population presents ROTEM values within the interquartile range of those previously reported in European studies. Black race, obesity, and preeclampsia were associated with hypercoagulable profiles.

Production of monoclonal antibodies for therapeutic purposes: A review.

Monoclonal antibodies (mAbs) have been used in the development of immunotherapies that target a variety of diseases, such as cancer, autoimmune diseases, and even viral infections; they play a key role in immunization and are expected after vaccination. However, some conditions do not promote the development of neutralizing antibodies. Production and use of mAbs, generated in biofactories, represent vast potential as aids in immunological responses when the organism cannot produce them on their own, these convey unique specificity by recognizing and targeting specific antigen. Antibodies can be defined as heterotetrametric glycoproteins of symmetric nature, and they participate as effector proteins in humoral responses. Additionally, there are different types of mAbs (murine, chimeric, humanized, human, mAbs as Antibody-drug conjugates and bispecific mAbs) discussed in the present work. When these molecules are produced in vitro as mAbs, several common techniques, such as hybridomas or phage display are used. There are several preferred cell lines that function as biofactories, for the production of mAbs, the selection of which rely on the variation of adaptability, productivity and both phenotypic and genotypic shifts. After the cell expression systems and culture techniques are used, there are diverse specialized downstream processes to achieve desired yield and isolation as well as product quality and characterization. Novel perspectives regarding these protocols represent a potential improvement for mAbs high-scale production.

Extending the phenotypes associated with TRIO gene variants in a cohort of 25 patients and review of the literature.

The TRIO gene encodes a rho guanine exchange factor, the function of which is to exchange GDP to GTP, and hence to activate Rho GTPases, and has been described to impact neurodevelopment. Specific genotype-to-phenotype correlations have been established previously describing striking differentiating features seen in variants located in specific domains of the TRIO gene that are associated with opposite effects on RAC1 activity. Currently, 32 cases with a TRIO gene alteration have been published in the medical literature. Here, we report an additional 25, previously unreported individuals who possess heterozygous TRIO variants and we review the literature. In addition, functional studies were performed on the c.4394A > G (N1465S) and c.6244-2A > G TRIO variants to provide evidence for their pathogenicity. Variants reported by the current study include missense variants, truncating nonsense variants, and an intragenic deletion. Clinical features were previously described and included developmental delay, learning difficulties, microcephaly, macrocephaly, seizures, behavioral issues (aggression, stereotypies), skeletal problems including short, tapering fingers and scoliosis, dental problems (overcrowding/delayed eruption), and variable facial features. Here, we report clinical features that have not been described previously, including specific structural brain malformations such as abnormalities of the corpus callosum and ventriculomegaly, additional psychological and dental issues along with a more recognizable facial gestalt linked to the specific domains of the TRIO gene and the effect of the variant upon the function of the encoded protein. This current study further strengthens the genotype-to-phenotype correlation that was previously established and extends the range of phenotypes to include structural brain abnormalities, additional skeletal, dental, and psychiatric issues.

Retrospective Analysis of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study by the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas. BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series. METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management. RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of patients being female. Symptomatic presentation comprised 40.9% of cases, and tumors were often located in the extra-adrenal retroperitoneum (67.1%). At baseline, the median maximum tumor diameter was 7.2 cm. One hundred sixteen (35.4%) patients underwent active surveillance, whereas 212 (64.6%) patients underwent resection with 74.5% of operative cases achieving an R0/R1 resection. Serial tumor evaluations showed that malignant transformation to neuroblastoma was rare (0.9%, N=3). Tumors undergoing surveillance had a median follow-up of 1.9 years, with 92.2% of ganglioneuromas stable in size. With a median follow-up of 3.0 years for resected tumors, 84.4% of patients were disease free after resections, whereas recurrences were observed in 4 (1.9%) patients. CONCLUSIONS: Most ganglioneuromas have indolent disease courses and rarely transform to neuroblastoma. Thus, active surveillance may be appropriate for benign and asymptomatic tumors particularly when the risks of surgery outweigh the benefits. For symptomatic or growing tumors, resection may be curative.

Bibliometric analysis and diagnostic efficacy of cone-beam computed tomography studies published in Imaging Science in Dentistry from 2011 to 2022.

Purpose: This bibliometric analysis aimed to provide a comprehensive overview of the characteristics, trends, and level of diagnostic efficacy of studies on cone-beam computed tomography (CBCT) published in Imaging Science in Dentistry (ISD) from 2011 to 2022. Materials and Methods: Publications related to CBCT identified in the electronic collection of ISD were selected according to eligibility criteria by 2 independent reviewers who collected data on the characteristics of the articles (year, authors, and country). The type and topic of studies were analyzed using VOSviewer v.1.6.18 (Centre for Science and Technology Studies, Leiden University, Leiden, Netherlands). The research articles were classified according to the hierarchical scale of diagnostic efficacy. Results: Of the 236 articles included, most were from South Korea and Brazil. Bong-Hae Cho and Yun-Hoa Jung were the most prolific authors on the topic of CBCT. The most frequently published types of studies were cross-sectional and laboratory-based. The most popular topics WERE related to the diagnosis of pathologies and/or alterations, as well as anatomical variations. On the diagnostic efficacy scale, most studies were rated level 1 (technical efficacy) or 2 (diagnostic accuracy efficacy). Conclusion: A steady increase was observed in publications related to CBCT, which are of both clinical and academic interest. The trends in these publications were analyzed, revealing that most are cross-sectional studies primarily exploring the capabilities of CBCT in diagnosing pathologies and/or changes in the oral and maxillofacial complex. These studies were typically classified as level 1 or 2 on the diagnostic efficacy scale.

Protection of hybrid immunity against SARS-CoV-2 reinfection and severe COVID-19 during periods of Omicron variant predominance in Mexico

BACKGROUNDWith widespread transmission of the Omicron SARS-CoV-2 variant, reinfections have become increasingly common. Here, we explored the role hybrid immunity, primary infection severity, and variant predominance on the risk of reinfection and severe COVID-19 during periods of Omicron predominance in Mexico. METHODSWe analyzed reinfections in Mexico in individuals with [≥]90 days from a previous primary infection using a national surveillance registry of SARS-CoV-2 cases from March 3rd, 2020, until August 13th, 2022. Immunity-generating events included primary infection, partial or full vaccination and vaccine boosting. Reinfections were matched by age and sex with controls with primary SARS-CoV-2 infection and negative RT-PCR or antigen test [≥]90 days after infection to explore risk factors for reinfection and reinfection-associated severe COVID-19. We also explored the protective role of heterologous vs. homologous vaccine boosters against reinfection or severe COVID-19 in fully vaccinated individuals. RESULTSWe detected 231,202 SARS-CoV-2 reinfections in Mexico, with most occurring in unvaccinated individuals (41.55%). Over 207,623 reinfections occurred during periods of Omicron (89.8%), BA.1 (36.74%) and BA.5 (33.67%) subvariant predominance and a case-fatality rate of 0.22%. Vaccination protected against reinfection, without significant influence of the order of immunity-generating events and provided >90% protection against severe reinfections. Heterologous booster schedules were associated with [~]11% and [~]54% lower risk for reinfection and reinfection-associated severe COVID-19 respectively, modified by time-elapsed since the last immunity-generating event. CONCLUSIONSSARS-CoV-2 reinfections have increased during periods of Omicron predominance. Hybrid immunity provides protection against reinfection and reinfection-associated severe COVID-19, with potential benefit from heterologous booster schemes. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for the terms "SARS-CoV-2" AND "reinfection" AND "hybrid immunity" until November 20th, 2022, and identified a few population studies previously conducted in Israel, Sweden, Qatar, United States and Canada which explored risk of reinfection and the protective role of hybrid immunity in individuals with one, two or three doses of COVID-19 vaccines, predominantly during periods of predominance of Omicron BA.1 and BA.2 subvariants. Notably, no studies were conducted in any Latin American country or reported on the benefit of heterologous booster schemes or the order of immunity-generating events. Added value of this studyWe report the results of nation-wide study in Mexico of over 230,000 SARS-CoV-2 reinfections, with [~]90% occurring during periods of Omicron predominance. We identified that vaccination provided additional benefit on reducing the risk of SARS-CoV-2 reinfection, with the highest benefit observed in individuals with complete vaccination and booster protocols prior to primary infection or with primary infection during periods of BA.1 and BA.2 subvariant predominance. Hybrid immunity also provides a substantial reduction in the risk of reinfection-associated severe COVID-19, with >90% reduction in risk compared to unvaccinated individuals with previous SARS-CoV-2 infection, regardless of the order of immunity-generating events. Finally, heterologous COVID-19 booster schedules were associated with [~]11% and [~]54% lower risk for reinfection and reinfection-associated severe COVID-19 respectively, modified by time-elapsed since the last immunity-generating event. Implications of all the available evidenceOur results support that COVID-19 vaccination and boosters provide additional benefit to protect against SARS-CoV-2 reinfection and reinfection-associated severe COVID-19. The use of heterologous boosters appears to provide additional protection in previously infected individuals and such schemes may prove beneficial to increase vaccination coverage as newer, more transmissible variants emerge.

Machine Learning-Based Analysis in the Management of Iatrogenic Bile Duct Injury During Cholecystectomy: a Nationwide Multicenter Study.

BACKGROUND: Iatrogenic bile duct injury (IBDI) is a challenging surgical complication. IBDI management can be guided by artificial intelligence models. Our study identified the factors associated with successful initial repair of IBDI and predicted the success of definitive repair based on patient risk levels. METHODS: This is a retrospective multi-institution cohort of patients with IBDI after cholecystectomy conducted between 1990 and 2020. We implemented a decision tree analysis to determine the factors that contribute to successful initial repair and developed a risk-scoring model based on the Comprehensive Complication Index. RESULTS: We analyzed 748 patients across 22 hospitals. Our decision tree model was 82.8% accurate in predicting the success of the initial repair. Non-type E (p < 0.01), treatment in specialized centers (p < 0.01), and surgical repair (p < 0.001) were associated with better prognosis. The risk-scoring model was 82.3% (79.0-85.3%, 95% confidence interval [CI]) and 71.7% (63.8-78.7%, 95% CI) accurate in predicting success in the development and validation cohorts, respectively. Surgical repair, successful initial repair, and repair between 2 and 6 weeks were associated with better outcomes. DISCUSSION: Machine learning algorithms for IBDI are a novel tool may help to improve the decision-making process and guide management of these patients.

The Medical Science Liaison Role in Spain: A Survey Capturing the Opinion of Medical Department Professionals.

BACKGROUND: Literature that addresses the role of Medical Science Liaison (MSL) is currently limited. To the best of our knowledge, this is the first survey in Spain that gathers opinions from professionals whose work is either in or related to the medical departments from pharmaceutical companies. METHODS: A survey delivered by the SurveyMonkey online platform was completed by 101 pharmaceutical industry professionals (medical advisor/manager, 31.7%; medical director, 26.7%; medical information, 12.9%; and MSL manager, 11.9%). RESULTS: The median score for the global impression of the MSL was 8.7. The collaboration goes beyond formation since 85.1% of the respondents believed that MSLs should actively collaborate in both clinical trials and investigator-initiated studies, they should have more involvement with market access (51.5%), and they play an important role in compliance (94.0%). There was a tendency toward granting MSLs more responsibilities in terms of budget (73.3%) and their participation in the elaboration of the Medical Plan (91.1%). This position was considered as a strategic partner both internally and externally (76.2%). CONCLUSION: MSL is a well-known field-based profile with increasing importance and responsibilities. MSLs represent a strategic position as internal collaborators in the company, whose success relies on cross-functional work. The MSL's profile is in constant development, currently facing challenges such as adapting to remote interactions, or providing a clear definition with the best metrics to measure their performance as a non-promotional position.

Micro-CT analysis of the mandibular bone microarchitecture of rats after radiotherapy and low-power laser therapy.

To investigate whether low-level laser therapy (LLLT), at different times of application (immediate and late) in the region of the parotid glands, has a distance effect on the microarchitecture of the trabecular bone in mandible of rats irradiated by volumetric modular arc therapy (VMAT). Thirty adult Wistar rats were randomly divided into placebo control groups (CG, n = 2), only radiotherapy (RG, n = 2), only LPLT (LG, n = 2), and two other groups using LLLT in the immediate time (24 h) (ILG, n = 12) and late (120 h) (LLG, n = 12) to radiotherapy by VMAT in a single dose of 12 Gy. LLLT with AsGaAl laser (660 nm, 100 mW), a spot size of 0.0028 cm2, was applied in three points in the region of the right parotid gland, with energy of 2 J/cm2, 20 s per point, for 10 consecutive days. After euthanasia, the right hemimandibles of each animal were dissected, prepared, and analyzed by computerized microtomography (micro-CT) and histomorphometry. The different groups were analyzed by the Tukey and Bonferroni multiple comparison tests. The micro-CT analysis found statistically significant differences between the groups, especially in the LLG, which had the highest average bone volume compared to the CG (p = 0.001) and ILG (p = 0.002) and a greater number of trabeculae than the CG (p = 0.000) and ILG (p = 0.031). The ILG also had a higher number of trabeculae than the CG (p = 0.005). Trabecula separation (Tb.Sp) was lower in the LLG (p = 0.000) and ILG (p = 0.002) when compared to the CG. In the histomorphometry, there was no statistical difference between the groups in relation to all the analyzed variables. Micro-CT analysis showed that the LLLT, even applied at a distance, both in the immediate and late VMAT times, has an effect on the mandibular bone microarchitecture by increasing the volume and number of trabeculae and decreasing the spaces between them.

Long-term efficacy and safety of vestronidase alfa enzyme replacement therapy in pediatric subjects < 5 years with mucopolysaccharidosis VII.

Mucopolysaccharidosis (MPS) VII is an ultra-rare, autosomal-recessive, metabolic disease caused by a deficiency of ß-glucuronidase, a lysosomal enzyme that hydrolyzes glycosaminoglycans (GAGs), including dermatan sulfate (DS), chondroitin sulfate, and heparan sulfate (HS). ß-glucuronidase deficiency leads to progressive accumulation of undegraded GAGs in lysosomes of affected tissues, which may cause hydrops fetalis, short stature, hepatosplenomegaly, and cognitive impairment. An open-label, multicenter, phase II study was conducted in 8 pediatric subjects <5 years of age with MPS VII. Subjects received the recombinant human ß-glucuronidase vestronidase alfa 4 mg/kg by intravenous infusion every other week for 48 weeks (treatment period). Those who completed the 48-week treatment were offered to continue treatment with vestronidase alfa 4 mg/kg for up to 240 weeks or until withdrawal of consent, discontinuation, or study termination (continuation period). The level of GAG excreted in urine (uGAG) above normal has been shown to correlate with disease severity and clinical outcomes in MPS diseases. Therefore, the primary efficacy endpoint of this study was to determine the mean percentage change in uGAG DS excretion from baseline to week 48. Statistically significant reductions in uGAG DS from baseline were observed at each visit (p < 0.0001), with a least square mean (standard error) percentage change of -60% (6.6) at week 4 (first post-baseline assessment) and -61% (6.41) at week 48 (final assessment during treatment period). Secondary efficacy endpoints included change from baseline to week 48 in growth and hepatosplenomegaly. Positive trends were observed toward increased standing height Z-score (mean [standard deviation] at baseline, -2.630 [1.17], n = 8; at week 48, -2.045 [0.27], n = 7) and growth velocity (mean [SD] Z-score at baseline, -2.59 [1.49], n = 4; at week 48, -0.39 [2.10], n = 4; p = 0.27). Hepatomegaly was resolved in 3 of 3 subjects assessed by ultrasound and in 5 of 6 subjects assessed by physical examination; splenomegaly was resolved in 1 of 3 subjects assessed by ultrasound and in 2 of 2 subjects assessed by physical examination. There were no new safety signals identified during this study. Mild-to-moderate infusion-associated reactions occurred in 4 (50%) subjects. In conclusion, long-term vestronidase alfa treatment demonstrated a rapid and sustained reduction in uGAGs, maintained growth, and improved hepatosplenomegaly in pediatric subjects with MPS VII <5 years of age. Trial registration: NCT02418455.

Crop succession and its reflections on soybean performance

The fluctuations in yield and consequently in production occurred due to climatic adversities in the main producing states of Brazil. Farming has changed over time, and past scenarios have shown high exploitation of natural resources focusing on soil tillage and conventional seeding methods. This study aimed to determine the yield performance of soybean grown under 10 consolidated crop succession systems. The experiment was conducted during the 2018/2019 crop season, before the research project entitled "Sustainable production systems with better use of biological and natural resources, with treatments arranged in a randomized block design and four replications". The treatments consisted of the following predecessor crops: Avena sativa, Avena strigosa, Triticum aestivum, Secale cereale, Brassica napus, Raphanus sativus, Avena strigosa + Raphanus sativus + Vicia sativa, Fallow, Avena strigosa + Lolium multiflorum, and Triticum aestivum ­ Fodder. Soybean was subsequently sown across winter crops. The succession that showed superior yield was Avena strigosa + Lolium multiflorum. This attribute was established by associating taller plants with the maximization of the number of grains per pod, hundred-grain mass, grain mass, and plant dry mass; in contrast, there was a lower emphasis on plant residue. The determining attributes for soybean yield were plant stand, plant height, the number of pods per plant, and total grain mass, with contrasts among groups composed of the succession of Avena sativa, Avena strigosa, Triticum aestivum, Secale cereale, and Brassica napus, distanced from Raphanus sativus, Avena strigosa + Raphanus sativus + Vicia sativa, Fallow, Avena strigosa + Lolium multiflorum, and Triticum aestivum - Fodder.